Environmental Dermatology

Tick-borne diseases are increasing in prevalence, likely due to climate change in combination with human movement into tick habitats.^1-3 The Ixodes genus of hard ticks is a common vector for the transmission of pathogenic viruses, bacteria, parasites, and toxins. Among these, Lyme disease, which is caused by Borrelia burgdorferi, is the most prevalent, followed by babesiosis and human granulocytic anaplasmosis (HGA), respectively.⁴ In Europe, tick-borne encephalitis is commonly encountered. More recently identified diseases transmitted by Ixodes ticks include Powassan virus and Borrelia miyamotoi infection; however, these diseases are less frequently encountered than other tick-borne diseases.^5,6

As tick-borne diseases become more prevalent, the likelihood of coinfection with more than one Ixodes-transmitted pathogen is increasing.⁷ Therefore, it is important for physicians who practice in endemic areas to be aware of the possibility of coinfection, which can alter clinical presentation, disease severity, and treatment response in tick-borne diseases. Additionally, public education on tick-bite prevention and prompt tick removal is necessary to combat the rising prevalence of these diseases.

Coinfection

Risk of coinfection with more than one tick-borne disease is contingent on the geographic distribution of the tick species as well as the particular pathogen’s prevalence within reservoir hosts in a given area (Figure). Most coinfections occur with B. burgdorferi and an additional pathogen, usually Anaplasma phagocytophilum (which causes human granulocytic anaplasmosis [HGA]) or Babesia microti (which causes babesiosis). In Europe, coinfection with tick-borne encephalitis virus may occur. There is limited evidence of human coinfection with B miyamotoi or Powassan virus, as isolated infection with either of these pathogens is rare.

In patients with Lyme disease, as many as 35% may have concurrent babesiosis, and as many as 12% may have concurrent HGA in endemic areas (eg, northeast and northern central United States).^7-9 Concurrent HGA and babesiosis in the absence of Lyme disease also has been documented.^7-9 Coinfection generally increases the diversity of presenting symptoms, often obscuring the primary diagnosis. In addition, these patients may have more severe and prolonged illness.^8,10,11

In endemic areas, coinfection with B burgdorferi and an additional pathogen should be suspected if a patient presents with typical symptoms of early Lyme disease, especially erythema migrans, along with (1) combination of fever, chills, and headache; (2) prolonged viral-like illness, particularly 48 hours after appropriate antibiotic treatment; and (3) unexplained blood dyscrasia.^7,11,12 When a patient presents with erythema migrans, it is unnecessary to test for HGA, as treatment of Lyme disease with doxycycline also is adequate for treating HGA; however, if systemic symptoms persist despite treatment, testing for babesiosis and other tick-borne illnesses should be considered, as babesiosis requires treatment with atovaquone plus azithromycin or clindamycin plus quinine.¹³

A complete blood count and peripheral blood smear can aid in the diagnosis of coinfection. The complete blood count may reveal leukopenia, anemia, or thrombocytopenia associated with HGA or babesiosis. The peripheral blood smear can reveal inclusions of intra-erythrocytic ring forms and tetrads (the “Maltese cross” appearance) in babesiosis and intragranulocytic morulae in HGA.¹² The most sensitive diagnostic tests for tick-borne diseases are organism-specific IgM and IgG serology for Lyme disease, babesiosis, and HGA and polymerase chain reaction for babesiosis and HGA.⁷

Prevention Strategies

The most effective means of controlling tick-borne disease is avoiding tick bites altogether. One method is to avoid spending time in high-risk areas that may be infested with ticks, particularly low-lying brush, where ticks are likely to hide.¹⁴ For individuals traveling in environments with a high risk of tick exposure, behavioral methods of avoidance are indicated, including wearing long pants and a shirt with long sleeves, tucking the shirt into the pants, and wearing closed-toe shoes. Wearing light-colored clothing may aid in tick identification and prompt removal prior to attachment. Permethrin-impregnated clothing has been proven to decrease the likelihood of tick bites in adults working outdoors.^15-17

Topical repellents also play a role in the prevention of tick-borne diseases. The most effective and safe synthetic repellents are N,N-diethyl-meta-toluamide (DEET); picaridin; p-menthane-3,8-diol; and insect repellent 3535 (IR3535)(ethyl butylacetylaminopropionate).^16-19 Plant-based repellents also are available, but their efficacy is strongly influenced by the surrounding environment (eg, temperature, humidity, organic matter).^20-22 Individuals also may be exposed to ticks following contact with domesticated animals and pets.^23,24 Tick prevention in pets with the use of ectoparasiticides should be directed by a qualified veterinarian.²⁵

Tick Removal

Following a bite, the tick should be removed promptly to avoid transmission of pathogens. Numerous commercial and in-home methods of tick removal are available, but not all are equally effective. Detachment techniques include removal with a card or commercially available radiofrequency device, lassoing, or freezing.^26,27 However, the most effective method is simple removal with tweezers. The tick should be grasped close to the skin surface and pulled upward with an even pressure. Commercially available tick-removal devices have not been shown to produce better outcomes than removal of the tick with tweezers.²⁸

Conclusion

When patients do not respond to therapy for presumed tick-borne infection, the diagnosis should be reconsidered. One important consideration is coinfection with a second organism. Prompt identification and removal of ticks can prevent disease transmission.

Tick-borne diseases are increasing in prevalence, likely due to climate change in combination with human movement into tick habitats.^1-3 The Ixodes genus of hard ticks is a common vector for the transmission of pathogenic viruses, bacteria, parasites, and toxins. Among these, Lyme disease, which is caused by Borrelia burgdorferi, is the most prevalent, followed by babesiosis and human granulocytic anaplasmosis (HGA), respectively.⁴ In Europe, tick-borne encephalitis is commonly encountered. More recently identified diseases transmitted by Ixodes ticks include Powassan virus and Borrelia miyamotoi infection; however, these diseases are less frequently encountered than other tick-borne diseases.^5,6

As tick-borne diseases become more prevalent, the likelihood of coinfection with more than one Ixodes-transmitted pathogen is increasing.⁷ Therefore, it is important for physicians who practice in endemic areas to be aware of the possibility of coinfection, which can alter clinical presentation, disease severity, and treatment response in tick-borne diseases. Additionally, public education on tick-bite prevention and prompt tick removal is necessary to combat the rising prevalence of these diseases.

Coinfection

Risk of coinfection with more than one tick-borne disease is contingent on the geographic distribution of the tick species as well as the particular pathogen’s prevalence within reservoir hosts in a given area (Figure). Most coinfections occur with B. burgdorferi and an additional pathogen, usually Anaplasma phagocytophilum (which causes human granulocytic anaplasmosis [HGA]) or Babesia microti (which causes babesiosis). In Europe, coinfection with tick-borne encephalitis virus may occur. There is limited evidence of human coinfection with B miyamotoi or Powassan virus, as isolated infection with either of these pathogens is rare.

In patients with Lyme disease, as many as 35% may have concurrent babesiosis, and as many as 12% may have concurrent HGA in endemic areas (eg, northeast and northern central United States).^7-9 Concurrent HGA and babesiosis in the absence of Lyme disease also has been documented.^7-9 Coinfection generally increases the diversity of presenting symptoms, often obscuring the primary diagnosis. In addition, these patients may have more severe and prolonged illness.^8,10,11

In endemic areas, coinfection with B burgdorferi and an additional pathogen should be suspected if a patient presents with typical symptoms of early Lyme disease, especially erythema migrans, along with (1) combination of fever, chills, and headache; (2) prolonged viral-like illness, particularly 48 hours after appropriate antibiotic treatment; and (3) unexplained blood dyscrasia.^7,11,12 When a patient presents with erythema migrans, it is unnecessary to test for HGA, as treatment of Lyme disease with doxycycline also is adequate for treating HGA; however, if systemic symptoms persist despite treatment, testing for babesiosis and other tick-borne illnesses should be considered, as babesiosis requires treatment with atovaquone plus azithromycin or clindamycin plus quinine.¹³

A complete blood count and peripheral blood smear can aid in the diagnosis of coinfection. The complete blood count may reveal leukopenia, anemia, or thrombocytopenia associated with HGA or babesiosis. The peripheral blood smear can reveal inclusions of intra-erythrocytic ring forms and tetrads (the “Maltese cross” appearance) in babesiosis and intragranulocytic morulae in HGA.¹² The most sensitive diagnostic tests for tick-borne diseases are organism-specific IgM and IgG serology for Lyme disease, babesiosis, and HGA and polymerase chain reaction for babesiosis and HGA.⁷

Prevention Strategies

The most effective means of controlling tick-borne disease is avoiding tick bites altogether. One method is to avoid spending time in high-risk areas that may be infested with ticks, particularly low-lying brush, where ticks are likely to hide.¹⁴ For individuals traveling in environments with a high risk of tick exposure, behavioral methods of avoidance are indicated, including wearing long pants and a shirt with long sleeves, tucking the shirt into the pants, and wearing closed-toe shoes. Wearing light-colored clothing may aid in tick identification and prompt removal prior to attachment. Permethrin-impregnated clothing has been proven to decrease the likelihood of tick bites in adults working outdoors.^15-17

Topical repellents also play a role in the prevention of tick-borne diseases. The most effective and safe synthetic repellents are N,N-diethyl-meta-toluamide (DEET); picaridin; p-menthane-3,8-diol; and insect repellent 3535 (IR3535)(ethyl butylacetylaminopropionate).^16-19 Plant-based repellents also are available, but their efficacy is strongly influenced by the surrounding environment (eg, temperature, humidity, organic matter).^20-22 Individuals also may be exposed to ticks following contact with domesticated animals and pets.^23,24 Tick prevention in pets with the use of ectoparasiticides should be directed by a qualified veterinarian.²⁵

Tick Removal

Following a bite, the tick should be removed promptly to avoid transmission of pathogens. Numerous commercial and in-home methods of tick removal are available, but not all are equally effective. Detachment techniques include removal with a card or commercially available radiofrequency device, lassoing, or freezing.^26,27 However, the most effective method is simple removal with tweezers. The tick should be grasped close to the skin surface and pulled upward with an even pressure. Commercially available tick-removal devices have not been shown to produce better outcomes than removal of the tick with tweezers.²⁸

Conclusion

When patients do not respond to therapy for presumed tick-borne infection, the diagnosis should be reconsidered. One important consideration is coinfection with a second organism. Prompt identification and removal of ticks can prevent disease transmission.

Tick-borne diseases are increasing in prevalence, likely due to climate change in combination with human movement into tick habitats.^1-3 The Ixodes genus of hard ticks is a common vector for the transmission of pathogenic viruses, bacteria, parasites, and toxins. Among these, Lyme disease, which is caused by Borrelia burgdorferi, is the most prevalent, followed by babesiosis and human granulocytic anaplasmosis (HGA), respectively.⁴ In Europe, tick-borne encephalitis is commonly encountered. More recently identified diseases transmitted by Ixodes ticks include Powassan virus and Borrelia miyamotoi infection; however, these diseases are less frequently encountered than other tick-borne diseases.^5,6

As tick-borne diseases become more prevalent, the likelihood of coinfection with more than one Ixodes-transmitted pathogen is increasing.⁷ Therefore, it is important for physicians who practice in endemic areas to be aware of the possibility of coinfection, which can alter clinical presentation, disease severity, and treatment response in tick-borne diseases. Additionally, public education on tick-bite prevention and prompt tick removal is necessary to combat the rising prevalence of these diseases.

Coinfection

Risk of coinfection with more than one tick-borne disease is contingent on the geographic distribution of the tick species as well as the particular pathogen’s prevalence within reservoir hosts in a given area (Figure). Most coinfections occur with B. burgdorferi and an additional pathogen, usually Anaplasma phagocytophilum (which causes human granulocytic anaplasmosis [HGA]) or Babesia microti (which causes babesiosis). In Europe, coinfection with tick-borne encephalitis virus may occur. There is limited evidence of human coinfection with B miyamotoi or Powassan virus, as isolated infection with either of these pathogens is rare.

In patients with Lyme disease, as many as 35% may have concurrent babesiosis, and as many as 12% may have concurrent HGA in endemic areas (eg, northeast and northern central United States).^7-9 Concurrent HGA and babesiosis in the absence of Lyme disease also has been documented.^7-9 Coinfection generally increases the diversity of presenting symptoms, often obscuring the primary diagnosis. In addition, these patients may have more severe and prolonged illness.^8,10,11

In endemic areas, coinfection with B burgdorferi and an additional pathogen should be suspected if a patient presents with typical symptoms of early Lyme disease, especially erythema migrans, along with (1) combination of fever, chills, and headache; (2) prolonged viral-like illness, particularly 48 hours after appropriate antibiotic treatment; and (3) unexplained blood dyscrasia.^7,11,12 When a patient presents with erythema migrans, it is unnecessary to test for HGA, as treatment of Lyme disease with doxycycline also is adequate for treating HGA; however, if systemic symptoms persist despite treatment, testing for babesiosis and other tick-borne illnesses should be considered, as babesiosis requires treatment with atovaquone plus azithromycin or clindamycin plus quinine.¹³

A complete blood count and peripheral blood smear can aid in the diagnosis of coinfection. The complete blood count may reveal leukopenia, anemia, or thrombocytopenia associated with HGA or babesiosis. The peripheral blood smear can reveal inclusions of intra-erythrocytic ring forms and tetrads (the “Maltese cross” appearance) in babesiosis and intragranulocytic morulae in HGA.¹² The most sensitive diagnostic tests for tick-borne diseases are organism-specific IgM and IgG serology for Lyme disease, babesiosis, and HGA and polymerase chain reaction for babesiosis and HGA.⁷

Prevention Strategies

The most effective means of controlling tick-borne disease is avoiding tick bites altogether. One method is to avoid spending time in high-risk areas that may be infested with ticks, particularly low-lying brush, where ticks are likely to hide.¹⁴ For individuals traveling in environments with a high risk of tick exposure, behavioral methods of avoidance are indicated, including wearing long pants and a shirt with long sleeves, tucking the shirt into the pants, and wearing closed-toe shoes. Wearing light-colored clothing may aid in tick identification and prompt removal prior to attachment. Permethrin-impregnated clothing has been proven to decrease the likelihood of tick bites in adults working outdoors.^15-17

Topical repellents also play a role in the prevention of tick-borne diseases. The most effective and safe synthetic repellents are N,N-diethyl-meta-toluamide (DEET); picaridin; p-menthane-3,8-diol; and insect repellent 3535 (IR3535)(ethyl butylacetylaminopropionate).^16-19 Plant-based repellents also are available, but their efficacy is strongly influenced by the surrounding environment (eg, temperature, humidity, organic matter).^20-22 Individuals also may be exposed to ticks following contact with domesticated animals and pets.^23,24 Tick prevention in pets with the use of ectoparasiticides should be directed by a qualified veterinarian.²⁵

Tick Removal

Following a bite, the tick should be removed promptly to avoid transmission of pathogens. Numerous commercial and in-home methods of tick removal are available, but not all are equally effective. Detachment techniques include removal with a card or commercially available radiofrequency device, lassoing, or freezing.^26,27 However, the most effective method is simple removal with tweezers. The tick should be grasped close to the skin surface and pulled upward with an even pressure. Commercially available tick-removal devices have not been shown to produce better outcomes than removal of the tick with tweezers.²⁸

Conclusion

When patients do not respond to therapy for presumed tick-borne infection, the diagnosis should be reconsidered. One important consideration is coinfection with a second organism. Prompt identification and removal of ticks can prevent disease transmission.

The Ixodes tick is prevalent in temperate climates worldwide. During a blood meal, pathogens may be transmitted from the tick to its host. Borrelia burgdorferi, a spirochete responsible for Lyme disease, is the most prevalent pathogen transmitted by Ixodes ticks.¹ Borrelia mayonii recently was identified as an additional cause of Lyme disease in the United States.²

The Ixodes tick also is associated with several less common pathogens, including Babesia microti and the tick-borne encephalitis virus, which have been recognized as Ixodes-associated pathogens for many years.^3,4 Other pathogens have been identified, including Anaplasma phagocytophilum, recognized in the 1990s as the cause of human granulocytic anaplasmosis, as well as the Powassan virus and Borrelia miyamotoi.^5-7 Additionally, tick paralysis has been associated with toxins in the saliva of various species of several genera of ticks, including some Ixodes species.⁸ Due to an overlap in geographic distribution (Figure) and disease presentations (eTable), it is important that physicians be familiar with these regional pathogens transmitted by Ixodes ticks.

Human Granulocytic Anaplasmosis

Formerly known as human granulocytic ehrlichiosis, human granulocytic anaplasmosis is caused by A phagocytophilum and is transmitted by Ixodes scapularis, Ixodes pacificus, and Ixodes persulcatus. The incidence of human granulocytic anaplasmosis in the United States increased 12-fold from 2001 to 2011.⁹

Presenting symptoms generally are nonspecific, including fever, night sweats, headache, myalgias, and arthralgias, often resulting in misdiagnosis as a viral infection. Laboratory abnormalities include mild transaminitis, leukopenia, and thrombocytopenia.^9,10 Although most infections resolve spontaneously, 3% of patients develop serious complications. The mortality rate is 0.6%.¹¹

A diagnosis of human granulocytic anaplasmosis should be suspected in patients with a viral-like illness and exposure to ticks in an endemic area. The diagnosis can be confirmed by polymerase chain reaction (PCR), acute- and convalescent-phase serologic testing, or direct fluorescent antibody screening. Characteristic morulae may be present in granulocytes.¹² Treatment typically includes doxycycline, which also covers B burgdorferi coinfection. When a diagnosis of human granulocytic anaplasmosis is suspected, treatment should never be delayed to await laboratory confirmation. If no clinical improvement is seen within 48 hours, alternate diagnoses or coinfection with B microti should be considered.¹⁰

Babesiosis

The protozoan B microti causes babesiosis in the United States, with Babesia divergens being more common in Europe.¹³ Reported cases of babesiosis in New York increased as much as 20-fold from 2001 to 2008.¹⁴ Transmission primarily is from the Ixodes tick but rarely can occur from blood transfusion.¹⁵ Tick attachment for at least 36 hours is required for transmission.¹³

The clinical presentation of babesiosis ranges from asymptomatic to fatal. Symptoms generally are nonspecific, resembling a viral infection and including headache, nausea, diarrhea, arthralgia, and myalgia. Laboratory evaluation may reveal hemolytic anemia, thrombocytopenia, transaminitis, and elevated blood urea nitrogen and creatinine levels.¹⁶ Rash is not typical. Resolution of symptoms generally occurs within 2 weeks of presentation, although anemia may persist for months.¹³ Severe disease is more common among elderly and immunocompromised patients. Complications include respiratory failure, renal failure, congestive heart failure, and disseminated intravascular coagulation. The mortality rate in the United States is approximately 10%.^10,16

A diagnosis of babesiosis is made based on the presence of flulike symptoms, laboratory results, and history of recent travel to an endemic area. A thin blood smear allows identification of the organism in erythrocytes as ring forms or tetrads (a “Maltese cross” appearance).¹⁷ Polymerase chain reaction is more sensitive than a blood smear, especially in early disease.¹⁸ Indirect fluorescent antibody testing is species-specific but cannot verify active infection.¹⁰

Treatment of babesiosis is indicated for symptomatic patients with active infection. Positive serology alone is not an indication for treatment. Asymptomatic patients with positive serology should have diagnostic testing repeated in 3 months with subsequent treatment if parasitemia persists. Mild disease is treated with atovaquone plus azithromycin or clindamycin plus quinine. Severe babesiosis is treated with quinine and intravenous clindamycin and may require exchange transfusion.¹⁰ Coinfection with B burgdorferi should be considered in patients with flulike symptoms and erythema migrans or treatment failure. Coinfection is diagnosed by Lyme serology plus PCR for B microti. This is an important consideration because treatment of babesiosis does not eradicate B burgdorferi infection.¹⁹

Powassan Virus

Powassan virus is a flavivirus that causes encephalitis. It is transmitted by Ixodes cookei (Powassan virus, lineage I) in the Great Lakes region and by I scapularis (Powassan virus, lineage II, or deer tick virus) in the northeastern United States. Transmission can occur within 15 minutes of tick attachment.^6,20,21

Patients typically present with fever, headache, altered mental status, seizures, and focal neurologic deficits. Gastrointestinal symptoms and rash also have been reported.²¹ The diagnosis is made based on clinical presentation and laboratory testing with PCR or enzyme-linked immunosorbent assay (ELISA). Cross-reactivity on ELISA exists, necessitating confirmation with a neutralizing antibody or PCR. Treatment is supportive. Corticosteroids and intravenous immunoglobulin have been proposed as treatment modalities, but evidence of their efficacy is limited.²²

Tick-borne Encephalitis

Tick-borne encephalitis is caused by the flavivirus tick-borne encephalitis virus in Europe and Asia. The tick-borne encephalitis virus is transmitted by Ixodes ricinus in Europe and by Ixodes persulcatus in eastern Russia, China, and Japan. It also has been associated with consumption of unpasteurized milk.^23,24

Tick-borne encephalitis presents in a biphasic pattern. The initial viremic phase can persist for as long as 8 days with headache, nausea, myalgia, and fever. One-third of patients then enter an asymptomatic phase, followed by virus penetration into the central nervous system. The neurologic phase produces continued headache and fever with photophobia, focal neurologic deficits, seizures, respiratory depression, or coma. Neurologic sequelae persist in 10% to 20% of patients.^25,26

In the viremic stage, diagnosis is made with PCR or culture. During the latent phase or neurologic phase, serologic testing for tick-borne encephalitis virus antibodies is indicated. Neutralizing antibody evaluation may be necessary due to cross-reactivity among flaviviruses.²⁷ Treatment is supportive. An inactivated vaccine is available for high-risk populations.²⁸

Borrelia miyamotoi Disease

Borrelia miyamotoi is a symbiont of the Ixodes tick formerly believed to have no pathogenic significance; however, B miyamotoi was isolated in febrile patients in Russia in 2011⁷ and was identified as a pathogen in both North America²⁹ and Europe in 2013.³⁰ Disease presentation includes nonspecific symptoms of fever, fatigue, headache, arthralgia, myalgia, and nausea. Rash is uncommon. Laboratory abnormalities include leukopenia, thrombocytopenia, and transaminitis.^31,32 Meningoencephalitis may occur in immunocompromised patients.^29,30

The diagnosis of B miyamotoi disease is confirmed by PCR or serology. An ELISA that is positive for B burgdorferi IgM but negative with confirmatory immunoblot suggests B miyamotoi disease. Seroconversion using a glpQ protein ELISA also can be assessed.³¹ If ELISA is positive, Lyme disease can be excluded because B burgdorferi does not possess g1pQ. Treatment is with doxycycline.³²

Tick Paralysis

Tick paralysis is an intoxication with holocyclotoxin from the saliva of gravid hard ticks. In the United States, intoxication is associated with ticks of various species of Amblyomma, Dermacentor, and Ixodes in the Northwest, Southeast, and Northeast. In Australia, intoxication is associated with Ixodes.³³ Patients present with weakness and fatigue, progressing to ascending flaccid paralysis with sensory sparing. The treatment is tick removal.^8,33

Conclusion

Arthropods carry many regional pathogens. Physicians outside of those regions should seek a travel history and be alert for imported disease.

The Ixodes tick is prevalent in temperate climates worldwide. During a blood meal, pathogens may be transmitted from the tick to its host. Borrelia burgdorferi, a spirochete responsible for Lyme disease, is the most prevalent pathogen transmitted by Ixodes ticks.¹ Borrelia mayonii recently was identified as an additional cause of Lyme disease in the United States.²

The Ixodes tick also is associated with several less common pathogens, including Babesia microti and the tick-borne encephalitis virus, which have been recognized as Ixodes-associated pathogens for many years.^3,4 Other pathogens have been identified, including Anaplasma phagocytophilum, recognized in the 1990s as the cause of human granulocytic anaplasmosis, as well as the Powassan virus and Borrelia miyamotoi.^5-7 Additionally, tick paralysis has been associated with toxins in the saliva of various species of several genera of ticks, including some Ixodes species.⁸ Due to an overlap in geographic distribution (Figure) and disease presentations (eTable), it is important that physicians be familiar with these regional pathogens transmitted by Ixodes ticks.

Human Granulocytic Anaplasmosis

Formerly known as human granulocytic ehrlichiosis, human granulocytic anaplasmosis is caused by A phagocytophilum and is transmitted by Ixodes scapularis, Ixodes pacificus, and Ixodes persulcatus. The incidence of human granulocytic anaplasmosis in the United States increased 12-fold from 2001 to 2011.⁹

Presenting symptoms generally are nonspecific, including fever, night sweats, headache, myalgias, and arthralgias, often resulting in misdiagnosis as a viral infection. Laboratory abnormalities include mild transaminitis, leukopenia, and thrombocytopenia.^9,10 Although most infections resolve spontaneously, 3% of patients develop serious complications. The mortality rate is 0.6%.¹¹

A diagnosis of human granulocytic anaplasmosis should be suspected in patients with a viral-like illness and exposure to ticks in an endemic area. The diagnosis can be confirmed by polymerase chain reaction (PCR), acute- and convalescent-phase serologic testing, or direct fluorescent antibody screening. Characteristic morulae may be present in granulocytes.¹² Treatment typically includes doxycycline, which also covers B burgdorferi coinfection. When a diagnosis of human granulocytic anaplasmosis is suspected, treatment should never be delayed to await laboratory confirmation. If no clinical improvement is seen within 48 hours, alternate diagnoses or coinfection with B microti should be considered.¹⁰

Babesiosis

The protozoan B microti causes babesiosis in the United States, with Babesia divergens being more common in Europe.¹³ Reported cases of babesiosis in New York increased as much as 20-fold from 2001 to 2008.¹⁴ Transmission primarily is from the Ixodes tick but rarely can occur from blood transfusion.¹⁵ Tick attachment for at least 36 hours is required for transmission.¹³

The clinical presentation of babesiosis ranges from asymptomatic to fatal. Symptoms generally are nonspecific, resembling a viral infection and including headache, nausea, diarrhea, arthralgia, and myalgia. Laboratory evaluation may reveal hemolytic anemia, thrombocytopenia, transaminitis, and elevated blood urea nitrogen and creatinine levels.¹⁶ Rash is not typical. Resolution of symptoms generally occurs within 2 weeks of presentation, although anemia may persist for months.¹³ Severe disease is more common among elderly and immunocompromised patients. Complications include respiratory failure, renal failure, congestive heart failure, and disseminated intravascular coagulation. The mortality rate in the United States is approximately 10%.^10,16

A diagnosis of babesiosis is made based on the presence of flulike symptoms, laboratory results, and history of recent travel to an endemic area. A thin blood smear allows identification of the organism in erythrocytes as ring forms or tetrads (a “Maltese cross” appearance).¹⁷ Polymerase chain reaction is more sensitive than a blood smear, especially in early disease.¹⁸ Indirect fluorescent antibody testing is species-specific but cannot verify active infection.¹⁰

Treatment of babesiosis is indicated for symptomatic patients with active infection. Positive serology alone is not an indication for treatment. Asymptomatic patients with positive serology should have diagnostic testing repeated in 3 months with subsequent treatment if parasitemia persists. Mild disease is treated with atovaquone plus azithromycin or clindamycin plus quinine. Severe babesiosis is treated with quinine and intravenous clindamycin and may require exchange transfusion.¹⁰ Coinfection with B burgdorferi should be considered in patients with flulike symptoms and erythema migrans or treatment failure. Coinfection is diagnosed by Lyme serology plus PCR for B microti. This is an important consideration because treatment of babesiosis does not eradicate B burgdorferi infection.¹⁹

Powassan Virus

Powassan virus is a flavivirus that causes encephalitis. It is transmitted by Ixodes cookei (Powassan virus, lineage I) in the Great Lakes region and by I scapularis (Powassan virus, lineage II, or deer tick virus) in the northeastern United States. Transmission can occur within 15 minutes of tick attachment.^6,20,21

Patients typically present with fever, headache, altered mental status, seizures, and focal neurologic deficits. Gastrointestinal symptoms and rash also have been reported.²¹ The diagnosis is made based on clinical presentation and laboratory testing with PCR or enzyme-linked immunosorbent assay (ELISA). Cross-reactivity on ELISA exists, necessitating confirmation with a neutralizing antibody or PCR. Treatment is supportive. Corticosteroids and intravenous immunoglobulin have been proposed as treatment modalities, but evidence of their efficacy is limited.²²

Tick-borne Encephalitis

Tick-borne encephalitis is caused by the flavivirus tick-borne encephalitis virus in Europe and Asia. The tick-borne encephalitis virus is transmitted by Ixodes ricinus in Europe and by Ixodes persulcatus in eastern Russia, China, and Japan. It also has been associated with consumption of unpasteurized milk.^23,24

Tick-borne encephalitis presents in a biphasic pattern. The initial viremic phase can persist for as long as 8 days with headache, nausea, myalgia, and fever. One-third of patients then enter an asymptomatic phase, followed by virus penetration into the central nervous system. The neurologic phase produces continued headache and fever with photophobia, focal neurologic deficits, seizures, respiratory depression, or coma. Neurologic sequelae persist in 10% to 20% of patients.^25,26

In the viremic stage, diagnosis is made with PCR or culture. During the latent phase or neurologic phase, serologic testing for tick-borne encephalitis virus antibodies is indicated. Neutralizing antibody evaluation may be necessary due to cross-reactivity among flaviviruses.²⁷ Treatment is supportive. An inactivated vaccine is available for high-risk populations.²⁸

Borrelia miyamotoi Disease

Borrelia miyamotoi is a symbiont of the Ixodes tick formerly believed to have no pathogenic significance; however, B miyamotoi was isolated in febrile patients in Russia in 2011⁷ and was identified as a pathogen in both North America²⁹ and Europe in 2013.³⁰ Disease presentation includes nonspecific symptoms of fever, fatigue, headache, arthralgia, myalgia, and nausea. Rash is uncommon. Laboratory abnormalities include leukopenia, thrombocytopenia, and transaminitis.^31,32 Meningoencephalitis may occur in immunocompromised patients.^29,30

The diagnosis of B miyamotoi disease is confirmed by PCR or serology. An ELISA that is positive for B burgdorferi IgM but negative with confirmatory immunoblot suggests B miyamotoi disease. Seroconversion using a glpQ protein ELISA also can be assessed.³¹ If ELISA is positive, Lyme disease can be excluded because B burgdorferi does not possess g1pQ. Treatment is with doxycycline.³²

Tick Paralysis

Tick paralysis is an intoxication with holocyclotoxin from the saliva of gravid hard ticks. In the United States, intoxication is associated with ticks of various species of Amblyomma, Dermacentor, and Ixodes in the Northwest, Southeast, and Northeast. In Australia, intoxication is associated with Ixodes.³³ Patients present with weakness and fatigue, progressing to ascending flaccid paralysis with sensory sparing. The treatment is tick removal.^8,33

Conclusion

Arthropods carry many regional pathogens. Physicians outside of those regions should seek a travel history and be alert for imported disease.

The Ixodes tick is prevalent in temperate climates worldwide. During a blood meal, pathogens may be transmitted from the tick to its host. Borrelia burgdorferi, a spirochete responsible for Lyme disease, is the most prevalent pathogen transmitted by Ixodes ticks.¹ Borrelia mayonii recently was identified as an additional cause of Lyme disease in the United States.²

The Ixodes tick also is associated with several less common pathogens, including Babesia microti and the tick-borne encephalitis virus, which have been recognized as Ixodes-associated pathogens for many years.^3,4 Other pathogens have been identified, including Anaplasma phagocytophilum, recognized in the 1990s as the cause of human granulocytic anaplasmosis, as well as the Powassan virus and Borrelia miyamotoi.^5-7 Additionally, tick paralysis has been associated with toxins in the saliva of various species of several genera of ticks, including some Ixodes species.⁸ Due to an overlap in geographic distribution (Figure) and disease presentations (eTable), it is important that physicians be familiar with these regional pathogens transmitted by Ixodes ticks.

Human Granulocytic Anaplasmosis

Formerly known as human granulocytic ehrlichiosis, human granulocytic anaplasmosis is caused by A phagocytophilum and is transmitted by Ixodes scapularis, Ixodes pacificus, and Ixodes persulcatus. The incidence of human granulocytic anaplasmosis in the United States increased 12-fold from 2001 to 2011.⁹

Presenting symptoms generally are nonspecific, including fever, night sweats, headache, myalgias, and arthralgias, often resulting in misdiagnosis as a viral infection. Laboratory abnormalities include mild transaminitis, leukopenia, and thrombocytopenia.^9,10 Although most infections resolve spontaneously, 3% of patients develop serious complications. The mortality rate is 0.6%.¹¹

A diagnosis of human granulocytic anaplasmosis should be suspected in patients with a viral-like illness and exposure to ticks in an endemic area. The diagnosis can be confirmed by polymerase chain reaction (PCR), acute- and convalescent-phase serologic testing, or direct fluorescent antibody screening. Characteristic morulae may be present in granulocytes.¹² Treatment typically includes doxycycline, which also covers B burgdorferi coinfection. When a diagnosis of human granulocytic anaplasmosis is suspected, treatment should never be delayed to await laboratory confirmation. If no clinical improvement is seen within 48 hours, alternate diagnoses or coinfection with B microti should be considered.¹⁰

Babesiosis

The protozoan B microti causes babesiosis in the United States, with Babesia divergens being more common in Europe.¹³ Reported cases of babesiosis in New York increased as much as 20-fold from 2001 to 2008.¹⁴ Transmission primarily is from the Ixodes tick but rarely can occur from blood transfusion.¹⁵ Tick attachment for at least 36 hours is required for transmission.¹³

The clinical presentation of babesiosis ranges from asymptomatic to fatal. Symptoms generally are nonspecific, resembling a viral infection and including headache, nausea, diarrhea, arthralgia, and myalgia. Laboratory evaluation may reveal hemolytic anemia, thrombocytopenia, transaminitis, and elevated blood urea nitrogen and creatinine levels.¹⁶ Rash is not typical. Resolution of symptoms generally occurs within 2 weeks of presentation, although anemia may persist for months.¹³ Severe disease is more common among elderly and immunocompromised patients. Complications include respiratory failure, renal failure, congestive heart failure, and disseminated intravascular coagulation. The mortality rate in the United States is approximately 10%.^10,16

A diagnosis of babesiosis is made based on the presence of flulike symptoms, laboratory results, and history of recent travel to an endemic area. A thin blood smear allows identification of the organism in erythrocytes as ring forms or tetrads (a “Maltese cross” appearance).¹⁷ Polymerase chain reaction is more sensitive than a blood smear, especially in early disease.¹⁸ Indirect fluorescent antibody testing is species-specific but cannot verify active infection.¹⁰

Treatment of babesiosis is indicated for symptomatic patients with active infection. Positive serology alone is not an indication for treatment. Asymptomatic patients with positive serology should have diagnostic testing repeated in 3 months with subsequent treatment if parasitemia persists. Mild disease is treated with atovaquone plus azithromycin or clindamycin plus quinine. Severe babesiosis is treated with quinine and intravenous clindamycin and may require exchange transfusion.¹⁰ Coinfection with B burgdorferi should be considered in patients with flulike symptoms and erythema migrans or treatment failure. Coinfection is diagnosed by Lyme serology plus PCR for B microti. This is an important consideration because treatment of babesiosis does not eradicate B burgdorferi infection.¹⁹

Powassan Virus

Powassan virus is a flavivirus that causes encephalitis. It is transmitted by Ixodes cookei (Powassan virus, lineage I) in the Great Lakes region and by I scapularis (Powassan virus, lineage II, or deer tick virus) in the northeastern United States. Transmission can occur within 15 minutes of tick attachment.^6,20,21

Patients typically present with fever, headache, altered mental status, seizures, and focal neurologic deficits. Gastrointestinal symptoms and rash also have been reported.²¹ The diagnosis is made based on clinical presentation and laboratory testing with PCR or enzyme-linked immunosorbent assay (ELISA). Cross-reactivity on ELISA exists, necessitating confirmation with a neutralizing antibody or PCR. Treatment is supportive. Corticosteroids and intravenous immunoglobulin have been proposed as treatment modalities, but evidence of their efficacy is limited.²²

Tick-borne Encephalitis

Tick-borne encephalitis is caused by the flavivirus tick-borne encephalitis virus in Europe and Asia. The tick-borne encephalitis virus is transmitted by Ixodes ricinus in Europe and by Ixodes persulcatus in eastern Russia, China, and Japan. It also has been associated with consumption of unpasteurized milk.^23,24

Tick-borne encephalitis presents in a biphasic pattern. The initial viremic phase can persist for as long as 8 days with headache, nausea, myalgia, and fever. One-third of patients then enter an asymptomatic phase, followed by virus penetration into the central nervous system. The neurologic phase produces continued headache and fever with photophobia, focal neurologic deficits, seizures, respiratory depression, or coma. Neurologic sequelae persist in 10% to 20% of patients.^25,26

In the viremic stage, diagnosis is made with PCR or culture. During the latent phase or neurologic phase, serologic testing for tick-borne encephalitis virus antibodies is indicated. Neutralizing antibody evaluation may be necessary due to cross-reactivity among flaviviruses.²⁷ Treatment is supportive. An inactivated vaccine is available for high-risk populations.²⁸

Borrelia miyamotoi Disease

Borrelia miyamotoi is a symbiont of the Ixodes tick formerly believed to have no pathogenic significance; however, B miyamotoi was isolated in febrile patients in Russia in 2011⁷ and was identified as a pathogen in both North America²⁹ and Europe in 2013.³⁰ Disease presentation includes nonspecific symptoms of fever, fatigue, headache, arthralgia, myalgia, and nausea. Rash is uncommon. Laboratory abnormalities include leukopenia, thrombocytopenia, and transaminitis.^31,32 Meningoencephalitis may occur in immunocompromised patients.^29,30

The diagnosis of B miyamotoi disease is confirmed by PCR or serology. An ELISA that is positive for B burgdorferi IgM but negative with confirmatory immunoblot suggests B miyamotoi disease. Seroconversion using a glpQ protein ELISA also can be assessed.³¹ If ELISA is positive, Lyme disease can be excluded because B burgdorferi does not possess g1pQ. Treatment is with doxycycline.³²

Tick Paralysis

Tick paralysis is an intoxication with holocyclotoxin from the saliva of gravid hard ticks. In the United States, intoxication is associated with ticks of various species of Amblyomma, Dermacentor, and Ixodes in the Northwest, Southeast, and Northeast. In Australia, intoxication is associated with Ixodes.³³ Patients present with weakness and fatigue, progressing to ascending flaccid paralysis with sensory sparing. The treatment is tick removal.^8,33

Conclusion

Arthropods carry many regional pathogens. Physicians outside of those regions should seek a travel history and be alert for imported disease.

Ticks are ectoparasitic hemophages that feed on mammals, reptiles, and birds. The Ixodidae family comprises the hard ticks. A hard dorsal plate, scutum, and capitulum that extends outward from the body are features that distinguish the hard tick. ¹Ixodes is the largest genus of hard ticks, with more than 250 species localized in temperate climates.² It has an inornate scutum and lacks festoons (Figure 1).¹ The Ixodes ricinus species complex accounts for most species relevant to the spread of human disease (Figure 2), with Ixodes scapularis in the northeastern, north midwestern, and southern United States; Ixodes pacificus in western United States; I ricinus in Europe and North Africa; and Ixodes persulcatus in Russia and Asia. Ixodes holocyclus is endemic to Australia.^3,4

Life Cycle

Ixodes species progress through 4 life stages—egg, larvae, nymph, and adult—during their 3-host life cycle. Lifespan is 2 to 6 years, varying with environmental factors. A blood meal is required between each stage. Female ticks have a small scutum, allowing the abdomen to engorge during meals (Figure 3).

Larvae hatch in the early summer and remain dormant until the spring, emerging as a nymph. Following a blood meal, the nymph molts and reemerges as an adult in autumn. During autumn and winter, the female lays as many as 2000 eggs that emerge in early summer.⁵ Nymphs are small and easily undetected for the duration required for pathogen transmission, making nymphs the stage most likely to transmit disease.⁶

The majority of tick-borne diseases present from May to July, corresponding to nymph activity. Fewer cases present in the autumn and early spring because the adult female feeds during cooler months.⁷

Larvae have 6 legs and are about the size of a sesame seed when engorged. Nymphs are slightly larger with 8 legs. Adults are largest and have 8 legs. Following a blood meal, the tick becomes engorged, increasing in size and lightening in color (Figure 3).¹

Ticks are found in low-lying shrubs and tall grass as well as on the forest floor. They search for a host by detecting CO₂, warmth, the smell of sweat, and the color white, prompting attachment.⁸ Habitats hospitable to Ixodes have expanded in the wake of climate, environmental, and socioeconomic changes, potentially contributing to the increasing incidence and expansion of zoonoses associated with this vector.^9,10

Local Reactions

A tick bite may induce local hypersensitivity, leading to a red papule or plaque at the bite site, followed by swelling, warmth, and erythema. A cellular immune reaction induces induration and pruritus. Hard ticks are less likely than soft ticks to cause a serious local reaction.^11,12

A variety of clinical and histologic features are observed following an arthropod bite. Histologically, acute tick bites show a neutrophilic infiltrate with fibrin deposition. Chronic reactions demonstrate a wedge-shaped, mixed infiltrate with prominent endothelial swelling. Eosinophilic cellulitis, or Wells syndrome, reveals tissue eosinophilia and flame figures.¹³ Tick mouthparts may be identified in the tissue. B-cell hyperplasia is seen in Borrelia lymphocytoma and is more common in Europe, presenting as erythematous to plum–colored nodules on the ear and areola.¹⁴

Lyme Disease

Disease manifestations vary by location. Lyme disease is associated with Borrelia burgdorferi and the recently identified Borrelia mayonii in the United States¹⁵; in Europe and Asia, acrodermatitis chronica atrophicans is associated with Borrelia afzelii and neuroborreliosis, with Borrelia garinii. Lyme disease is the most common tick-borne illness in the United States.¹⁶ The I ricinus species complex is the most common vector harboring Borrelia species.¹⁷ At least 36 hours of tick adherence is required for disease transmission.¹⁸ The incubation period is 3 to 20 days (median, 12 days).¹⁹

Clinical Findings
Erythema migrans is the most characteristic sign, seen in 80% of cases of Lyme disease. The typical rash is a centrifugally spreading, erythematous, annular patch with central clearing at the site of the tick bite.²⁰ Atypical rashes include vesicular, indurated, ulcerated, and follicular variants.²¹ Histopathology commonly shows a superficial and deep perivascular lymphocytic infiltrate with plasma cells, histiocytes, and eosinophils.²² Typically, the rash resolves in 3 to 5 weeks.¹⁸

Early disseminated Lyme disease can present with any of the following findings: multiple erythema migrans; neurologic involvement, including cranial nerve palsy and meningitis; and Lyme carditis, which may result in atrioventricular block.^23,24 Late findings include arthritis, encephalopathy, and polyneuropathy. A late cutaneous manifestation, acrodermatitis chronica atrophicans, is rare in the United States but occurs in as many as 10% of Lyme disease cases in Europe. An initial inflammatory response manifests as blue-red erythema and edema of the extensor surfaces of the extremities, commonly on the dorsal hands, feet, elbows, and knees. Firm fibrotic nodules may develop later over the olecranon and patella.^23,24

The term chronic Lyme disease has been used to describe the persistence of symptoms after treatment; however, large clinical trials have not detected a difference in symptom frequency between patients with a history of Lyme disease and matched controls.^25,26 Many patients with chronic Lyme disease may instead have posttreatment Lyme disease syndrome, described as nonspecific symptoms including fatigue, arthralgia, and decreased mental acuity following treatment of confirmed Lyme disease. Symptoms generally improve within 1 year.²⁷

Laboratory Testing
The gold standard for laboratory diagnosis of Lyme disease is 2-tiered serologic testing. First, an enzyme immunoassay or immunofluorescence assay is used to screen for antibodies. A Western blot follows if the result of the screen is positive or equivocal. Western blot testing for IgM and IgG is used when illness duration is less than 4 weeks; after 4 weeks, a Western blot for IgG alone is sufficient.^27,28 The 2-tiered test has 99% specificity. Sensitivity increases with duration of disease (29%–40% with erythema migrans; 42%–87% in early disseminated disease; 97%–100% in late disease).^29,30 A false-positive result can occur in the presence of infectious mononucleosis, an autoimmune disorder, and syphilis. If serologic testing is negative and suspicion remains high, testing should be repeated in 2 to 4 weeks.³¹ When a patient in a Lyme-endemic area presents with typical erythema migrans, serologic testing is unnecessary prior to treatment.³²

Management
Treatment of Lyme disease centers on antibiotic therapy (Table). First-line treatment of early disseminated disease is doxycycline for 14 days (range, 10–21 days).²⁷ In pregnant women, children younger than 8 years, and tetracycline-allergic patients, amoxicillin or cefuroxime axetil for 14 days (range, 14–21 days) may be used.³³ For erythema migrans without complications, doxycycline for 10 days is effective. Complications that require hospitalization are treated with intravenous ceftriaxone.²⁷ Re-treatment in patients with posttreatment Lyme disease syndrome is not recommended.³⁴ Prophylaxis with a single dose of doxycycline 200 mg may be indicated when all of the following conditions are met: (1) the patient is in an area where more than 20% of Ixodes ticks are infected with B burgdorferi, (2) the attached tick is I scapularis, (3) the tick has been attached for more than 36 hours, and (4) treatment is begun within 72 hours of tick removal.²⁷

Ticks are ectoparasitic hemophages that feed on mammals, reptiles, and birds. The Ixodidae family comprises the hard ticks. A hard dorsal plate, scutum, and capitulum that extends outward from the body are features that distinguish the hard tick. ¹Ixodes is the largest genus of hard ticks, with more than 250 species localized in temperate climates.² It has an inornate scutum and lacks festoons (Figure 1).¹ The Ixodes ricinus species complex accounts for most species relevant to the spread of human disease (Figure 2), with Ixodes scapularis in the northeastern, north midwestern, and southern United States; Ixodes pacificus in western United States; I ricinus in Europe and North Africa; and Ixodes persulcatus in Russia and Asia. Ixodes holocyclus is endemic to Australia.^3,4

Life Cycle

Ixodes species progress through 4 life stages—egg, larvae, nymph, and adult—during their 3-host life cycle. Lifespan is 2 to 6 years, varying with environmental factors. A blood meal is required between each stage. Female ticks have a small scutum, allowing the abdomen to engorge during meals (Figure 3).

Larvae hatch in the early summer and remain dormant until the spring, emerging as a nymph. Following a blood meal, the nymph molts and reemerges as an adult in autumn. During autumn and winter, the female lays as many as 2000 eggs that emerge in early summer.⁵ Nymphs are small and easily undetected for the duration required for pathogen transmission, making nymphs the stage most likely to transmit disease.⁶

The majority of tick-borne diseases present from May to July, corresponding to nymph activity. Fewer cases present in the autumn and early spring because the adult female feeds during cooler months.⁷

Larvae have 6 legs and are about the size of a sesame seed when engorged. Nymphs are slightly larger with 8 legs. Adults are largest and have 8 legs. Following a blood meal, the tick becomes engorged, increasing in size and lightening in color (Figure 3).¹

Ticks are found in low-lying shrubs and tall grass as well as on the forest floor. They search for a host by detecting CO₂, warmth, the smell of sweat, and the color white, prompting attachment.⁸ Habitats hospitable to Ixodes have expanded in the wake of climate, environmental, and socioeconomic changes, potentially contributing to the increasing incidence and expansion of zoonoses associated with this vector.^9,10

Local Reactions

A tick bite may induce local hypersensitivity, leading to a red papule or plaque at the bite site, followed by swelling, warmth, and erythema. A cellular immune reaction induces induration and pruritus. Hard ticks are less likely than soft ticks to cause a serious local reaction.^11,12

A variety of clinical and histologic features are observed following an arthropod bite. Histologically, acute tick bites show a neutrophilic infiltrate with fibrin deposition. Chronic reactions demonstrate a wedge-shaped, mixed infiltrate with prominent endothelial swelling. Eosinophilic cellulitis, or Wells syndrome, reveals tissue eosinophilia and flame figures.¹³ Tick mouthparts may be identified in the tissue. B-cell hyperplasia is seen in Borrelia lymphocytoma and is more common in Europe, presenting as erythematous to plum–colored nodules on the ear and areola.¹⁴

Lyme Disease

Disease manifestations vary by location. Lyme disease is associated with Borrelia burgdorferi and the recently identified Borrelia mayonii in the United States¹⁵; in Europe and Asia, acrodermatitis chronica atrophicans is associated with Borrelia afzelii and neuroborreliosis, with Borrelia garinii. Lyme disease is the most common tick-borne illness in the United States.¹⁶ The I ricinus species complex is the most common vector harboring Borrelia species.¹⁷ At least 36 hours of tick adherence is required for disease transmission.¹⁸ The incubation period is 3 to 20 days (median, 12 days).¹⁹

Clinical Findings
Erythema migrans is the most characteristic sign, seen in 80% of cases of Lyme disease. The typical rash is a centrifugally spreading, erythematous, annular patch with central clearing at the site of the tick bite.²⁰ Atypical rashes include vesicular, indurated, ulcerated, and follicular variants.²¹ Histopathology commonly shows a superficial and deep perivascular lymphocytic infiltrate with plasma cells, histiocytes, and eosinophils.²² Typically, the rash resolves in 3 to 5 weeks.¹⁸

Early disseminated Lyme disease can present with any of the following findings: multiple erythema migrans; neurologic involvement, including cranial nerve palsy and meningitis; and Lyme carditis, which may result in atrioventricular block.^23,24 Late findings include arthritis, encephalopathy, and polyneuropathy. A late cutaneous manifestation, acrodermatitis chronica atrophicans, is rare in the United States but occurs in as many as 10% of Lyme disease cases in Europe. An initial inflammatory response manifests as blue-red erythema and edema of the extensor surfaces of the extremities, commonly on the dorsal hands, feet, elbows, and knees. Firm fibrotic nodules may develop later over the olecranon and patella.^23,24

The term chronic Lyme disease has been used to describe the persistence of symptoms after treatment; however, large clinical trials have not detected a difference in symptom frequency between patients with a history of Lyme disease and matched controls.^25,26 Many patients with chronic Lyme disease may instead have posttreatment Lyme disease syndrome, described as nonspecific symptoms including fatigue, arthralgia, and decreased mental acuity following treatment of confirmed Lyme disease. Symptoms generally improve within 1 year.²⁷

Laboratory Testing
The gold standard for laboratory diagnosis of Lyme disease is 2-tiered serologic testing. First, an enzyme immunoassay or immunofluorescence assay is used to screen for antibodies. A Western blot follows if the result of the screen is positive or equivocal. Western blot testing for IgM and IgG is used when illness duration is less than 4 weeks; after 4 weeks, a Western blot for IgG alone is sufficient.^27,28 The 2-tiered test has 99% specificity. Sensitivity increases with duration of disease (29%–40% with erythema migrans; 42%–87% in early disseminated disease; 97%–100% in late disease).^29,30 A false-positive result can occur in the presence of infectious mononucleosis, an autoimmune disorder, and syphilis. If serologic testing is negative and suspicion remains high, testing should be repeated in 2 to 4 weeks.³¹ When a patient in a Lyme-endemic area presents with typical erythema migrans, serologic testing is unnecessary prior to treatment.³²

Management
Treatment of Lyme disease centers on antibiotic therapy (Table). First-line treatment of early disseminated disease is doxycycline for 14 days (range, 10–21 days).²⁷ In pregnant women, children younger than 8 years, and tetracycline-allergic patients, amoxicillin or cefuroxime axetil for 14 days (range, 14–21 days) may be used.³³ For erythema migrans without complications, doxycycline for 10 days is effective. Complications that require hospitalization are treated with intravenous ceftriaxone.²⁷ Re-treatment in patients with posttreatment Lyme disease syndrome is not recommended.³⁴ Prophylaxis with a single dose of doxycycline 200 mg may be indicated when all of the following conditions are met: (1) the patient is in an area where more than 20% of Ixodes ticks are infected with B burgdorferi, (2) the attached tick is I scapularis, (3) the tick has been attached for more than 36 hours, and (4) treatment is begun within 72 hours of tick removal.²⁷

Ticks are ectoparasitic hemophages that feed on mammals, reptiles, and birds. The Ixodidae family comprises the hard ticks. A hard dorsal plate, scutum, and capitulum that extends outward from the body are features that distinguish the hard tick. ¹Ixodes is the largest genus of hard ticks, with more than 250 species localized in temperate climates.² It has an inornate scutum and lacks festoons (Figure 1).¹ The Ixodes ricinus species complex accounts for most species relevant to the spread of human disease (Figure 2), with Ixodes scapularis in the northeastern, north midwestern, and southern United States; Ixodes pacificus in western United States; I ricinus in Europe and North Africa; and Ixodes persulcatus in Russia and Asia. Ixodes holocyclus is endemic to Australia.^3,4

Life Cycle

Ixodes species progress through 4 life stages—egg, larvae, nymph, and adult—during their 3-host life cycle. Lifespan is 2 to 6 years, varying with environmental factors. A blood meal is required between each stage. Female ticks have a small scutum, allowing the abdomen to engorge during meals (Figure 3).

Larvae hatch in the early summer and remain dormant until the spring, emerging as a nymph. Following a blood meal, the nymph molts and reemerges as an adult in autumn. During autumn and winter, the female lays as many as 2000 eggs that emerge in early summer.⁵ Nymphs are small and easily undetected for the duration required for pathogen transmission, making nymphs the stage most likely to transmit disease.⁶

The majority of tick-borne diseases present from May to July, corresponding to nymph activity. Fewer cases present in the autumn and early spring because the adult female feeds during cooler months.⁷

Larvae have 6 legs and are about the size of a sesame seed when engorged. Nymphs are slightly larger with 8 legs. Adults are largest and have 8 legs. Following a blood meal, the tick becomes engorged, increasing in size and lightening in color (Figure 3).¹

Ticks are found in low-lying shrubs and tall grass as well as on the forest floor. They search for a host by detecting CO₂, warmth, the smell of sweat, and the color white, prompting attachment.⁸ Habitats hospitable to Ixodes have expanded in the wake of climate, environmental, and socioeconomic changes, potentially contributing to the increasing incidence and expansion of zoonoses associated with this vector.^9,10

Local Reactions

A tick bite may induce local hypersensitivity, leading to a red papule or plaque at the bite site, followed by swelling, warmth, and erythema. A cellular immune reaction induces induration and pruritus. Hard ticks are less likely than soft ticks to cause a serious local reaction.^11,12

A variety of clinical and histologic features are observed following an arthropod bite. Histologically, acute tick bites show a neutrophilic infiltrate with fibrin deposition. Chronic reactions demonstrate a wedge-shaped, mixed infiltrate with prominent endothelial swelling. Eosinophilic cellulitis, or Wells syndrome, reveals tissue eosinophilia and flame figures.¹³ Tick mouthparts may be identified in the tissue. B-cell hyperplasia is seen in Borrelia lymphocytoma and is more common in Europe, presenting as erythematous to plum–colored nodules on the ear and areola.¹⁴

Lyme Disease

Disease manifestations vary by location. Lyme disease is associated with Borrelia burgdorferi and the recently identified Borrelia mayonii in the United States¹⁵; in Europe and Asia, acrodermatitis chronica atrophicans is associated with Borrelia afzelii and neuroborreliosis, with Borrelia garinii. Lyme disease is the most common tick-borne illness in the United States.¹⁶ The I ricinus species complex is the most common vector harboring Borrelia species.¹⁷ At least 36 hours of tick adherence is required for disease transmission.¹⁸ The incubation period is 3 to 20 days (median, 12 days).¹⁹

Clinical Findings
Erythema migrans is the most characteristic sign, seen in 80% of cases of Lyme disease. The typical rash is a centrifugally spreading, erythematous, annular patch with central clearing at the site of the tick bite.²⁰ Atypical rashes include vesicular, indurated, ulcerated, and follicular variants.²¹ Histopathology commonly shows a superficial and deep perivascular lymphocytic infiltrate with plasma cells, histiocytes, and eosinophils.²² Typically, the rash resolves in 3 to 5 weeks.¹⁸

Early disseminated Lyme disease can present with any of the following findings: multiple erythema migrans; neurologic involvement, including cranial nerve palsy and meningitis; and Lyme carditis, which may result in atrioventricular block.^23,24 Late findings include arthritis, encephalopathy, and polyneuropathy. A late cutaneous manifestation, acrodermatitis chronica atrophicans, is rare in the United States but occurs in as many as 10% of Lyme disease cases in Europe. An initial inflammatory response manifests as blue-red erythema and edema of the extensor surfaces of the extremities, commonly on the dorsal hands, feet, elbows, and knees. Firm fibrotic nodules may develop later over the olecranon and patella.^23,24

The term chronic Lyme disease has been used to describe the persistence of symptoms after treatment; however, large clinical trials have not detected a difference in symptom frequency between patients with a history of Lyme disease and matched controls.^25,26 Many patients with chronic Lyme disease may instead have posttreatment Lyme disease syndrome, described as nonspecific symptoms including fatigue, arthralgia, and decreased mental acuity following treatment of confirmed Lyme disease. Symptoms generally improve within 1 year.²⁷

Laboratory Testing
The gold standard for laboratory diagnosis of Lyme disease is 2-tiered serologic testing. First, an enzyme immunoassay or immunofluorescence assay is used to screen for antibodies. A Western blot follows if the result of the screen is positive or equivocal. Western blot testing for IgM and IgG is used when illness duration is less than 4 weeks; after 4 weeks, a Western blot for IgG alone is sufficient.^27,28 The 2-tiered test has 99% specificity. Sensitivity increases with duration of disease (29%–40% with erythema migrans; 42%–87% in early disseminated disease; 97%–100% in late disease).^29,30 A false-positive result can occur in the presence of infectious mononucleosis, an autoimmune disorder, and syphilis. If serologic testing is negative and suspicion remains high, testing should be repeated in 2 to 4 weeks.³¹ When a patient in a Lyme-endemic area presents with typical erythema migrans, serologic testing is unnecessary prior to treatment.³²

Management
Treatment of Lyme disease centers on antibiotic therapy (Table). First-line treatment of early disseminated disease is doxycycline for 14 days (range, 10–21 days).²⁷ In pregnant women, children younger than 8 years, and tetracycline-allergic patients, amoxicillin or cefuroxime axetil for 14 days (range, 14–21 days) may be used.³³ For erythema migrans without complications, doxycycline for 10 days is effective. Complications that require hospitalization are treated with intravenous ceftriaxone.²⁷ Re-treatment in patients with posttreatment Lyme disease syndrome is not recommended.³⁴ Prophylaxis with a single dose of doxycycline 200 mg may be indicated when all of the following conditions are met: (1) the patient is in an area where more than 20% of Ixodes ticks are infected with B burgdorferi, (2) the attached tick is I scapularis, (3) the tick has been attached for more than 36 hours, and (4) treatment is begun within 72 hours of tick removal.²⁷

Identification

Phlebotomine sand flies are the only member of the Psychodidae family that are capable of taking blood.¹ The mouthparts of the sand fly are toothed distally, and the maxilla and mandible are utilized in a sawtooth fashion to take a bloodmeal.² The flies are very small (ie, only 1.5–3.5 mm in length), which makes their identification difficult.¹ Sand flies can be distinguished by the appearance of their wings, which often are covered in hair and extend across the back in a V shape.³ The adult sand fly is hairy with a 6- to 8-segmented abdomen, and the color can range from gray to yellow to brown.² Phlebotomine sand flies can be further identified by their long antennae, dark eyes, and small heads (Figure).²

As is the case with all Diptera, the sand fly goes through 4 complete life stages from egg to larva to pupa to adult.³ Female sand flies will lay their eggs following a blood meal and have been found to take multiple blood meals in a single cycle.² On average, the eggs will hatch in 6 to 17 days but are temperature dependent.³ The subsequent larvae and pupa stages last 20 to 30 days and 6 to 13 days, respectively.¹ The larvae are white in color with short antennae and dark heads.⁴ Sand flies prefer to lay their eggs in areas where adequate resting places are available and where their larvae will thrive.^4,5 The larvae require warm moist environments to succeed and thus are commonly found in animal burrows.³ Once fully developed, the adult sand fly can live up to 6 weeks.²

Sand Fly Vector

Although it is more common in rural forested areas, the sand fly also can be found in urban areas, including heavily populated cities in Brazil.⁶ Sand flies are most active during hot humid seasons but depending on the local climate may remain active year-round.^1,7 For example, in tropical regions of Asia, the number of sand flies increases substantially during the monsoon season compared to the dry season.² Phlebotomine sand flies are most active at dusk and during the night⁵ but may become agitated during the daytime if their environment is disturbed.¹

Host selection usually is broad and includes a wide variety of vertebrates.² In the United States, host species are thought to include small rodents, foxes, armadillos, and opossums.⁸ One study found that visceral leishmaniasis in foxhounds is able to develop fully in sand flies, thus posing an emerging risk to the American population.⁹

Distribution

The Phlebotominae family contains approximately 700 different species of sand flies but only 21 are known vectors of disease.¹⁰ The great majority belong to 1 of 3 genuses: Phlebotomus, Sergentomyia, and Lutzomyia.¹¹ The vectors are commonly divided into Old World species, dominated by the Phlebotomus genus, and New World species, which exclusively refers to the Lutzomyia genus.³ The Old World and New World distinction helps to classify the various vectors and subsequently the diseases they transmit. Old World refers to those vectors found in Southwest and Central Asia, the Indian subcontinent, the Middle East, and East Africa, as well as Southern Europe.⁶ New World refers to vectors found predominantly in Brazil and other parts of Latin America but also Mexico and the United States.⁶ Sand flies are found to be endemic in 90 countries and on each continent, except Australia.⁵ Although the vector can be found in a variety of environments, sand flies prefer moist environments that typify tropical and subtropical climates, thus it is not surprising that the highest diversity of Phlebotominae in the world can be found in the Amazon basin.¹²

Disease Transmission

Leishmania refers to a genus of intracellular protozoa found in both the Old World and the New World that causes a variety of clinical syndromes.⁵ Approximately 20 Leishmania species are known to cause human disease that includes localized cutaneous, diffuse cutaneous, mucosal cutaneous, and visceral infections.¹³ Cases of all forms of leishmaniasis worldwide have increased rapidly over the last few decades from multiple factors including war in endemic regions, increased numbers of immunodeficient individuals, and increased travel to endemic areas.¹⁴ In the United States, leishmaniasis is caused by both imported and autochthonous forms of transmission and often mirrors recent travel and immigration patterns.^14,15

Sand flies also serve as vectors for sandfly fever, also known as Pappataci fever. Although sandfly fever commonly causes a mild febrile illness, it has been shown to be a considerable cause of aseptic meningitis.¹⁶ A number of novel Phleboviruses have been isolated as causes of sandfly fever, including Massilia virus, Granada virus, and Punique virus.^16-18 A form of sandfly fever caused by the Toscana virus has a predilection for the nervous system and can cause encephalitis.¹⁹ Sandfly fever can be found in both the Old World and New World and thus poses a global risk.² Additionally, Phlebotominae also have been found to transmit the Changuinola virus, a type of bunyavirus that is known to cause febrile illness in Panama.²⁰ Vesicular stomatitis, also carried by sand flies, is a known cause of febrile disease in North and South America, including the United States.² In 2013, the Niakha virus, a novel type of Rhabdoviridae, was isolated from Phlebotominae in Senegal.²¹ The sand fly is noted to transmit another type of Rhabdoviridae in India and Africa, known as the Chandipura virus.²² Although originally thought to cause mild febrile disease, it was the primary cause of multiple outbreaks of fatal encephalitis in India in 2003^23,24 and again in 2012.²²

Sand flies also are known to serve as vectors for the bacterium Bartonella bacilliformis, which is responsible for bartonellosis.²⁵ The disease is divided into 2 forms, which can occur separately or in succession, and is endemic to the Andes region of Peru, Ecuador, and Colombia. The first form is Oroya fever, an acute febrile hemolytic anemia that is fatal in 40% to 88% of cases without intervention.²⁵ This bacterium also causes verruga peruana, an endemic form of bacillary angiomatosis that can persist for years.² Two reports suggested that bartonellosis also can be caused by Bartonella rochalimae and Candidatus Bartonella ancashi.^26,27

Vector Control

Prevention is key to reducing the risk of the various diseases caused by the Phlebotominae vector. Vector control often falls into a few categories, including residual sprays, barriers, and topical repellants.³ It appears that residual sprays applied to houses and animal shelters are the most utilized and effective form of control, with the pyrethroid insecticides having the highest sand fly–specific toxicity.^3,28 Insecticides also have been applied to animal burrows where sand flies are known to reproduce; one study in Kenya showed a 90% reduction in the sand fly population following treatment of termite and animal burrows with a pyrethroid spray.²⁹ Studies by Perich et al^30,31 in 1995 and 2003 showed that using barrier sprays can be an effective protective measure. The investigators applied a 100-m barrier using a pyrethroid spray on vegetation and reported a notable decrease in sand flies for over an 80-day period.^30,31

For personal protection, barrier methods are important adjunct methods of preventing individual exposures. Due to the small size of sand flies, ordinary bed nets are not effective and those treated with insecticides should be used,¹⁵ which may ultimately prove to be the most sustainable way to prevent sand fly–borne disease.³² Protective attire also should be worn, as sand flies are not able to penetrate clothing.² N,N-diethyl-meta-toluamide (DEET)–based repellants should be applied to exposed skin.¹⁵ Finally, it is important to avoid exposure from dusk to dawn when sand flies are most active.¹⁵

Rise in Autochthonous Cutaneous Leishmaniasis in the United States

With the increased amount of worldwide tourism, especially to endemic areas, providers will continue to see rising numbers of leishmaniasis in the United States. It is difficult to determine the incidence of the disease in the United States, but one study has shown that leishmaniasis accounts for 143 of every 1000 dermatologic diseases acquired by South American tourists.^33,34 In addition, the number of autochthonous cases reported in the United States continues to grow. Although only 29 cases were reported between 1903 and 1996, 13 cases were reported between 2000 and 2008.³⁵ Another report in 2013 described an additional 3 cases in the states of Texas and Oklahoma.³⁵ The cases have continued to move in a northeasterly pattern, suggesting a possible shift in the location of sand fly populations. Each of these cases in which a specific species of Leishmania was identified showed transmission of Leishmania mexicana.³⁵ Most cases of cutaneous disease have occurred in Texas and Oklahoma. The first known case outside of this region was reported in 2014 in North Dakota.⁸ Leishmania donovani, brought into the United States with European foxhounds, also is spreading.⁸ One species of sand fly, Leishmania shannoni, has now been discovered in 16 states,^36-42 where it serves as a potential vector for L mexicana.^43,44

Identification

Phlebotomine sand flies are the only member of the Psychodidae family that are capable of taking blood.¹ The mouthparts of the sand fly are toothed distally, and the maxilla and mandible are utilized in a sawtooth fashion to take a bloodmeal.² The flies are very small (ie, only 1.5–3.5 mm in length), which makes their identification difficult.¹ Sand flies can be distinguished by the appearance of their wings, which often are covered in hair and extend across the back in a V shape.³ The adult sand fly is hairy with a 6- to 8-segmented abdomen, and the color can range from gray to yellow to brown.² Phlebotomine sand flies can be further identified by their long antennae, dark eyes, and small heads (Figure).²

As is the case with all Diptera, the sand fly goes through 4 complete life stages from egg to larva to pupa to adult.³ Female sand flies will lay their eggs following a blood meal and have been found to take multiple blood meals in a single cycle.² On average, the eggs will hatch in 6 to 17 days but are temperature dependent.³ The subsequent larvae and pupa stages last 20 to 30 days and 6 to 13 days, respectively.¹ The larvae are white in color with short antennae and dark heads.⁴ Sand flies prefer to lay their eggs in areas where adequate resting places are available and where their larvae will thrive.^4,5 The larvae require warm moist environments to succeed and thus are commonly found in animal burrows.³ Once fully developed, the adult sand fly can live up to 6 weeks.²

Sand Fly Vector

Although it is more common in rural forested areas, the sand fly also can be found in urban areas, including heavily populated cities in Brazil.⁶ Sand flies are most active during hot humid seasons but depending on the local climate may remain active year-round.^1,7 For example, in tropical regions of Asia, the number of sand flies increases substantially during the monsoon season compared to the dry season.² Phlebotomine sand flies are most active at dusk and during the night⁵ but may become agitated during the daytime if their environment is disturbed.¹

Host selection usually is broad and includes a wide variety of vertebrates.² In the United States, host species are thought to include small rodents, foxes, armadillos, and opossums.⁸ One study found that visceral leishmaniasis in foxhounds is able to develop fully in sand flies, thus posing an emerging risk to the American population.⁹

Distribution

The Phlebotominae family contains approximately 700 different species of sand flies but only 21 are known vectors of disease.¹⁰ The great majority belong to 1 of 3 genuses: Phlebotomus, Sergentomyia, and Lutzomyia.¹¹ The vectors are commonly divided into Old World species, dominated by the Phlebotomus genus, and New World species, which exclusively refers to the Lutzomyia genus.³ The Old World and New World distinction helps to classify the various vectors and subsequently the diseases they transmit. Old World refers to those vectors found in Southwest and Central Asia, the Indian subcontinent, the Middle East, and East Africa, as well as Southern Europe.⁶ New World refers to vectors found predominantly in Brazil and other parts of Latin America but also Mexico and the United States.⁶ Sand flies are found to be endemic in 90 countries and on each continent, except Australia.⁵ Although the vector can be found in a variety of environments, sand flies prefer moist environments that typify tropical and subtropical climates, thus it is not surprising that the highest diversity of Phlebotominae in the world can be found in the Amazon basin.¹²

Disease Transmission

Leishmania refers to a genus of intracellular protozoa found in both the Old World and the New World that causes a variety of clinical syndromes.⁵ Approximately 20 Leishmania species are known to cause human disease that includes localized cutaneous, diffuse cutaneous, mucosal cutaneous, and visceral infections.¹³ Cases of all forms of leishmaniasis worldwide have increased rapidly over the last few decades from multiple factors including war in endemic regions, increased numbers of immunodeficient individuals, and increased travel to endemic areas.¹⁴ In the United States, leishmaniasis is caused by both imported and autochthonous forms of transmission and often mirrors recent travel and immigration patterns.^14,15

Sand flies also serve as vectors for sandfly fever, also known as Pappataci fever. Although sandfly fever commonly causes a mild febrile illness, it has been shown to be a considerable cause of aseptic meningitis.¹⁶ A number of novel Phleboviruses have been isolated as causes of sandfly fever, including Massilia virus, Granada virus, and Punique virus.^16-18 A form of sandfly fever caused by the Toscana virus has a predilection for the nervous system and can cause encephalitis.¹⁹ Sandfly fever can be found in both the Old World and New World and thus poses a global risk.² Additionally, Phlebotominae also have been found to transmit the Changuinola virus, a type of bunyavirus that is known to cause febrile illness in Panama.²⁰ Vesicular stomatitis, also carried by sand flies, is a known cause of febrile disease in North and South America, including the United States.² In 2013, the Niakha virus, a novel type of Rhabdoviridae, was isolated from Phlebotominae in Senegal.²¹ The sand fly is noted to transmit another type of Rhabdoviridae in India and Africa, known as the Chandipura virus.²² Although originally thought to cause mild febrile disease, it was the primary cause of multiple outbreaks of fatal encephalitis in India in 2003^23,24 and again in 2012.²²

Sand flies also are known to serve as vectors for the bacterium Bartonella bacilliformis, which is responsible for bartonellosis.²⁵ The disease is divided into 2 forms, which can occur separately or in succession, and is endemic to the Andes region of Peru, Ecuador, and Colombia. The first form is Oroya fever, an acute febrile hemolytic anemia that is fatal in 40% to 88% of cases without intervention.²⁵ This bacterium also causes verruga peruana, an endemic form of bacillary angiomatosis that can persist for years.² Two reports suggested that bartonellosis also can be caused by Bartonella rochalimae and Candidatus Bartonella ancashi.^26,27

Vector Control

Prevention is key to reducing the risk of the various diseases caused by the Phlebotominae vector. Vector control often falls into a few categories, including residual sprays, barriers, and topical repellants.³ It appears that residual sprays applied to houses and animal shelters are the most utilized and effective form of control, with the pyrethroid insecticides having the highest sand fly–specific toxicity.^3,28 Insecticides also have been applied to animal burrows where sand flies are known to reproduce; one study in Kenya showed a 90% reduction in the sand fly population following treatment of termite and animal burrows with a pyrethroid spray.²⁹ Studies by Perich et al^30,31 in 1995 and 2003 showed that using barrier sprays can be an effective protective measure. The investigators applied a 100-m barrier using a pyrethroid spray on vegetation and reported a notable decrease in sand flies for over an 80-day period.^30,31

For personal protection, barrier methods are important adjunct methods of preventing individual exposures. Due to the small size of sand flies, ordinary bed nets are not effective and those treated with insecticides should be used,¹⁵ which may ultimately prove to be the most sustainable way to prevent sand fly–borne disease.³² Protective attire also should be worn, as sand flies are not able to penetrate clothing.² N,N-diethyl-meta-toluamide (DEET)–based repellants should be applied to exposed skin.¹⁵ Finally, it is important to avoid exposure from dusk to dawn when sand flies are most active.¹⁵

Rise in Autochthonous Cutaneous Leishmaniasis in the United States

With the increased amount of worldwide tourism, especially to endemic areas, providers will continue to see rising numbers of leishmaniasis in the United States. It is difficult to determine the incidence of the disease in the United States, but one study has shown that leishmaniasis accounts for 143 of every 1000 dermatologic diseases acquired by South American tourists.^33,34 In addition, the number of autochthonous cases reported in the United States continues to grow. Although only 29 cases were reported between 1903 and 1996, 13 cases were reported between 2000 and 2008.³⁵ Another report in 2013 described an additional 3 cases in the states of Texas and Oklahoma.³⁵ The cases have continued to move in a northeasterly pattern, suggesting a possible shift in the location of sand fly populations. Each of these cases in which a specific species of Leishmania was identified showed transmission of Leishmania mexicana.³⁵ Most cases of cutaneous disease have occurred in Texas and Oklahoma. The first known case outside of this region was reported in 2014 in North Dakota.⁸ Leishmania donovani, brought into the United States with European foxhounds, also is spreading.⁸ One species of sand fly, Leishmania shannoni, has now been discovered in 16 states,^36-42 where it serves as a potential vector for L mexicana.^43,44

Identification

Phlebotomine sand flies are the only member of the Psychodidae family that are capable of taking blood.¹ The mouthparts of the sand fly are toothed distally, and the maxilla and mandible are utilized in a sawtooth fashion to take a bloodmeal.² The flies are very small (ie, only 1.5–3.5 mm in length), which makes their identification difficult.¹ Sand flies can be distinguished by the appearance of their wings, which often are covered in hair and extend across the back in a V shape.³ The adult sand fly is hairy with a 6- to 8-segmented abdomen, and the color can range from gray to yellow to brown.² Phlebotomine sand flies can be further identified by their long antennae, dark eyes, and small heads (Figure).²

As is the case with all Diptera, the sand fly goes through 4 complete life stages from egg to larva to pupa to adult.³ Female sand flies will lay their eggs following a blood meal and have been found to take multiple blood meals in a single cycle.² On average, the eggs will hatch in 6 to 17 days but are temperature dependent.³ The subsequent larvae and pupa stages last 20 to 30 days and 6 to 13 days, respectively.¹ The larvae are white in color with short antennae and dark heads.⁴ Sand flies prefer to lay their eggs in areas where adequate resting places are available and where their larvae will thrive.^4,5 The larvae require warm moist environments to succeed and thus are commonly found in animal burrows.³ Once fully developed, the adult sand fly can live up to 6 weeks.²

Sand Fly Vector

Although it is more common in rural forested areas, the sand fly also can be found in urban areas, including heavily populated cities in Brazil.⁶ Sand flies are most active during hot humid seasons but depending on the local climate may remain active year-round.^1,7 For example, in tropical regions of Asia, the number of sand flies increases substantially during the monsoon season compared to the dry season.² Phlebotomine sand flies are most active at dusk and during the night⁵ but may become agitated during the daytime if their environment is disturbed.¹

Host selection usually is broad and includes a wide variety of vertebrates.² In the United States, host species are thought to include small rodents, foxes, armadillos, and opossums.⁸ One study found that visceral leishmaniasis in foxhounds is able to develop fully in sand flies, thus posing an emerging risk to the American population.⁹

Distribution

The Phlebotominae family contains approximately 700 different species of sand flies but only 21 are known vectors of disease.¹⁰ The great majority belong to 1 of 3 genuses: Phlebotomus, Sergentomyia, and Lutzomyia.¹¹ The vectors are commonly divided into Old World species, dominated by the Phlebotomus genus, and New World species, which exclusively refers to the Lutzomyia genus.³ The Old World and New World distinction helps to classify the various vectors and subsequently the diseases they transmit. Old World refers to those vectors found in Southwest and Central Asia, the Indian subcontinent, the Middle East, and East Africa, as well as Southern Europe.⁶ New World refers to vectors found predominantly in Brazil and other parts of Latin America but also Mexico and the United States.⁶ Sand flies are found to be endemic in 90 countries and on each continent, except Australia.⁵ Although the vector can be found in a variety of environments, sand flies prefer moist environments that typify tropical and subtropical climates, thus it is not surprising that the highest diversity of Phlebotominae in the world can be found in the Amazon basin.¹²

Disease Transmission

Leishmania refers to a genus of intracellular protozoa found in both the Old World and the New World that causes a variety of clinical syndromes.⁵ Approximately 20 Leishmania species are known to cause human disease that includes localized cutaneous, diffuse cutaneous, mucosal cutaneous, and visceral infections.¹³ Cases of all forms of leishmaniasis worldwide have increased rapidly over the last few decades from multiple factors including war in endemic regions, increased numbers of immunodeficient individuals, and increased travel to endemic areas.¹⁴ In the United States, leishmaniasis is caused by both imported and autochthonous forms of transmission and often mirrors recent travel and immigration patterns.^14,15

Sand flies also serve as vectors for sandfly fever, also known as Pappataci fever. Although sandfly fever commonly causes a mild febrile illness, it has been shown to be a considerable cause of aseptic meningitis.¹⁶ A number of novel Phleboviruses have been isolated as causes of sandfly fever, including Massilia virus, Granada virus, and Punique virus.^16-18 A form of sandfly fever caused by the Toscana virus has a predilection for the nervous system and can cause encephalitis.¹⁹ Sandfly fever can be found in both the Old World and New World and thus poses a global risk.² Additionally, Phlebotominae also have been found to transmit the Changuinola virus, a type of bunyavirus that is known to cause febrile illness in Panama.²⁰ Vesicular stomatitis, also carried by sand flies, is a known cause of febrile disease in North and South America, including the United States.² In 2013, the Niakha virus, a novel type of Rhabdoviridae, was isolated from Phlebotominae in Senegal.²¹ The sand fly is noted to transmit another type of Rhabdoviridae in India and Africa, known as the Chandipura virus.²² Although originally thought to cause mild febrile disease, it was the primary cause of multiple outbreaks of fatal encephalitis in India in 2003^23,24 and again in 2012.²²

Sand flies also are known to serve as vectors for the bacterium Bartonella bacilliformis, which is responsible for bartonellosis.²⁵ The disease is divided into 2 forms, which can occur separately or in succession, and is endemic to the Andes region of Peru, Ecuador, and Colombia. The first form is Oroya fever, an acute febrile hemolytic anemia that is fatal in 40% to 88% of cases without intervention.²⁵ This bacterium also causes verruga peruana, an endemic form of bacillary angiomatosis that can persist for years.² Two reports suggested that bartonellosis also can be caused by Bartonella rochalimae and Candidatus Bartonella ancashi.^26,27

Vector Control

Prevention is key to reducing the risk of the various diseases caused by the Phlebotominae vector. Vector control often falls into a few categories, including residual sprays, barriers, and topical repellants.³ It appears that residual sprays applied to houses and animal shelters are the most utilized and effective form of control, with the pyrethroid insecticides having the highest sand fly–specific toxicity.^3,28 Insecticides also have been applied to animal burrows where sand flies are known to reproduce; one study in Kenya showed a 90% reduction in the sand fly population following treatment of termite and animal burrows with a pyrethroid spray.²⁹ Studies by Perich et al^30,31 in 1995 and 2003 showed that using barrier sprays can be an effective protective measure. The investigators applied a 100-m barrier using a pyrethroid spray on vegetation and reported a notable decrease in sand flies for over an 80-day period.^30,31

For personal protection, barrier methods are important adjunct methods of preventing individual exposures. Due to the small size of sand flies, ordinary bed nets are not effective and those treated with insecticides should be used,¹⁵ which may ultimately prove to be the most sustainable way to prevent sand fly–borne disease.³² Protective attire also should be worn, as sand flies are not able to penetrate clothing.² N,N-diethyl-meta-toluamide (DEET)–based repellants should be applied to exposed skin.¹⁵ Finally, it is important to avoid exposure from dusk to dawn when sand flies are most active.¹⁵

Rise in Autochthonous Cutaneous Leishmaniasis in the United States

With the increased amount of worldwide tourism, especially to endemic areas, providers will continue to see rising numbers of leishmaniasis in the United States. It is difficult to determine the incidence of the disease in the United States, but one study has shown that leishmaniasis accounts for 143 of every 1000 dermatologic diseases acquired by South American tourists.^33,34 In addition, the number of autochthonous cases reported in the United States continues to grow. Although only 29 cases were reported between 1903 and 1996, 13 cases were reported between 2000 and 2008.³⁵ Another report in 2013 described an additional 3 cases in the states of Texas and Oklahoma.³⁵ The cases have continued to move in a northeasterly pattern, suggesting a possible shift in the location of sand fly populations. Each of these cases in which a specific species of Leishmania was identified showed transmission of Leishmania mexicana.³⁵ Most cases of cutaneous disease have occurred in Texas and Oklahoma. The first known case outside of this region was reported in 2014 in North Dakota.⁸ Leishmania donovani, brought into the United States with European foxhounds, also is spreading.⁸ One species of sand fly, Leishmania shannoni, has now been discovered in 16 states,^36-42 where it serves as a potential vector for L mexicana.^43,44

Background and Distribution

The Dermacentor ticks belong to the family Ixodidae (hard ticks). The 2 best-known ticks of the genus are Dermacentor andersoni (Rocky Mountain wood tick)(Figure, A) and Dermacentor variabilis (American dog tick)(Figure, B). The Dermacentor ticks are large ticks with small anterior mouthparts that attach to a rectangular basis capituli (Figure, A). Both ticks exhibit widely spaced eyes and posterior festoons as well as bifid coxa 1 (the attachment site for the first pair of legs) and enlarged coxa 4. As adults, these ticks display an ornate hard dorsal plate, or scutum, with numerous pits. Female ticks have a much smaller scutum, allowing for abdominal engorgement during feeding.¹ Although D andersoni tends to have a brown to yellow hue, the specimens of D variabilis display a somewhat silver color pattern.

Dermacentor ticks can be found throughout most of North America, with the northern distribution limits of both species previously occurring in the province of Saskatchewan, Canada. Although the range of D andersoni has remained relatively stable within this distribution, the distribution of D variabilis recently has expanded westward and northward of these limits.² The ranges of the 2 species overlap in certain areas, though D andersoni primarily is found in the Rocky Mountain and northwestern states as well as southwestern Canada, whereas D variabilis can be found throughout most parts of the United States, except in the Rocky Mountain states.³ Within these regions the ticks can be found in heavily wooded areas, but they most commonly inhabit fields with tall grass, crops, bushes, and shrubbery, often clustering where these types of vegetation form clearly defined edges.⁴ The diseases transmitted by the Dermacentor ticks include Rocky Mountain spotted fever (RMSF), Colorado tick fever, tularemia, tick paralysis, and even human monocytic erlichiosis, though Amblyomma americanum is the major vector for human monocytic erlichiosis.

Rocky Mountain Spotted Fever

Both species of ticks are known to serve as vectors for RMSF, but D variabilis is the major vector in the United States, especially in the eastern and southeastern parts of the United States. Overall, the majority of cases occur in North Carolina, South Carolina, Tennessee, and Oklahoma,⁵ with North Carolina having the highest incidence. In endemic areas, RMSF should be suspected in any patient with fever and headache, and empiric treatment with antibiotics should be started while awaiting the results of diagnostic tests. Serologic testing with indirect fluorescent antibodies is widely available and is considered the best method for detection; although the sensitivity is poor during the first 10 to 12 days of infection, it increases to 94% during days 14 to 21.⁶ Therapeutic decisions should be influenced by clinical suspicion and epidemiologic data. Treatment should be started promptly and should never be delayed until confirmatory tests are available. Doxycycline is considered the gold standard therapy in both adults and children, with a typical treatment duration of 10 days. The only other recommended agent for pregnant women in the first or second trimesters or patients with severe hypersensitivity reactions to tetracyclines is chloramphenicol.⁷

Colorado Tick Fever

Colorado tick fever, also known as mountain fever, is an arboviral infection transmitted by D andersoni. Its distribution coincides with the tick’s natural geographic range in the western United States and Rocky Mountains. Colorado tick fever causes an acute febrile illness consisting of chills, headaches, myalgia, retro-orbital pain, and malaise, which tend to occur within 3 to 5 days of the tick bite. Some cases may be accompanied by a nonspecific rash that may be morbilliform or petechial in appearance. Notably, approximately half of all patients will experience transient resolution of symptoms for 24 to 48 hours followed by a recurrence of fever, a phenomenon that has been referred to as saddleback fever. Routine laboratory findings may include leukopenia, thrombocytopenia, and a peripheral smear with atypical lymphocytes. Reverse transcription polymerase chain reaction is both sensitive and specific for detecting viral loads in the blood during the first week of infection, though testing does not alter management, which is largely supportive.⁸

Tularemia

Tularemia is a relatively rare disease but has been documented in every US state except Hawaii.⁹ The disease is caused by Francisella tularensis, a small, aerobic, gram-negative coccobacillus transmitted via inhalation, bitingflies, or tick bites; the most common ticks to transmit the disease include D andersoni, D variabilis, and A americanum.¹⁰ Clinical manifestations depend on the form of exposure, with tick bites most often resulting in an ulcerated skin lesion at the site of the vector bite accompanied by regional lymphadenopathy and systemic symptoms such as fever, chills, myalgia, and headache.¹¹ Mucosal manifestations such as pharyngitis, conjunctivitis, and other ocular lesions also are commonly seen. Diagnosis most frequently is made using serology because F tularensis is both challenging and dangerous to culture; in fact, because of the high risk of contagion, F tularensis should only be cultured in biosafety level 3 laboratories. Polymerase chain reaction assays can be used on tissue samples with decent sensitivity (78%) and specificity (96%); however, these assays cannot distinguish between Francisella subspecies and are not readily available to most clinicians.¹² First-line therapy for the treatment of tularemia is streptomycin given as twice-daily intramuscular injections over the course of 7 to 10 days. Alternative agents include gentamicin, ciprofloxacin, imipenem, doxycycline, and chloramphenicol.¹⁰ Because tularemia is relatively rare, a high index of suspicion is necessary to reduce the morbidity and mortality associated with the disease.

Tick Paralysis

More than 40 different species of ticks have been implicated worldwide as causes of tick paralysis, though D andersoni has been the most common in North America. Female patients account for most cases, possibly because long hair conceals ticks on the scalp or neck, the preferred attachment locations for Dermacentor ticks.¹³ The classic presentation of tick paralysis is an acute, flaccid, ascending paralysis that occurs from a neurotoxin in the tick saliva that impairs afferent nerve signal propagation.^14,15 The paralysis progresses over hours to days and typically occurs 5 to 6 days after attachment of the tick. Notably, there is no associated fever with tick paralysis, and without intervention, patients may die of respiratory failure. Overall, the condition carries a fatality rate of nearly 10%¹⁶ but reverses rapidly if the tick is identified and removed.

Protection against tick bites and tick-borne illnesses includes avoidance of infested areas, treatment of populated habitats with insecticide sprays, use of topical repellants prior to outdoor activities, and diligent full-body tick checks upon return from tick-heavy areas. Permethrin can be used to treat clothing and remains protective through multiple washings. Ticks typically survive washing of untreated clothing but are killed by prolonged drying in a dryer. Pets may be treated with oral, intramuscular, or topical agents prescribed by a veterinarian to prevent tick attachments.

Conclusion

Accurate identification of Dermacentor ticks allows for appropriate surveillance for associated diseases and can improve patient outcomes. Patients who engage in outdoor activities in endemic areas should take steps to avoid exposure, use appropriate acaricides and repellents, and perform tick checks after returning indoors.

Background and Distribution

The Dermacentor ticks belong to the family Ixodidae (hard ticks). The 2 best-known ticks of the genus are Dermacentor andersoni (Rocky Mountain wood tick)(Figure, A) and Dermacentor variabilis (American dog tick)(Figure, B). The Dermacentor ticks are large ticks with small anterior mouthparts that attach to a rectangular basis capituli (Figure, A). Both ticks exhibit widely spaced eyes and posterior festoons as well as bifid coxa 1 (the attachment site for the first pair of legs) and enlarged coxa 4. As adults, these ticks display an ornate hard dorsal plate, or scutum, with numerous pits. Female ticks have a much smaller scutum, allowing for abdominal engorgement during feeding.¹ Although D andersoni tends to have a brown to yellow hue, the specimens of D variabilis display a somewhat silver color pattern.

Dermacentor ticks can be found throughout most of North America, with the northern distribution limits of both species previously occurring in the province of Saskatchewan, Canada. Although the range of D andersoni has remained relatively stable within this distribution, the distribution of D variabilis recently has expanded westward and northward of these limits.² The ranges of the 2 species overlap in certain areas, though D andersoni primarily is found in the Rocky Mountain and northwestern states as well as southwestern Canada, whereas D variabilis can be found throughout most parts of the United States, except in the Rocky Mountain states.³ Within these regions the ticks can be found in heavily wooded areas, but they most commonly inhabit fields with tall grass, crops, bushes, and shrubbery, often clustering where these types of vegetation form clearly defined edges.⁴ The diseases transmitted by the Dermacentor ticks include Rocky Mountain spotted fever (RMSF), Colorado tick fever, tularemia, tick paralysis, and even human monocytic erlichiosis, though Amblyomma americanum is the major vector for human monocytic erlichiosis.

Rocky Mountain Spotted Fever

Both species of ticks are known to serve as vectors for RMSF, but D variabilis is the major vector in the United States, especially in the eastern and southeastern parts of the United States. Overall, the majority of cases occur in North Carolina, South Carolina, Tennessee, and Oklahoma,⁵ with North Carolina having the highest incidence. In endemic areas, RMSF should be suspected in any patient with fever and headache, and empiric treatment with antibiotics should be started while awaiting the results of diagnostic tests. Serologic testing with indirect fluorescent antibodies is widely available and is considered the best method for detection; although the sensitivity is poor during the first 10 to 12 days of infection, it increases to 94% during days 14 to 21.⁶ Therapeutic decisions should be influenced by clinical suspicion and epidemiologic data. Treatment should be started promptly and should never be delayed until confirmatory tests are available. Doxycycline is considered the gold standard therapy in both adults and children, with a typical treatment duration of 10 days. The only other recommended agent for pregnant women in the first or second trimesters or patients with severe hypersensitivity reactions to tetracyclines is chloramphenicol.⁷

Colorado Tick Fever

Colorado tick fever, also known as mountain fever, is an arboviral infection transmitted by D andersoni. Its distribution coincides with the tick’s natural geographic range in the western United States and Rocky Mountains. Colorado tick fever causes an acute febrile illness consisting of chills, headaches, myalgia, retro-orbital pain, and malaise, which tend to occur within 3 to 5 days of the tick bite. Some cases may be accompanied by a nonspecific rash that may be morbilliform or petechial in appearance. Notably, approximately half of all patients will experience transient resolution of symptoms for 24 to 48 hours followed by a recurrence of fever, a phenomenon that has been referred to as saddleback fever. Routine laboratory findings may include leukopenia, thrombocytopenia, and a peripheral smear with atypical lymphocytes. Reverse transcription polymerase chain reaction is both sensitive and specific for detecting viral loads in the blood during the first week of infection, though testing does not alter management, which is largely supportive.⁸

Tularemia

Tularemia is a relatively rare disease but has been documented in every US state except Hawaii.⁹ The disease is caused by Francisella tularensis, a small, aerobic, gram-negative coccobacillus transmitted via inhalation, bitingflies, or tick bites; the most common ticks to transmit the disease include D andersoni, D variabilis, and A americanum.¹⁰ Clinical manifestations depend on the form of exposure, with tick bites most often resulting in an ulcerated skin lesion at the site of the vector bite accompanied by regional lymphadenopathy and systemic symptoms such as fever, chills, myalgia, and headache.¹¹ Mucosal manifestations such as pharyngitis, conjunctivitis, and other ocular lesions also are commonly seen. Diagnosis most frequently is made using serology because F tularensis is both challenging and dangerous to culture; in fact, because of the high risk of contagion, F tularensis should only be cultured in biosafety level 3 laboratories. Polymerase chain reaction assays can be used on tissue samples with decent sensitivity (78%) and specificity (96%); however, these assays cannot distinguish between Francisella subspecies and are not readily available to most clinicians.¹² First-line therapy for the treatment of tularemia is streptomycin given as twice-daily intramuscular injections over the course of 7 to 10 days. Alternative agents include gentamicin, ciprofloxacin, imipenem, doxycycline, and chloramphenicol.¹⁰ Because tularemia is relatively rare, a high index of suspicion is necessary to reduce the morbidity and mortality associated with the disease.

Tick Paralysis

More than 40 different species of ticks have been implicated worldwide as causes of tick paralysis, though D andersoni has been the most common in North America. Female patients account for most cases, possibly because long hair conceals ticks on the scalp or neck, the preferred attachment locations for Dermacentor ticks.¹³ The classic presentation of tick paralysis is an acute, flaccid, ascending paralysis that occurs from a neurotoxin in the tick saliva that impairs afferent nerve signal propagation.^14,15 The paralysis progresses over hours to days and typically occurs 5 to 6 days after attachment of the tick. Notably, there is no associated fever with tick paralysis, and without intervention, patients may die of respiratory failure. Overall, the condition carries a fatality rate of nearly 10%¹⁶ but reverses rapidly if the tick is identified and removed.

Protection against tick bites and tick-borne illnesses includes avoidance of infested areas, treatment of populated habitats with insecticide sprays, use of topical repellants prior to outdoor activities, and diligent full-body tick checks upon return from tick-heavy areas. Permethrin can be used to treat clothing and remains protective through multiple washings. Ticks typically survive washing of untreated clothing but are killed by prolonged drying in a dryer. Pets may be treated with oral, intramuscular, or topical agents prescribed by a veterinarian to prevent tick attachments.

Conclusion

Accurate identification of Dermacentor ticks allows for appropriate surveillance for associated diseases and can improve patient outcomes. Patients who engage in outdoor activities in endemic areas should take steps to avoid exposure, use appropriate acaricides and repellents, and perform tick checks after returning indoors.

Background and Distribution

The Dermacentor ticks belong to the family Ixodidae (hard ticks). The 2 best-known ticks of the genus are Dermacentor andersoni (Rocky Mountain wood tick)(Figure, A) and Dermacentor variabilis (American dog tick)(Figure, B). The Dermacentor ticks are large ticks with small anterior mouthparts that attach to a rectangular basis capituli (Figure, A). Both ticks exhibit widely spaced eyes and posterior festoons as well as bifid coxa 1 (the attachment site for the first pair of legs) and enlarged coxa 4. As adults, these ticks display an ornate hard dorsal plate, or scutum, with numerous pits. Female ticks have a much smaller scutum, allowing for abdominal engorgement during feeding.¹ Although D andersoni tends to have a brown to yellow hue, the specimens of D variabilis display a somewhat silver color pattern.

Dermacentor ticks can be found throughout most of North America, with the northern distribution limits of both species previously occurring in the province of Saskatchewan, Canada. Although the range of D andersoni has remained relatively stable within this distribution, the distribution of D variabilis recently has expanded westward and northward of these limits.² The ranges of the 2 species overlap in certain areas, though D andersoni primarily is found in the Rocky Mountain and northwestern states as well as southwestern Canada, whereas D variabilis can be found throughout most parts of the United States, except in the Rocky Mountain states.³ Within these regions the ticks can be found in heavily wooded areas, but they most commonly inhabit fields with tall grass, crops, bushes, and shrubbery, often clustering where these types of vegetation form clearly defined edges.⁴ The diseases transmitted by the Dermacentor ticks include Rocky Mountain spotted fever (RMSF), Colorado tick fever, tularemia, tick paralysis, and even human monocytic erlichiosis, though Amblyomma americanum is the major vector for human monocytic erlichiosis.

Rocky Mountain Spotted Fever

Both species of ticks are known to serve as vectors for RMSF, but D variabilis is the major vector in the United States, especially in the eastern and southeastern parts of the United States. Overall, the majority of cases occur in North Carolina, South Carolina, Tennessee, and Oklahoma,⁵ with North Carolina having the highest incidence. In endemic areas, RMSF should be suspected in any patient with fever and headache, and empiric treatment with antibiotics should be started while awaiting the results of diagnostic tests. Serologic testing with indirect fluorescent antibodies is widely available and is considered the best method for detection; although the sensitivity is poor during the first 10 to 12 days of infection, it increases to 94% during days 14 to 21.⁶ Therapeutic decisions should be influenced by clinical suspicion and epidemiologic data. Treatment should be started promptly and should never be delayed until confirmatory tests are available. Doxycycline is considered the gold standard therapy in both adults and children, with a typical treatment duration of 10 days. The only other recommended agent for pregnant women in the first or second trimesters or patients with severe hypersensitivity reactions to tetracyclines is chloramphenicol.⁷

Colorado Tick Fever

Colorado tick fever, also known as mountain fever, is an arboviral infection transmitted by D andersoni. Its distribution coincides with the tick’s natural geographic range in the western United States and Rocky Mountains. Colorado tick fever causes an acute febrile illness consisting of chills, headaches, myalgia, retro-orbital pain, and malaise, which tend to occur within 3 to 5 days of the tick bite. Some cases may be accompanied by a nonspecific rash that may be morbilliform or petechial in appearance. Notably, approximately half of all patients will experience transient resolution of symptoms for 24 to 48 hours followed by a recurrence of fever, a phenomenon that has been referred to as saddleback fever. Routine laboratory findings may include leukopenia, thrombocytopenia, and a peripheral smear with atypical lymphocytes. Reverse transcription polymerase chain reaction is both sensitive and specific for detecting viral loads in the blood during the first week of infection, though testing does not alter management, which is largely supportive.⁸

Tularemia

Tularemia is a relatively rare disease but has been documented in every US state except Hawaii.⁹ The disease is caused by Francisella tularensis, a small, aerobic, gram-negative coccobacillus transmitted via inhalation, bitingflies, or tick bites; the most common ticks to transmit the disease include D andersoni, D variabilis, and A americanum.¹⁰ Clinical manifestations depend on the form of exposure, with tick bites most often resulting in an ulcerated skin lesion at the site of the vector bite accompanied by regional lymphadenopathy and systemic symptoms such as fever, chills, myalgia, and headache.¹¹ Mucosal manifestations such as pharyngitis, conjunctivitis, and other ocular lesions also are commonly seen. Diagnosis most frequently is made using serology because F tularensis is both challenging and dangerous to culture; in fact, because of the high risk of contagion, F tularensis should only be cultured in biosafety level 3 laboratories. Polymerase chain reaction assays can be used on tissue samples with decent sensitivity (78%) and specificity (96%); however, these assays cannot distinguish between Francisella subspecies and are not readily available to most clinicians.¹² First-line therapy for the treatment of tularemia is streptomycin given as twice-daily intramuscular injections over the course of 7 to 10 days. Alternative agents include gentamicin, ciprofloxacin, imipenem, doxycycline, and chloramphenicol.¹⁰ Because tularemia is relatively rare, a high index of suspicion is necessary to reduce the morbidity and mortality associated with the disease.

Tick Paralysis

More than 40 different species of ticks have been implicated worldwide as causes of tick paralysis, though D andersoni has been the most common in North America. Female patients account for most cases, possibly because long hair conceals ticks on the scalp or neck, the preferred attachment locations for Dermacentor ticks.¹³ The classic presentation of tick paralysis is an acute, flaccid, ascending paralysis that occurs from a neurotoxin in the tick saliva that impairs afferent nerve signal propagation.^14,15 The paralysis progresses over hours to days and typically occurs 5 to 6 days after attachment of the tick. Notably, there is no associated fever with tick paralysis, and without intervention, patients may die of respiratory failure. Overall, the condition carries a fatality rate of nearly 10%¹⁶ but reverses rapidly if the tick is identified and removed.

Protection against tick bites and tick-borne illnesses includes avoidance of infested areas, treatment of populated habitats with insecticide sprays, use of topical repellants prior to outdoor activities, and diligent full-body tick checks upon return from tick-heavy areas. Permethrin can be used to treat clothing and remains protective through multiple washings. Ticks typically survive washing of untreated clothing but are killed by prolonged drying in a dryer. Pets may be treated with oral, intramuscular, or topical agents prescribed by a veterinarian to prevent tick attachments.

Conclusion

Accurate identification of Dermacentor ticks allows for appropriate surveillance for associated diseases and can improve patient outcomes. Patients who engage in outdoor activities in endemic areas should take steps to avoid exposure, use appropriate acaricides and repellents, and perform tick checks after returning indoors.

The head louse (Pediculus humanus capitis) is a blood-sucking arthropod of the suborder Anoplura. Lice are obligate human parasites that have infested humans since antiquity. Pediculosis capitis is an infestation of the scalp by head lice. It is estimated that 6 to 12 million individuals in the United States are affected with head lice per year.¹ Resistance to topical chemical pediculicides is widespread, and new agents have been developed to address this gap in care.

Characteristics of Head Lice

The head louse is a tan-gray–colored, wingless insect measuring approximately 2- to 3-mm long with 3 body segments. It has 6 legs with claws used to grasp individual hairs, and it moves by crawling; it does not fly or jump.^2,3 The head louse has an elongated abdomen and a small head with short antennae and anterior piercing mouthparts (Figure 1).⁴ Nits are transparent, flask-shaped, 0.5- to 0.8-mm egg cases found firmly cemented to the hair shafts approximately 1 to 4 mm above the level of the scalp (Figure 2).⁵ The head louse resides on scalp hair and feeds off the scalp itself. Both lice and nits can be present throughout the scalp but are most commonly found in the postauricular and occipital scalp.^3,4

Female lice live approximately 30 days and lay 5 to 10 eggs per day. Eggs incubate individually in nits laid close to the scalp for 8 to 10 days before hatching.^1,6 The newly hatched nymphs (also called instars) have multiple exoskeletons that are shed as they grow.⁷ Nymphs mature into adults in approximately 2 weeks, and the life cycle begins again.⁸ Head lice are obligate human parasites, feeding approximately every 4 to 6 hours on the blood of the host; however, they can survive up to 4 days without a blood meal on fomites if the climate and conditions are favorable.^5,9

Epidemiology and Transmission

Head lice infestations commonly occur in children aged 3 to 11 years and are more prevalent in girls and women.^1,10 Infestation rates are not reliably recorded, and few population-based studies have been performed; however, it is estimated that 6 to 12 million individuals are infested annually in the United States.¹ Prevalence in some European populations has been estimated to range from 1% to 20%.¹¹ A 2008 literature review found that worldwide prevalence varied across populations from 0.7% to 59%.¹⁰

Transmission occurs most frequently from direct head-to-head contact. One study found that transmission is most likely to occur when hairs are arranged in a parallel alignment and move slowly in relation to one another.¹² Although controversial and probably less notable, transmission also may occur indirectly via fomites or the sharing of hairbrushes, hats, or other headgear.^13,14 Classrooms are a common place for transmission.¹ A 2009 study in Germany found an increase in health department consultations for head lice when schools reopened after vacations. The investigators also found that pediculicide sales peaked from mid-September through October, subsequent to schools reopening after the summer holiday.¹⁵ There is some evidence that overcrowded housing also can lead to increased incidence and transmission.^16,17 There is no consistent correlation of infestation with socioeconomic status.^1,17,18

Clinical Manifestations and Diagnosis

Clinically, patients with head lice present with scalp pruritus and sometimes posterior cervical or occipital lymphadenopathy. Pediculosis also can be asymptomatic. With the first exposure, symptoms may not develop for up to 4 to 6 weeks as the immune system develops sensitivity to the louse saliva.⁶ Bite reactions consisting of papules or wheals are related to immune sensitization.⁵ Louse feces and excoriations from scratching to relieve itch also may be present on examination. Secondary infection of excoriations also is possible.¹

Diagnosis of an active infestation is made by identifying living lice. Because lice move quickly and can be difficult to detect, tightly attached nits on the hair shaft within 4 mm of the scalp are at least indicative of a historic infestation and can be suggestive of active infestation.^1,19 Dermoscopy is a helpful tool in differentiating eggs containing nymphs from the empty cases of hatched lice and also from amorphous pseudonits (hair casts)(Figure 3).^19,20 Wet combing improves the accuracy of diagnosing an active infection.²¹

Treatment

Effective treatment of head lice requires eradication of all living lice as well as louse eggs. Topically applied pyrethroids, including pyrethrin shampoos and mousses and permethrin lotion 1%, are considered the first-line therapy.⁸ Pyrethroids are over-the-counter treatments that act by interfering with sodium transport in the louse, causing depolarization of the neuromembranes and respiratory paralysis.²² Pyrethrins are natural compounds derived from the chrysanthemum plant; permethrin is a synthetic compound. Pyrethrins often are combined with piperonyl butoxide, an insecticide synergist that improves efficacy by inhibiting pyrethrin catabolism.²³ Resistance to pyrethroids has become an increasingly important problem in the United States and worldwide.

Malathion lotion 0.5% is another therapeutic option for head lice. Malathion is a prescription organophosphate cholinesterase inhibitor that also causes respiratory paralysis of the louse and is one of the few treatments that is ovicidal.²² It was withdrawn from the market in 1995 due to its flammability and a theoretical risk of respiratory depression if ingested; however, it was reintroduced in 1999 and remains an effective treatment option with little resistance in the United States.²⁴

Lindane 1% (shampoo and lotion), an organochloride compound that acts by causing neuronal hyperstimulation and eventual paralysis of lice, is no longer recommended due to its serious side effects, including central nervous system toxicity and increased risk of seizure.^8,24

New US Food and Drug Administration–Approved Therapies
Newer topical treatments include benzyl alcohol lotion 5%, spinosad topical suspension 0.9%, ivermectin lotion 0.5%, and dimethicone-based products. Benzyl alcohol was approved by the US Food and Drug Administration (FDA) in 2009 and is available in the United States by prescription.²⁵ Benzyl alcohol kills lice by asphyxiation. Phase 2 and 3 clinical trials showed significant treatment success 1 day posttreatment (fewer live lice than the vehicle alone; P=.004) and 2 weeks posttreatment (absence of live lice compared to the vehicle alone; P=.001).²⁶

Spinosad was approved by the FDA in 2011 and is available in the United States by prescription.²⁵ It contains the compounds spinosyn A and spinosyn D, which are naturally derived through fermentation by the soil bacterium Saccharopolyspora spinosa. It also contains benzyl alcohol. Spinosad paralyzes lice by disrupting neuronal activity and is at least partially ovicidal.²⁷ Phase 3 clinical trials published in 2009 showed that spinosad was significantly more effective than permethrin in eradicating head lice (P<.001).²⁸

Topical ivermectin was approved by the FDA in 2012 for prescription use.²⁵ It acts on chloride ion channels, causing hyperpolarization of the muscle cells of lice and resulting in paralysis and death. Oral ivermectin (200 μg/kg) given once and repeated in 10 days is not FDA approved for the treatment of head lice but has shown some effectiveness and is sometimes used.⁸ A comparison study of topical versus oral ivermectin published in 2014 found that eradication was achieved in 88% (n=27) of topical ivermectin users after 1 treatment and 100% (n=31) after 2 treatments. Oral ivermectin produced cure rates of 45% (n=14) after 1 treatment and 97% (n=30) after 2 treatments. Both topical and oral ivermectin treatments are well tolerated.²⁹

Physically Acting Preparations
Products with a physical mode of action are a new attractive option for treatment of pediculosis because the development of resistance is less likely. Studies of silicone-based fluids that physically occlude the respiratory system of the louse, such as dimethicone liquid gel 4%, have shown superiority over treatment with pyrethroids.^30,31 Although the safety of dimethicone has been demonstrated, silicone-based treatments have not yet been widely adopted in the United States and are not currently used as a first-line treatment.³² However, use of such physically acting pediculicides may in time surpass traditional neurotoxic treatments due to their low susceptibility to resistance and good safety profile.^33,34

Alternative Therapies
Nonchemical treatments for head lice that have shown variable success include wet combing, hot air treatments, and varying occlusive treatments. Physical removal via wet combing requires persistent repeated treatments over several weeks; for example, wet combing may be performed every 3 days for at least 2 weeks or until no head lice are detected on 4 consecutive occasions.³⁵ Cure rates range from 38% to 75% with wet combing as a sole treatment of head lice.³⁶ Because this treatment has minimal risks and no adverse side effects, it can be considered as an alternative treatment for some patients.

Hot air treatments also have been studied. A 2006 study showed that a hot air treatment device had the potential to eradicate head lice, most likely by desiccation. Specifically, 30 minutes of exposure to hot air (at 58.9°F, slightly cooler than a standard hair dryer) using the custom-built device resulted in 98% mortality of eggs and 80% mortality of hatched lice.³⁷ Large randomized controlled trials of hot air treatments have not been performed.

Other alternative treatments include plant-derived oils. A laboratory study of essential oils found that spearmint, cassia, and clove showed pediculicidal activity similar to malathion with improved ovicidal activity.³⁸ However, there is a potential for development of contact dermatitis from essential oils.

Complete Eradication of Head Lice
Removal of nits is an important component of effective lice eradication. Biochemical analysis has revealed that the nit sheath of the head louse is similar in composition to amyloid, rendering it difficult to design products that will unravel the nit sheath while leaving human hair undamaged.³⁹ Because pediculicides are not necessarily ovicidal and complete physical nit removal is difficult to achieve, re-treatment in 7 to 10 days often is advisable to ensure that lice in all stages of the life cycle have been killed.⁴ Treatment of any secondary bacterial infection also is important. Although transmission of lice via fomites is less likely than from head-to-head contact, the cleaning of hats, hairbrushes, and linens is prudent. Diagnosing and treating infested close contacts also is essential to achieving eradication.⁴ Coordinated surveillance, education, and treatment efforts in high-risk communities can help detect asymptomatic cases and control local epidemics in a cost-effective manner.⁴⁰ However, “no nit” policies at schools likely cause a net harm, as nit removal is difficult and children with nonviable nits are then excluded from the classroom.⁵

Treatment Resistance
Resistance to topical neurotoxic treatments is becoming increasingly common.^41-43 Therefore, it is important to identify local patterns of resistance, if possible, when selecting a therapy for head lice. Improper usage, changes in pediculicide formulations and packaging, decreased product efficacy, and natural selection have all contributed to this rise in resistance.⁷ Additionally, due to protection from multiple exoskeletons and the natural molting process as they mature into adults, nymphs may only receive a sublethal dose when exposed to pediculicides, contributing further to resistance.⁷ Resistance to synthetic pyrethroids is most predominant, likely due to selection pressure because permethrin historically has been the most widely used insecticide for pediculosis. A 2014 study found that the frequency of sodium-channel insensitivity to pyrethroids, also known as knockdown resistance (or kdr), in US head louse populations collected over a 10-year period was 84.4% and approached 100% in some communities in recent years.⁴⁴ This evidence strongly supports the use of alternative therapeutic categories to effectively eradicate head lice infestations.

Conclusion

Head lice infestation is common in children, and although it is not harmful to the host, it can be an irritating and symptomatic problem and can lead to notable distress, missed days of school, and secondary infections. Identifying active adult lice is the gold standard for diagnosis. Current recommended treatments include pyrethroids as the first-line therapy; however, resistance to these neurotoxic agents is becoming increasingly common. Alternative therapies such as newer neurotoxic agents or pediculicides with physical mechanisms of action (eg, dimethicone-based products) should be considered, particularly in regions where resistance is known to be high. Education about head lice, proper use of treatment, and coordinated diagnosis are necessary for effective management of this problem.

The head louse (Pediculus humanus capitis) is a blood-sucking arthropod of the suborder Anoplura. Lice are obligate human parasites that have infested humans since antiquity. Pediculosis capitis is an infestation of the scalp by head lice. It is estimated that 6 to 12 million individuals in the United States are affected with head lice per year.¹ Resistance to topical chemical pediculicides is widespread, and new agents have been developed to address this gap in care.

Characteristics of Head Lice

The head louse is a tan-gray–colored, wingless insect measuring approximately 2- to 3-mm long with 3 body segments. It has 6 legs with claws used to grasp individual hairs, and it moves by crawling; it does not fly or jump.^2,3 The head louse has an elongated abdomen and a small head with short antennae and anterior piercing mouthparts (Figure 1).⁴ Nits are transparent, flask-shaped, 0.5- to 0.8-mm egg cases found firmly cemented to the hair shafts approximately 1 to 4 mm above the level of the scalp (Figure 2).⁵ The head louse resides on scalp hair and feeds off the scalp itself. Both lice and nits can be present throughout the scalp but are most commonly found in the postauricular and occipital scalp.^3,4

Female lice live approximately 30 days and lay 5 to 10 eggs per day. Eggs incubate individually in nits laid close to the scalp for 8 to 10 days before hatching.^1,6 The newly hatched nymphs (also called instars) have multiple exoskeletons that are shed as they grow.⁷ Nymphs mature into adults in approximately 2 weeks, and the life cycle begins again.⁸ Head lice are obligate human parasites, feeding approximately every 4 to 6 hours on the blood of the host; however, they can survive up to 4 days without a blood meal on fomites if the climate and conditions are favorable.^5,9

Epidemiology and Transmission

Head lice infestations commonly occur in children aged 3 to 11 years and are more prevalent in girls and women.^1,10 Infestation rates are not reliably recorded, and few population-based studies have been performed; however, it is estimated that 6 to 12 million individuals are infested annually in the United States.¹ Prevalence in some European populations has been estimated to range from 1% to 20%.¹¹ A 2008 literature review found that worldwide prevalence varied across populations from 0.7% to 59%.¹⁰

Transmission occurs most frequently from direct head-to-head contact. One study found that transmission is most likely to occur when hairs are arranged in a parallel alignment and move slowly in relation to one another.¹² Although controversial and probably less notable, transmission also may occur indirectly via fomites or the sharing of hairbrushes, hats, or other headgear.^13,14 Classrooms are a common place for transmission.¹ A 2009 study in Germany found an increase in health department consultations for head lice when schools reopened after vacations. The investigators also found that pediculicide sales peaked from mid-September through October, subsequent to schools reopening after the summer holiday.¹⁵ There is some evidence that overcrowded housing also can lead to increased incidence and transmission.^16,17 There is no consistent correlation of infestation with socioeconomic status.^1,17,18

Clinical Manifestations and Diagnosis

Clinically, patients with head lice present with scalp pruritus and sometimes posterior cervical or occipital lymphadenopathy. Pediculosis also can be asymptomatic. With the first exposure, symptoms may not develop for up to 4 to 6 weeks as the immune system develops sensitivity to the louse saliva.⁶ Bite reactions consisting of papules or wheals are related to immune sensitization.⁵ Louse feces and excoriations from scratching to relieve itch also may be present on examination. Secondary infection of excoriations also is possible.¹

Diagnosis of an active infestation is made by identifying living lice. Because lice move quickly and can be difficult to detect, tightly attached nits on the hair shaft within 4 mm of the scalp are at least indicative of a historic infestation and can be suggestive of active infestation.^1,19 Dermoscopy is a helpful tool in differentiating eggs containing nymphs from the empty cases of hatched lice and also from amorphous pseudonits (hair casts)(Figure 3).^19,20 Wet combing improves the accuracy of diagnosing an active infection.²¹

Treatment

Effective treatment of head lice requires eradication of all living lice as well as louse eggs. Topically applied pyrethroids, including pyrethrin shampoos and mousses and permethrin lotion 1%, are considered the first-line therapy.⁸ Pyrethroids are over-the-counter treatments that act by interfering with sodium transport in the louse, causing depolarization of the neuromembranes and respiratory paralysis.²² Pyrethrins are natural compounds derived from the chrysanthemum plant; permethrin is a synthetic compound. Pyrethrins often are combined with piperonyl butoxide, an insecticide synergist that improves efficacy by inhibiting pyrethrin catabolism.²³ Resistance to pyrethroids has become an increasingly important problem in the United States and worldwide.

Malathion lotion 0.5% is another therapeutic option for head lice. Malathion is a prescription organophosphate cholinesterase inhibitor that also causes respiratory paralysis of the louse and is one of the few treatments that is ovicidal.²² It was withdrawn from the market in 1995 due to its flammability and a theoretical risk of respiratory depression if ingested; however, it was reintroduced in 1999 and remains an effective treatment option with little resistance in the United States.²⁴

Lindane 1% (shampoo and lotion), an organochloride compound that acts by causing neuronal hyperstimulation and eventual paralysis of lice, is no longer recommended due to its serious side effects, including central nervous system toxicity and increased risk of seizure.^8,24

New US Food and Drug Administration–Approved Therapies
Newer topical treatments include benzyl alcohol lotion 5%, spinosad topical suspension 0.9%, ivermectin lotion 0.5%, and dimethicone-based products. Benzyl alcohol was approved by the US Food and Drug Administration (FDA) in 2009 and is available in the United States by prescription.²⁵ Benzyl alcohol kills lice by asphyxiation. Phase 2 and 3 clinical trials showed significant treatment success 1 day posttreatment (fewer live lice than the vehicle alone; P=.004) and 2 weeks posttreatment (absence of live lice compared to the vehicle alone; P=.001).²⁶

Spinosad was approved by the FDA in 2011 and is available in the United States by prescription.²⁵ It contains the compounds spinosyn A and spinosyn D, which are naturally derived through fermentation by the soil bacterium Saccharopolyspora spinosa. It also contains benzyl alcohol. Spinosad paralyzes lice by disrupting neuronal activity and is at least partially ovicidal.²⁷ Phase 3 clinical trials published in 2009 showed that spinosad was significantly more effective than permethrin in eradicating head lice (P<.001).²⁸

Topical ivermectin was approved by the FDA in 2012 for prescription use.²⁵ It acts on chloride ion channels, causing hyperpolarization of the muscle cells of lice and resulting in paralysis and death. Oral ivermectin (200 μg/kg) given once and repeated in 10 days is not FDA approved for the treatment of head lice but has shown some effectiveness and is sometimes used.⁸ A comparison study of topical versus oral ivermectin published in 2014 found that eradication was achieved in 88% (n=27) of topical ivermectin users after 1 treatment and 100% (n=31) after 2 treatments. Oral ivermectin produced cure rates of 45% (n=14) after 1 treatment and 97% (n=30) after 2 treatments. Both topical and oral ivermectin treatments are well tolerated.²⁹

Physically Acting Preparations
Products with a physical mode of action are a new attractive option for treatment of pediculosis because the development of resistance is less likely. Studies of silicone-based fluids that physically occlude the respiratory system of the louse, such as dimethicone liquid gel 4%, have shown superiority over treatment with pyrethroids.^30,31 Although the safety of dimethicone has been demonstrated, silicone-based treatments have not yet been widely adopted in the United States and are not currently used as a first-line treatment.³² However, use of such physically acting pediculicides may in time surpass traditional neurotoxic treatments due to their low susceptibility to resistance and good safety profile.^33,34

Alternative Therapies
Nonchemical treatments for head lice that have shown variable success include wet combing, hot air treatments, and varying occlusive treatments. Physical removal via wet combing requires persistent repeated treatments over several weeks; for example, wet combing may be performed every 3 days for at least 2 weeks or until no head lice are detected on 4 consecutive occasions.³⁵ Cure rates range from 38% to 75% with wet combing as a sole treatment of head lice.³⁶ Because this treatment has minimal risks and no adverse side effects, it can be considered as an alternative treatment for some patients.

Hot air treatments also have been studied. A 2006 study showed that a hot air treatment device had the potential to eradicate head lice, most likely by desiccation. Specifically, 30 minutes of exposure to hot air (at 58.9°F, slightly cooler than a standard hair dryer) using the custom-built device resulted in 98% mortality of eggs and 80% mortality of hatched lice.³⁷ Large randomized controlled trials of hot air treatments have not been performed.

Other alternative treatments include plant-derived oils. A laboratory study of essential oils found that spearmint, cassia, and clove showed pediculicidal activity similar to malathion with improved ovicidal activity.³⁸ However, there is a potential for development of contact dermatitis from essential oils.

Complete Eradication of Head Lice
Removal of nits is an important component of effective lice eradication. Biochemical analysis has revealed that the nit sheath of the head louse is similar in composition to amyloid, rendering it difficult to design products that will unravel the nit sheath while leaving human hair undamaged.³⁹ Because pediculicides are not necessarily ovicidal and complete physical nit removal is difficult to achieve, re-treatment in 7 to 10 days often is advisable to ensure that lice in all stages of the life cycle have been killed.⁴ Treatment of any secondary bacterial infection also is important. Although transmission of lice via fomites is less likely than from head-to-head contact, the cleaning of hats, hairbrushes, and linens is prudent. Diagnosing and treating infested close contacts also is essential to achieving eradication.⁴ Coordinated surveillance, education, and treatment efforts in high-risk communities can help detect asymptomatic cases and control local epidemics in a cost-effective manner.⁴⁰ However, “no nit” policies at schools likely cause a net harm, as nit removal is difficult and children with nonviable nits are then excluded from the classroom.⁵

Treatment Resistance
Resistance to topical neurotoxic treatments is becoming increasingly common.^41-43 Therefore, it is important to identify local patterns of resistance, if possible, when selecting a therapy for head lice. Improper usage, changes in pediculicide formulations and packaging, decreased product efficacy, and natural selection have all contributed to this rise in resistance.⁷ Additionally, due to protection from multiple exoskeletons and the natural molting process as they mature into adults, nymphs may only receive a sublethal dose when exposed to pediculicides, contributing further to resistance.⁷ Resistance to synthetic pyrethroids is most predominant, likely due to selection pressure because permethrin historically has been the most widely used insecticide for pediculosis. A 2014 study found that the frequency of sodium-channel insensitivity to pyrethroids, also known as knockdown resistance (or kdr), in US head louse populations collected over a 10-year period was 84.4% and approached 100% in some communities in recent years.⁴⁴ This evidence strongly supports the use of alternative therapeutic categories to effectively eradicate head lice infestations.

Conclusion

Head lice infestation is common in children, and although it is not harmful to the host, it can be an irritating and symptomatic problem and can lead to notable distress, missed days of school, and secondary infections. Identifying active adult lice is the gold standard for diagnosis. Current recommended treatments include pyrethroids as the first-line therapy; however, resistance to these neurotoxic agents is becoming increasingly common. Alternative therapies such as newer neurotoxic agents or pediculicides with physical mechanisms of action (eg, dimethicone-based products) should be considered, particularly in regions where resistance is known to be high. Education about head lice, proper use of treatment, and coordinated diagnosis are necessary for effective management of this problem.

The head louse (Pediculus humanus capitis) is a blood-sucking arthropod of the suborder Anoplura. Lice are obligate human parasites that have infested humans since antiquity. Pediculosis capitis is an infestation of the scalp by head lice. It is estimated that 6 to 12 million individuals in the United States are affected with head lice per year.¹ Resistance to topical chemical pediculicides is widespread, and new agents have been developed to address this gap in care.

Characteristics of Head Lice

The head louse is a tan-gray–colored, wingless insect measuring approximately 2- to 3-mm long with 3 body segments. It has 6 legs with claws used to grasp individual hairs, and it moves by crawling; it does not fly or jump.^2,3 The head louse has an elongated abdomen and a small head with short antennae and anterior piercing mouthparts (Figure 1).⁴ Nits are transparent, flask-shaped, 0.5- to 0.8-mm egg cases found firmly cemented to the hair shafts approximately 1 to 4 mm above the level of the scalp (Figure 2).⁵ The head louse resides on scalp hair and feeds off the scalp itself. Both lice and nits can be present throughout the scalp but are most commonly found in the postauricular and occipital scalp.^3,4

Female lice live approximately 30 days and lay 5 to 10 eggs per day. Eggs incubate individually in nits laid close to the scalp for 8 to 10 days before hatching.^1,6 The newly hatched nymphs (also called instars) have multiple exoskeletons that are shed as they grow.⁷ Nymphs mature into adults in approximately 2 weeks, and the life cycle begins again.⁸ Head lice are obligate human parasites, feeding approximately every 4 to 6 hours on the blood of the host; however, they can survive up to 4 days without a blood meal on fomites if the climate and conditions are favorable.^5,9

Epidemiology and Transmission

Head lice infestations commonly occur in children aged 3 to 11 years and are more prevalent in girls and women.^1,10 Infestation rates are not reliably recorded, and few population-based studies have been performed; however, it is estimated that 6 to 12 million individuals are infested annually in the United States.¹ Prevalence in some European populations has been estimated to range from 1% to 20%.¹¹ A 2008 literature review found that worldwide prevalence varied across populations from 0.7% to 59%.¹⁰

Transmission occurs most frequently from direct head-to-head contact. One study found that transmission is most likely to occur when hairs are arranged in a parallel alignment and move slowly in relation to one another.¹² Although controversial and probably less notable, transmission also may occur indirectly via fomites or the sharing of hairbrushes, hats, or other headgear.^13,14 Classrooms are a common place for transmission.¹ A 2009 study in Germany found an increase in health department consultations for head lice when schools reopened after vacations. The investigators also found that pediculicide sales peaked from mid-September through October, subsequent to schools reopening after the summer holiday.¹⁵ There is some evidence that overcrowded housing also can lead to increased incidence and transmission.^16,17 There is no consistent correlation of infestation with socioeconomic status.^1,17,18

Clinical Manifestations and Diagnosis

Clinically, patients with head lice present with scalp pruritus and sometimes posterior cervical or occipital lymphadenopathy. Pediculosis also can be asymptomatic. With the first exposure, symptoms may not develop for up to 4 to 6 weeks as the immune system develops sensitivity to the louse saliva.⁶ Bite reactions consisting of papules or wheals are related to immune sensitization.⁵ Louse feces and excoriations from scratching to relieve itch also may be present on examination. Secondary infection of excoriations also is possible.¹

Diagnosis of an active infestation is made by identifying living lice. Because lice move quickly and can be difficult to detect, tightly attached nits on the hair shaft within 4 mm of the scalp are at least indicative of a historic infestation and can be suggestive of active infestation.^1,19 Dermoscopy is a helpful tool in differentiating eggs containing nymphs from the empty cases of hatched lice and also from amorphous pseudonits (hair casts)(Figure 3).^19,20 Wet combing improves the accuracy of diagnosing an active infection.²¹

Treatment

Effective treatment of head lice requires eradication of all living lice as well as louse eggs. Topically applied pyrethroids, including pyrethrin shampoos and mousses and permethrin lotion 1%, are considered the first-line therapy.⁸ Pyrethroids are over-the-counter treatments that act by interfering with sodium transport in the louse, causing depolarization of the neuromembranes and respiratory paralysis.²² Pyrethrins are natural compounds derived from the chrysanthemum plant; permethrin is a synthetic compound. Pyrethrins often are combined with piperonyl butoxide, an insecticide synergist that improves efficacy by inhibiting pyrethrin catabolism.²³ Resistance to pyrethroids has become an increasingly important problem in the United States and worldwide.

Malathion lotion 0.5% is another therapeutic option for head lice. Malathion is a prescription organophosphate cholinesterase inhibitor that also causes respiratory paralysis of the louse and is one of the few treatments that is ovicidal.²² It was withdrawn from the market in 1995 due to its flammability and a theoretical risk of respiratory depression if ingested; however, it was reintroduced in 1999 and remains an effective treatment option with little resistance in the United States.²⁴

Lindane 1% (shampoo and lotion), an organochloride compound that acts by causing neuronal hyperstimulation and eventual paralysis of lice, is no longer recommended due to its serious side effects, including central nervous system toxicity and increased risk of seizure.^8,24

New US Food and Drug Administration–Approved Therapies
Newer topical treatments include benzyl alcohol lotion 5%, spinosad topical suspension 0.9%, ivermectin lotion 0.5%, and dimethicone-based products. Benzyl alcohol was approved by the US Food and Drug Administration (FDA) in 2009 and is available in the United States by prescription.²⁵ Benzyl alcohol kills lice by asphyxiation. Phase 2 and 3 clinical trials showed significant treatment success 1 day posttreatment (fewer live lice than the vehicle alone; P=.004) and 2 weeks posttreatment (absence of live lice compared to the vehicle alone; P=.001).²⁶

Spinosad was approved by the FDA in 2011 and is available in the United States by prescription.²⁵ It contains the compounds spinosyn A and spinosyn D, which are naturally derived through fermentation by the soil bacterium Saccharopolyspora spinosa. It also contains benzyl alcohol. Spinosad paralyzes lice by disrupting neuronal activity and is at least partially ovicidal.²⁷ Phase 3 clinical trials published in 2009 showed that spinosad was significantly more effective than permethrin in eradicating head lice (P<.001).²⁸

Topical ivermectin was approved by the FDA in 2012 for prescription use.²⁵ It acts on chloride ion channels, causing hyperpolarization of the muscle cells of lice and resulting in paralysis and death. Oral ivermectin (200 μg/kg) given once and repeated in 10 days is not FDA approved for the treatment of head lice but has shown some effectiveness and is sometimes used.⁸ A comparison study of topical versus oral ivermectin published in 2014 found that eradication was achieved in 88% (n=27) of topical ivermectin users after 1 treatment and 100% (n=31) after 2 treatments. Oral ivermectin produced cure rates of 45% (n=14) after 1 treatment and 97% (n=30) after 2 treatments. Both topical and oral ivermectin treatments are well tolerated.²⁹

Physically Acting Preparations
Products with a physical mode of action are a new attractive option for treatment of pediculosis because the development of resistance is less likely. Studies of silicone-based fluids that physically occlude the respiratory system of the louse, such as dimethicone liquid gel 4%, have shown superiority over treatment with pyrethroids.^30,31 Although the safety of dimethicone has been demonstrated, silicone-based treatments have not yet been widely adopted in the United States and are not currently used as a first-line treatment.³² However, use of such physically acting pediculicides may in time surpass traditional neurotoxic treatments due to their low susceptibility to resistance and good safety profile.^33,34

Alternative Therapies
Nonchemical treatments for head lice that have shown variable success include wet combing, hot air treatments, and varying occlusive treatments. Physical removal via wet combing requires persistent repeated treatments over several weeks; for example, wet combing may be performed every 3 days for at least 2 weeks or until no head lice are detected on 4 consecutive occasions.³⁵ Cure rates range from 38% to 75% with wet combing as a sole treatment of head lice.³⁶ Because this treatment has minimal risks and no adverse side effects, it can be considered as an alternative treatment for some patients.

Hot air treatments also have been studied. A 2006 study showed that a hot air treatment device had the potential to eradicate head lice, most likely by desiccation. Specifically, 30 minutes of exposure to hot air (at 58.9°F, slightly cooler than a standard hair dryer) using the custom-built device resulted in 98% mortality of eggs and 80% mortality of hatched lice.³⁷ Large randomized controlled trials of hot air treatments have not been performed.

Other alternative treatments include plant-derived oils. A laboratory study of essential oils found that spearmint, cassia, and clove showed pediculicidal activity similar to malathion with improved ovicidal activity.³⁸ However, there is a potential for development of contact dermatitis from essential oils.

Complete Eradication of Head Lice
Removal of nits is an important component of effective lice eradication. Biochemical analysis has revealed that the nit sheath of the head louse is similar in composition to amyloid, rendering it difficult to design products that will unravel the nit sheath while leaving human hair undamaged.³⁹ Because pediculicides are not necessarily ovicidal and complete physical nit removal is difficult to achieve, re-treatment in 7 to 10 days often is advisable to ensure that lice in all stages of the life cycle have been killed.⁴ Treatment of any secondary bacterial infection also is important. Although transmission of lice via fomites is less likely than from head-to-head contact, the cleaning of hats, hairbrushes, and linens is prudent. Diagnosing and treating infested close contacts also is essential to achieving eradication.⁴ Coordinated surveillance, education, and treatment efforts in high-risk communities can help detect asymptomatic cases and control local epidemics in a cost-effective manner.⁴⁰ However, “no nit” policies at schools likely cause a net harm, as nit removal is difficult and children with nonviable nits are then excluded from the classroom.⁵

Treatment Resistance
Resistance to topical neurotoxic treatments is becoming increasingly common.^41-43 Therefore, it is important to identify local patterns of resistance, if possible, when selecting a therapy for head lice. Improper usage, changes in pediculicide formulations and packaging, decreased product efficacy, and natural selection have all contributed to this rise in resistance.⁷ Additionally, due to protection from multiple exoskeletons and the natural molting process as they mature into adults, nymphs may only receive a sublethal dose when exposed to pediculicides, contributing further to resistance.⁷ Resistance to synthetic pyrethroids is most predominant, likely due to selection pressure because permethrin historically has been the most widely used insecticide for pediculosis. A 2014 study found that the frequency of sodium-channel insensitivity to pyrethroids, also known as knockdown resistance (or kdr), in US head louse populations collected over a 10-year period was 84.4% and approached 100% in some communities in recent years.⁴⁴ This evidence strongly supports the use of alternative therapeutic categories to effectively eradicate head lice infestations.

Conclusion

Head lice infestation is common in children, and although it is not harmful to the host, it can be an irritating and symptomatic problem and can lead to notable distress, missed days of school, and secondary infections. Identifying active adult lice is the gold standard for diagnosis. Current recommended treatments include pyrethroids as the first-line therapy; however, resistance to these neurotoxic agents is becoming increasingly common. Alternative therapies such as newer neurotoxic agents or pediculicides with physical mechanisms of action (eg, dimethicone-based products) should be considered, particularly in regions where resistance is known to be high. Education about head lice, proper use of treatment, and coordinated diagnosis are necessary for effective management of this problem.

Scabies is caused by the mite Sarcoptes scabiei var hominis.¹ It is in the arthropod class Arachnida, subclass Acari, and family Sarcoptidae.² Historically, scabies was first described in the Old Testament and by Aristotle,² but the causative organism was not identified until 1687 using a light microscope.³ Scabies affects all age groups, races, and social classes and is globally widespread. It is most prevalent in developing tropical countries.¹ It is estimated that 300 million individuals worldwide are infested with scabies mites annually, with the highest burden in young children.^4-7 In industrialized societies, infections often are seen in young adults and in institutional settings such as nursing homes.⁸ Scabies disproportionately impacts impoverished communities with crowded living conditions, poor hygiene and nutrition, and substandard housing^.5,9 Controlling the spread of the disease in these communities presents challenges but is important because of the connection between scabies and chronic kidney disease.¹⁰ As such, scabies represents a major health problem in the developing world and has been the focus of major health initiatives.^1,11

Identifying Characteristics

Adult females are 0.4-mm long and 0.3-mm wide, with males being smaller. Adult nymphs have 8 legs and larvae have 6 legs. Scabies mites are distinguishable from other arachnids by the position of a distinct gnathosoma and the lack of a division between the abdomen and cephalothorax.¹² They are ovoid with a small anterior cephalic and caudal thoracoabdominal portion with hairlike projections coming off from the rudimentary legs. They can crawl as fast as 2.5 cm per minute on warm skin.² The life cycle of the mite begins after mating: the male mite dies, and the female lays up to 3 eggs per day, which hatch in 3 to 4 days,² in skin burrows within the stratum granulosum.¹² Maturation from larva to adult takes 10 to 14 days.¹² A female mite can live for 4 to 6 weeks and can produce up to 40 ova (Figure 1).

Disease Transmission

Without a host, mites are able to survive and remain capable of infestation for 24 to 36 hours at 21°C and 40% to 80% relative humidity. Lower temperatures and higher humidity prolong survival, but infectivity decreases the longer they are without a host.¹³

An adult human with ordinary scabies will have an average of 12 adult female mites on the body surface at a given time.¹⁴ However, hundreds of mites can be found in neglected children in underprivileged communities and millions in patients with crusted scabies.¹³ Transmission of typical scabies requires close direct skin-to-skin contact for 15 to 20 minutes.^2,8 Transmission from clothing or fomites are an unlikely source of infestation with the exception of patients who are heavily infested such as in crusted scabies.¹² In adults, sexual contact is an important method of transmission,¹² and patients with scabies should be screened for other sexually transmitted diseases.⁸

Clinical Manifestations

Signs of scabies on the skin include burrows, erythematous papules, and generalized pruritus (Figure 2).¹² The scalp, face, and neck frequently are involved in infants and children,² and the hands, wrists, elbows, genitalia, axillae, umbilicus, belt line, nipples, and buttocks commonly are involved in adults.¹² Itching is characteristically worse at night.⁸ In tropical climates, patients with scabies are predisposed to secondary bacterial skin infections, particularly Streptococcus pyogenes (group A streptococci). The association between scabies and pyoderma caused by group A streptococci has been well established.^15,16 Mika et al¹⁰ suggested that local complement inhibition plays an important role in the development of pyoderma in scabies-infested skin. A relationship between scabies and poststreptococcal glomerulonephritis (PSGN) has been established.^11,17 An outbreak of PSGN in Brazil following an epidemic of Streptococcus zooepidemicus resulted in a high prevalence of renal abnormalities (mean follow-up, 5.4 years).¹⁸ In an aboriginal population with high rates of end-stage renal disease, follow-up in children 6 to 18 years after an epidemic of PSGN (mean follow-up, 14.6 years) showed that risk for overt proteinuria was more than 6 times greater than in healthy controls (95% confidence interval, 2.2-16.9).¹⁹ Scabies skin infestations and infections are endemic in many remote aboriginal communities²⁰ where 70% of children younger than 2 years have chronic scabies and skin sores.²¹ In Dhaka, an urban slum in Bangladesh, the incidence of at least one scabies infection in children younger than 6 years was 952 per 1000 per year. In urban settlements in Dhaka, 49% (288/589) of infested children were not treated for up to 44 weeks after the characteristic signs and symptoms had developed due to restricted access to health care.²² In Brazil, scabies is hyperendemic in many poor communities and slums and is commonly associated with considerable morbidity.²³ Edison et al²⁴ reported that scabies and bacterial superinfections cause substantial morbidity among American Samoan children, with superinfections present in 53% (604/1139) of children diagnosed with scabies. Steer et al²⁵ found that impetigo and scabies had been underestimated in Fiji where 25.6% and 18.5% of primary school children and 12.2% and 14.0% of infants had impetigo and scabies, respectively. In a systematic review of scabies and impetigo prevalence, Romani et al²⁶ concluded that scabies and associated impetigo are common problems in the developing world that disproportionately affect children and communities in underprivileged areas and tropical countries, with the Pacific and Latin American regions having the highest prevalence of scabies. Scabies represents a major health concern worldwide due to the strong relationship between scabies and secondary infection.²⁷

Prevention and Control in the Developing World

Low-cost diagnostic equipment can play a key role in the definitive diagnosis and management of scabies outbreaks in the developing world. Micali et al²⁸ found that a $30 videomicroscope was as effective in scabies diagnosis as a $20,000 videodermatoscope. Because of the low cost of benzyl benzoate, it is commonly used as a first-line drug in many parts of the world,¹³ whereas permethrin cream 5% is the standard treatment in the developed world.²⁹ Recognition of the role of scabies in patients with pyoderma is key, and one study indicated clinically apparent scabies went unnoticed by physicians in 52% of patients presenting with skin lesions.³⁰ Drug shortages also can contribute to a high prevalence of scabies infestation in the community.³¹ Mass treatment with ivermectin has proven to be an effective means of reducing the prevalence of many parasitic diseases,^1,32,33 and it shows great promise for crusted scabies, institutional outbreaks, and mass administration in highly endemic communites.⁸ However, there is evidence of ivermectin tolerance among mites, which could undermine the success of mass drug administration.³⁴ Another important consideration is population mobility and the risk for rapid reintroduction of scabies infection across regions.³⁵

Complicating disease control are the socioeconomic factors associated with scabies in the developing world. Families with scabies infestation typically do not own their homes, are less likely to have constant electricity, have a lower monthly income, and live in substandard housing.²⁰ Families can spend a substantial part of their household income on treatment, impacting what they can spend on food.^8,11 In addition to medication, control of scabies requires community education and involvement, along with access to primary care and attention to living conditions and environmental factors.^34,36

Scabies is caused by the mite Sarcoptes scabiei var hominis.¹ It is in the arthropod class Arachnida, subclass Acari, and family Sarcoptidae.² Historically, scabies was first described in the Old Testament and by Aristotle,² but the causative organism was not identified until 1687 using a light microscope.³ Scabies affects all age groups, races, and social classes and is globally widespread. It is most prevalent in developing tropical countries.¹ It is estimated that 300 million individuals worldwide are infested with scabies mites annually, with the highest burden in young children.^4-7 In industrialized societies, infections often are seen in young adults and in institutional settings such as nursing homes.⁸ Scabies disproportionately impacts impoverished communities with crowded living conditions, poor hygiene and nutrition, and substandard housing^.5,9 Controlling the spread of the disease in these communities presents challenges but is important because of the connection between scabies and chronic kidney disease.¹⁰ As such, scabies represents a major health problem in the developing world and has been the focus of major health initiatives.^1,11

Identifying Characteristics

Adult females are 0.4-mm long and 0.3-mm wide, with males being smaller. Adult nymphs have 8 legs and larvae have 6 legs. Scabies mites are distinguishable from other arachnids by the position of a distinct gnathosoma and the lack of a division between the abdomen and cephalothorax.¹² They are ovoid with a small anterior cephalic and caudal thoracoabdominal portion with hairlike projections coming off from the rudimentary legs. They can crawl as fast as 2.5 cm per minute on warm skin.² The life cycle of the mite begins after mating: the male mite dies, and the female lays up to 3 eggs per day, which hatch in 3 to 4 days,² in skin burrows within the stratum granulosum.¹² Maturation from larva to adult takes 10 to 14 days.¹² A female mite can live for 4 to 6 weeks and can produce up to 40 ova (Figure 1).

Disease Transmission

Without a host, mites are able to survive and remain capable of infestation for 24 to 36 hours at 21°C and 40% to 80% relative humidity. Lower temperatures and higher humidity prolong survival, but infectivity decreases the longer they are without a host.¹³

An adult human with ordinary scabies will have an average of 12 adult female mites on the body surface at a given time.¹⁴ However, hundreds of mites can be found in neglected children in underprivileged communities and millions in patients with crusted scabies.¹³ Transmission of typical scabies requires close direct skin-to-skin contact for 15 to 20 minutes.^2,8 Transmission from clothing or fomites are an unlikely source of infestation with the exception of patients who are heavily infested such as in crusted scabies.¹² In adults, sexual contact is an important method of transmission,¹² and patients with scabies should be screened for other sexually transmitted diseases.⁸

Clinical Manifestations

Signs of scabies on the skin include burrows, erythematous papules, and generalized pruritus (Figure 2).¹² The scalp, face, and neck frequently are involved in infants and children,² and the hands, wrists, elbows, genitalia, axillae, umbilicus, belt line, nipples, and buttocks commonly are involved in adults.¹² Itching is characteristically worse at night.⁸ In tropical climates, patients with scabies are predisposed to secondary bacterial skin infections, particularly Streptococcus pyogenes (group A streptococci). The association between scabies and pyoderma caused by group A streptococci has been well established.^15,16 Mika et al¹⁰ suggested that local complement inhibition plays an important role in the development of pyoderma in scabies-infested skin. A relationship between scabies and poststreptococcal glomerulonephritis (PSGN) has been established.^11,17 An outbreak of PSGN in Brazil following an epidemic of Streptococcus zooepidemicus resulted in a high prevalence of renal abnormalities (mean follow-up, 5.4 years).¹⁸ In an aboriginal population with high rates of end-stage renal disease, follow-up in children 6 to 18 years after an epidemic of PSGN (mean follow-up, 14.6 years) showed that risk for overt proteinuria was more than 6 times greater than in healthy controls (95% confidence interval, 2.2-16.9).¹⁹ Scabies skin infestations and infections are endemic in many remote aboriginal communities²⁰ where 70% of children younger than 2 years have chronic scabies and skin sores.²¹ In Dhaka, an urban slum in Bangladesh, the incidence of at least one scabies infection in children younger than 6 years was 952 per 1000 per year. In urban settlements in Dhaka, 49% (288/589) of infested children were not treated for up to 44 weeks after the characteristic signs and symptoms had developed due to restricted access to health care.²² In Brazil, scabies is hyperendemic in many poor communities and slums and is commonly associated with considerable morbidity.²³ Edison et al²⁴ reported that scabies and bacterial superinfections cause substantial morbidity among American Samoan children, with superinfections present in 53% (604/1139) of children diagnosed with scabies. Steer et al²⁵ found that impetigo and scabies had been underestimated in Fiji where 25.6% and 18.5% of primary school children and 12.2% and 14.0% of infants had impetigo and scabies, respectively. In a systematic review of scabies and impetigo prevalence, Romani et al²⁶ concluded that scabies and associated impetigo are common problems in the developing world that disproportionately affect children and communities in underprivileged areas and tropical countries, with the Pacific and Latin American regions having the highest prevalence of scabies. Scabies represents a major health concern worldwide due to the strong relationship between scabies and secondary infection.²⁷

Prevention and Control in the Developing World

Low-cost diagnostic equipment can play a key role in the definitive diagnosis and management of scabies outbreaks in the developing world. Micali et al²⁸ found that a $30 videomicroscope was as effective in scabies diagnosis as a $20,000 videodermatoscope. Because of the low cost of benzyl benzoate, it is commonly used as a first-line drug in many parts of the world,¹³ whereas permethrin cream 5% is the standard treatment in the developed world.²⁹ Recognition of the role of scabies in patients with pyoderma is key, and one study indicated clinically apparent scabies went unnoticed by physicians in 52% of patients presenting with skin lesions.³⁰ Drug shortages also can contribute to a high prevalence of scabies infestation in the community.³¹ Mass treatment with ivermectin has proven to be an effective means of reducing the prevalence of many parasitic diseases,^1,32,33 and it shows great promise for crusted scabies, institutional outbreaks, and mass administration in highly endemic communites.⁸ However, there is evidence of ivermectin tolerance among mites, which could undermine the success of mass drug administration.³⁴ Another important consideration is population mobility and the risk for rapid reintroduction of scabies infection across regions.³⁵

Complicating disease control are the socioeconomic factors associated with scabies in the developing world. Families with scabies infestation typically do not own their homes, are less likely to have constant electricity, have a lower monthly income, and live in substandard housing.²⁰ Families can spend a substantial part of their household income on treatment, impacting what they can spend on food.^8,11 In addition to medication, control of scabies requires community education and involvement, along with access to primary care and attention to living conditions and environmental factors.^34,36

Scabies is caused by the mite Sarcoptes scabiei var hominis.¹ It is in the arthropod class Arachnida, subclass Acari, and family Sarcoptidae.² Historically, scabies was first described in the Old Testament and by Aristotle,² but the causative organism was not identified until 1687 using a light microscope.³ Scabies affects all age groups, races, and social classes and is globally widespread. It is most prevalent in developing tropical countries.¹ It is estimated that 300 million individuals worldwide are infested with scabies mites annually, with the highest burden in young children.^4-7 In industrialized societies, infections often are seen in young adults and in institutional settings such as nursing homes.⁸ Scabies disproportionately impacts impoverished communities with crowded living conditions, poor hygiene and nutrition, and substandard housing^.5,9 Controlling the spread of the disease in these communities presents challenges but is important because of the connection between scabies and chronic kidney disease.¹⁰ As such, scabies represents a major health problem in the developing world and has been the focus of major health initiatives.^1,11

Identifying Characteristics

Adult females are 0.4-mm long and 0.3-mm wide, with males being smaller. Adult nymphs have 8 legs and larvae have 6 legs. Scabies mites are distinguishable from other arachnids by the position of a distinct gnathosoma and the lack of a division between the abdomen and cephalothorax.¹² They are ovoid with a small anterior cephalic and caudal thoracoabdominal portion with hairlike projections coming off from the rudimentary legs. They can crawl as fast as 2.5 cm per minute on warm skin.² The life cycle of the mite begins after mating: the male mite dies, and the female lays up to 3 eggs per day, which hatch in 3 to 4 days,² in skin burrows within the stratum granulosum.¹² Maturation from larva to adult takes 10 to 14 days.¹² A female mite can live for 4 to 6 weeks and can produce up to 40 ova (Figure 1).

Disease Transmission

Without a host, mites are able to survive and remain capable of infestation for 24 to 36 hours at 21°C and 40% to 80% relative humidity. Lower temperatures and higher humidity prolong survival, but infectivity decreases the longer they are without a host.¹³

An adult human with ordinary scabies will have an average of 12 adult female mites on the body surface at a given time.¹⁴ However, hundreds of mites can be found in neglected children in underprivileged communities and millions in patients with crusted scabies.¹³ Transmission of typical scabies requires close direct skin-to-skin contact for 15 to 20 minutes.^2,8 Transmission from clothing or fomites are an unlikely source of infestation with the exception of patients who are heavily infested such as in crusted scabies.¹² In adults, sexual contact is an important method of transmission,¹² and patients with scabies should be screened for other sexually transmitted diseases.⁸

Clinical Manifestations

Signs of scabies on the skin include burrows, erythematous papules, and generalized pruritus (Figure 2).¹² The scalp, face, and neck frequently are involved in infants and children,² and the hands, wrists, elbows, genitalia, axillae, umbilicus, belt line, nipples, and buttocks commonly are involved in adults.¹² Itching is characteristically worse at night.⁸ In tropical climates, patients with scabies are predisposed to secondary bacterial skin infections, particularly Streptococcus pyogenes (group A streptococci). The association between scabies and pyoderma caused by group A streptococci has been well established.^15,16 Mika et al¹⁰ suggested that local complement inhibition plays an important role in the development of pyoderma in scabies-infested skin. A relationship between scabies and poststreptococcal glomerulonephritis (PSGN) has been established.^11,17 An outbreak of PSGN in Brazil following an epidemic of Streptococcus zooepidemicus resulted in a high prevalence of renal abnormalities (mean follow-up, 5.4 years).¹⁸ In an aboriginal population with high rates of end-stage renal disease, follow-up in children 6 to 18 years after an epidemic of PSGN (mean follow-up, 14.6 years) showed that risk for overt proteinuria was more than 6 times greater than in healthy controls (95% confidence interval, 2.2-16.9).¹⁹ Scabies skin infestations and infections are endemic in many remote aboriginal communities²⁰ where 70% of children younger than 2 years have chronic scabies and skin sores.²¹ In Dhaka, an urban slum in Bangladesh, the incidence of at least one scabies infection in children younger than 6 years was 952 per 1000 per year. In urban settlements in Dhaka, 49% (288/589) of infested children were not treated for up to 44 weeks after the characteristic signs and symptoms had developed due to restricted access to health care.²² In Brazil, scabies is hyperendemic in many poor communities and slums and is commonly associated with considerable morbidity.²³ Edison et al²⁴ reported that scabies and bacterial superinfections cause substantial morbidity among American Samoan children, with superinfections present in 53% (604/1139) of children diagnosed with scabies. Steer et al²⁵ found that impetigo and scabies had been underestimated in Fiji where 25.6% and 18.5% of primary school children and 12.2% and 14.0% of infants had impetigo and scabies, respectively. In a systematic review of scabies and impetigo prevalence, Romani et al²⁶ concluded that scabies and associated impetigo are common problems in the developing world that disproportionately affect children and communities in underprivileged areas and tropical countries, with the Pacific and Latin American regions having the highest prevalence of scabies. Scabies represents a major health concern worldwide due to the strong relationship between scabies and secondary infection.²⁷

Prevention and Control in the Developing World

Low-cost diagnostic equipment can play a key role in the definitive diagnosis and management of scabies outbreaks in the developing world. Micali et al²⁸ found that a $30 videomicroscope was as effective in scabies diagnosis as a $20,000 videodermatoscope. Because of the low cost of benzyl benzoate, it is commonly used as a first-line drug in many parts of the world,¹³ whereas permethrin cream 5% is the standard treatment in the developed world.²⁹ Recognition of the role of scabies in patients with pyoderma is key, and one study indicated clinically apparent scabies went unnoticed by physicians in 52% of patients presenting with skin lesions.³⁰ Drug shortages also can contribute to a high prevalence of scabies infestation in the community.³¹ Mass treatment with ivermectin has proven to be an effective means of reducing the prevalence of many parasitic diseases,^1,32,33 and it shows great promise for crusted scabies, institutional outbreaks, and mass administration in highly endemic communites.⁸ However, there is evidence of ivermectin tolerance among mites, which could undermine the success of mass drug administration.³⁴ Another important consideration is population mobility and the risk for rapid reintroduction of scabies infection across regions.³⁵

Complicating disease control are the socioeconomic factors associated with scabies in the developing world. Families with scabies infestation typically do not own their homes, are less likely to have constant electricity, have a lower monthly income, and live in substandard housing.²⁰ Families can spend a substantial part of their household income on treatment, impacting what they can spend on food.^8,11 In addition to medication, control of scabies requires community education and involvement, along with access to primary care and attention to living conditions and environmental factors.^34,36

Delusional infestation is the fixed false belief of skin infestation with a pathogen. Patients will often bring “proof” of their infestation to their visit to a physician. The presentation of a specimen was previously referred to by several names that reflected the receptacle that the patient utilized to bring the specimen (eg, a baggie or matchbox), but now the more encompassing term specimen sign is employed.¹ Establishing rapport with the patient is critically important in the treatment of delusional infestation. Examining the specimen samples brought by the patient is a simple manner of communicating to a patient that the clinician is empathetic to and respectful of his/her concerns.^2,3 The specimens often consist of dirt, dust, debris, fibers, and skin flakes and fragments, but they also have been reported to contain flies and insect parts.^4,5 In our case, the patient captured a minute brown scavenger beetle with adhesive tape.

Case Report

A woman in her mid-30s with a history of generalized anxiety disorder presented to the dermatology clinic with a concern of bugs infesting her skin. The symptoms occurred just after she moved into a new home with her family approximately 4 months prior to presentation. She felt the home was not cleaned properly, but they could not afford to move. She reported a crawling sensation that she identified as bugs biting her all over her body. Prior to presentation in the dermatology clinic, she and her family were treated by primary care for scabies 3 times with permethrin cream, and she was prescribed 1 course of oral ivermectin. She reported seeing bugs all over her house, which led her to clean her home and clothing many times. She was more concerned now because she thought her 2 children also were starting to be affected.

Physical examination revealed pressured speech, and the patient became tearful several times. The skin demonstrated several excoriations in various stages of healing on the breasts, legs, and upper back, as well as small scars in the same distribution. She brought several specimens stuck to clear tape to the visit. Examination of the specimens revealed fabric fibers; various debris; and a small, brown, 6-legged beetle with punctate indentations in rows along the wing covers (Figure). The head was narrower than the thorax, which was narrower than the abdomen.

We diagnosed the patient with a delusional infestation and discussed the beetle that we saw when examining the specimen the patient brought to the clinic. We provided reassurance that the minute brown scavenger beetle is not pathogenic and was present incidentally. Thus far, the patient has been resistant to initiating specific therapy for the delusional infestation, such as risperidone, olanzapine, or pimozide. We continue regular follow-up appointments with the patient to continue building the therapeutic relationship and revisiting the subject of treatment.

Comment

Minute brown scavenger beetles are arthropod members of the family Latridiidae. They also are commonly referred to as plaster or mold beetles. They are small (0.8–3.0 mm) and can be found in moist environments such as dead and rotting foliage, bird’s nests, debris, moist wallpaper/plaster, and stored products. They feed exclusively on fungus, such as mold and mildew, and pose no threat to humans.⁶ It is important for clinicians to recognize the appearance of the minute brown scavenger beetle so as not to mistake it for a pathogenic arthropod in patients presenting with delusional parasitosis.

Delusional infestation is the fixed false belief of skin infestation with a pathogen. Patients will often bring “proof” of their infestation to their visit to a physician. The presentation of a specimen was previously referred to by several names that reflected the receptacle that the patient utilized to bring the specimen (eg, a baggie or matchbox), but now the more encompassing term specimen sign is employed.¹ Establishing rapport with the patient is critically important in the treatment of delusional infestation. Examining the specimen samples brought by the patient is a simple manner of communicating to a patient that the clinician is empathetic to and respectful of his/her concerns.^2,3 The specimens often consist of dirt, dust, debris, fibers, and skin flakes and fragments, but they also have been reported to contain flies and insect parts.^4,5 In our case, the patient captured a minute brown scavenger beetle with adhesive tape.

Case Report

A woman in her mid-30s with a history of generalized anxiety disorder presented to the dermatology clinic with a concern of bugs infesting her skin. The symptoms occurred just after she moved into a new home with her family approximately 4 months prior to presentation. She felt the home was not cleaned properly, but they could not afford to move. She reported a crawling sensation that she identified as bugs biting her all over her body. Prior to presentation in the dermatology clinic, she and her family were treated by primary care for scabies 3 times with permethrin cream, and she was prescribed 1 course of oral ivermectin. She reported seeing bugs all over her house, which led her to clean her home and clothing many times. She was more concerned now because she thought her 2 children also were starting to be affected.

Physical examination revealed pressured speech, and the patient became tearful several times. The skin demonstrated several excoriations in various stages of healing on the breasts, legs, and upper back, as well as small scars in the same distribution. She brought several specimens stuck to clear tape to the visit. Examination of the specimens revealed fabric fibers; various debris; and a small, brown, 6-legged beetle with punctate indentations in rows along the wing covers (Figure). The head was narrower than the thorax, which was narrower than the abdomen.

We diagnosed the patient with a delusional infestation and discussed the beetle that we saw when examining the specimen the patient brought to the clinic. We provided reassurance that the minute brown scavenger beetle is not pathogenic and was present incidentally. Thus far, the patient has been resistant to initiating specific therapy for the delusional infestation, such as risperidone, olanzapine, or pimozide. We continue regular follow-up appointments with the patient to continue building the therapeutic relationship and revisiting the subject of treatment.

Comment

Minute brown scavenger beetles are arthropod members of the family Latridiidae. They also are commonly referred to as plaster or mold beetles. They are small (0.8–3.0 mm) and can be found in moist environments such as dead and rotting foliage, bird’s nests, debris, moist wallpaper/plaster, and stored products. They feed exclusively on fungus, such as mold and mildew, and pose no threat to humans.⁶ It is important for clinicians to recognize the appearance of the minute brown scavenger beetle so as not to mistake it for a pathogenic arthropod in patients presenting with delusional parasitosis.

Delusional infestation is the fixed false belief of skin infestation with a pathogen. Patients will often bring “proof” of their infestation to their visit to a physician. The presentation of a specimen was previously referred to by several names that reflected the receptacle that the patient utilized to bring the specimen (eg, a baggie or matchbox), but now the more encompassing term specimen sign is employed.¹ Establishing rapport with the patient is critically important in the treatment of delusional infestation. Examining the specimen samples brought by the patient is a simple manner of communicating to a patient that the clinician is empathetic to and respectful of his/her concerns.^2,3 The specimens often consist of dirt, dust, debris, fibers, and skin flakes and fragments, but they also have been reported to contain flies and insect parts.^4,5 In our case, the patient captured a minute brown scavenger beetle with adhesive tape.

Case Report

A woman in her mid-30s with a history of generalized anxiety disorder presented to the dermatology clinic with a concern of bugs infesting her skin. The symptoms occurred just after she moved into a new home with her family approximately 4 months prior to presentation. She felt the home was not cleaned properly, but they could not afford to move. She reported a crawling sensation that she identified as bugs biting her all over her body. Prior to presentation in the dermatology clinic, she and her family were treated by primary care for scabies 3 times with permethrin cream, and she was prescribed 1 course of oral ivermectin. She reported seeing bugs all over her house, which led her to clean her home and clothing many times. She was more concerned now because she thought her 2 children also were starting to be affected.

Physical examination revealed pressured speech, and the patient became tearful several times. The skin demonstrated several excoriations in various stages of healing on the breasts, legs, and upper back, as well as small scars in the same distribution. She brought several specimens stuck to clear tape to the visit. Examination of the specimens revealed fabric fibers; various debris; and a small, brown, 6-legged beetle with punctate indentations in rows along the wing covers (Figure). The head was narrower than the thorax, which was narrower than the abdomen.

We diagnosed the patient with a delusional infestation and discussed the beetle that we saw when examining the specimen the patient brought to the clinic. We provided reassurance that the minute brown scavenger beetle is not pathogenic and was present incidentally. Thus far, the patient has been resistant to initiating specific therapy for the delusional infestation, such as risperidone, olanzapine, or pimozide. We continue regular follow-up appointments with the patient to continue building the therapeutic relationship and revisiting the subject of treatment.

Comment

Minute brown scavenger beetles are arthropod members of the family Latridiidae. They also are commonly referred to as plaster or mold beetles. They are small (0.8–3.0 mm) and can be found in moist environments such as dead and rotting foliage, bird’s nests, debris, moist wallpaper/plaster, and stored products. They feed exclusively on fungus, such as mold and mildew, and pose no threat to humans.⁶ It is important for clinicians to recognize the appearance of the minute brown scavenger beetle so as not to mistake it for a pathogenic arthropod in patients presenting with delusional parasitosis.

Identifying Characteristics

The sticktight flea (Echidnophaga gallinacea) earns its name by embedding its head in the host's skin using broad and serrated laciniae and can feed at one site for up to 19 days.¹ It differs in morphology from dog (Ctenocephalides canis) and cat (Ctenocephalides felis) fleas, lacking genal (mustache area) and promotal (back of the head) ctenidia (combs), and is half the size of the cat flea. It has 2 pairs of setae (hairs) behind the antennae with an anteriorly flattened head (Figure). 

Disease Transmission

Although its primary host is poultry and it also is known as the stickfast or chicken flea, the sticktight flea has been found in many species of birds and mammals, including humans. It is becoming more common in dogs in many parts of the world, including the United States,^2-5 and has been found to be the most common flea on dogs in areas of South Africa.⁶ Other noted hosts of E gallinacea are rodents, cottontail rabbits, cats, ground squirrels, and pigs.^7-14 Human infestation occurs from exposure to affected animals.¹⁵ As blood feeders, fleas have long been known to serve as vectors for many diseases, including bubonic plague, typhus, and tularemia, as well as an intermediate host of the dog tapeworm (Dipylidium caninum).⁵Rickettsia felis, belonging to the spotted fever group, is an emerging infectious disease in humans commonly found in the cat flea (C felis) but also has been detected in E gallinacea.⁷Echidnophaga gallinacea is found worldwide in the tropics, subtropics, and temperate zones, and it is the only representative of the genus found in the United States.¹ Given the wide range of wild and domestic animal hosts and wide geographic distribution for E gallinacea, it represents an increasing risk for humans.

Echidnophaga gallinacea favors feeding from fleshy areas without thick fur or plumage. In birds, the area around the eyes, comb, and wattles is included; in dogs, it can be the eyes, in between the toes, and in the genital area.¹ Flea bites cause irritation and itching for hosts including humans, typically resulting in clusters of firm, pruritic, erythematous papules with a central punctum.¹⁵ Severe bites also may lead to bullous lesions. In birds, symptoms can be extreme, with infestation around the eyes leading to swelling and blindness, a decline in egg production, weight loss, and death in young birds.¹ Similar to other fleas, E gallinacea is wingless and depends on jumping onto a host for transmission, which can be from the ground, carpeting and flooring, furniture, or another host. Fleas are champion jumpers (relative to body size) and can jump 100 times their length.¹⁶

Management

Treating sticktight fleas can be tricky, as they embed tightly into the host's skin. Animals should be treated by a qualified veterinarian. Removal of attached fleas in humans requires grasping the flea firmly with tweezers and pulling from the skin. If the infestation is considerable, malathion 5% liquid or gel can be applied. Patients can treat itching with topical steroids and antipruritic creams, and oral antihistamines can be used to relieve symptoms and reduce the likelihood of damaged skin as well as the potential for secondary infection. The flea-infested environment should be treated with insecticides. For treatment of hard surfaces, dichlorvos and propetamphos are effective. Organophosphates work well on fabric and carpeting. Domestic pets and livestock may be treated by a veterinarian with agents such as fipronil, selamectin, imidacloprid, metaflumizone, nitenpyram, lufenuron, methoprene, and pyriproxyfen.
 

Identifying Characteristics

The sticktight flea (Echidnophaga gallinacea) earns its name by embedding its head in the host's skin using broad and serrated laciniae and can feed at one site for up to 19 days.¹ It differs in morphology from dog (Ctenocephalides canis) and cat (Ctenocephalides felis) fleas, lacking genal (mustache area) and promotal (back of the head) ctenidia (combs), and is half the size of the cat flea. It has 2 pairs of setae (hairs) behind the antennae with an anteriorly flattened head (Figure). 

Disease Transmission

Although its primary host is poultry and it also is known as the stickfast or chicken flea, the sticktight flea has been found in many species of birds and mammals, including humans. It is becoming more common in dogs in many parts of the world, including the United States,^2-5 and has been found to be the most common flea on dogs in areas of South Africa.⁶ Other noted hosts of E gallinacea are rodents, cottontail rabbits, cats, ground squirrels, and pigs.^7-14 Human infestation occurs from exposure to affected animals.¹⁵ As blood feeders, fleas have long been known to serve as vectors for many diseases, including bubonic plague, typhus, and tularemia, as well as an intermediate host of the dog tapeworm (Dipylidium caninum).⁵Rickettsia felis, belonging to the spotted fever group, is an emerging infectious disease in humans commonly found in the cat flea (C felis) but also has been detected in E gallinacea.⁷Echidnophaga gallinacea is found worldwide in the tropics, subtropics, and temperate zones, and it is the only representative of the genus found in the United States.¹ Given the wide range of wild and domestic animal hosts and wide geographic distribution for E gallinacea, it represents an increasing risk for humans.

Echidnophaga gallinacea favors feeding from fleshy areas without thick fur or plumage. In birds, the area around the eyes, comb, and wattles is included; in dogs, it can be the eyes, in between the toes, and in the genital area.¹ Flea bites cause irritation and itching for hosts including humans, typically resulting in clusters of firm, pruritic, erythematous papules with a central punctum.¹⁵ Severe bites also may lead to bullous lesions. In birds, symptoms can be extreme, with infestation around the eyes leading to swelling and blindness, a decline in egg production, weight loss, and death in young birds.¹ Similar to other fleas, E gallinacea is wingless and depends on jumping onto a host for transmission, which can be from the ground, carpeting and flooring, furniture, or another host. Fleas are champion jumpers (relative to body size) and can jump 100 times their length.¹⁶

Management

Treating sticktight fleas can be tricky, as they embed tightly into the host's skin. Animals should be treated by a qualified veterinarian. Removal of attached fleas in humans requires grasping the flea firmly with tweezers and pulling from the skin. If the infestation is considerable, malathion 5% liquid or gel can be applied. Patients can treat itching with topical steroids and antipruritic creams, and oral antihistamines can be used to relieve symptoms and reduce the likelihood of damaged skin as well as the potential for secondary infection. The flea-infested environment should be treated with insecticides. For treatment of hard surfaces, dichlorvos and propetamphos are effective. Organophosphates work well on fabric and carpeting. Domestic pets and livestock may be treated by a veterinarian with agents such as fipronil, selamectin, imidacloprid, metaflumizone, nitenpyram, lufenuron, methoprene, and pyriproxyfen.
 

Identifying Characteristics

The sticktight flea (Echidnophaga gallinacea) earns its name by embedding its head in the host's skin using broad and serrated laciniae and can feed at one site for up to 19 days.¹ It differs in morphology from dog (Ctenocephalides canis) and cat (Ctenocephalides felis) fleas, lacking genal (mustache area) and promotal (back of the head) ctenidia (combs), and is half the size of the cat flea. It has 2 pairs of setae (hairs) behind the antennae with an anteriorly flattened head (Figure). 

Disease Transmission

Although its primary host is poultry and it also is known as the stickfast or chicken flea, the sticktight flea has been found in many species of birds and mammals, including humans. It is becoming more common in dogs in many parts of the world, including the United States,^2-5 and has been found to be the most common flea on dogs in areas of South Africa.⁶ Other noted hosts of E gallinacea are rodents, cottontail rabbits, cats, ground squirrels, and pigs.^7-14 Human infestation occurs from exposure to affected animals.¹⁵ As blood feeders, fleas have long been known to serve as vectors for many diseases, including bubonic plague, typhus, and tularemia, as well as an intermediate host of the dog tapeworm (Dipylidium caninum).⁵Rickettsia felis, belonging to the spotted fever group, is an emerging infectious disease in humans commonly found in the cat flea (C felis) but also has been detected in E gallinacea.⁷Echidnophaga gallinacea is found worldwide in the tropics, subtropics, and temperate zones, and it is the only representative of the genus found in the United States.¹ Given the wide range of wild and domestic animal hosts and wide geographic distribution for E gallinacea, it represents an increasing risk for humans.

Echidnophaga gallinacea favors feeding from fleshy areas without thick fur or plumage. In birds, the area around the eyes, comb, and wattles is included; in dogs, it can be the eyes, in between the toes, and in the genital area.¹ Flea bites cause irritation and itching for hosts including humans, typically resulting in clusters of firm, pruritic, erythematous papules with a central punctum.¹⁵ Severe bites also may lead to bullous lesions. In birds, symptoms can be extreme, with infestation around the eyes leading to swelling and blindness, a decline in egg production, weight loss, and death in young birds.¹ Similar to other fleas, E gallinacea is wingless and depends on jumping onto a host for transmission, which can be from the ground, carpeting and flooring, furniture, or another host. Fleas are champion jumpers (relative to body size) and can jump 100 times their length.¹⁶

Management

Treating sticktight fleas can be tricky, as they embed tightly into the host's skin. Animals should be treated by a qualified veterinarian. Removal of attached fleas in humans requires grasping the flea firmly with tweezers and pulling from the skin. If the infestation is considerable, malathion 5% liquid or gel can be applied. Patients can treat itching with topical steroids and antipruritic creams, and oral antihistamines can be used to relieve symptoms and reduce the likelihood of damaged skin as well as the potential for secondary infection. The flea-infested environment should be treated with insecticides. For treatment of hard surfaces, dichlorvos and propetamphos are effective. Organophosphates work well on fabric and carpeting. Domestic pets and livestock may be treated by a veterinarian with agents such as fipronil, selamectin, imidacloprid, metaflumizone, nitenpyram, lufenuron, methoprene, and pyriproxyfen.
 

Identifying Characteristics and Disease Transmission

Chiggers belong to the Trombiculidae family of mites and also are referred to as harvest mites, harvest bugs, harvest lice, mower’s mites, and redbugs.¹ The term chigger specifically describes the larval stage of this mite’s life cycle, as it is the only stage responsible for chigger bites. The nymph and adult phases feed on vegetable matter. Trombiculid mites are most often found in forests, grassy areas, gardens, and moist areas of soil near bodies of water. Trombicula alfreddugesi is the most common species in the United States, and these mites mainly live in the southeastern and south central regions of the country. Conversely, Trombicula autumnalis is most predominant in Western Europe and East Asia.¹

The life cycle of the mite includes the egg, larval, nymphal, and adult stages.² Due to their need for air humidity greater than 80%, mites lay their eggs on low leaves, blades of grass, or on the ground. They spend most of their lives on vegetation no more than 30 cm above ground level.³ Eggs remain dormant for approximately 6 days until the hatching of the prelarvae, which have 6 legs and are nonfeeding. It takes another 6 days for the prelarvae to mature into larvae. Measuring 0.15 to 0.3 mm in length, mite larvae are a mere fraction of the size of adult mites, which generally are 1 to 2 mm in length, and are bright red or brown-red in color (Figure 1).

The biting larvae have many acceptable hosts including turtles, toads, birds, small mammals, and humans, which act as accidental hosts. Larvae remain on vegetation waiting for a suitable host to pass by so they may attach to its skin and remain there for several days. In the exploration for an ideal area to begin feeding (eg, thin epidermis,⁴ localized increased air humidity⁵), larvae can travel extensively on the skin; however, they often are stopped by tight-fitting sections of clothing (eg, waistbands), so bites are mostly found in clusters. To feed, mite larvae latch onto the skin using chelicerae, jawlike appendages found in the front of the mouth in arachnids.⁶ They then inject digestive enzymes that liquefy epidermal cells on direct contact, which results in the formation of a stylostome from which the mites may suck up lymph fluid and broken down tissue.⁷ Although the actual initial bite is painless, this feeding process leads to the localized inflammation and irritation noticed by infested patients.⁸

The classic clinical presentation includes severe pruritus and cutaneous swelling as well as erythema caused by the combination of several factors, such as enzyme-induced cellular mechanical damage, human immune response, and sometimes a superimposed bacterial infection. Papules and papulovesicles appear in groups, most commonly affecting the legs and waistline (Figure 2).⁹ Itching generally occurs within hours of larval latching and subsides within 72 hours. Cutaneous lesions typically take 1 to 2 weeks to heal. In some rare cases, patients may react with urticarial, bullous, or morbilliform eruptions, and the inflammation and pruritus can last for weeks.⁶ Summer penile syndrome has been noted in boys who display a local hypersensitivity to chigger bites.¹⁰ This syndrome represents a triad of penile swelling, dysuria, and pruritus, which lasts for a few days to a few weeks.

Disease Management

Because the lesions are self-healing, treatment is focused on symptomatic relief of itching by means of topical antipruritics (eg, camphor and menthol, pramoxine lotion) or oral antihistamines (eg, diphenhydramine, hydroxyzine). Potent topical corticosteroids may be used to alleviate inflammation and pruritus, especially when occluded under plastic wrap to increase absorption. In severe cases, an intralesional triamcinolone acetonide (2.5–5 mg/mL) injection may be required.⁹ The best practice, however, is to take preventative measures to avoid becoming a host for the mites. Patients should take special care when traveling in infested areas by completely covering their skin, tucking pant cuffs into their socks, and applying products containing DEET (N,N-diethyl-meta-toluamide or N,N-diethyl-3-methylbenzamide) to the skin and clothing. The odds of prevention are increased even further when clothing also is treated with permethrin.¹¹

In parts of Asia and Australia, these mites may transmit Orientia tsutsugamushi, the organism responsible for scrub typhus, through their saliva during a bite.¹² Scrub typhus is associated with an eschar, as well as fever, intense headache, and diffuse myalgia. It responds well to treatment with doxycycline 100 mg twice daily.¹³ Studies investigating genetic material found in trombiculid mites across the globe have detected Ehrlichia-specific DNA in Spain,¹⁴Borrelia-specific DNA in the Czech Republic,^15,16 and Hantavirus-specific RNA in Texas.¹⁷ There is evidence that the mites play a role in maintenance of zoonotic reservoirs, while humans are infected via ingestion or inhalation of infectious rodent extreta.¹⁸

Identifying Characteristics and Disease Transmission

Chiggers belong to the Trombiculidae family of mites and also are referred to as harvest mites, harvest bugs, harvest lice, mower’s mites, and redbugs.¹ The term chigger specifically describes the larval stage of this mite’s life cycle, as it is the only stage responsible for chigger bites. The nymph and adult phases feed on vegetable matter. Trombiculid mites are most often found in forests, grassy areas, gardens, and moist areas of soil near bodies of water. Trombicula alfreddugesi is the most common species in the United States, and these mites mainly live in the southeastern and south central regions of the country. Conversely, Trombicula autumnalis is most predominant in Western Europe and East Asia.¹

The life cycle of the mite includes the egg, larval, nymphal, and adult stages.² Due to their need for air humidity greater than 80%, mites lay their eggs on low leaves, blades of grass, or on the ground. They spend most of their lives on vegetation no more than 30 cm above ground level.³ Eggs remain dormant for approximately 6 days until the hatching of the prelarvae, which have 6 legs and are nonfeeding. It takes another 6 days for the prelarvae to mature into larvae. Measuring 0.15 to 0.3 mm in length, mite larvae are a mere fraction of the size of adult mites, which generally are 1 to 2 mm in length, and are bright red or brown-red in color (Figure 1).

The biting larvae have many acceptable hosts including turtles, toads, birds, small mammals, and humans, which act as accidental hosts. Larvae remain on vegetation waiting for a suitable host to pass by so they may attach to its skin and remain there for several days. In the exploration for an ideal area to begin feeding (eg, thin epidermis,⁴ localized increased air humidity⁵), larvae can travel extensively on the skin; however, they often are stopped by tight-fitting sections of clothing (eg, waistbands), so bites are mostly found in clusters. To feed, mite larvae latch onto the skin using chelicerae, jawlike appendages found in the front of the mouth in arachnids.⁶ They then inject digestive enzymes that liquefy epidermal cells on direct contact, which results in the formation of a stylostome from which the mites may suck up lymph fluid and broken down tissue.⁷ Although the actual initial bite is painless, this feeding process leads to the localized inflammation and irritation noticed by infested patients.⁸

The classic clinical presentation includes severe pruritus and cutaneous swelling as well as erythema caused by the combination of several factors, such as enzyme-induced cellular mechanical damage, human immune response, and sometimes a superimposed bacterial infection. Papules and papulovesicles appear in groups, most commonly affecting the legs and waistline (Figure 2).⁹ Itching generally occurs within hours of larval latching and subsides within 72 hours. Cutaneous lesions typically take 1 to 2 weeks to heal. In some rare cases, patients may react with urticarial, bullous, or morbilliform eruptions, and the inflammation and pruritus can last for weeks.⁶ Summer penile syndrome has been noted in boys who display a local hypersensitivity to chigger bites.¹⁰ This syndrome represents a triad of penile swelling, dysuria, and pruritus, which lasts for a few days to a few weeks.

Disease Management

Because the lesions are self-healing, treatment is focused on symptomatic relief of itching by means of topical antipruritics (eg, camphor and menthol, pramoxine lotion) or oral antihistamines (eg, diphenhydramine, hydroxyzine). Potent topical corticosteroids may be used to alleviate inflammation and pruritus, especially when occluded under plastic wrap to increase absorption. In severe cases, an intralesional triamcinolone acetonide (2.5–5 mg/mL) injection may be required.⁹ The best practice, however, is to take preventative measures to avoid becoming a host for the mites. Patients should take special care when traveling in infested areas by completely covering their skin, tucking pant cuffs into their socks, and applying products containing DEET (N,N-diethyl-meta-toluamide or N,N-diethyl-3-methylbenzamide) to the skin and clothing. The odds of prevention are increased even further when clothing also is treated with permethrin.¹¹

In parts of Asia and Australia, these mites may transmit Orientia tsutsugamushi, the organism responsible for scrub typhus, through their saliva during a bite.¹² Scrub typhus is associated with an eschar, as well as fever, intense headache, and diffuse myalgia. It responds well to treatment with doxycycline 100 mg twice daily.¹³ Studies investigating genetic material found in trombiculid mites across the globe have detected Ehrlichia-specific DNA in Spain,¹⁴Borrelia-specific DNA in the Czech Republic,^15,16 and Hantavirus-specific RNA in Texas.¹⁷ There is evidence that the mites play a role in maintenance of zoonotic reservoirs, while humans are infected via ingestion or inhalation of infectious rodent extreta.¹⁸

Identifying Characteristics and Disease Transmission

Chiggers belong to the Trombiculidae family of mites and also are referred to as harvest mites, harvest bugs, harvest lice, mower’s mites, and redbugs.¹ The term chigger specifically describes the larval stage of this mite’s life cycle, as it is the only stage responsible for chigger bites. The nymph and adult phases feed on vegetable matter. Trombiculid mites are most often found in forests, grassy areas, gardens, and moist areas of soil near bodies of water. Trombicula alfreddugesi is the most common species in the United States, and these mites mainly live in the southeastern and south central regions of the country. Conversely, Trombicula autumnalis is most predominant in Western Europe and East Asia.¹

The life cycle of the mite includes the egg, larval, nymphal, and adult stages.² Due to their need for air humidity greater than 80%, mites lay their eggs on low leaves, blades of grass, or on the ground. They spend most of their lives on vegetation no more than 30 cm above ground level.³ Eggs remain dormant for approximately 6 days until the hatching of the prelarvae, which have 6 legs and are nonfeeding. It takes another 6 days for the prelarvae to mature into larvae. Measuring 0.15 to 0.3 mm in length, mite larvae are a mere fraction of the size of adult mites, which generally are 1 to 2 mm in length, and are bright red or brown-red in color (Figure 1).

The biting larvae have many acceptable hosts including turtles, toads, birds, small mammals, and humans, which act as accidental hosts. Larvae remain on vegetation waiting for a suitable host to pass by so they may attach to its skin and remain there for several days. In the exploration for an ideal area to begin feeding (eg, thin epidermis,⁴ localized increased air humidity⁵), larvae can travel extensively on the skin; however, they often are stopped by tight-fitting sections of clothing (eg, waistbands), so bites are mostly found in clusters. To feed, mite larvae latch onto the skin using chelicerae, jawlike appendages found in the front of the mouth in arachnids.⁶ They then inject digestive enzymes that liquefy epidermal cells on direct contact, which results in the formation of a stylostome from which the mites may suck up lymph fluid and broken down tissue.⁷ Although the actual initial bite is painless, this feeding process leads to the localized inflammation and irritation noticed by infested patients.⁸

The classic clinical presentation includes severe pruritus and cutaneous swelling as well as erythema caused by the combination of several factors, such as enzyme-induced cellular mechanical damage, human immune response, and sometimes a superimposed bacterial infection. Papules and papulovesicles appear in groups, most commonly affecting the legs and waistline (Figure 2).⁹ Itching generally occurs within hours of larval latching and subsides within 72 hours. Cutaneous lesions typically take 1 to 2 weeks to heal. In some rare cases, patients may react with urticarial, bullous, or morbilliform eruptions, and the inflammation and pruritus can last for weeks.⁶ Summer penile syndrome has been noted in boys who display a local hypersensitivity to chigger bites.¹⁰ This syndrome represents a triad of penile swelling, dysuria, and pruritus, which lasts for a few days to a few weeks.

Disease Management

Because the lesions are self-healing, treatment is focused on symptomatic relief of itching by means of topical antipruritics (eg, camphor and menthol, pramoxine lotion) or oral antihistamines (eg, diphenhydramine, hydroxyzine). Potent topical corticosteroids may be used to alleviate inflammation and pruritus, especially when occluded under plastic wrap to increase absorption. In severe cases, an intralesional triamcinolone acetonide (2.5–5 mg/mL) injection may be required.⁹ The best practice, however, is to take preventative measures to avoid becoming a host for the mites. Patients should take special care when traveling in infested areas by completely covering their skin, tucking pant cuffs into their socks, and applying products containing DEET (N,N-diethyl-meta-toluamide or N,N-diethyl-3-methylbenzamide) to the skin and clothing. The odds of prevention are increased even further when clothing also is treated with permethrin.¹¹

In parts of Asia and Australia, these mites may transmit Orientia tsutsugamushi, the organism responsible for scrub typhus, through their saliva during a bite.¹² Scrub typhus is associated with an eschar, as well as fever, intense headache, and diffuse myalgia. It responds well to treatment with doxycycline 100 mg twice daily.¹³ Studies investigating genetic material found in trombiculid mites across the globe have detected Ehrlichia-specific DNA in Spain,¹⁴Borrelia-specific DNA in the Czech Republic,^15,16 and Hantavirus-specific RNA in Texas.¹⁷ There is evidence that the mites play a role in maintenance of zoonotic reservoirs, while humans are infected via ingestion or inhalation of infectious rodent extreta.¹⁸