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Secondary Syphilis Mimicking Molluscum Contagiosum in the Beard Area of an AIDS Patient
To the Editor:
A 46-year-old man with a history of AIDS (viral load, 28,186 copies/mL; CD4 count, 22 cells/μL) presented with a 40-lb weight loss over the last 6 months as well as dysphagia and a new-onset pruritic facial eruption of 1 week’s duration. The facial lesions quickly spread to involve the beard area and the upper neck. His medical history was notable for nicotine dependence, seborrheic dermatitis, molluscum contagiosum (MC), treated neurosyphilis and latent tuberculosis, hypertension, a liver mass suspected to be a hemangioma, and erythrocytosis. He was diagnosed with human immunodeficiency virus infection 19 years prior to presentation and was not compliant with the prescribed highly active antiretroviral therapy.
Skin examination revealed multiple discrete and coalescing, 2- to 12-mm, nonumbilicated, hyperkeratotic papules and nodules localized to the left and right beard areas (Figure 1A). A few discrete, 2- to 5-mm, umbilicated papules were noted in the right beard area (Figure 1B), as well as on the right side of the neck (Figure 1C), buttocks, and legs. Mild erythema with yellow-white scale was present in the alar creases. Examination of the oropharyngeal mucosa revealed multiple thick white plaques that were easily scraped off with a tongue depressor. Examination of the palms, soles, and anogenital areas was normal.
A punch biopsy of a nonumbilicated hyperkeratotic papule from the left beard area demonstrated spongiosis; neutrophilic microabscess formation; plasma cells; and a superficial and deep perivascular, predominantly lymphohistiocytic infiltrate (Figure 2A). Spirochete immunohistochemical staining of tissue highlighted abundant organisms in the dermoepidermal junction and vascular endothelial cells (Figure 2B). Other tissue stains for bacteria, including acid-fast bacilli, and fungi were negative. Bacterial culture of tissue from the lesion in the left beard area grew Staphylococcus aureus. Results of acid-fast and fungal cultures of tissue were negative. Shave biopsy of the umbilicated papule on the right side of the neck demonstrated classic invagination of the epidermis into the dermis and intracytoplasmic viral inclusions consistent with MC (Figure 2C). Spirochete immunohistochemical staining of the same tissue sample was negative (Figure 2D).
Serum rapid plasma reagin was reactive with a titer of 1:128 compared to the last known reactive rapid plasma reagin titer of 1:1 five years prior to presentation. A fluorescent treponemal antibody absorption test and VDRL test of cerebrospinal fluid was nonreactive. Fungal, bacterial, and acid-fast cultures of cerebral spinal fluid and a cryptococcal antigen test were negative. Serum cryptococcal antigen and coccidioides complement fixation tests were negative. Cytomegalovirus plasma polymerase chain reaction and urine histoplasma antigen testing were negative. Computed tomography of the chest revealed a new 1.9×1.6×2.1-cm3 cavitary lesion with distal tree-in-bud opacities in the lingula of the left lung. Acid-fast blood culture was negative, and acid-fast sputum culture was positive for Mycobacterium kansasii.
The cutaneous pathology findings and serologic findings confirmed the diagnoses of cutaneous secondary syphilis (SS) in the beard area and MC on the right side of the neck. Clinical diagnoses of seborrheic dermatitis of the alar creases and esophageal candidiasis also were made. The patient was treated with intramuscular penicillin G 2.4 million U once weekly for 3 weeks. The lesions confined to the beard area rapidly resolved within 7 days after the first dose of antibiotics, which further supported the diagnosis of localized cutaneous SS. Fluconazole 100 mg once daily was prescribed for the esophageal candidiasis, and he also was started on a regimen of rifampin 600 mg once daily, isoniazid 300 mg once daily, ethambutol 1200 mg once daily, and pyrazinamide 1500 mg once daily.
Syphilis is well known as the great masquerader due to its many possible manifestations. Many patients present with typical palmar and plantar dermatoses.1 Other documented SS presentations include eruptions ranging from a few to diffusely disseminated maculopapular lesions with or without scale on the trunk and upper extremities; pustular and nodular lesions of the face; alopecia; grayish white patches on the oral mucosa; and ulcerative, psoriasiform, follicular, and lichenoid lesions.2 Cutaneous SS has not been commonly reported in a localized distribution to the beard area with a clinical appearance mimicking hyperkeratotic MC lesions.3 Secondary syphilis is not known to spread through autoinoculation, presumably from shaving (as in our case), as might occur with other cutaneous infectious processes such as MC, verruca vulgaris, S aureus, and dermatophytosis in the beard area.
The differential diagnosis for hyperkeratotic papules and nodules localized to the beard area in human immunodeficiency virus–infected males includes MC, verruca vulgaris, chronic verrucous varicella-zoster virus, crusted scabies, tuberculosis verrucosa cutis, hypertrophic lichen planus, and disseminated deep fungal infections including cryptococcosis and coccidioidomycosis. In the setting of immunosuppression, the diagnosis of hyperkeratotic MC was favored in our patient given the co-location of classic umbilicated MC lesions with the hyperkeratotic papules and nodules. It is common to see MC autoinoculated in the beard area in men from shaving, as well as for MC to present in an atypical manner, particularly as hyperkeratotic lesions, in patients with AIDS.4 The predominant localized beard distribution and lack of other mucocutaneous manifestations of SS at presentation supported a clinical diagnosis of hyperkeratotic MC in our patient.
Unique presentations of SS have been documented, including nodular lesions of the face, but they typically have been accompanied by other stigmata of SS such as the classic palmoplantar or truncal maculopapular rash.3 One notable difference in our case was the localized beard distribution of the syphilitic cutaneous lesions in a man with AIDS. Our case reinforces the importance of cutaneous biopsies in immunocompromised patients. It is known that SS spreads hematogenously; however, in our case it was suspected that the new lesions may have spread locally through autoinoculation via beard hair removal, as the hyperkeratotic lesions were limited to the beard area. Koebnerization secondary to trauma induced by beard hair removal was considered in this case; however, koebnerization is known to occur in noninfectious dermatologic conditions, such as psoriasis, lichen planus, lichen nitidus, and vitiligo, but not in infections such as syphilis. Our case is pivotal in raising the question of whether SS can be autoinoculated in the beard area.
- Baughn RE, Musher DM. Secondary syphilitic lesions. Clin Microbiol Rev. 2005;18:205-216.
- Dourmishev LA, Dourmishev AL. Syphilis: uncommon presentations in adults. Clin Dermatol. 2005;23:555-564.
- Cohen SE, Klausner JD, Engelman J, et al. Syphilis in the modern era: an update for physicians. Infect Dis Clin North Am. 2013;27:705-722.
- Filo-Rogulska M, Pindycka-Plaszcznska M, Januszewski K, et al. Disseminated atypical molluscum contagiosum as a presenting symptom of HIV infection. Postepy Dermatol Alergol. 2013;30:56-58.
To the Editor:
A 46-year-old man with a history of AIDS (viral load, 28,186 copies/mL; CD4 count, 22 cells/μL) presented with a 40-lb weight loss over the last 6 months as well as dysphagia and a new-onset pruritic facial eruption of 1 week’s duration. The facial lesions quickly spread to involve the beard area and the upper neck. His medical history was notable for nicotine dependence, seborrheic dermatitis, molluscum contagiosum (MC), treated neurosyphilis and latent tuberculosis, hypertension, a liver mass suspected to be a hemangioma, and erythrocytosis. He was diagnosed with human immunodeficiency virus infection 19 years prior to presentation and was not compliant with the prescribed highly active antiretroviral therapy.
Skin examination revealed multiple discrete and coalescing, 2- to 12-mm, nonumbilicated, hyperkeratotic papules and nodules localized to the left and right beard areas (Figure 1A). A few discrete, 2- to 5-mm, umbilicated papules were noted in the right beard area (Figure 1B), as well as on the right side of the neck (Figure 1C), buttocks, and legs. Mild erythema with yellow-white scale was present in the alar creases. Examination of the oropharyngeal mucosa revealed multiple thick white plaques that were easily scraped off with a tongue depressor. Examination of the palms, soles, and anogenital areas was normal.
A punch biopsy of a nonumbilicated hyperkeratotic papule from the left beard area demonstrated spongiosis; neutrophilic microabscess formation; plasma cells; and a superficial and deep perivascular, predominantly lymphohistiocytic infiltrate (Figure 2A). Spirochete immunohistochemical staining of tissue highlighted abundant organisms in the dermoepidermal junction and vascular endothelial cells (Figure 2B). Other tissue stains for bacteria, including acid-fast bacilli, and fungi were negative. Bacterial culture of tissue from the lesion in the left beard area grew Staphylococcus aureus. Results of acid-fast and fungal cultures of tissue were negative. Shave biopsy of the umbilicated papule on the right side of the neck demonstrated classic invagination of the epidermis into the dermis and intracytoplasmic viral inclusions consistent with MC (Figure 2C). Spirochete immunohistochemical staining of the same tissue sample was negative (Figure 2D).
Serum rapid plasma reagin was reactive with a titer of 1:128 compared to the last known reactive rapid plasma reagin titer of 1:1 five years prior to presentation. A fluorescent treponemal antibody absorption test and VDRL test of cerebrospinal fluid was nonreactive. Fungal, bacterial, and acid-fast cultures of cerebral spinal fluid and a cryptococcal antigen test were negative. Serum cryptococcal antigen and coccidioides complement fixation tests were negative. Cytomegalovirus plasma polymerase chain reaction and urine histoplasma antigen testing were negative. Computed tomography of the chest revealed a new 1.9×1.6×2.1-cm3 cavitary lesion with distal tree-in-bud opacities in the lingula of the left lung. Acid-fast blood culture was negative, and acid-fast sputum culture was positive for Mycobacterium kansasii.
The cutaneous pathology findings and serologic findings confirmed the diagnoses of cutaneous secondary syphilis (SS) in the beard area and MC on the right side of the neck. Clinical diagnoses of seborrheic dermatitis of the alar creases and esophageal candidiasis also were made. The patient was treated with intramuscular penicillin G 2.4 million U once weekly for 3 weeks. The lesions confined to the beard area rapidly resolved within 7 days after the first dose of antibiotics, which further supported the diagnosis of localized cutaneous SS. Fluconazole 100 mg once daily was prescribed for the esophageal candidiasis, and he also was started on a regimen of rifampin 600 mg once daily, isoniazid 300 mg once daily, ethambutol 1200 mg once daily, and pyrazinamide 1500 mg once daily.
Syphilis is well known as the great masquerader due to its many possible manifestations. Many patients present with typical palmar and plantar dermatoses.1 Other documented SS presentations include eruptions ranging from a few to diffusely disseminated maculopapular lesions with or without scale on the trunk and upper extremities; pustular and nodular lesions of the face; alopecia; grayish white patches on the oral mucosa; and ulcerative, psoriasiform, follicular, and lichenoid lesions.2 Cutaneous SS has not been commonly reported in a localized distribution to the beard area with a clinical appearance mimicking hyperkeratotic MC lesions.3 Secondary syphilis is not known to spread through autoinoculation, presumably from shaving (as in our case), as might occur with other cutaneous infectious processes such as MC, verruca vulgaris, S aureus, and dermatophytosis in the beard area.
The differential diagnosis for hyperkeratotic papules and nodules localized to the beard area in human immunodeficiency virus–infected males includes MC, verruca vulgaris, chronic verrucous varicella-zoster virus, crusted scabies, tuberculosis verrucosa cutis, hypertrophic lichen planus, and disseminated deep fungal infections including cryptococcosis and coccidioidomycosis. In the setting of immunosuppression, the diagnosis of hyperkeratotic MC was favored in our patient given the co-location of classic umbilicated MC lesions with the hyperkeratotic papules and nodules. It is common to see MC autoinoculated in the beard area in men from shaving, as well as for MC to present in an atypical manner, particularly as hyperkeratotic lesions, in patients with AIDS.4 The predominant localized beard distribution and lack of other mucocutaneous manifestations of SS at presentation supported a clinical diagnosis of hyperkeratotic MC in our patient.
Unique presentations of SS have been documented, including nodular lesions of the face, but they typically have been accompanied by other stigmata of SS such as the classic palmoplantar or truncal maculopapular rash.3 One notable difference in our case was the localized beard distribution of the syphilitic cutaneous lesions in a man with AIDS. Our case reinforces the importance of cutaneous biopsies in immunocompromised patients. It is known that SS spreads hematogenously; however, in our case it was suspected that the new lesions may have spread locally through autoinoculation via beard hair removal, as the hyperkeratotic lesions were limited to the beard area. Koebnerization secondary to trauma induced by beard hair removal was considered in this case; however, koebnerization is known to occur in noninfectious dermatologic conditions, such as psoriasis, lichen planus, lichen nitidus, and vitiligo, but not in infections such as syphilis. Our case is pivotal in raising the question of whether SS can be autoinoculated in the beard area.
To the Editor:
A 46-year-old man with a history of AIDS (viral load, 28,186 copies/mL; CD4 count, 22 cells/μL) presented with a 40-lb weight loss over the last 6 months as well as dysphagia and a new-onset pruritic facial eruption of 1 week’s duration. The facial lesions quickly spread to involve the beard area and the upper neck. His medical history was notable for nicotine dependence, seborrheic dermatitis, molluscum contagiosum (MC), treated neurosyphilis and latent tuberculosis, hypertension, a liver mass suspected to be a hemangioma, and erythrocytosis. He was diagnosed with human immunodeficiency virus infection 19 years prior to presentation and was not compliant with the prescribed highly active antiretroviral therapy.
Skin examination revealed multiple discrete and coalescing, 2- to 12-mm, nonumbilicated, hyperkeratotic papules and nodules localized to the left and right beard areas (Figure 1A). A few discrete, 2- to 5-mm, umbilicated papules were noted in the right beard area (Figure 1B), as well as on the right side of the neck (Figure 1C), buttocks, and legs. Mild erythema with yellow-white scale was present in the alar creases. Examination of the oropharyngeal mucosa revealed multiple thick white plaques that were easily scraped off with a tongue depressor. Examination of the palms, soles, and anogenital areas was normal.
A punch biopsy of a nonumbilicated hyperkeratotic papule from the left beard area demonstrated spongiosis; neutrophilic microabscess formation; plasma cells; and a superficial and deep perivascular, predominantly lymphohistiocytic infiltrate (Figure 2A). Spirochete immunohistochemical staining of tissue highlighted abundant organisms in the dermoepidermal junction and vascular endothelial cells (Figure 2B). Other tissue stains for bacteria, including acid-fast bacilli, and fungi were negative. Bacterial culture of tissue from the lesion in the left beard area grew Staphylococcus aureus. Results of acid-fast and fungal cultures of tissue were negative. Shave biopsy of the umbilicated papule on the right side of the neck demonstrated classic invagination of the epidermis into the dermis and intracytoplasmic viral inclusions consistent with MC (Figure 2C). Spirochete immunohistochemical staining of the same tissue sample was negative (Figure 2D).
Serum rapid plasma reagin was reactive with a titer of 1:128 compared to the last known reactive rapid plasma reagin titer of 1:1 five years prior to presentation. A fluorescent treponemal antibody absorption test and VDRL test of cerebrospinal fluid was nonreactive. Fungal, bacterial, and acid-fast cultures of cerebral spinal fluid and a cryptococcal antigen test were negative. Serum cryptococcal antigen and coccidioides complement fixation tests were negative. Cytomegalovirus plasma polymerase chain reaction and urine histoplasma antigen testing were negative. Computed tomography of the chest revealed a new 1.9×1.6×2.1-cm3 cavitary lesion with distal tree-in-bud opacities in the lingula of the left lung. Acid-fast blood culture was negative, and acid-fast sputum culture was positive for Mycobacterium kansasii.
The cutaneous pathology findings and serologic findings confirmed the diagnoses of cutaneous secondary syphilis (SS) in the beard area and MC on the right side of the neck. Clinical diagnoses of seborrheic dermatitis of the alar creases and esophageal candidiasis also were made. The patient was treated with intramuscular penicillin G 2.4 million U once weekly for 3 weeks. The lesions confined to the beard area rapidly resolved within 7 days after the first dose of antibiotics, which further supported the diagnosis of localized cutaneous SS. Fluconazole 100 mg once daily was prescribed for the esophageal candidiasis, and he also was started on a regimen of rifampin 600 mg once daily, isoniazid 300 mg once daily, ethambutol 1200 mg once daily, and pyrazinamide 1500 mg once daily.
Syphilis is well known as the great masquerader due to its many possible manifestations. Many patients present with typical palmar and plantar dermatoses.1 Other documented SS presentations include eruptions ranging from a few to diffusely disseminated maculopapular lesions with or without scale on the trunk and upper extremities; pustular and nodular lesions of the face; alopecia; grayish white patches on the oral mucosa; and ulcerative, psoriasiform, follicular, and lichenoid lesions.2 Cutaneous SS has not been commonly reported in a localized distribution to the beard area with a clinical appearance mimicking hyperkeratotic MC lesions.3 Secondary syphilis is not known to spread through autoinoculation, presumably from shaving (as in our case), as might occur with other cutaneous infectious processes such as MC, verruca vulgaris, S aureus, and dermatophytosis in the beard area.
The differential diagnosis for hyperkeratotic papules and nodules localized to the beard area in human immunodeficiency virus–infected males includes MC, verruca vulgaris, chronic verrucous varicella-zoster virus, crusted scabies, tuberculosis verrucosa cutis, hypertrophic lichen planus, and disseminated deep fungal infections including cryptococcosis and coccidioidomycosis. In the setting of immunosuppression, the diagnosis of hyperkeratotic MC was favored in our patient given the co-location of classic umbilicated MC lesions with the hyperkeratotic papules and nodules. It is common to see MC autoinoculated in the beard area in men from shaving, as well as for MC to present in an atypical manner, particularly as hyperkeratotic lesions, in patients with AIDS.4 The predominant localized beard distribution and lack of other mucocutaneous manifestations of SS at presentation supported a clinical diagnosis of hyperkeratotic MC in our patient.
Unique presentations of SS have been documented, including nodular lesions of the face, but they typically have been accompanied by other stigmata of SS such as the classic palmoplantar or truncal maculopapular rash.3 One notable difference in our case was the localized beard distribution of the syphilitic cutaneous lesions in a man with AIDS. Our case reinforces the importance of cutaneous biopsies in immunocompromised patients. It is known that SS spreads hematogenously; however, in our case it was suspected that the new lesions may have spread locally through autoinoculation via beard hair removal, as the hyperkeratotic lesions were limited to the beard area. Koebnerization secondary to trauma induced by beard hair removal was considered in this case; however, koebnerization is known to occur in noninfectious dermatologic conditions, such as psoriasis, lichen planus, lichen nitidus, and vitiligo, but not in infections such as syphilis. Our case is pivotal in raising the question of whether SS can be autoinoculated in the beard area.
- Baughn RE, Musher DM. Secondary syphilitic lesions. Clin Microbiol Rev. 2005;18:205-216.
- Dourmishev LA, Dourmishev AL. Syphilis: uncommon presentations in adults. Clin Dermatol. 2005;23:555-564.
- Cohen SE, Klausner JD, Engelman J, et al. Syphilis in the modern era: an update for physicians. Infect Dis Clin North Am. 2013;27:705-722.
- Filo-Rogulska M, Pindycka-Plaszcznska M, Januszewski K, et al. Disseminated atypical molluscum contagiosum as a presenting symptom of HIV infection. Postepy Dermatol Alergol. 2013;30:56-58.
- Baughn RE, Musher DM. Secondary syphilitic lesions. Clin Microbiol Rev. 2005;18:205-216.
- Dourmishev LA, Dourmishev AL. Syphilis: uncommon presentations in adults. Clin Dermatol. 2005;23:555-564.
- Cohen SE, Klausner JD, Engelman J, et al. Syphilis in the modern era: an update for physicians. Infect Dis Clin North Am. 2013;27:705-722.
- Filo-Rogulska M, Pindycka-Plaszcznska M, Januszewski K, et al. Disseminated atypical molluscum contagiosum as a presenting symptom of HIV infection. Postepy Dermatol Alergol. 2013;30:56-58.
Practice Points
- Recognize typical and atypical presentations of secondary syphilis (SS).
- This case reinforces the importance of cutaneous biopsies in immunocompromised patients.
- Consider the possibility of autoinoculation in SS.
ACIP approves child and adolescent vaccination schedule for 2020
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted unanimously to approve the child and adolescent immunization schedule for 2020.
Candice Robinson, MD, MPH, of the CDC’s National Center for Immunization and Respiratory Diseases, said at the CDC’s October meeting of ACIP. Updates reflect changes in language in the adult vaccination schedule, notably the change in the definition of “contraindication.” The updated wording in the Notes substitutes “not recommended or contraindicated” instead of the word “contraindicated” only.
Another notable change was the addition of information on adolescent vaccination of children who received the meningococcal ACWY vaccine before 10 years of age. For “children in whom boosters are not recommended due to an ongoing or increased risk of meningococcal disease” (such as a healthy child traveling to an endemic area), they should receive MenACWY according to the recommended adolescent schedule. But those children for whom boosters are recommended because of increased disease risk from conditions including complement deficiency, HIV, or asplenia should “follow the booster schedule for persons at increased risk.”
Other changes include restructuring of the notes for the live attenuated influenza vaccine (LAIV) in special situations. The schedule now uses a bulleted list to show that LAIV should not be used in the following circumstances:
- Having history of severe allergic reaction to a previous vaccine or vaccine component.
- Using aspirin or a salicylate-containing medication.
- Being aged 2-4 years with a history of asthma or wheezing.
- Having immunocompromised conditions.
- Having anatomic or functional asplenia.
- Having cochlear implants.
- Experiencing cerebrospinal fluid–oropharyngeal communication.
- Having immunocompromised close contacts or caregivers.
- Being pregnant.
- Having received flu antivirals within the previous 48 hours.
In addition, language on shared clinical decision-making was added to the notes on the meningococcal B vaccine for adolescents and young adults aged 18-23 years not at increased risk. Based on shared clinical decision making, the recommendation is a “two-dose series of Bexsero at least 1 month apart” or “two-dose series of Trumenba at least 6 months apart; if dose two is administered earlier than 6 months, administer a third dose at least 4 months after dose two.”
Several vaccines’ Notes sections, including hepatitis B and meningococcal disease, added links to detailed recommendations in the corresponding issues of the CDC’s Morbidity and Mortality Weekly Report, to allow clinicians easy access to additional information.
View the current Child & Adolescent Vaccination Schedule here.
The ACIP members had no financial conflicts to disclose.
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted unanimously to approve the child and adolescent immunization schedule for 2020.
Candice Robinson, MD, MPH, of the CDC’s National Center for Immunization and Respiratory Diseases, said at the CDC’s October meeting of ACIP. Updates reflect changes in language in the adult vaccination schedule, notably the change in the definition of “contraindication.” The updated wording in the Notes substitutes “not recommended or contraindicated” instead of the word “contraindicated” only.
Another notable change was the addition of information on adolescent vaccination of children who received the meningococcal ACWY vaccine before 10 years of age. For “children in whom boosters are not recommended due to an ongoing or increased risk of meningococcal disease” (such as a healthy child traveling to an endemic area), they should receive MenACWY according to the recommended adolescent schedule. But those children for whom boosters are recommended because of increased disease risk from conditions including complement deficiency, HIV, or asplenia should “follow the booster schedule for persons at increased risk.”
Other changes include restructuring of the notes for the live attenuated influenza vaccine (LAIV) in special situations. The schedule now uses a bulleted list to show that LAIV should not be used in the following circumstances:
- Having history of severe allergic reaction to a previous vaccine or vaccine component.
- Using aspirin or a salicylate-containing medication.
- Being aged 2-4 years with a history of asthma or wheezing.
- Having immunocompromised conditions.
- Having anatomic or functional asplenia.
- Having cochlear implants.
- Experiencing cerebrospinal fluid–oropharyngeal communication.
- Having immunocompromised close contacts or caregivers.
- Being pregnant.
- Having received flu antivirals within the previous 48 hours.
In addition, language on shared clinical decision-making was added to the notes on the meningococcal B vaccine for adolescents and young adults aged 18-23 years not at increased risk. Based on shared clinical decision making, the recommendation is a “two-dose series of Bexsero at least 1 month apart” or “two-dose series of Trumenba at least 6 months apart; if dose two is administered earlier than 6 months, administer a third dose at least 4 months after dose two.”
Several vaccines’ Notes sections, including hepatitis B and meningococcal disease, added links to detailed recommendations in the corresponding issues of the CDC’s Morbidity and Mortality Weekly Report, to allow clinicians easy access to additional information.
View the current Child & Adolescent Vaccination Schedule here.
The ACIP members had no financial conflicts to disclose.
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted unanimously to approve the child and adolescent immunization schedule for 2020.
Candice Robinson, MD, MPH, of the CDC’s National Center for Immunization and Respiratory Diseases, said at the CDC’s October meeting of ACIP. Updates reflect changes in language in the adult vaccination schedule, notably the change in the definition of “contraindication.” The updated wording in the Notes substitutes “not recommended or contraindicated” instead of the word “contraindicated” only.
Another notable change was the addition of information on adolescent vaccination of children who received the meningococcal ACWY vaccine before 10 years of age. For “children in whom boosters are not recommended due to an ongoing or increased risk of meningococcal disease” (such as a healthy child traveling to an endemic area), they should receive MenACWY according to the recommended adolescent schedule. But those children for whom boosters are recommended because of increased disease risk from conditions including complement deficiency, HIV, or asplenia should “follow the booster schedule for persons at increased risk.”
Other changes include restructuring of the notes for the live attenuated influenza vaccine (LAIV) in special situations. The schedule now uses a bulleted list to show that LAIV should not be used in the following circumstances:
- Having history of severe allergic reaction to a previous vaccine or vaccine component.
- Using aspirin or a salicylate-containing medication.
- Being aged 2-4 years with a history of asthma or wheezing.
- Having immunocompromised conditions.
- Having anatomic or functional asplenia.
- Having cochlear implants.
- Experiencing cerebrospinal fluid–oropharyngeal communication.
- Having immunocompromised close contacts or caregivers.
- Being pregnant.
- Having received flu antivirals within the previous 48 hours.
In addition, language on shared clinical decision-making was added to the notes on the meningococcal B vaccine for adolescents and young adults aged 18-23 years not at increased risk. Based on shared clinical decision making, the recommendation is a “two-dose series of Bexsero at least 1 month apart” or “two-dose series of Trumenba at least 6 months apart; if dose two is administered earlier than 6 months, administer a third dose at least 4 months after dose two.”
Several vaccines’ Notes sections, including hepatitis B and meningococcal disease, added links to detailed recommendations in the corresponding issues of the CDC’s Morbidity and Mortality Weekly Report, to allow clinicians easy access to additional information.
View the current Child & Adolescent Vaccination Schedule here.
The ACIP members had no financial conflicts to disclose.
FROM AN ACIP MEETING
ACIP approves 2020 adult vaccination schedule
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted unanimously to approve the adult immunization schedule for 2020, although some fine-tuning may occur before publication.
“Some of the wordsmithing may be done later,” ACIP executive secretary Amanda Cohn, MD, said at the ACIP October meeting.
Key updates to the schedule included a change in wording for the definition of the red bars on the table to include “not recommended or contraindicated” instead of only the word “contraindicated.” Committee members were especially interested in changing this wording to guide clinicians in use of the live attenuated influenza vaccine because of its potential value in vaccinating health care personnel.
Other updates include language that vaccination of adolescents and young adults aged 16-23 years who are not at increased risk for meningococcal disease should be vaccinated as follows: “Based on shared clinical decision making, 2-dose series MenB-4C at least 1 month apart or 2-dose series MenB-FHbp at 0, 6 months.”
Similarly, clinical decision-making language was added to the notes for the pneumococcal polysaccharide vaccine (PPSV23) and the 13-valent pneumococcal conjugate vaccine (PCV13).
The routine vaccination calls for only one dose of PPSV23 given on or after the individual’s 65th birthday. Then, based on shared clinical decision making, a dose of PCV13 is recommended for immunocompetent individuals aged 65 years and older. The notes also state that, based on shared clinical decision making, PCV13 and PPSV23 should not be given in the same visit and, if both will be given, PCV13 should be first and should be given 1 year before PPSV23. In addition, “PPSV23 should be given at least 5 years after any previous PPSV23 dose.”
The schedule also adds shared clinical decision making to the notes on human papillomavirus vaccination for adults aged 27-45 years.
The committee members acknowledged the increasing complexity of the adult vaccination schedule, but several members agreed that it is accessible to many clinicians.
“We can’t let the perfect be the enemy of the good” said Jason Goldman, MD, liaison representing the American College of Physicians. “Those who want to learn the schedule will learn it; the health system will learn it,” even if not every specialist does.
The table “is something to draw you in,” said Sandra Fryhofer, MD, an internist who is liaison for the American Medical Association. The notes provide more details.
More specific information about contraindications for patients with cochlear implants, which also came up in the discussion, may be added to the schedule at a later date.
View the current adult vaccination schedule here.
The ACIP members had no financial conflicts to disclose.
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted unanimously to approve the adult immunization schedule for 2020, although some fine-tuning may occur before publication.
“Some of the wordsmithing may be done later,” ACIP executive secretary Amanda Cohn, MD, said at the ACIP October meeting.
Key updates to the schedule included a change in wording for the definition of the red bars on the table to include “not recommended or contraindicated” instead of only the word “contraindicated.” Committee members were especially interested in changing this wording to guide clinicians in use of the live attenuated influenza vaccine because of its potential value in vaccinating health care personnel.
Other updates include language that vaccination of adolescents and young adults aged 16-23 years who are not at increased risk for meningococcal disease should be vaccinated as follows: “Based on shared clinical decision making, 2-dose series MenB-4C at least 1 month apart or 2-dose series MenB-FHbp at 0, 6 months.”
Similarly, clinical decision-making language was added to the notes for the pneumococcal polysaccharide vaccine (PPSV23) and the 13-valent pneumococcal conjugate vaccine (PCV13).
The routine vaccination calls for only one dose of PPSV23 given on or after the individual’s 65th birthday. Then, based on shared clinical decision making, a dose of PCV13 is recommended for immunocompetent individuals aged 65 years and older. The notes also state that, based on shared clinical decision making, PCV13 and PPSV23 should not be given in the same visit and, if both will be given, PCV13 should be first and should be given 1 year before PPSV23. In addition, “PPSV23 should be given at least 5 years after any previous PPSV23 dose.”
The schedule also adds shared clinical decision making to the notes on human papillomavirus vaccination for adults aged 27-45 years.
The committee members acknowledged the increasing complexity of the adult vaccination schedule, but several members agreed that it is accessible to many clinicians.
“We can’t let the perfect be the enemy of the good” said Jason Goldman, MD, liaison representing the American College of Physicians. “Those who want to learn the schedule will learn it; the health system will learn it,” even if not every specialist does.
The table “is something to draw you in,” said Sandra Fryhofer, MD, an internist who is liaison for the American Medical Association. The notes provide more details.
More specific information about contraindications for patients with cochlear implants, which also came up in the discussion, may be added to the schedule at a later date.
View the current adult vaccination schedule here.
The ACIP members had no financial conflicts to disclose.
The Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices voted unanimously to approve the adult immunization schedule for 2020, although some fine-tuning may occur before publication.
“Some of the wordsmithing may be done later,” ACIP executive secretary Amanda Cohn, MD, said at the ACIP October meeting.
Key updates to the schedule included a change in wording for the definition of the red bars on the table to include “not recommended or contraindicated” instead of only the word “contraindicated.” Committee members were especially interested in changing this wording to guide clinicians in use of the live attenuated influenza vaccine because of its potential value in vaccinating health care personnel.
Other updates include language that vaccination of adolescents and young adults aged 16-23 years who are not at increased risk for meningococcal disease should be vaccinated as follows: “Based on shared clinical decision making, 2-dose series MenB-4C at least 1 month apart or 2-dose series MenB-FHbp at 0, 6 months.”
Similarly, clinical decision-making language was added to the notes for the pneumococcal polysaccharide vaccine (PPSV23) and the 13-valent pneumococcal conjugate vaccine (PCV13).
The routine vaccination calls for only one dose of PPSV23 given on or after the individual’s 65th birthday. Then, based on shared clinical decision making, a dose of PCV13 is recommended for immunocompetent individuals aged 65 years and older. The notes also state that, based on shared clinical decision making, PCV13 and PPSV23 should not be given in the same visit and, if both will be given, PCV13 should be first and should be given 1 year before PPSV23. In addition, “PPSV23 should be given at least 5 years after any previous PPSV23 dose.”
The schedule also adds shared clinical decision making to the notes on human papillomavirus vaccination for adults aged 27-45 years.
The committee members acknowledged the increasing complexity of the adult vaccination schedule, but several members agreed that it is accessible to many clinicians.
“We can’t let the perfect be the enemy of the good” said Jason Goldman, MD, liaison representing the American College of Physicians. “Those who want to learn the schedule will learn it; the health system will learn it,” even if not every specialist does.
The table “is something to draw you in,” said Sandra Fryhofer, MD, an internist who is liaison for the American Medical Association. The notes provide more details.
More specific information about contraindications for patients with cochlear implants, which also came up in the discussion, may be added to the schedule at a later date.
View the current adult vaccination schedule here.
The ACIP members had no financial conflicts to disclose.
ACIP plans flu review for older adults
according to data presented at a meeting of the Centers for Disease Control and Prevention’s ACIP.
Lynette Brammer of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD) presented a surveillance update of the flu season in the United States so far. Overall, the influenza A(H3N2) viruses are predominant, although dominance varies in different regions of the country, and it is too soon to predict what strain will dominate later in the season.
“While two of the four vaccine components were updated for the Southern Hemisphere, the components selected for the 2019-2020 Northern Hemisphere vaccine, at this time, look appropriate for the season,” she said.
In other flu news, Lisa Groskopf, MD, of the NCIRD discussed the influenza work group’s plans for a meta-analysis to assess the relative benefit of different vaccines for older adults, in light of the growing variety of products available.
Currently, no preferential recommendations have been made for a specific vaccine for a particular age group. “There’s a dearth of data comparing these vaccines to one another,” said Dr. Groskopf. She added that, because vaccine effectiveness varies by season, the generalizability of effectiveness data is another challenge.
The work group’s systematic review and meta-analysis is designed to compare the high-dose inactivated influenza vaccine (HD-IIV), the adjuvanted inactivated influenza vaccine (aIIV), and the recombinant influenza vaccine (RIV). The study will include adults aged 65 years and older who receive trivalent or quadrivalent HD-IIV, aIIV, or RIV, compared with those who receive another influenza vaccine, a noninfluenza control vaccine, placebo, or no vaccine. The outcomes will include data on safety and effectiveness of the vaccines, Dr. Groskopf said.
In addition to safety and effectiveness, manufacturers such as Sanofi Pasteur continue to collect data on the success of available vaccines and develop new ones. Lee-Jah Chang, MD, of Sanofi Pasteur presented results of a noninferiority study of the company’s investigational high-dose quadrivalent influenza vaccine (QIV-HD; including two prevailing B viruses) versus the high-dose trivalent influenza vaccine (TID-HD). The study was conducted at 35 sites in the United States and included 2,670 adults aged 65 years and older.
Overall, the reactogenicity profile for patients given QIV-HD was similar to that of TID-HD, and approximately 5% of patients in the QIV group reported an immediate adverse event, Dr. Chang said. However, no related deaths or related adverse events of special interest occurred in any of the study groups.
Sanofi plans to pursue licensure of the QIV-HD vaccine, with a Center for Biologics Evaluation and Research action date of Nov. 4, 2019, said Dr. Chang. If the vaccine is licensed, it should be available for purchase by health care providers in the first quarter of 2020.
The ACIP members had no financial conflicts to disclose.
according to data presented at a meeting of the Centers for Disease Control and Prevention’s ACIP.
Lynette Brammer of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD) presented a surveillance update of the flu season in the United States so far. Overall, the influenza A(H3N2) viruses are predominant, although dominance varies in different regions of the country, and it is too soon to predict what strain will dominate later in the season.
“While two of the four vaccine components were updated for the Southern Hemisphere, the components selected for the 2019-2020 Northern Hemisphere vaccine, at this time, look appropriate for the season,” she said.
In other flu news, Lisa Groskopf, MD, of the NCIRD discussed the influenza work group’s plans for a meta-analysis to assess the relative benefit of different vaccines for older adults, in light of the growing variety of products available.
Currently, no preferential recommendations have been made for a specific vaccine for a particular age group. “There’s a dearth of data comparing these vaccines to one another,” said Dr. Groskopf. She added that, because vaccine effectiveness varies by season, the generalizability of effectiveness data is another challenge.
The work group’s systematic review and meta-analysis is designed to compare the high-dose inactivated influenza vaccine (HD-IIV), the adjuvanted inactivated influenza vaccine (aIIV), and the recombinant influenza vaccine (RIV). The study will include adults aged 65 years and older who receive trivalent or quadrivalent HD-IIV, aIIV, or RIV, compared with those who receive another influenza vaccine, a noninfluenza control vaccine, placebo, or no vaccine. The outcomes will include data on safety and effectiveness of the vaccines, Dr. Groskopf said.
In addition to safety and effectiveness, manufacturers such as Sanofi Pasteur continue to collect data on the success of available vaccines and develop new ones. Lee-Jah Chang, MD, of Sanofi Pasteur presented results of a noninferiority study of the company’s investigational high-dose quadrivalent influenza vaccine (QIV-HD; including two prevailing B viruses) versus the high-dose trivalent influenza vaccine (TID-HD). The study was conducted at 35 sites in the United States and included 2,670 adults aged 65 years and older.
Overall, the reactogenicity profile for patients given QIV-HD was similar to that of TID-HD, and approximately 5% of patients in the QIV group reported an immediate adverse event, Dr. Chang said. However, no related deaths or related adverse events of special interest occurred in any of the study groups.
Sanofi plans to pursue licensure of the QIV-HD vaccine, with a Center for Biologics Evaluation and Research action date of Nov. 4, 2019, said Dr. Chang. If the vaccine is licensed, it should be available for purchase by health care providers in the first quarter of 2020.
The ACIP members had no financial conflicts to disclose.
according to data presented at a meeting of the Centers for Disease Control and Prevention’s ACIP.
Lynette Brammer of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD) presented a surveillance update of the flu season in the United States so far. Overall, the influenza A(H3N2) viruses are predominant, although dominance varies in different regions of the country, and it is too soon to predict what strain will dominate later in the season.
“While two of the four vaccine components were updated for the Southern Hemisphere, the components selected for the 2019-2020 Northern Hemisphere vaccine, at this time, look appropriate for the season,” she said.
In other flu news, Lisa Groskopf, MD, of the NCIRD discussed the influenza work group’s plans for a meta-analysis to assess the relative benefit of different vaccines for older adults, in light of the growing variety of products available.
Currently, no preferential recommendations have been made for a specific vaccine for a particular age group. “There’s a dearth of data comparing these vaccines to one another,” said Dr. Groskopf. She added that, because vaccine effectiveness varies by season, the generalizability of effectiveness data is another challenge.
The work group’s systematic review and meta-analysis is designed to compare the high-dose inactivated influenza vaccine (HD-IIV), the adjuvanted inactivated influenza vaccine (aIIV), and the recombinant influenza vaccine (RIV). The study will include adults aged 65 years and older who receive trivalent or quadrivalent HD-IIV, aIIV, or RIV, compared with those who receive another influenza vaccine, a noninfluenza control vaccine, placebo, or no vaccine. The outcomes will include data on safety and effectiveness of the vaccines, Dr. Groskopf said.
In addition to safety and effectiveness, manufacturers such as Sanofi Pasteur continue to collect data on the success of available vaccines and develop new ones. Lee-Jah Chang, MD, of Sanofi Pasteur presented results of a noninferiority study of the company’s investigational high-dose quadrivalent influenza vaccine (QIV-HD; including two prevailing B viruses) versus the high-dose trivalent influenza vaccine (TID-HD). The study was conducted at 35 sites in the United States and included 2,670 adults aged 65 years and older.
Overall, the reactogenicity profile for patients given QIV-HD was similar to that of TID-HD, and approximately 5% of patients in the QIV group reported an immediate adverse event, Dr. Chang said. However, no related deaths or related adverse events of special interest occurred in any of the study groups.
Sanofi plans to pursue licensure of the QIV-HD vaccine, with a Center for Biologics Evaluation and Research action date of Nov. 4, 2019, said Dr. Chang. If the vaccine is licensed, it should be available for purchase by health care providers in the first quarter of 2020.
The ACIP members had no financial conflicts to disclose.
REPORTING FROM AN ACIP MEETING
ACIP recommends two options for pertussis vaccination
Either the Tdap or Td vaccine is an acceptable option for pertussis vaccination in most situations, recommended the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
In a unanimous 14-0 vote at the October meeting,
Safety data showed no differences in safety concerns between Tdap and Td, including data from pregnant women, said Fiona Havers, MD, of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD), Atlanta.
Several of the ACIP members noted that the revised language to include both Tdap and Td reflects the increased use of Tdap and allows for maximum flexibility in clinical settings.
The revised language advises that booster doses of “either Td or Tdap” every 10 years throughout life are recommended for continued protection against tetanus and diphtheria. In addition, either Td or Tdap should be used if a tetanus toxoid–containing vaccine is indicated for prophylaxis in nonpregnant individuals.
For catch-up recommendations, which also apply to pregnant women, the committee approved the following wording for a series of three doses for individuals aged 7-18 years and 19 years and older who have never been vaccinated, that “the preferred schedule is a dose of Tdap (preferably the first dose), followed by either Tdap or Td at least 4 weeks afterward and another dose of either Td or Tdap 6-12 months later.” Individuals in these same age groups who are not fully vaccinated should receive one dose of Tdap, and a dose of either Td or Tdap if additional doses are needed.
The committee also voted unanimously 14-0 to accept the updated wording for pertussis vaccination in the Vaccines for Children program.
The ACIP members had no financial conflicts to disclose.
Either the Tdap or Td vaccine is an acceptable option for pertussis vaccination in most situations, recommended the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
In a unanimous 14-0 vote at the October meeting,
Safety data showed no differences in safety concerns between Tdap and Td, including data from pregnant women, said Fiona Havers, MD, of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD), Atlanta.
Several of the ACIP members noted that the revised language to include both Tdap and Td reflects the increased use of Tdap and allows for maximum flexibility in clinical settings.
The revised language advises that booster doses of “either Td or Tdap” every 10 years throughout life are recommended for continued protection against tetanus and diphtheria. In addition, either Td or Tdap should be used if a tetanus toxoid–containing vaccine is indicated for prophylaxis in nonpregnant individuals.
For catch-up recommendations, which also apply to pregnant women, the committee approved the following wording for a series of three doses for individuals aged 7-18 years and 19 years and older who have never been vaccinated, that “the preferred schedule is a dose of Tdap (preferably the first dose), followed by either Tdap or Td at least 4 weeks afterward and another dose of either Td or Tdap 6-12 months later.” Individuals in these same age groups who are not fully vaccinated should receive one dose of Tdap, and a dose of either Td or Tdap if additional doses are needed.
The committee also voted unanimously 14-0 to accept the updated wording for pertussis vaccination in the Vaccines for Children program.
The ACIP members had no financial conflicts to disclose.
Either the Tdap or Td vaccine is an acceptable option for pertussis vaccination in most situations, recommended the Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices.
In a unanimous 14-0 vote at the October meeting,
Safety data showed no differences in safety concerns between Tdap and Td, including data from pregnant women, said Fiona Havers, MD, of the CDC’s National Center for Immunization and Respiratory Diseases (NCIRD), Atlanta.
Several of the ACIP members noted that the revised language to include both Tdap and Td reflects the increased use of Tdap and allows for maximum flexibility in clinical settings.
The revised language advises that booster doses of “either Td or Tdap” every 10 years throughout life are recommended for continued protection against tetanus and diphtheria. In addition, either Td or Tdap should be used if a tetanus toxoid–containing vaccine is indicated for prophylaxis in nonpregnant individuals.
For catch-up recommendations, which also apply to pregnant women, the committee approved the following wording for a series of three doses for individuals aged 7-18 years and 19 years and older who have never been vaccinated, that “the preferred schedule is a dose of Tdap (preferably the first dose), followed by either Tdap or Td at least 4 weeks afterward and another dose of either Td or Tdap 6-12 months later.” Individuals in these same age groups who are not fully vaccinated should receive one dose of Tdap, and a dose of either Td or Tdap if additional doses are needed.
The committee also voted unanimously 14-0 to accept the updated wording for pertussis vaccination in the Vaccines for Children program.
The ACIP members had no financial conflicts to disclose.
FROM AN ACIP MEETING
New test edges closer to rapid, accurate ID of active TB
A new point-of-care assay designed with machine learning offers improved accuracy for rapid identification of active tuberculosis (TB) infection, according to investigators.
Rushdy Ahmad, PhD, of the Broad Institute of MIT and Harvard in Cambridge, Mass., and colleagues. When fully developed, such a test could improve interventions for the most vulnerable patients, such as those with HIV, among whom TB often goes undiagnosed.
“Rapid and accurate diagnosis of active TB with current sputum-based diagnostic tools remains challenging in high-burden, resource-limited settings,” the investigators wrote. Their report is in Science Translational Medicine.
They went on to explain the gap that currently exists between microscopy, which is operator dependent and insensitive, and newer technologies, such as nucleic acid amplification, which are more sensitive but heavily resource dependent. “Furthermore, two of the most vulnerable and highly affected groups – young children and adults with HIV infection – are unlikely to be diagnosed using sputum because of difficulty obtaining sputum and low bacillary loads in the sample.”
To look for a more practical option, the investigators drew blood from 406 patients with chronic cough. Then, using a bead-based immunoassay with machine learning, the investigators identified four blood proteins associated with active TB infection: interleukin-6 (IL-6), IL-8, IL-18, and vascular endothelial growth factor (VEGF). Blind validation of 317 samples from patients with chronic cough in Asia, Africa, and South America showed that the four biomarkers offered a sensitivity of 80% and a specificity of 65%. By adding a fifth biomarker, an antibody against TB antigen Ag85B, the investigators were able to raise accuracy figures to 86% sensitivity and 69% specificity.
Adding even more biomarkers could theoretically raise accuracy even further, according to the investigators. The WHO minimal performance thresholds are 90% sensitivity and 70% specificity, with optimal targets slightly higher, at 95% sensitivity and 80% specificity. Although these standards have not yet been met, the investigators plan on testing the existing assay in real-world scenarios while simultaneously aiming to make it better.
“A near-term goal is ... to incrementally improve the marker panel up to an anticipated 6- to 10-plex assay,” the investigators wrote. “However, given the urgency of the problem, the possibility of incremental improvements will not delay platform refinement and field testing.”
The Bill and Melinda Gates Foundation funded the study. The investigators reported additional relationships with Quanterix Corporation and FIND.
SOURCE: Ahmad et al. Sci Transl Med. 2019 Oct 23. doi: 10.1126/scitranslmed.aaw8287.
A new point-of-care assay designed with machine learning offers improved accuracy for rapid identification of active tuberculosis (TB) infection, according to investigators.
Rushdy Ahmad, PhD, of the Broad Institute of MIT and Harvard in Cambridge, Mass., and colleagues. When fully developed, such a test could improve interventions for the most vulnerable patients, such as those with HIV, among whom TB often goes undiagnosed.
“Rapid and accurate diagnosis of active TB with current sputum-based diagnostic tools remains challenging in high-burden, resource-limited settings,” the investigators wrote. Their report is in Science Translational Medicine.
They went on to explain the gap that currently exists between microscopy, which is operator dependent and insensitive, and newer technologies, such as nucleic acid amplification, which are more sensitive but heavily resource dependent. “Furthermore, two of the most vulnerable and highly affected groups – young children and adults with HIV infection – are unlikely to be diagnosed using sputum because of difficulty obtaining sputum and low bacillary loads in the sample.”
To look for a more practical option, the investigators drew blood from 406 patients with chronic cough. Then, using a bead-based immunoassay with machine learning, the investigators identified four blood proteins associated with active TB infection: interleukin-6 (IL-6), IL-8, IL-18, and vascular endothelial growth factor (VEGF). Blind validation of 317 samples from patients with chronic cough in Asia, Africa, and South America showed that the four biomarkers offered a sensitivity of 80% and a specificity of 65%. By adding a fifth biomarker, an antibody against TB antigen Ag85B, the investigators were able to raise accuracy figures to 86% sensitivity and 69% specificity.
Adding even more biomarkers could theoretically raise accuracy even further, according to the investigators. The WHO minimal performance thresholds are 90% sensitivity and 70% specificity, with optimal targets slightly higher, at 95% sensitivity and 80% specificity. Although these standards have not yet been met, the investigators plan on testing the existing assay in real-world scenarios while simultaneously aiming to make it better.
“A near-term goal is ... to incrementally improve the marker panel up to an anticipated 6- to 10-plex assay,” the investigators wrote. “However, given the urgency of the problem, the possibility of incremental improvements will not delay platform refinement and field testing.”
The Bill and Melinda Gates Foundation funded the study. The investigators reported additional relationships with Quanterix Corporation and FIND.
SOURCE: Ahmad et al. Sci Transl Med. 2019 Oct 23. doi: 10.1126/scitranslmed.aaw8287.
A new point-of-care assay designed with machine learning offers improved accuracy for rapid identification of active tuberculosis (TB) infection, according to investigators.
Rushdy Ahmad, PhD, of the Broad Institute of MIT and Harvard in Cambridge, Mass., and colleagues. When fully developed, such a test could improve interventions for the most vulnerable patients, such as those with HIV, among whom TB often goes undiagnosed.
“Rapid and accurate diagnosis of active TB with current sputum-based diagnostic tools remains challenging in high-burden, resource-limited settings,” the investigators wrote. Their report is in Science Translational Medicine.
They went on to explain the gap that currently exists between microscopy, which is operator dependent and insensitive, and newer technologies, such as nucleic acid amplification, which are more sensitive but heavily resource dependent. “Furthermore, two of the most vulnerable and highly affected groups – young children and adults with HIV infection – are unlikely to be diagnosed using sputum because of difficulty obtaining sputum and low bacillary loads in the sample.”
To look for a more practical option, the investigators drew blood from 406 patients with chronic cough. Then, using a bead-based immunoassay with machine learning, the investigators identified four blood proteins associated with active TB infection: interleukin-6 (IL-6), IL-8, IL-18, and vascular endothelial growth factor (VEGF). Blind validation of 317 samples from patients with chronic cough in Asia, Africa, and South America showed that the four biomarkers offered a sensitivity of 80% and a specificity of 65%. By adding a fifth biomarker, an antibody against TB antigen Ag85B, the investigators were able to raise accuracy figures to 86% sensitivity and 69% specificity.
Adding even more biomarkers could theoretically raise accuracy even further, according to the investigators. The WHO minimal performance thresholds are 90% sensitivity and 70% specificity, with optimal targets slightly higher, at 95% sensitivity and 80% specificity. Although these standards have not yet been met, the investigators plan on testing the existing assay in real-world scenarios while simultaneously aiming to make it better.
“A near-term goal is ... to incrementally improve the marker panel up to an anticipated 6- to 10-plex assay,” the investigators wrote. “However, given the urgency of the problem, the possibility of incremental improvements will not delay platform refinement and field testing.”
The Bill and Melinda Gates Foundation funded the study. The investigators reported additional relationships with Quanterix Corporation and FIND.
SOURCE: Ahmad et al. Sci Transl Med. 2019 Oct 23. doi: 10.1126/scitranslmed.aaw8287.
FROM SCIENCE TRANSLATIONAL MEDICINE
Key clinical point: A new point-of-care assay designed with machine learning offers improved accuracy for rapid identification of active tuberculosis (TB) infection.
Major finding: The assay had a sensitivity of 86%.
Study details: A machine learning and validation study involving patients with chronic cough from multiple countries.
Disclosures: The Bill and Melinda Gates Foundation funded the study. The investigators reported relationships with Quanterix Corporation and FIND.
Source: Ahmad et al. Sci Transl Med. 2019 Oct 23. doi: 10.1126/scitranslmed.aaw8287.
Rare mixed HCV genotypes found in men who have sex with men
A low percentage of mixed genotypes of hepatitis C virus (HCV) was found in a small study of recently infected HIV+ and HIV– men who have sex with men (MSM) according to a report by Thuy Nguyen, PhD, of the University of North Carolina, Chapel Hill, and colleagues published in the International Journal of Antimicrobial Agents.
The researchers assessed 58 HCV-infected individuals with a median age of 38.5 years, 50 of whom were HIV positive and 18 of whom were HIV negative. Most of the patients were MSM (85.3%), with the rest of unknown sexual orientation. HCV genotyping by Sanger found types GT1a, GT4d, GT3a, and GT2k infection in 47.1%, 41.2%, 8.8%, and 2.9% of the individuals.
After eliminating suspected contaminations, three patients (4.4%) were found with mixed GT infections All three patients were infected with HCV for the first time; two-thirds were coinfected with HIV. The mixed GTs comprised only GT4d and GT1a at different ratios. Mixed infections are potentially problematic when using direct-acting antiviral therapy without broad-spectrum activity, according to the researchers. In this case, however, all HCV patients achieved treatment success.
“From a public health perspective, the MSM population engaging in high-risk behaviors still requires special attention in terms of mixed infections compared with the general HCV-infected population with a regular monitoring of anti-HCV treatment response, particularly when pangenotypic treatment is not used,” the researchers concluded.
The study was funded by the French government; the authors reported having no conflicts.
SOURCE: Nguyen T et al. Int J Antimicrobial Agents. 2019. 54[4]:523-7.
A low percentage of mixed genotypes of hepatitis C virus (HCV) was found in a small study of recently infected HIV+ and HIV– men who have sex with men (MSM) according to a report by Thuy Nguyen, PhD, of the University of North Carolina, Chapel Hill, and colleagues published in the International Journal of Antimicrobial Agents.
The researchers assessed 58 HCV-infected individuals with a median age of 38.5 years, 50 of whom were HIV positive and 18 of whom were HIV negative. Most of the patients were MSM (85.3%), with the rest of unknown sexual orientation. HCV genotyping by Sanger found types GT1a, GT4d, GT3a, and GT2k infection in 47.1%, 41.2%, 8.8%, and 2.9% of the individuals.
After eliminating suspected contaminations, three patients (4.4%) were found with mixed GT infections All three patients were infected with HCV for the first time; two-thirds were coinfected with HIV. The mixed GTs comprised only GT4d and GT1a at different ratios. Mixed infections are potentially problematic when using direct-acting antiviral therapy without broad-spectrum activity, according to the researchers. In this case, however, all HCV patients achieved treatment success.
“From a public health perspective, the MSM population engaging in high-risk behaviors still requires special attention in terms of mixed infections compared with the general HCV-infected population with a regular monitoring of anti-HCV treatment response, particularly when pangenotypic treatment is not used,” the researchers concluded.
The study was funded by the French government; the authors reported having no conflicts.
SOURCE: Nguyen T et al. Int J Antimicrobial Agents. 2019. 54[4]:523-7.
A low percentage of mixed genotypes of hepatitis C virus (HCV) was found in a small study of recently infected HIV+ and HIV– men who have sex with men (MSM) according to a report by Thuy Nguyen, PhD, of the University of North Carolina, Chapel Hill, and colleagues published in the International Journal of Antimicrobial Agents.
The researchers assessed 58 HCV-infected individuals with a median age of 38.5 years, 50 of whom were HIV positive and 18 of whom were HIV negative. Most of the patients were MSM (85.3%), with the rest of unknown sexual orientation. HCV genotyping by Sanger found types GT1a, GT4d, GT3a, and GT2k infection in 47.1%, 41.2%, 8.8%, and 2.9% of the individuals.
After eliminating suspected contaminations, three patients (4.4%) were found with mixed GT infections All three patients were infected with HCV for the first time; two-thirds were coinfected with HIV. The mixed GTs comprised only GT4d and GT1a at different ratios. Mixed infections are potentially problematic when using direct-acting antiviral therapy without broad-spectrum activity, according to the researchers. In this case, however, all HCV patients achieved treatment success.
“From a public health perspective, the MSM population engaging in high-risk behaviors still requires special attention in terms of mixed infections compared with the general HCV-infected population with a regular monitoring of anti-HCV treatment response, particularly when pangenotypic treatment is not used,” the researchers concluded.
The study was funded by the French government; the authors reported having no conflicts.
SOURCE: Nguyen T et al. Int J Antimicrobial Agents. 2019. 54[4]:523-7.
FROM THE INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS
Vitamin C–based regimens in sepsis plausible, need more data, expert says
NEW ORLEANS – While further data are awaited on the role of vitamin C, thiamine, and steroids in sepsis, there is at least biologic plausibility for using the combination, and clinical equipoise that supports continued enrollment of patients in the ongoing randomized, controlled VICTAS trial, according to that study’s principal investigator.
“There is tremendous biologic plausibility for giving vitamin C in sepsis,” said Jon Sevransky, MD, professor of medicine at Emory University in Atlanta. But until more data are available on vitamin C–based regimens, those who choose to use vitamin C with thiamine and steroids in this setting need to ensure that glucose is being measured appropriately, he warned.
“If you decide that vitamin C is right for your patient, prior to having enough data – so if you’re doing a Hail Mary, or a ‘this patient is sick, and it’s probably not going to hurt them’ – please make sure that you measure your glucose with something that uses whole blood, which is either a blood gas or sending it down to the core lab, because otherwise, you might get an inaccurate result,” Dr. Sevransky said at the annual meeting of the American College of Chest Physicians.
Results from the randomized, placebo-controlled Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) trial may be available within the next few months, according to Dr. Sevransky, who noted that the trial was funded for 500 patients, which provides an 80% probability of showing an absolute risk reduction of 10% in mortality.
The primary endpoint of the phase 3 trial is vasopressor and ventilator-free days at 30 days after randomization, while 30-day mortality has been described as “the key secondary outcome” by Dr. Sevransky and colleagues in a recent report on the trial design.
Clinicians have been “captivated” by the potential benefit of vitamin C, thiamine, and hydrocortisone in patients with severe sepsis and septic shock, as published in CHEST in June 2017, Dr. Sevransky said. In that study, reported by Paul E. Marik, MD, and colleagues, hospital mortality was 8.5% for the treatment group, versus 40.4% in the control group, a significant difference.
That retrospective, single-center study had a number of limitations, however, including its before-and-after design and the use of steroids in the comparator arm. In addition, little information was available on antibiotics or fluids given at the time of the intervention, according to Dr. Sevransky.
In results of the CITRIS-ALI randomized clinical trial, just published in JAMA, intravenous administration of high-dose vitamin C in patients with sepsis and acute respiratory distress syndrome (ARDS) failed to significantly reduce organ failure scores or biomarkers of inflammation and vascular injury.
In an exploratory analysis of CITRIS-ALI, mortality at day 28 was 29.8% for the treatment group and 46.3% for placebo, with a statistically significant difference between Kaplan-Meier survival curves for the two arms, according to the investigators.
That exploratory result from CITRIS-ALI, however, is indicative of “something that needs further study,” Dr. Sevransky cautioned. “In summary, I hope I told you that biologic plausibility is present for vitamin C, thiamine, and steroids. I think that, and this is my own personal opinion, that evidence to date allows for randomization of patients, that there’s current equipoise.”
Dr. Sevransky disclosed current grant support from the Biomedical Advanced Research and Development Authority (BARDA) and the Marcus Foundation, as well as a stipend from Critical Care Medicine related to work as an associate editor. He is also a medical advisor to Project Hope and ARDS Foundation and a member of the Surviving Sepsis guideline committees.
SOURCE: Sevransky J et al. Chest 2019.
NEW ORLEANS – While further data are awaited on the role of vitamin C, thiamine, and steroids in sepsis, there is at least biologic plausibility for using the combination, and clinical equipoise that supports continued enrollment of patients in the ongoing randomized, controlled VICTAS trial, according to that study’s principal investigator.
“There is tremendous biologic plausibility for giving vitamin C in sepsis,” said Jon Sevransky, MD, professor of medicine at Emory University in Atlanta. But until more data are available on vitamin C–based regimens, those who choose to use vitamin C with thiamine and steroids in this setting need to ensure that glucose is being measured appropriately, he warned.
“If you decide that vitamin C is right for your patient, prior to having enough data – so if you’re doing a Hail Mary, or a ‘this patient is sick, and it’s probably not going to hurt them’ – please make sure that you measure your glucose with something that uses whole blood, which is either a blood gas or sending it down to the core lab, because otherwise, you might get an inaccurate result,” Dr. Sevransky said at the annual meeting of the American College of Chest Physicians.
Results from the randomized, placebo-controlled Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) trial may be available within the next few months, according to Dr. Sevransky, who noted that the trial was funded for 500 patients, which provides an 80% probability of showing an absolute risk reduction of 10% in mortality.
The primary endpoint of the phase 3 trial is vasopressor and ventilator-free days at 30 days after randomization, while 30-day mortality has been described as “the key secondary outcome” by Dr. Sevransky and colleagues in a recent report on the trial design.
Clinicians have been “captivated” by the potential benefit of vitamin C, thiamine, and hydrocortisone in patients with severe sepsis and septic shock, as published in CHEST in June 2017, Dr. Sevransky said. In that study, reported by Paul E. Marik, MD, and colleagues, hospital mortality was 8.5% for the treatment group, versus 40.4% in the control group, a significant difference.
That retrospective, single-center study had a number of limitations, however, including its before-and-after design and the use of steroids in the comparator arm. In addition, little information was available on antibiotics or fluids given at the time of the intervention, according to Dr. Sevransky.
In results of the CITRIS-ALI randomized clinical trial, just published in JAMA, intravenous administration of high-dose vitamin C in patients with sepsis and acute respiratory distress syndrome (ARDS) failed to significantly reduce organ failure scores or biomarkers of inflammation and vascular injury.
In an exploratory analysis of CITRIS-ALI, mortality at day 28 was 29.8% for the treatment group and 46.3% for placebo, with a statistically significant difference between Kaplan-Meier survival curves for the two arms, according to the investigators.
That exploratory result from CITRIS-ALI, however, is indicative of “something that needs further study,” Dr. Sevransky cautioned. “In summary, I hope I told you that biologic plausibility is present for vitamin C, thiamine, and steroids. I think that, and this is my own personal opinion, that evidence to date allows for randomization of patients, that there’s current equipoise.”
Dr. Sevransky disclosed current grant support from the Biomedical Advanced Research and Development Authority (BARDA) and the Marcus Foundation, as well as a stipend from Critical Care Medicine related to work as an associate editor. He is also a medical advisor to Project Hope and ARDS Foundation and a member of the Surviving Sepsis guideline committees.
SOURCE: Sevransky J et al. Chest 2019.
NEW ORLEANS – While further data are awaited on the role of vitamin C, thiamine, and steroids in sepsis, there is at least biologic plausibility for using the combination, and clinical equipoise that supports continued enrollment of patients in the ongoing randomized, controlled VICTAS trial, according to that study’s principal investigator.
“There is tremendous biologic plausibility for giving vitamin C in sepsis,” said Jon Sevransky, MD, professor of medicine at Emory University in Atlanta. But until more data are available on vitamin C–based regimens, those who choose to use vitamin C with thiamine and steroids in this setting need to ensure that glucose is being measured appropriately, he warned.
“If you decide that vitamin C is right for your patient, prior to having enough data – so if you’re doing a Hail Mary, or a ‘this patient is sick, and it’s probably not going to hurt them’ – please make sure that you measure your glucose with something that uses whole blood, which is either a blood gas or sending it down to the core lab, because otherwise, you might get an inaccurate result,” Dr. Sevransky said at the annual meeting of the American College of Chest Physicians.
Results from the randomized, placebo-controlled Vitamin C, Thiamine, and Steroids in Sepsis (VICTAS) trial may be available within the next few months, according to Dr. Sevransky, who noted that the trial was funded for 500 patients, which provides an 80% probability of showing an absolute risk reduction of 10% in mortality.
The primary endpoint of the phase 3 trial is vasopressor and ventilator-free days at 30 days after randomization, while 30-day mortality has been described as “the key secondary outcome” by Dr. Sevransky and colleagues in a recent report on the trial design.
Clinicians have been “captivated” by the potential benefit of vitamin C, thiamine, and hydrocortisone in patients with severe sepsis and septic shock, as published in CHEST in June 2017, Dr. Sevransky said. In that study, reported by Paul E. Marik, MD, and colleagues, hospital mortality was 8.5% for the treatment group, versus 40.4% in the control group, a significant difference.
That retrospective, single-center study had a number of limitations, however, including its before-and-after design and the use of steroids in the comparator arm. In addition, little information was available on antibiotics or fluids given at the time of the intervention, according to Dr. Sevransky.
In results of the CITRIS-ALI randomized clinical trial, just published in JAMA, intravenous administration of high-dose vitamin C in patients with sepsis and acute respiratory distress syndrome (ARDS) failed to significantly reduce organ failure scores or biomarkers of inflammation and vascular injury.
In an exploratory analysis of CITRIS-ALI, mortality at day 28 was 29.8% for the treatment group and 46.3% for placebo, with a statistically significant difference between Kaplan-Meier survival curves for the two arms, according to the investigators.
That exploratory result from CITRIS-ALI, however, is indicative of “something that needs further study,” Dr. Sevransky cautioned. “In summary, I hope I told you that biologic plausibility is present for vitamin C, thiamine, and steroids. I think that, and this is my own personal opinion, that evidence to date allows for randomization of patients, that there’s current equipoise.”
Dr. Sevransky disclosed current grant support from the Biomedical Advanced Research and Development Authority (BARDA) and the Marcus Foundation, as well as a stipend from Critical Care Medicine related to work as an associate editor. He is also a medical advisor to Project Hope and ARDS Foundation and a member of the Surviving Sepsis guideline committees.
SOURCE: Sevransky J et al. Chest 2019.
EXPERT ANALYSIS FROM CHEST 2019
In-hospital flu shot reduced readmissions in pneumonia patients
NEW ORLEANS – In-hospital flu shots were rare, yet linked to a lower readmission rate for patients hospitalized with community-acquired pneumonia in a recent retrospective study, suggesting a “missed opportunity” to improve outcomes for these patients, an investigator said.
Less than 2% of patients admitted for community-acquired pneumonia (CAP) received in-hospital influenza vaccination, yet receiving it was linked to a 20% reduction in readmissions, according to investigator Kam Sing Ho, MD, a resident at Mount Sinai St. Luke’s, New York.
Those patients who were readmitted had a significantly higher death rate vs. index admissions, Dr. Ho said in a poster discussion session at the annual meeting of the American College of Chest Physicians.
“I know (vaccines) are pretty much pushed out to the outpatient setting, but given what we showed here in this abstract, I think there’s a role for influenza vaccines to be a discussion in the hospital,” Dr. Ho said in his presentation.
The retrospective analysis was based on 825,906 adult hospital admissions with a primary diagnosis of CAP in data from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project (HCUP). Of that large cohort, just 14,047 (1.91%) received in-hospital influenza vaccination, according to Dr. Ho.
In-hospital influenza vaccination independently predicted a lower risk of readmission (hazard ratio, 0.821; 95% confidence interval, 0.69-0.98; P less than .02) in a propensity score matching analysis that included 9,777 CAP patients who received the vaccination and 9,777 with similar demographic and clinical characteristics.
Private insurance and high-income status also predicted lower risk of readmission in the analysis, while by contrast, factors associated with higher risk of readmission included advanced age, Medicare insurance, and respiratory failure, among other factors, Dr. Ho reported.
The overall 30-day rate of readmission in the study was 11.9%, and of those readmissions, the great majority (about 80%) were due to pneumonia, he said.
The rate of death in the hospital was 2.96% for CAP patients who were readmitted, versus 1.11% for the index admissions (P less than .001), Dr. Ho reported. Moreover, readmissions were associated with nearly half a million hospital days and $1 billion in costs and $3.67 billion in charges.
Based on these findings, Dr. Ho and colleagues hope to incorporate routine influenza vaccination for all adults hospitalized with CAP.
“We’re always under pressure to do so much for patients that we can’t comprehensively do everything. But the 20% reduction in the risk of coming back, I think that’s significant,” Dr. Ho said in an interview.
The authors reported having no disclosures related to this research.
This article was updated 10/23/2019.
SOURCE: Ho KS, et al. CHEST 2019. doi: 10.1016/j.chest.2019.08.450.
NEW ORLEANS – In-hospital flu shots were rare, yet linked to a lower readmission rate for patients hospitalized with community-acquired pneumonia in a recent retrospective study, suggesting a “missed opportunity” to improve outcomes for these patients, an investigator said.
Less than 2% of patients admitted for community-acquired pneumonia (CAP) received in-hospital influenza vaccination, yet receiving it was linked to a 20% reduction in readmissions, according to investigator Kam Sing Ho, MD, a resident at Mount Sinai St. Luke’s, New York.
Those patients who were readmitted had a significantly higher death rate vs. index admissions, Dr. Ho said in a poster discussion session at the annual meeting of the American College of Chest Physicians.
“I know (vaccines) are pretty much pushed out to the outpatient setting, but given what we showed here in this abstract, I think there’s a role for influenza vaccines to be a discussion in the hospital,” Dr. Ho said in his presentation.
The retrospective analysis was based on 825,906 adult hospital admissions with a primary diagnosis of CAP in data from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project (HCUP). Of that large cohort, just 14,047 (1.91%) received in-hospital influenza vaccination, according to Dr. Ho.
In-hospital influenza vaccination independently predicted a lower risk of readmission (hazard ratio, 0.821; 95% confidence interval, 0.69-0.98; P less than .02) in a propensity score matching analysis that included 9,777 CAP patients who received the vaccination and 9,777 with similar demographic and clinical characteristics.
Private insurance and high-income status also predicted lower risk of readmission in the analysis, while by contrast, factors associated with higher risk of readmission included advanced age, Medicare insurance, and respiratory failure, among other factors, Dr. Ho reported.
The overall 30-day rate of readmission in the study was 11.9%, and of those readmissions, the great majority (about 80%) were due to pneumonia, he said.
The rate of death in the hospital was 2.96% for CAP patients who were readmitted, versus 1.11% for the index admissions (P less than .001), Dr. Ho reported. Moreover, readmissions were associated with nearly half a million hospital days and $1 billion in costs and $3.67 billion in charges.
Based on these findings, Dr. Ho and colleagues hope to incorporate routine influenza vaccination for all adults hospitalized with CAP.
“We’re always under pressure to do so much for patients that we can’t comprehensively do everything. But the 20% reduction in the risk of coming back, I think that’s significant,” Dr. Ho said in an interview.
The authors reported having no disclosures related to this research.
This article was updated 10/23/2019.
SOURCE: Ho KS, et al. CHEST 2019. doi: 10.1016/j.chest.2019.08.450.
NEW ORLEANS – In-hospital flu shots were rare, yet linked to a lower readmission rate for patients hospitalized with community-acquired pneumonia in a recent retrospective study, suggesting a “missed opportunity” to improve outcomes for these patients, an investigator said.
Less than 2% of patients admitted for community-acquired pneumonia (CAP) received in-hospital influenza vaccination, yet receiving it was linked to a 20% reduction in readmissions, according to investigator Kam Sing Ho, MD, a resident at Mount Sinai St. Luke’s, New York.
Those patients who were readmitted had a significantly higher death rate vs. index admissions, Dr. Ho said in a poster discussion session at the annual meeting of the American College of Chest Physicians.
“I know (vaccines) are pretty much pushed out to the outpatient setting, but given what we showed here in this abstract, I think there’s a role for influenza vaccines to be a discussion in the hospital,” Dr. Ho said in his presentation.
The retrospective analysis was based on 825,906 adult hospital admissions with a primary diagnosis of CAP in data from the Agency for Healthcare Research and Quality Healthcare Cost and Utilization Project (HCUP). Of that large cohort, just 14,047 (1.91%) received in-hospital influenza vaccination, according to Dr. Ho.
In-hospital influenza vaccination independently predicted a lower risk of readmission (hazard ratio, 0.821; 95% confidence interval, 0.69-0.98; P less than .02) in a propensity score matching analysis that included 9,777 CAP patients who received the vaccination and 9,777 with similar demographic and clinical characteristics.
Private insurance and high-income status also predicted lower risk of readmission in the analysis, while by contrast, factors associated with higher risk of readmission included advanced age, Medicare insurance, and respiratory failure, among other factors, Dr. Ho reported.
The overall 30-day rate of readmission in the study was 11.9%, and of those readmissions, the great majority (about 80%) were due to pneumonia, he said.
The rate of death in the hospital was 2.96% for CAP patients who were readmitted, versus 1.11% for the index admissions (P less than .001), Dr. Ho reported. Moreover, readmissions were associated with nearly half a million hospital days and $1 billion in costs and $3.67 billion in charges.
Based on these findings, Dr. Ho and colleagues hope to incorporate routine influenza vaccination for all adults hospitalized with CAP.
“We’re always under pressure to do so much for patients that we can’t comprehensively do everything. But the 20% reduction in the risk of coming back, I think that’s significant,” Dr. Ho said in an interview.
The authors reported having no disclosures related to this research.
This article was updated 10/23/2019.
SOURCE: Ho KS, et al. CHEST 2019. doi: 10.1016/j.chest.2019.08.450.
REPORTING FROM CHEST 2019
Pulmonary Hemorrhage as the Initial Presentation of AIDS-Related Kaposi Sarcoma
To the Editor:
Kaposi sarcoma (KS) is an angioproliferative tumor of endothelial origin associated with human herpesvirus 8 infection. It is one of the most prevalent opportunistic infections associated with AIDS and is considered an AIDS-defining illness. In the general population, the incidence of KS is 1 in 100,000 worldwide.1 At the onset of the human immunodeficiency virus (HIV) epidemic in the early 1980s, 25% of individuals with AIDS were found to have KS at the time of AIDS diagnosis. Beginning in the mid-1980s and early 1990s with the introduction of highly active antiretroviral therapy (HAART), the incidence of KS declined to 2% to 4%,2 likely secondary to restoration of immune response.3
The clinical course of KS ranges from benign to severe, involving both cutaneous and visceral forms of disease. Cutaneous KS is the most common form of disease and typically characterizes the initial presentation. It is classically described as violaceous patches, papules, or plaques that can become confluent, forming larger tumors over time. Biopsy of cutaneous lesions may vary based on the clinical morphology. The patch stage typically is characterized by abnormal proliferating vessels surrounding larger ectatic vessels.4 Vascular spaces are more jagged and lined by thin endothelial cells extending into the dermis, forming the classic promontory sign.5 In the plaque stage, the vascular infiltrate becomes more diffuse, involving the dermis and subcutis, and there is proliferation of spindle cells.4 In the nodular stage, spindle-shaped tumor cells form fascicles and vascular spaces become more dilated.4,5 Advanced lesions are further associated with hyaline globules staining positive with periodic acid–Schiff.4 Lymphocytes, plasma cells, and hemosiderin-laden macrophages are admixed within this pathologic architecture.4,5
Visceral KS most commonly occurs in the oropharynx, respiratory tract, and gastrointestinal tract, and rarely is the initial presentation of disease. Classically, visceral KS is an aggressive, potentially life-threatening form of disease and has been found to have a much worse prognosis than cutaneous KS alone. Pulmonary involvement is the second most common site of extracutaneous KS and is known as the most severely life-threatening form of disease.1 Interestingly, since the advent of HAART, the incidence of KS with involvement of the visceral organs has declined at a more dramatic rate than cutaneous KS alone.3 Therefore, although more aggressive in nature, KS with visceral features has become increasingly rare and should be largely preventable given advances in AIDS therapy. We present a case of advanced AIDS-related KS with pulmonary involvement that is rarely seen after the advent of HAART.
A 39-year-old man with HIV diagnosed 8 years prior presented with fever, chest pain, progressive dyspnea, and hemoptysis of 5 months’ duration. At the time, he was nonadherent to medications and had poor follow-up with primary care physicians. At presentation he was tachycardic (149 beats per minute), tachypneic (26 breaths per minute), and his oxygen saturation was 80% on room air. Physical examination of the skin revealed asymptomatic violaceous penile lesions that the patient reported had been present for the last 8 months (Figure 1). Pertinent laboratory values included an HIV-1 viral load of 480,135 copies/mL (reference range, <20 copies/mL) and CD4 count of 14 cells/mm3 (reference range, 480–1700 cells/mm3). A chest radiograph was obtained and revealed bibasilar opacities compatible with a pleural and/or parenchymal process. Bronchoscopy was then performed and revealed bloody secretions throughout the tracheobronchial tree.
Histologic examination of biopsies of the penile lesions revealed spindle cell proliferation with hemorrhage (Figure 2A) that stained positively for HHV-8 (Figure 2B), consistent with KS. Biopsies taken during bronchoscopy similarly revealed spindle cells with hemorrhage (Figure 3). The patient was diagnosed with AIDS-related KS with visceral involvement of the lung parenchyma and tracheobronchial tree. The patient was then admitted to the medical intensive care unit and intubated. Therapy with HAART and paclitaxel was initiated. After 7 days of poor response to therapy, the family opted for terminal extubation and comfort care measures. The patient died hours later.
This case report describes the classic phenomenon of AIDS-related KS in a patient with a long-standing history of immunocompromise. Even in the era of HAART, this patient developed a severe form of visceral KS with involvement of the respiratory tract and lung parenchyma.
Since the advent of HAART for the treatment of HIV/AIDS, the incidence of KS, both visceral and cutaneous forms, has dramatically declined; the risk for visceral KS declined by more than 50% but less than 30% for cutaneous KS, supporting the observation that although visceral involvement has classically been noted as the more aggressive and life-threatening form of disease, HAART appears to have a stronger effect on visceral disease than cutaneous disease.3 Although the overall impact of AIDS-defining illnesses has substantially improved over the years, those with AIDS infection remain at risk for opportunistic illness.2
It has been shown that HAART therapy leads to response in more than 50% of cases of KS.5 The administration of HAART in KS patients is associated with improved survival and an 80% reduced risk of death, even when started after KS is diagnosed.6 In a comparison of the differences in clinical manifestations of KS between patients who were already receiving HAART at the time of KS diagnosis to those who were not on HAART, it was shown that patients already on therapy presented with less aggressive clinical features. A smaller percentage of patients who were already on HAART at KS diagnosis presented with visceral disease compared to those who were not on therapy.7
It is evident that treatment of AIDS patients with HAART is not only first-line therapy for the disease but also the best preventative measure against development of KS. Management of KS also centers around the initiation of HAART if the patient is not already maintained on the proper therapy.8 In addition to HAART, treatment options for visceral KS include a variety of chemotherapeutic agents, including but not limited to the use of single-agent adriamycin, vinblastine, paclitaxel, and thalidomide, or combination therapies.
Although notable advances have been made in the management of AIDS patients, this case highlights the need for clinicians to be aware of the risk for KS in the context of immunocompromise. Specifically, patients with advanced AIDS who are not adherent to HAART or who have a poor response to therapy have an amplified risk for developing KS in general as well as an increased risk for developing more severe visceral KS. Maintenance of patients with HAART is shown to greatly reduce the risk for both cutaneous and visceral KS; therefore, patient adherence with therapy is of utmost importance in preventing the occurrence of this deadly disease and its complications. Appropriate follow-up should be made, ensuring that these patients at high risk are adherent to therapy and have proper access to medical care to allow for prevention and early identification of potential complications.
- La Ferla L, Pinzone MR, Nunnari G, et al. Kaposi’s sarcoma in HIV-positive patients: the state of art in the HARRT-era. Eur Rev Med Pharmacol Sci. 2013;17:2354-2365.
- Engels EA, Pfeiffer RM, Goedert JJ, et al; HIV/AIDS Cancer Match Study. Trends in cancer risk among people with AIDS in the United States 1980-2002. AIDS. 2006;20:1645-1654.
- Grabar S, Abraham B, Mahamat A, et al. Differential impact of combination antiretroviral therapy in preventing Kaposi’s sarcoma with and without visceral involvement. JCO. 2006;24:3408-3414.
- Grayson W, Pantanowitz L. Histological variants of cutaneous Kaposi sarcoma [published online July 25, 2008]. Diagn Pathol. 2008;3:31.
- Radu O, Pantanowitz L. Kaposi sarcoma. Arch Pathol Lab Med. 2013;137:289-294.
- Tam HK, Zhang ZF, Jacobson LP, et al. Effect of highly active antiretroviral therapy on survival among HIV-infected men with Kaposi sarcoma or non-Hodgkin lymphoma. Int J Cancer. 2002;98:916-922.
- Nasti G, Martellotta F, Berretta M, et al. Impact of highly active antiretroviral therapy on the presenting features and outcome of patients with acquired immunodeficiency syndrome-related Kaposi sarcoma. Cancer. 2003;98:2440-2446.
- Dupont C, Vasseur E, Beauchet A, et al. Long-term efficacy on Kaposi’s sarcoma of highly active antriretroviral therapy in a cohort of HIV-positive patients. AIDS. 2000;14:987-993.
To the Editor:
Kaposi sarcoma (KS) is an angioproliferative tumor of endothelial origin associated with human herpesvirus 8 infection. It is one of the most prevalent opportunistic infections associated with AIDS and is considered an AIDS-defining illness. In the general population, the incidence of KS is 1 in 100,000 worldwide.1 At the onset of the human immunodeficiency virus (HIV) epidemic in the early 1980s, 25% of individuals with AIDS were found to have KS at the time of AIDS diagnosis. Beginning in the mid-1980s and early 1990s with the introduction of highly active antiretroviral therapy (HAART), the incidence of KS declined to 2% to 4%,2 likely secondary to restoration of immune response.3
The clinical course of KS ranges from benign to severe, involving both cutaneous and visceral forms of disease. Cutaneous KS is the most common form of disease and typically characterizes the initial presentation. It is classically described as violaceous patches, papules, or plaques that can become confluent, forming larger tumors over time. Biopsy of cutaneous lesions may vary based on the clinical morphology. The patch stage typically is characterized by abnormal proliferating vessels surrounding larger ectatic vessels.4 Vascular spaces are more jagged and lined by thin endothelial cells extending into the dermis, forming the classic promontory sign.5 In the plaque stage, the vascular infiltrate becomes more diffuse, involving the dermis and subcutis, and there is proliferation of spindle cells.4 In the nodular stage, spindle-shaped tumor cells form fascicles and vascular spaces become more dilated.4,5 Advanced lesions are further associated with hyaline globules staining positive with periodic acid–Schiff.4 Lymphocytes, plasma cells, and hemosiderin-laden macrophages are admixed within this pathologic architecture.4,5
Visceral KS most commonly occurs in the oropharynx, respiratory tract, and gastrointestinal tract, and rarely is the initial presentation of disease. Classically, visceral KS is an aggressive, potentially life-threatening form of disease and has been found to have a much worse prognosis than cutaneous KS alone. Pulmonary involvement is the second most common site of extracutaneous KS and is known as the most severely life-threatening form of disease.1 Interestingly, since the advent of HAART, the incidence of KS with involvement of the visceral organs has declined at a more dramatic rate than cutaneous KS alone.3 Therefore, although more aggressive in nature, KS with visceral features has become increasingly rare and should be largely preventable given advances in AIDS therapy. We present a case of advanced AIDS-related KS with pulmonary involvement that is rarely seen after the advent of HAART.
A 39-year-old man with HIV diagnosed 8 years prior presented with fever, chest pain, progressive dyspnea, and hemoptysis of 5 months’ duration. At the time, he was nonadherent to medications and had poor follow-up with primary care physicians. At presentation he was tachycardic (149 beats per minute), tachypneic (26 breaths per minute), and his oxygen saturation was 80% on room air. Physical examination of the skin revealed asymptomatic violaceous penile lesions that the patient reported had been present for the last 8 months (Figure 1). Pertinent laboratory values included an HIV-1 viral load of 480,135 copies/mL (reference range, <20 copies/mL) and CD4 count of 14 cells/mm3 (reference range, 480–1700 cells/mm3). A chest radiograph was obtained and revealed bibasilar opacities compatible with a pleural and/or parenchymal process. Bronchoscopy was then performed and revealed bloody secretions throughout the tracheobronchial tree.
Histologic examination of biopsies of the penile lesions revealed spindle cell proliferation with hemorrhage (Figure 2A) that stained positively for HHV-8 (Figure 2B), consistent with KS. Biopsies taken during bronchoscopy similarly revealed spindle cells with hemorrhage (Figure 3). The patient was diagnosed with AIDS-related KS with visceral involvement of the lung parenchyma and tracheobronchial tree. The patient was then admitted to the medical intensive care unit and intubated. Therapy with HAART and paclitaxel was initiated. After 7 days of poor response to therapy, the family opted for terminal extubation and comfort care measures. The patient died hours later.
This case report describes the classic phenomenon of AIDS-related KS in a patient with a long-standing history of immunocompromise. Even in the era of HAART, this patient developed a severe form of visceral KS with involvement of the respiratory tract and lung parenchyma.
Since the advent of HAART for the treatment of HIV/AIDS, the incidence of KS, both visceral and cutaneous forms, has dramatically declined; the risk for visceral KS declined by more than 50% but less than 30% for cutaneous KS, supporting the observation that although visceral involvement has classically been noted as the more aggressive and life-threatening form of disease, HAART appears to have a stronger effect on visceral disease than cutaneous disease.3 Although the overall impact of AIDS-defining illnesses has substantially improved over the years, those with AIDS infection remain at risk for opportunistic illness.2
It has been shown that HAART therapy leads to response in more than 50% of cases of KS.5 The administration of HAART in KS patients is associated with improved survival and an 80% reduced risk of death, even when started after KS is diagnosed.6 In a comparison of the differences in clinical manifestations of KS between patients who were already receiving HAART at the time of KS diagnosis to those who were not on HAART, it was shown that patients already on therapy presented with less aggressive clinical features. A smaller percentage of patients who were already on HAART at KS diagnosis presented with visceral disease compared to those who were not on therapy.7
It is evident that treatment of AIDS patients with HAART is not only first-line therapy for the disease but also the best preventative measure against development of KS. Management of KS also centers around the initiation of HAART if the patient is not already maintained on the proper therapy.8 In addition to HAART, treatment options for visceral KS include a variety of chemotherapeutic agents, including but not limited to the use of single-agent adriamycin, vinblastine, paclitaxel, and thalidomide, or combination therapies.
Although notable advances have been made in the management of AIDS patients, this case highlights the need for clinicians to be aware of the risk for KS in the context of immunocompromise. Specifically, patients with advanced AIDS who are not adherent to HAART or who have a poor response to therapy have an amplified risk for developing KS in general as well as an increased risk for developing more severe visceral KS. Maintenance of patients with HAART is shown to greatly reduce the risk for both cutaneous and visceral KS; therefore, patient adherence with therapy is of utmost importance in preventing the occurrence of this deadly disease and its complications. Appropriate follow-up should be made, ensuring that these patients at high risk are adherent to therapy and have proper access to medical care to allow for prevention and early identification of potential complications.
To the Editor:
Kaposi sarcoma (KS) is an angioproliferative tumor of endothelial origin associated with human herpesvirus 8 infection. It is one of the most prevalent opportunistic infections associated with AIDS and is considered an AIDS-defining illness. In the general population, the incidence of KS is 1 in 100,000 worldwide.1 At the onset of the human immunodeficiency virus (HIV) epidemic in the early 1980s, 25% of individuals with AIDS were found to have KS at the time of AIDS diagnosis. Beginning in the mid-1980s and early 1990s with the introduction of highly active antiretroviral therapy (HAART), the incidence of KS declined to 2% to 4%,2 likely secondary to restoration of immune response.3
The clinical course of KS ranges from benign to severe, involving both cutaneous and visceral forms of disease. Cutaneous KS is the most common form of disease and typically characterizes the initial presentation. It is classically described as violaceous patches, papules, or plaques that can become confluent, forming larger tumors over time. Biopsy of cutaneous lesions may vary based on the clinical morphology. The patch stage typically is characterized by abnormal proliferating vessels surrounding larger ectatic vessels.4 Vascular spaces are more jagged and lined by thin endothelial cells extending into the dermis, forming the classic promontory sign.5 In the plaque stage, the vascular infiltrate becomes more diffuse, involving the dermis and subcutis, and there is proliferation of spindle cells.4 In the nodular stage, spindle-shaped tumor cells form fascicles and vascular spaces become more dilated.4,5 Advanced lesions are further associated with hyaline globules staining positive with periodic acid–Schiff.4 Lymphocytes, plasma cells, and hemosiderin-laden macrophages are admixed within this pathologic architecture.4,5
Visceral KS most commonly occurs in the oropharynx, respiratory tract, and gastrointestinal tract, and rarely is the initial presentation of disease. Classically, visceral KS is an aggressive, potentially life-threatening form of disease and has been found to have a much worse prognosis than cutaneous KS alone. Pulmonary involvement is the second most common site of extracutaneous KS and is known as the most severely life-threatening form of disease.1 Interestingly, since the advent of HAART, the incidence of KS with involvement of the visceral organs has declined at a more dramatic rate than cutaneous KS alone.3 Therefore, although more aggressive in nature, KS with visceral features has become increasingly rare and should be largely preventable given advances in AIDS therapy. We present a case of advanced AIDS-related KS with pulmonary involvement that is rarely seen after the advent of HAART.
A 39-year-old man with HIV diagnosed 8 years prior presented with fever, chest pain, progressive dyspnea, and hemoptysis of 5 months’ duration. At the time, he was nonadherent to medications and had poor follow-up with primary care physicians. At presentation he was tachycardic (149 beats per minute), tachypneic (26 breaths per minute), and his oxygen saturation was 80% on room air. Physical examination of the skin revealed asymptomatic violaceous penile lesions that the patient reported had been present for the last 8 months (Figure 1). Pertinent laboratory values included an HIV-1 viral load of 480,135 copies/mL (reference range, <20 copies/mL) and CD4 count of 14 cells/mm3 (reference range, 480–1700 cells/mm3). A chest radiograph was obtained and revealed bibasilar opacities compatible with a pleural and/or parenchymal process. Bronchoscopy was then performed and revealed bloody secretions throughout the tracheobronchial tree.
Histologic examination of biopsies of the penile lesions revealed spindle cell proliferation with hemorrhage (Figure 2A) that stained positively for HHV-8 (Figure 2B), consistent with KS. Biopsies taken during bronchoscopy similarly revealed spindle cells with hemorrhage (Figure 3). The patient was diagnosed with AIDS-related KS with visceral involvement of the lung parenchyma and tracheobronchial tree. The patient was then admitted to the medical intensive care unit and intubated. Therapy with HAART and paclitaxel was initiated. After 7 days of poor response to therapy, the family opted for terminal extubation and comfort care measures. The patient died hours later.
This case report describes the classic phenomenon of AIDS-related KS in a patient with a long-standing history of immunocompromise. Even in the era of HAART, this patient developed a severe form of visceral KS with involvement of the respiratory tract and lung parenchyma.
Since the advent of HAART for the treatment of HIV/AIDS, the incidence of KS, both visceral and cutaneous forms, has dramatically declined; the risk for visceral KS declined by more than 50% but less than 30% for cutaneous KS, supporting the observation that although visceral involvement has classically been noted as the more aggressive and life-threatening form of disease, HAART appears to have a stronger effect on visceral disease than cutaneous disease.3 Although the overall impact of AIDS-defining illnesses has substantially improved over the years, those with AIDS infection remain at risk for opportunistic illness.2
It has been shown that HAART therapy leads to response in more than 50% of cases of KS.5 The administration of HAART in KS patients is associated with improved survival and an 80% reduced risk of death, even when started after KS is diagnosed.6 In a comparison of the differences in clinical manifestations of KS between patients who were already receiving HAART at the time of KS diagnosis to those who were not on HAART, it was shown that patients already on therapy presented with less aggressive clinical features. A smaller percentage of patients who were already on HAART at KS diagnosis presented with visceral disease compared to those who were not on therapy.7
It is evident that treatment of AIDS patients with HAART is not only first-line therapy for the disease but also the best preventative measure against development of KS. Management of KS also centers around the initiation of HAART if the patient is not already maintained on the proper therapy.8 In addition to HAART, treatment options for visceral KS include a variety of chemotherapeutic agents, including but not limited to the use of single-agent adriamycin, vinblastine, paclitaxel, and thalidomide, or combination therapies.
Although notable advances have been made in the management of AIDS patients, this case highlights the need for clinicians to be aware of the risk for KS in the context of immunocompromise. Specifically, patients with advanced AIDS who are not adherent to HAART or who have a poor response to therapy have an amplified risk for developing KS in general as well as an increased risk for developing more severe visceral KS. Maintenance of patients with HAART is shown to greatly reduce the risk for both cutaneous and visceral KS; therefore, patient adherence with therapy is of utmost importance in preventing the occurrence of this deadly disease and its complications. Appropriate follow-up should be made, ensuring that these patients at high risk are adherent to therapy and have proper access to medical care to allow for prevention and early identification of potential complications.
- La Ferla L, Pinzone MR, Nunnari G, et al. Kaposi’s sarcoma in HIV-positive patients: the state of art in the HARRT-era. Eur Rev Med Pharmacol Sci. 2013;17:2354-2365.
- Engels EA, Pfeiffer RM, Goedert JJ, et al; HIV/AIDS Cancer Match Study. Trends in cancer risk among people with AIDS in the United States 1980-2002. AIDS. 2006;20:1645-1654.
- Grabar S, Abraham B, Mahamat A, et al. Differential impact of combination antiretroviral therapy in preventing Kaposi’s sarcoma with and without visceral involvement. JCO. 2006;24:3408-3414.
- Grayson W, Pantanowitz L. Histological variants of cutaneous Kaposi sarcoma [published online July 25, 2008]. Diagn Pathol. 2008;3:31.
- Radu O, Pantanowitz L. Kaposi sarcoma. Arch Pathol Lab Med. 2013;137:289-294.
- Tam HK, Zhang ZF, Jacobson LP, et al. Effect of highly active antiretroviral therapy on survival among HIV-infected men with Kaposi sarcoma or non-Hodgkin lymphoma. Int J Cancer. 2002;98:916-922.
- Nasti G, Martellotta F, Berretta M, et al. Impact of highly active antiretroviral therapy on the presenting features and outcome of patients with acquired immunodeficiency syndrome-related Kaposi sarcoma. Cancer. 2003;98:2440-2446.
- Dupont C, Vasseur E, Beauchet A, et al. Long-term efficacy on Kaposi’s sarcoma of highly active antriretroviral therapy in a cohort of HIV-positive patients. AIDS. 2000;14:987-993.
- La Ferla L, Pinzone MR, Nunnari G, et al. Kaposi’s sarcoma in HIV-positive patients: the state of art in the HARRT-era. Eur Rev Med Pharmacol Sci. 2013;17:2354-2365.
- Engels EA, Pfeiffer RM, Goedert JJ, et al; HIV/AIDS Cancer Match Study. Trends in cancer risk among people with AIDS in the United States 1980-2002. AIDS. 2006;20:1645-1654.
- Grabar S, Abraham B, Mahamat A, et al. Differential impact of combination antiretroviral therapy in preventing Kaposi’s sarcoma with and without visceral involvement. JCO. 2006;24:3408-3414.
- Grayson W, Pantanowitz L. Histological variants of cutaneous Kaposi sarcoma [published online July 25, 2008]. Diagn Pathol. 2008;3:31.
- Radu O, Pantanowitz L. Kaposi sarcoma. Arch Pathol Lab Med. 2013;137:289-294.
- Tam HK, Zhang ZF, Jacobson LP, et al. Effect of highly active antiretroviral therapy on survival among HIV-infected men with Kaposi sarcoma or non-Hodgkin lymphoma. Int J Cancer. 2002;98:916-922.
- Nasti G, Martellotta F, Berretta M, et al. Impact of highly active antiretroviral therapy on the presenting features and outcome of patients with acquired immunodeficiency syndrome-related Kaposi sarcoma. Cancer. 2003;98:2440-2446.
- Dupont C, Vasseur E, Beauchet A, et al. Long-term efficacy on Kaposi’s sarcoma of highly active antriretroviral therapy in a cohort of HIV-positive patients. AIDS. 2000;14:987-993.
Practice Points
- Visceral Kaposi sarcoma (KS) should be considered in patients with unexplained systemic symptoms in the setting of poorly controlled human immunodeficiency virus (HIV).
- If cutaneous KS is diagnosed in an HIV patient, a detailed history and physical examination should be undertaken to evaluate for signs of systemic disease.