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Don’t let a foodborne illness dampen the holiday season
According to the Centers for Disease Control and Prevention, a foodborne disease occurs in one in six persons (48 million), resulting in 128,000 hospitalizations and 3,000 deaths annually in the United States. The Foodborne Active Surveillance Network (FoodNet) of the CDC’s Emerging Infections Program monitors cases of eight laboratory diagnosed infections from 10 U.S. sites (covering 15% of the U.S. population). Monitored organisms include Campylobacter, Cyclospora, Listeria, Salmonella, Shiga toxin–producing Escherichia coli (STEC), Shigella, Vibrio, and Yersinia. In 2018, FoodNet identified 25,606 cases of infection, 5,893 hospitalizations, and 120 deaths. The incidence of infection (cases/100,000) was highest for Campylobacter (20), Salmonella (18), STEC (6), Shigella (5), Vibrio (1), Yersinia (0.9), Cyclospora (0.7), and Listeria (0.3). How might these pathogens affect your patients? First, a quick review about the four more common infections. Treatment is beyond the scope of our discussion and you are referred to the 2018-2021 Red Book for assistance. The goal of this column is to prevent your patients from becoming a statistic this holiday season.
Campylobacter
It has been the most common infection reported in FoodNet since 2013. Clinically, patients present with fever, abdominal pain, and nonbloody diarrhea. However, bloody diarrhea maybe the only symptom in neonates and young infants. Abdominal pain can mimic acute appendicitis or intussusception. Bacteremia is rare but has been reported in the elderly and in some patients with underlying conditions. During convalescence, immunoreactive complications including Guillain-Barré syndrome, reactive arthritis, and erythema nodosum may occur. In patients with diarrhea, Campylobacter jejuni and C. coli are the most frequently isolated species.
Campylobacter is present in the intestinal tract of both domestic and wild birds and animals. Transmission is via consumption of contaminated food or water. Undercooked poultry, untreated water, and unpasteurized milk are the three main vehicles of transmission. Campylobacter can be isolated in stool and blood, however isolation from stool requires special media. Rehydration is the primary therapy. Use of azithromycin or erythromycin can shorten both the duration of symptoms and bacterial shedding.
Salmonella
Nontyphoidal salmonella (NTS) are responsible for a variety of infections including asymptomatic carriage, gastroenteritis, bacteremia, and serious focal infections. Gastroenteritis is the most common illness and is manifested as diarrhea, abdominal pain, and fever. If bacteremia occurs, up to 10% of patients will develop focal infections. Invasive disease occurs most frequently in infants, persons with hemoglobinopathies, immunosuppressive disorders, and malignancies. The genus Salmonella is divided into two species, S. enterica and S. bongori with S. enterica subspecies accounting for about half of culture-confirmed Salmonella isolates reported by public health laboratories.
Although infections are more common in the summer, infections can occur year-round. In 2018, the CDC investigated at least 15 food-related NTS outbreaks and 6 have been investigated so far in 2019. In industrialized countries, acquisition usually occurs from ingestion of poultry, eggs, and milk products. Infection also has been reported after animal contact and consumption of fresh produce, meats, and contaminated water. Ground beef is the source of the November 2019 outbreak of S. dublin. Diarrhea develops within 12-72 hours. Salmonella can be isolated from stool, blood, and urine. Treatment usually is not indicated for uncomplicated gastroenteritis. While benefit has not been proven, it is recommended for those at increased risk for developing invasive disease.
Shigella
Shigella is the classic cause of colonic or dysenteric diarrhea. Humans are the primary hosts but other primates can be infected. Transmission occurs through direct person-to-person spread, from ingestion of contaminated food and water, and contact with contaminated inanimate objects. Bacteria can survive up to 6 months in food and 30 days in water. As few as 10 organisms can initiate disease. Typically mucoid or bloody diarrhea with abdominal cramps and fever occurs 1-7 days following exposure. Isolation is from stool. Bacteremia is unusual. Therapy is recommended for severe disease.
Shiga toxin–producing Escherichia coli (STEC)
STEC causes hemorrhagic colitis, which can be complicated by hemolytic uremic syndrome. While E. coli O157:H7 is the serotype most often implicated, other serotypes can cause disease. STEC is shed in feces of cattle and other animals. Infection most often is associated with ingestion of undercooked ground beef, but outbreaks also have confirmed that contaminated leafy vegetables, drinking water, peanut butter, and unpasteurized milk have been the source. Symptoms usually develop 3 to 4 days after exposure. Stools initially may be nonbloody. Abdominal pain and bloody diarrhea occur over the next 2-3 days. Fever often is absent or low grade. Stools should be sent for culture and Shiga toxin for diagnosis. Antimicrobial treatment generally is not warranted if STEC is suspected or diagnosed.
Prevention
It seems so simple. Here are the basic guidelines:
- Clean. Wash hands and surfaces frequently.
- Separate. Separate raw meats and eggs from other foods.
- Cook. Cook all meats to the right temperature.
- Chill. Refrigerate food properly.
Finally, two comments about food poisoning:
Abrupt onset of nausea, vomiting and abdominal cramping due to staphylococcal food poisoning begins 30 minutes to 6 hours after ingestion of food contaminated by enterotoxigenic strains of Staphylococcus aureus which is usually introduced by a food preparer with a purulent lesion. Food left at room temperature allows bacteria to multiply and produce a heat stable toxin. Individuals with purulent lesions of the hands, face, eyes, or nose should not be involved with food preparation.
Clostridium perfringens is the second most common bacterial cause of food poisoning. Symptoms (watery diarrhea and cramping) begin 6-24 hours after ingestion of C. perfringens spores not killed during cooking, which now have multiplied in food left at room temperature that was inadequately reheated. Illness is caused by the production of enterotoxin in the intestine. Outbreaks occur most often in November and December.
This article was updated on 11/12/19.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].
Information sources
1. foodsafety.gov
2. cdc.gov/foodsafety
3. The United States Department of Agriculture Meat and Poultry Hotline: 888-674-6854
4. Appendix VII: Clinical syndromes associated with foodborne diseases, Red Book online, 31st ed. (Washington DC: Red Book online, 2018, pp. 1086-92).
5. Foodkeeper App available at the App store. Provides appropriate food storage information; food recalls also are available.
According to the Centers for Disease Control and Prevention, a foodborne disease occurs in one in six persons (48 million), resulting in 128,000 hospitalizations and 3,000 deaths annually in the United States. The Foodborne Active Surveillance Network (FoodNet) of the CDC’s Emerging Infections Program monitors cases of eight laboratory diagnosed infections from 10 U.S. sites (covering 15% of the U.S. population). Monitored organisms include Campylobacter, Cyclospora, Listeria, Salmonella, Shiga toxin–producing Escherichia coli (STEC), Shigella, Vibrio, and Yersinia. In 2018, FoodNet identified 25,606 cases of infection, 5,893 hospitalizations, and 120 deaths. The incidence of infection (cases/100,000) was highest for Campylobacter (20), Salmonella (18), STEC (6), Shigella (5), Vibrio (1), Yersinia (0.9), Cyclospora (0.7), and Listeria (0.3). How might these pathogens affect your patients? First, a quick review about the four more common infections. Treatment is beyond the scope of our discussion and you are referred to the 2018-2021 Red Book for assistance. The goal of this column is to prevent your patients from becoming a statistic this holiday season.
Campylobacter
It has been the most common infection reported in FoodNet since 2013. Clinically, patients present with fever, abdominal pain, and nonbloody diarrhea. However, bloody diarrhea maybe the only symptom in neonates and young infants. Abdominal pain can mimic acute appendicitis or intussusception. Bacteremia is rare but has been reported in the elderly and in some patients with underlying conditions. During convalescence, immunoreactive complications including Guillain-Barré syndrome, reactive arthritis, and erythema nodosum may occur. In patients with diarrhea, Campylobacter jejuni and C. coli are the most frequently isolated species.
Campylobacter is present in the intestinal tract of both domestic and wild birds and animals. Transmission is via consumption of contaminated food or water. Undercooked poultry, untreated water, and unpasteurized milk are the three main vehicles of transmission. Campylobacter can be isolated in stool and blood, however isolation from stool requires special media. Rehydration is the primary therapy. Use of azithromycin or erythromycin can shorten both the duration of symptoms and bacterial shedding.
Salmonella
Nontyphoidal salmonella (NTS) are responsible for a variety of infections including asymptomatic carriage, gastroenteritis, bacteremia, and serious focal infections. Gastroenteritis is the most common illness and is manifested as diarrhea, abdominal pain, and fever. If bacteremia occurs, up to 10% of patients will develop focal infections. Invasive disease occurs most frequently in infants, persons with hemoglobinopathies, immunosuppressive disorders, and malignancies. The genus Salmonella is divided into two species, S. enterica and S. bongori with S. enterica subspecies accounting for about half of culture-confirmed Salmonella isolates reported by public health laboratories.
Although infections are more common in the summer, infections can occur year-round. In 2018, the CDC investigated at least 15 food-related NTS outbreaks and 6 have been investigated so far in 2019. In industrialized countries, acquisition usually occurs from ingestion of poultry, eggs, and milk products. Infection also has been reported after animal contact and consumption of fresh produce, meats, and contaminated water. Ground beef is the source of the November 2019 outbreak of S. dublin. Diarrhea develops within 12-72 hours. Salmonella can be isolated from stool, blood, and urine. Treatment usually is not indicated for uncomplicated gastroenteritis. While benefit has not been proven, it is recommended for those at increased risk for developing invasive disease.
Shigella
Shigella is the classic cause of colonic or dysenteric diarrhea. Humans are the primary hosts but other primates can be infected. Transmission occurs through direct person-to-person spread, from ingestion of contaminated food and water, and contact with contaminated inanimate objects. Bacteria can survive up to 6 months in food and 30 days in water. As few as 10 organisms can initiate disease. Typically mucoid or bloody diarrhea with abdominal cramps and fever occurs 1-7 days following exposure. Isolation is from stool. Bacteremia is unusual. Therapy is recommended for severe disease.
Shiga toxin–producing Escherichia coli (STEC)
STEC causes hemorrhagic colitis, which can be complicated by hemolytic uremic syndrome. While E. coli O157:H7 is the serotype most often implicated, other serotypes can cause disease. STEC is shed in feces of cattle and other animals. Infection most often is associated with ingestion of undercooked ground beef, but outbreaks also have confirmed that contaminated leafy vegetables, drinking water, peanut butter, and unpasteurized milk have been the source. Symptoms usually develop 3 to 4 days after exposure. Stools initially may be nonbloody. Abdominal pain and bloody diarrhea occur over the next 2-3 days. Fever often is absent or low grade. Stools should be sent for culture and Shiga toxin for diagnosis. Antimicrobial treatment generally is not warranted if STEC is suspected or diagnosed.
Prevention
It seems so simple. Here are the basic guidelines:
- Clean. Wash hands and surfaces frequently.
- Separate. Separate raw meats and eggs from other foods.
- Cook. Cook all meats to the right temperature.
- Chill. Refrigerate food properly.
Finally, two comments about food poisoning:
Abrupt onset of nausea, vomiting and abdominal cramping due to staphylococcal food poisoning begins 30 minutes to 6 hours after ingestion of food contaminated by enterotoxigenic strains of Staphylococcus aureus which is usually introduced by a food preparer with a purulent lesion. Food left at room temperature allows bacteria to multiply and produce a heat stable toxin. Individuals with purulent lesions of the hands, face, eyes, or nose should not be involved with food preparation.
Clostridium perfringens is the second most common bacterial cause of food poisoning. Symptoms (watery diarrhea and cramping) begin 6-24 hours after ingestion of C. perfringens spores not killed during cooking, which now have multiplied in food left at room temperature that was inadequately reheated. Illness is caused by the production of enterotoxin in the intestine. Outbreaks occur most often in November and December.
This article was updated on 11/12/19.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].
Information sources
1. foodsafety.gov
2. cdc.gov/foodsafety
3. The United States Department of Agriculture Meat and Poultry Hotline: 888-674-6854
4. Appendix VII: Clinical syndromes associated with foodborne diseases, Red Book online, 31st ed. (Washington DC: Red Book online, 2018, pp. 1086-92).
5. Foodkeeper App available at the App store. Provides appropriate food storage information; food recalls also are available.
According to the Centers for Disease Control and Prevention, a foodborne disease occurs in one in six persons (48 million), resulting in 128,000 hospitalizations and 3,000 deaths annually in the United States. The Foodborne Active Surveillance Network (FoodNet) of the CDC’s Emerging Infections Program monitors cases of eight laboratory diagnosed infections from 10 U.S. sites (covering 15% of the U.S. population). Monitored organisms include Campylobacter, Cyclospora, Listeria, Salmonella, Shiga toxin–producing Escherichia coli (STEC), Shigella, Vibrio, and Yersinia. In 2018, FoodNet identified 25,606 cases of infection, 5,893 hospitalizations, and 120 deaths. The incidence of infection (cases/100,000) was highest for Campylobacter (20), Salmonella (18), STEC (6), Shigella (5), Vibrio (1), Yersinia (0.9), Cyclospora (0.7), and Listeria (0.3). How might these pathogens affect your patients? First, a quick review about the four more common infections. Treatment is beyond the scope of our discussion and you are referred to the 2018-2021 Red Book for assistance. The goal of this column is to prevent your patients from becoming a statistic this holiday season.
Campylobacter
It has been the most common infection reported in FoodNet since 2013. Clinically, patients present with fever, abdominal pain, and nonbloody diarrhea. However, bloody diarrhea maybe the only symptom in neonates and young infants. Abdominal pain can mimic acute appendicitis or intussusception. Bacteremia is rare but has been reported in the elderly and in some patients with underlying conditions. During convalescence, immunoreactive complications including Guillain-Barré syndrome, reactive arthritis, and erythema nodosum may occur. In patients with diarrhea, Campylobacter jejuni and C. coli are the most frequently isolated species.
Campylobacter is present in the intestinal tract of both domestic and wild birds and animals. Transmission is via consumption of contaminated food or water. Undercooked poultry, untreated water, and unpasteurized milk are the three main vehicles of transmission. Campylobacter can be isolated in stool and blood, however isolation from stool requires special media. Rehydration is the primary therapy. Use of azithromycin or erythromycin can shorten both the duration of symptoms and bacterial shedding.
Salmonella
Nontyphoidal salmonella (NTS) are responsible for a variety of infections including asymptomatic carriage, gastroenteritis, bacteremia, and serious focal infections. Gastroenteritis is the most common illness and is manifested as diarrhea, abdominal pain, and fever. If bacteremia occurs, up to 10% of patients will develop focal infections. Invasive disease occurs most frequently in infants, persons with hemoglobinopathies, immunosuppressive disorders, and malignancies. The genus Salmonella is divided into two species, S. enterica and S. bongori with S. enterica subspecies accounting for about half of culture-confirmed Salmonella isolates reported by public health laboratories.
Although infections are more common in the summer, infections can occur year-round. In 2018, the CDC investigated at least 15 food-related NTS outbreaks and 6 have been investigated so far in 2019. In industrialized countries, acquisition usually occurs from ingestion of poultry, eggs, and milk products. Infection also has been reported after animal contact and consumption of fresh produce, meats, and contaminated water. Ground beef is the source of the November 2019 outbreak of S. dublin. Diarrhea develops within 12-72 hours. Salmonella can be isolated from stool, blood, and urine. Treatment usually is not indicated for uncomplicated gastroenteritis. While benefit has not been proven, it is recommended for those at increased risk for developing invasive disease.
Shigella
Shigella is the classic cause of colonic or dysenteric diarrhea. Humans are the primary hosts but other primates can be infected. Transmission occurs through direct person-to-person spread, from ingestion of contaminated food and water, and contact with contaminated inanimate objects. Bacteria can survive up to 6 months in food and 30 days in water. As few as 10 organisms can initiate disease. Typically mucoid or bloody diarrhea with abdominal cramps and fever occurs 1-7 days following exposure. Isolation is from stool. Bacteremia is unusual. Therapy is recommended for severe disease.
Shiga toxin–producing Escherichia coli (STEC)
STEC causes hemorrhagic colitis, which can be complicated by hemolytic uremic syndrome. While E. coli O157:H7 is the serotype most often implicated, other serotypes can cause disease. STEC is shed in feces of cattle and other animals. Infection most often is associated with ingestion of undercooked ground beef, but outbreaks also have confirmed that contaminated leafy vegetables, drinking water, peanut butter, and unpasteurized milk have been the source. Symptoms usually develop 3 to 4 days after exposure. Stools initially may be nonbloody. Abdominal pain and bloody diarrhea occur over the next 2-3 days. Fever often is absent or low grade. Stools should be sent for culture and Shiga toxin for diagnosis. Antimicrobial treatment generally is not warranted if STEC is suspected or diagnosed.
Prevention
It seems so simple. Here are the basic guidelines:
- Clean. Wash hands and surfaces frequently.
- Separate. Separate raw meats and eggs from other foods.
- Cook. Cook all meats to the right temperature.
- Chill. Refrigerate food properly.
Finally, two comments about food poisoning:
Abrupt onset of nausea, vomiting and abdominal cramping due to staphylococcal food poisoning begins 30 minutes to 6 hours after ingestion of food contaminated by enterotoxigenic strains of Staphylococcus aureus which is usually introduced by a food preparer with a purulent lesion. Food left at room temperature allows bacteria to multiply and produce a heat stable toxin. Individuals with purulent lesions of the hands, face, eyes, or nose should not be involved with food preparation.
Clostridium perfringens is the second most common bacterial cause of food poisoning. Symptoms (watery diarrhea and cramping) begin 6-24 hours after ingestion of C. perfringens spores not killed during cooking, which now have multiplied in food left at room temperature that was inadequately reheated. Illness is caused by the production of enterotoxin in the intestine. Outbreaks occur most often in November and December.
This article was updated on 11/12/19.
Dr. Word is a pediatric infectious disease specialist and director of the Houston Travel Medicine Clinic. She said she had no relevant financial disclosures. Email her at [email protected].
Information sources
1. foodsafety.gov
2. cdc.gov/foodsafety
3. The United States Department of Agriculture Meat and Poultry Hotline: 888-674-6854
4. Appendix VII: Clinical syndromes associated with foodborne diseases, Red Book online, 31st ed. (Washington DC: Red Book online, 2018, pp. 1086-92).
5. Foodkeeper App available at the App store. Provides appropriate food storage information; food recalls also are available.
Oral vs. IV antibiotic therapy in early treatment of complex bone and joint infections
Background: The standard of care for complex bone and joint infections includes the use of IV antibiotics. A prior meta-analysis suggested that the outcomes for bone and joint infections treated with oral and IV antibiotics are similar.
Study design: Randomized, controlled trial.
Setting: Twenty-six U.K. sites during June 2010–October 2015.
Synopsis: The study enrolled 1,054 adults with bone or joint infections who would have been treated with 6 weeks of IV antibiotics; they were then randomized to receive either IV or oral antibiotics. Treatment regimens were selected by infectious disease specialists. The rate of the primary endpoint, definite treatment failure at 1 year after randomization, was 14.6% in the intravenous group and 13.2% in the oral group. The difference in the risk of definite treatment failure between the two groups was –1.4% (95% confidence interval, –5.6 to 2.9), which met the predefined noninferiority criteria. The use of oral antibiotics also was associated with a shorter hospital stay and fewer complications. The conclusions of the trial are limited by the open-label design. An associated editorial advocated for additional research before widespread change to current treatment recommendations.
Bottom line: Bone and joint infections treated with oral versus IV antibiotics may have similar treatment failure rates.
Citation: Li HK et al. Oral versus intravenous antibiotics for bone and joint infection. N Eng J Med. 2019 Jan 31;380(5):425-36.
Dr. Roy is a hospitalist at Beth Israel Deaconess Medical Center and instructor in medicine at Harvard Medical School.
Background: The standard of care for complex bone and joint infections includes the use of IV antibiotics. A prior meta-analysis suggested that the outcomes for bone and joint infections treated with oral and IV antibiotics are similar.
Study design: Randomized, controlled trial.
Setting: Twenty-six U.K. sites during June 2010–October 2015.
Synopsis: The study enrolled 1,054 adults with bone or joint infections who would have been treated with 6 weeks of IV antibiotics; they were then randomized to receive either IV or oral antibiotics. Treatment regimens were selected by infectious disease specialists. The rate of the primary endpoint, definite treatment failure at 1 year after randomization, was 14.6% in the intravenous group and 13.2% in the oral group. The difference in the risk of definite treatment failure between the two groups was –1.4% (95% confidence interval, –5.6 to 2.9), which met the predefined noninferiority criteria. The use of oral antibiotics also was associated with a shorter hospital stay and fewer complications. The conclusions of the trial are limited by the open-label design. An associated editorial advocated for additional research before widespread change to current treatment recommendations.
Bottom line: Bone and joint infections treated with oral versus IV antibiotics may have similar treatment failure rates.
Citation: Li HK et al. Oral versus intravenous antibiotics for bone and joint infection. N Eng J Med. 2019 Jan 31;380(5):425-36.
Dr. Roy is a hospitalist at Beth Israel Deaconess Medical Center and instructor in medicine at Harvard Medical School.
Background: The standard of care for complex bone and joint infections includes the use of IV antibiotics. A prior meta-analysis suggested that the outcomes for bone and joint infections treated with oral and IV antibiotics are similar.
Study design: Randomized, controlled trial.
Setting: Twenty-six U.K. sites during June 2010–October 2015.
Synopsis: The study enrolled 1,054 adults with bone or joint infections who would have been treated with 6 weeks of IV antibiotics; they were then randomized to receive either IV or oral antibiotics. Treatment regimens were selected by infectious disease specialists. The rate of the primary endpoint, definite treatment failure at 1 year after randomization, was 14.6% in the intravenous group and 13.2% in the oral group. The difference in the risk of definite treatment failure between the two groups was –1.4% (95% confidence interval, –5.6 to 2.9), which met the predefined noninferiority criteria. The use of oral antibiotics also was associated with a shorter hospital stay and fewer complications. The conclusions of the trial are limited by the open-label design. An associated editorial advocated for additional research before widespread change to current treatment recommendations.
Bottom line: Bone and joint infections treated with oral versus IV antibiotics may have similar treatment failure rates.
Citation: Li HK et al. Oral versus intravenous antibiotics for bone and joint infection. N Eng J Med. 2019 Jan 31;380(5):425-36.
Dr. Roy is a hospitalist at Beth Israel Deaconess Medical Center and instructor in medicine at Harvard Medical School.
Tide beginning to turn on vaccine hesitancy
NEW ORLEANS –
The shift began with the measles outbreak in Southern California in late 2014, he said. According to the Centers for Disease Control and Prevention, 125 measles cases with rash that occurred between Dec. 28, 2014, and Feb. 8, 2015, were confirmed in U.S. residents. Of these, 100 were California residents (MMWR. 2015 Feb 20;64[06];153-4).
“This outbreak spread ultimately to 25 states and involved 189 people,” Dr. Offit said at the annual meeting of the American Academy of Pediatrics. “It was in the news almost every day. As a consequence, there were measles outbreaks in New York, New Jersey, Florida, Oregon, and Texas, and Washington, which began to turn the public sentiment against the antivaccine movement.”
Even longstanding skeptics are changing their tune. Dr. Offit, professor of pediatrics in the division of infectious diseases at the Children’s Hospital of Philadelphia, cited a recent study from the Autism Science Foundation which found that 85% of parents of children with autism spectrum disorder don’t believe that vaccines cause the condition. “Although there will be parents who continue to believe that vaccines cause autism, most parents of children with autism don’t believe that,” he said. “Also, it’s a little hard to make your case that vaccines are dangerous and that you shouldn’t get them in the midst of outbreaks.”
Perhaps the greatest pushback against antivaccination efforts has been made in the legal arena. In 2019 alone, legislators in California banned parents from not vaccinating their kids because of personal beliefs, while lawmakers in New York repealed the religious exemption to vaccinate, those in Maine repealed the religious and philosophical exemption, those in New Jersey required detailed written explanation for religious exemption, and those in Washington State repealed the philosophical exemption for the MMR vaccine.
Pushback also is apparent on various social media platforms. For example, Dr. Offit said, Pinterest restricts vaccine search results to curb the spread of misinformation, YouTube removes ads from antivaccine channels, Amazon Prime has pulled antivaccination documentaries from its video service, and Facebook has taken steps to curb misinformation about vaccines. “With outbreaks and with children suffering, the media and public sentiment has largely turned against those who are vehemently against vaccines,” he said. “I’m talking about an angry, politically connected, lawyer-backed group of people who are conspiracy theorists, [those] who no matter what you say, they’re going to believe there’s a conspiracy theory to hurt their children and not believe you. When that group becomes big enough and you start to see outbreaks like we’ve seen, then it becomes an issue. That’s where it comes down to legislation. Is it your inalienable right as a U.S. citizen to allow your child to catch and transmit a potentially fatal infection? That’s what we’re struggling with now.”
When meeting with parents who are skeptical about vaccines or refuse their children to have them, Dr. Offit advises clinicians to “go down swinging” in favor of vaccination. He shared how his wife, Bonnie, a pediatrician who practices in suburban Philadelphia, counsels parents who raise such concerns. “The way she handled it initially was to do the best she could to eventually get people vaccinated,” he said. “She was successful about one-quarter of the time. Then she drew a line. She started saying to parents, ‘Look; don’t put me in a position where you are asking me to practice substandard care. I can’t send them out of this room knowing that there’s more measles out there, knowing that there’s mumps out there, knowing that there’s whooping cough out there, knowing that there’s pneumococcus and varicella out there. If this child leaves this office and is hurt by any of those viruses or bacteria and I knew I could have done something to prevent it, I couldn’t live with myself. If you’re going to let this child out without being vaccinated I can’t see you anymore because I’m responsible for the health of this child.’ With that [approach], she has been far more successful. Because at some level, if you continue to see that patient, you’re tacitly agreeing that it’s okay to [not vaccinate].”
In 2000, Dr. Offit and colleagues created the Vaccine Education Center at Children’s Hospital of Philadelphia, which provides complete, up-to-date, and reliable information about vaccines to parents and clinicians. It summarizes the purpose of each vaccine, and the relative risks and benefits in easy-to-read language. The CDC also maintains updated information about vaccines and immunizations on its web site. For his part, Dr. Offit tells parents that passing on an opportunity to vaccinate their child is not a risk-free choice. “If you choose not to get a vaccine you probably will get away with it, but you might not,” he said. “You are playing a game of Russian roulette. It may not be five empty chambers and one bullet, but maybe it’s 100,000 empty chambers and one bullet. There’s a bullet there.”
Dr. Offit reported having no relevant financial disclosures.
NEW ORLEANS –
The shift began with the measles outbreak in Southern California in late 2014, he said. According to the Centers for Disease Control and Prevention, 125 measles cases with rash that occurred between Dec. 28, 2014, and Feb. 8, 2015, were confirmed in U.S. residents. Of these, 100 were California residents (MMWR. 2015 Feb 20;64[06];153-4).
“This outbreak spread ultimately to 25 states and involved 189 people,” Dr. Offit said at the annual meeting of the American Academy of Pediatrics. “It was in the news almost every day. As a consequence, there were measles outbreaks in New York, New Jersey, Florida, Oregon, and Texas, and Washington, which began to turn the public sentiment against the antivaccine movement.”
Even longstanding skeptics are changing their tune. Dr. Offit, professor of pediatrics in the division of infectious diseases at the Children’s Hospital of Philadelphia, cited a recent study from the Autism Science Foundation which found that 85% of parents of children with autism spectrum disorder don’t believe that vaccines cause the condition. “Although there will be parents who continue to believe that vaccines cause autism, most parents of children with autism don’t believe that,” he said. “Also, it’s a little hard to make your case that vaccines are dangerous and that you shouldn’t get them in the midst of outbreaks.”
Perhaps the greatest pushback against antivaccination efforts has been made in the legal arena. In 2019 alone, legislators in California banned parents from not vaccinating their kids because of personal beliefs, while lawmakers in New York repealed the religious exemption to vaccinate, those in Maine repealed the religious and philosophical exemption, those in New Jersey required detailed written explanation for religious exemption, and those in Washington State repealed the philosophical exemption for the MMR vaccine.
Pushback also is apparent on various social media platforms. For example, Dr. Offit said, Pinterest restricts vaccine search results to curb the spread of misinformation, YouTube removes ads from antivaccine channels, Amazon Prime has pulled antivaccination documentaries from its video service, and Facebook has taken steps to curb misinformation about vaccines. “With outbreaks and with children suffering, the media and public sentiment has largely turned against those who are vehemently against vaccines,” he said. “I’m talking about an angry, politically connected, lawyer-backed group of people who are conspiracy theorists, [those] who no matter what you say, they’re going to believe there’s a conspiracy theory to hurt their children and not believe you. When that group becomes big enough and you start to see outbreaks like we’ve seen, then it becomes an issue. That’s where it comes down to legislation. Is it your inalienable right as a U.S. citizen to allow your child to catch and transmit a potentially fatal infection? That’s what we’re struggling with now.”
When meeting with parents who are skeptical about vaccines or refuse their children to have them, Dr. Offit advises clinicians to “go down swinging” in favor of vaccination. He shared how his wife, Bonnie, a pediatrician who practices in suburban Philadelphia, counsels parents who raise such concerns. “The way she handled it initially was to do the best she could to eventually get people vaccinated,” he said. “She was successful about one-quarter of the time. Then she drew a line. She started saying to parents, ‘Look; don’t put me in a position where you are asking me to practice substandard care. I can’t send them out of this room knowing that there’s more measles out there, knowing that there’s mumps out there, knowing that there’s whooping cough out there, knowing that there’s pneumococcus and varicella out there. If this child leaves this office and is hurt by any of those viruses or bacteria and I knew I could have done something to prevent it, I couldn’t live with myself. If you’re going to let this child out without being vaccinated I can’t see you anymore because I’m responsible for the health of this child.’ With that [approach], she has been far more successful. Because at some level, if you continue to see that patient, you’re tacitly agreeing that it’s okay to [not vaccinate].”
In 2000, Dr. Offit and colleagues created the Vaccine Education Center at Children’s Hospital of Philadelphia, which provides complete, up-to-date, and reliable information about vaccines to parents and clinicians. It summarizes the purpose of each vaccine, and the relative risks and benefits in easy-to-read language. The CDC also maintains updated information about vaccines and immunizations on its web site. For his part, Dr. Offit tells parents that passing on an opportunity to vaccinate their child is not a risk-free choice. “If you choose not to get a vaccine you probably will get away with it, but you might not,” he said. “You are playing a game of Russian roulette. It may not be five empty chambers and one bullet, but maybe it’s 100,000 empty chambers and one bullet. There’s a bullet there.”
Dr. Offit reported having no relevant financial disclosures.
NEW ORLEANS –
The shift began with the measles outbreak in Southern California in late 2014, he said. According to the Centers for Disease Control and Prevention, 125 measles cases with rash that occurred between Dec. 28, 2014, and Feb. 8, 2015, were confirmed in U.S. residents. Of these, 100 were California residents (MMWR. 2015 Feb 20;64[06];153-4).
“This outbreak spread ultimately to 25 states and involved 189 people,” Dr. Offit said at the annual meeting of the American Academy of Pediatrics. “It was in the news almost every day. As a consequence, there were measles outbreaks in New York, New Jersey, Florida, Oregon, and Texas, and Washington, which began to turn the public sentiment against the antivaccine movement.”
Even longstanding skeptics are changing their tune. Dr. Offit, professor of pediatrics in the division of infectious diseases at the Children’s Hospital of Philadelphia, cited a recent study from the Autism Science Foundation which found that 85% of parents of children with autism spectrum disorder don’t believe that vaccines cause the condition. “Although there will be parents who continue to believe that vaccines cause autism, most parents of children with autism don’t believe that,” he said. “Also, it’s a little hard to make your case that vaccines are dangerous and that you shouldn’t get them in the midst of outbreaks.”
Perhaps the greatest pushback against antivaccination efforts has been made in the legal arena. In 2019 alone, legislators in California banned parents from not vaccinating their kids because of personal beliefs, while lawmakers in New York repealed the religious exemption to vaccinate, those in Maine repealed the religious and philosophical exemption, those in New Jersey required detailed written explanation for religious exemption, and those in Washington State repealed the philosophical exemption for the MMR vaccine.
Pushback also is apparent on various social media platforms. For example, Dr. Offit said, Pinterest restricts vaccine search results to curb the spread of misinformation, YouTube removes ads from antivaccine channels, Amazon Prime has pulled antivaccination documentaries from its video service, and Facebook has taken steps to curb misinformation about vaccines. “With outbreaks and with children suffering, the media and public sentiment has largely turned against those who are vehemently against vaccines,” he said. “I’m talking about an angry, politically connected, lawyer-backed group of people who are conspiracy theorists, [those] who no matter what you say, they’re going to believe there’s a conspiracy theory to hurt their children and not believe you. When that group becomes big enough and you start to see outbreaks like we’ve seen, then it becomes an issue. That’s where it comes down to legislation. Is it your inalienable right as a U.S. citizen to allow your child to catch and transmit a potentially fatal infection? That’s what we’re struggling with now.”
When meeting with parents who are skeptical about vaccines or refuse their children to have them, Dr. Offit advises clinicians to “go down swinging” in favor of vaccination. He shared how his wife, Bonnie, a pediatrician who practices in suburban Philadelphia, counsels parents who raise such concerns. “The way she handled it initially was to do the best she could to eventually get people vaccinated,” he said. “She was successful about one-quarter of the time. Then she drew a line. She started saying to parents, ‘Look; don’t put me in a position where you are asking me to practice substandard care. I can’t send them out of this room knowing that there’s more measles out there, knowing that there’s mumps out there, knowing that there’s whooping cough out there, knowing that there’s pneumococcus and varicella out there. If this child leaves this office and is hurt by any of those viruses or bacteria and I knew I could have done something to prevent it, I couldn’t live with myself. If you’re going to let this child out without being vaccinated I can’t see you anymore because I’m responsible for the health of this child.’ With that [approach], she has been far more successful. Because at some level, if you continue to see that patient, you’re tacitly agreeing that it’s okay to [not vaccinate].”
In 2000, Dr. Offit and colleagues created the Vaccine Education Center at Children’s Hospital of Philadelphia, which provides complete, up-to-date, and reliable information about vaccines to parents and clinicians. It summarizes the purpose of each vaccine, and the relative risks and benefits in easy-to-read language. The CDC also maintains updated information about vaccines and immunizations on its web site. For his part, Dr. Offit tells parents that passing on an opportunity to vaccinate their child is not a risk-free choice. “If you choose not to get a vaccine you probably will get away with it, but you might not,” he said. “You are playing a game of Russian roulette. It may not be five empty chambers and one bullet, but maybe it’s 100,000 empty chambers and one bullet. There’s a bullet there.”
Dr. Offit reported having no relevant financial disclosures.
EXPERT ANALYSIS FROM AAP 2019
HDV combo therapy reduces viral loads
BOSTON – For most patients with chronic hepatitis D virus (HDV) infection, combination therapy with lonafarnib, ritonavir, and peginterferon may significantly decrease viral loads, based on interim results from the phase IIa LIFT trial.
After 6 months of therapy, more than one-third of evaluable patients (37%) achieved undetectable levels of HDV RNA in serum, according to lead author Christopher Koh, MD, of the National Institute of Diabetes, Digestive and Kidney Diseases at the National Institutes of Health and colleagues.
The open-label LIFT trial, which is ongoing, initially recruited 26 patients with HDV RNA who had serum levels of at least 40 IU/mL (lower limit of quantification). After starting tenofovir or entecavir, patients began a combination regimen of twice-daily oral lonafarnib (50 mg) and ritonavir (100 mg) plus weekly subcutaneous injections of Peginterferon Lambda-1a (180 mcg).
The median patient age was 40 years, with a slightly higher proportion of male participants (60%). Approximately half of the patients were of Asian descent (52%), followed by patients who were white (32%), or African (16%). The investigators reported median baseline measurements of modified histology activity index (9) and Ishak fibrosis stage (3), as well as serum levels of alanine aminotransferase (64 IU/mL), aspartate aminotransferase (47 IU/mL), hepatitis B virus DNA (less than 21 IU/mL), and log HDV RNA (4.74 IU/mL), with this latter measurement serving as a key determinant of efficacy.
After 12 weeks of therapy, the median decrease in HDV RNA among 21 evaluable patients was 3.6 log IU/mL with an interquartile range from 2.6 to 4.2 (P less than .0001). Of these patients, 5 (24%) achieved undetectable levels of HDV RNA, while another 5 tested below the lower limit of quantification.
Following an additional 12 weeks of therapy, 19 patients remained evaluable, among whom the median decrease in HDV RNA was 3.4 log IU/mL with an interquartile range from 2.9 to 4.5 (P less than .0001). Seven of these patients (37%) achieved undetectable HDV RNA, whereas 3 others fell below the lower limit of quantification. Furthermore, 18 out of 19 of these patients (95%) experienced a decline in HDV RNA of more than 2 log IU/mL.
According to the investigators, the trial regimen was safe and well tolerated. Adverse events were mild to moderate; most common were anemia, hyperbilirubinemia, weight loss, and gastrointestinal issues. Doses were reduced in three patients while four others discontinued therapy prematurely.
“These interim results support continued exploration of this therapeutic combination in HDV,” the investigators concluded.
The above findings will be presented in an oral abstract session at the annual meeting of the American Association for the Study of Liver Diseases.
The investigators disclosed relationships with I-Cubed Therapeutics, Eiger BioPharmaceuticals, Riboscience, and others.
SOURCE: Koh C et al. The Liver Meeting 2019. Abstract LO8.
BOSTON – For most patients with chronic hepatitis D virus (HDV) infection, combination therapy with lonafarnib, ritonavir, and peginterferon may significantly decrease viral loads, based on interim results from the phase IIa LIFT trial.
After 6 months of therapy, more than one-third of evaluable patients (37%) achieved undetectable levels of HDV RNA in serum, according to lead author Christopher Koh, MD, of the National Institute of Diabetes, Digestive and Kidney Diseases at the National Institutes of Health and colleagues.
The open-label LIFT trial, which is ongoing, initially recruited 26 patients with HDV RNA who had serum levels of at least 40 IU/mL (lower limit of quantification). After starting tenofovir or entecavir, patients began a combination regimen of twice-daily oral lonafarnib (50 mg) and ritonavir (100 mg) plus weekly subcutaneous injections of Peginterferon Lambda-1a (180 mcg).
The median patient age was 40 years, with a slightly higher proportion of male participants (60%). Approximately half of the patients were of Asian descent (52%), followed by patients who were white (32%), or African (16%). The investigators reported median baseline measurements of modified histology activity index (9) and Ishak fibrosis stage (3), as well as serum levels of alanine aminotransferase (64 IU/mL), aspartate aminotransferase (47 IU/mL), hepatitis B virus DNA (less than 21 IU/mL), and log HDV RNA (4.74 IU/mL), with this latter measurement serving as a key determinant of efficacy.
After 12 weeks of therapy, the median decrease in HDV RNA among 21 evaluable patients was 3.6 log IU/mL with an interquartile range from 2.6 to 4.2 (P less than .0001). Of these patients, 5 (24%) achieved undetectable levels of HDV RNA, while another 5 tested below the lower limit of quantification.
Following an additional 12 weeks of therapy, 19 patients remained evaluable, among whom the median decrease in HDV RNA was 3.4 log IU/mL with an interquartile range from 2.9 to 4.5 (P less than .0001). Seven of these patients (37%) achieved undetectable HDV RNA, whereas 3 others fell below the lower limit of quantification. Furthermore, 18 out of 19 of these patients (95%) experienced a decline in HDV RNA of more than 2 log IU/mL.
According to the investigators, the trial regimen was safe and well tolerated. Adverse events were mild to moderate; most common were anemia, hyperbilirubinemia, weight loss, and gastrointestinal issues. Doses were reduced in three patients while four others discontinued therapy prematurely.
“These interim results support continued exploration of this therapeutic combination in HDV,” the investigators concluded.
The above findings will be presented in an oral abstract session at the annual meeting of the American Association for the Study of Liver Diseases.
The investigators disclosed relationships with I-Cubed Therapeutics, Eiger BioPharmaceuticals, Riboscience, and others.
SOURCE: Koh C et al. The Liver Meeting 2019. Abstract LO8.
BOSTON – For most patients with chronic hepatitis D virus (HDV) infection, combination therapy with lonafarnib, ritonavir, and peginterferon may significantly decrease viral loads, based on interim results from the phase IIa LIFT trial.
After 6 months of therapy, more than one-third of evaluable patients (37%) achieved undetectable levels of HDV RNA in serum, according to lead author Christopher Koh, MD, of the National Institute of Diabetes, Digestive and Kidney Diseases at the National Institutes of Health and colleagues.
The open-label LIFT trial, which is ongoing, initially recruited 26 patients with HDV RNA who had serum levels of at least 40 IU/mL (lower limit of quantification). After starting tenofovir or entecavir, patients began a combination regimen of twice-daily oral lonafarnib (50 mg) and ritonavir (100 mg) plus weekly subcutaneous injections of Peginterferon Lambda-1a (180 mcg).
The median patient age was 40 years, with a slightly higher proportion of male participants (60%). Approximately half of the patients were of Asian descent (52%), followed by patients who were white (32%), or African (16%). The investigators reported median baseline measurements of modified histology activity index (9) and Ishak fibrosis stage (3), as well as serum levels of alanine aminotransferase (64 IU/mL), aspartate aminotransferase (47 IU/mL), hepatitis B virus DNA (less than 21 IU/mL), and log HDV RNA (4.74 IU/mL), with this latter measurement serving as a key determinant of efficacy.
After 12 weeks of therapy, the median decrease in HDV RNA among 21 evaluable patients was 3.6 log IU/mL with an interquartile range from 2.6 to 4.2 (P less than .0001). Of these patients, 5 (24%) achieved undetectable levels of HDV RNA, while another 5 tested below the lower limit of quantification.
Following an additional 12 weeks of therapy, 19 patients remained evaluable, among whom the median decrease in HDV RNA was 3.4 log IU/mL with an interquartile range from 2.9 to 4.5 (P less than .0001). Seven of these patients (37%) achieved undetectable HDV RNA, whereas 3 others fell below the lower limit of quantification. Furthermore, 18 out of 19 of these patients (95%) experienced a decline in HDV RNA of more than 2 log IU/mL.
According to the investigators, the trial regimen was safe and well tolerated. Adverse events were mild to moderate; most common were anemia, hyperbilirubinemia, weight loss, and gastrointestinal issues. Doses were reduced in three patients while four others discontinued therapy prematurely.
“These interim results support continued exploration of this therapeutic combination in HDV,” the investigators concluded.
The above findings will be presented in an oral abstract session at the annual meeting of the American Association for the Study of Liver Diseases.
The investigators disclosed relationships with I-Cubed Therapeutics, Eiger BioPharmaceuticals, Riboscience, and others.
SOURCE: Koh C et al. The Liver Meeting 2019. Abstract LO8.
REPORTING FROM THE LIVER MEETING 2019
Key clinical point: For most patients with chronic hepatitis D virus infection, combination therapy with lonafarnib, ritonavir, and peginterferon may significantly decrease viral loads.
Major finding: After 6 months of therapy, 37% of evaluable patients achieved undetectable levels of hepatitis D virus RNA.
Study details: The phase IIa open-label LIFT trial involving 26 patients with chronic hepatitis delta virus (HDV).
Disclosures: The investigators disclosed relationships with I-Cubed Therapeutics, Eiger BioPharmaceuticals, Riboscience, and others.
Source: Koh C et al. The Liver Meeting 2019. Abstract LO8.
Hepatitis C vaccine alters viral trajectory, but fails in chronic infection protection
BOSTON – A prime-boost hepatitis C virus (HCV) vaccine regimen did not protect against chronic infection, but it did evoke immune responses and differences in viral trajectory, according to investigators in what is believed to be the first randomized, placebo-controlled efficacy trial in this setting.
There were no apparent safety concerns with the vaccine according to investigators, led by Kimberly Page, PhD, MPH, of the University of New Mexico, Albuquerque.
“A safe and effective vaccine to prevent chronic hepatitis C virus infection is essential to reduce transmission,” Dr. Page and coauthors said in a late-breaking abstract of the study results, which will be presented at the annual meeting of the American Association for the Study of Liver Diseases.
The phase 1/2 trial described by Dr. Page and colleagues included 455 adults at risk of HCV infection because of injection drug use. They were randomized to vaccine, which consisted of a recombinant chimpanzee adenovirus-3 vectored vaccine prime plus a recombinant Modified Vaccinia virus Ankara boost, or to two doses of placebo at days 0 and 56 of the study.
There was no difference in chronic HCV infection at 6 months, the primary endpoint of the study. There were 14 chronically infected participants in the vaccine group, as well as 14 in the placebo group, for an overall incidence of infection of 13.0/100 person-years, Dr. Page and coauthors reported in the abstract.
However, there were significant differences in HCV RNA geometric mean peak at 1 month, which was 193,795 IU/L in the vaccine group and 1,078,092 IU/L in the placebo group, according to investigators. Similarly, geometric mean fold rise after infection was 0.2 in the vaccine group and 13.5 in the placebo group.
A total of 78% of vaccinated individuals had T-cell responses to at least one vaccine antigen pool, investigators said, adding that the vaccine was safe, well tolerated, and not associated with any serious adverse events.
Dr. Page had no disclosures related to the abstract.
SOURCE: Page K et al. The Liver Meeting 2019. Abstract LP17.
BOSTON – A prime-boost hepatitis C virus (HCV) vaccine regimen did not protect against chronic infection, but it did evoke immune responses and differences in viral trajectory, according to investigators in what is believed to be the first randomized, placebo-controlled efficacy trial in this setting.
There were no apparent safety concerns with the vaccine according to investigators, led by Kimberly Page, PhD, MPH, of the University of New Mexico, Albuquerque.
“A safe and effective vaccine to prevent chronic hepatitis C virus infection is essential to reduce transmission,” Dr. Page and coauthors said in a late-breaking abstract of the study results, which will be presented at the annual meeting of the American Association for the Study of Liver Diseases.
The phase 1/2 trial described by Dr. Page and colleagues included 455 adults at risk of HCV infection because of injection drug use. They were randomized to vaccine, which consisted of a recombinant chimpanzee adenovirus-3 vectored vaccine prime plus a recombinant Modified Vaccinia virus Ankara boost, or to two doses of placebo at days 0 and 56 of the study.
There was no difference in chronic HCV infection at 6 months, the primary endpoint of the study. There were 14 chronically infected participants in the vaccine group, as well as 14 in the placebo group, for an overall incidence of infection of 13.0/100 person-years, Dr. Page and coauthors reported in the abstract.
However, there were significant differences in HCV RNA geometric mean peak at 1 month, which was 193,795 IU/L in the vaccine group and 1,078,092 IU/L in the placebo group, according to investigators. Similarly, geometric mean fold rise after infection was 0.2 in the vaccine group and 13.5 in the placebo group.
A total of 78% of vaccinated individuals had T-cell responses to at least one vaccine antigen pool, investigators said, adding that the vaccine was safe, well tolerated, and not associated with any serious adverse events.
Dr. Page had no disclosures related to the abstract.
SOURCE: Page K et al. The Liver Meeting 2019. Abstract LP17.
BOSTON – A prime-boost hepatitis C virus (HCV) vaccine regimen did not protect against chronic infection, but it did evoke immune responses and differences in viral trajectory, according to investigators in what is believed to be the first randomized, placebo-controlled efficacy trial in this setting.
There were no apparent safety concerns with the vaccine according to investigators, led by Kimberly Page, PhD, MPH, of the University of New Mexico, Albuquerque.
“A safe and effective vaccine to prevent chronic hepatitis C virus infection is essential to reduce transmission,” Dr. Page and coauthors said in a late-breaking abstract of the study results, which will be presented at the annual meeting of the American Association for the Study of Liver Diseases.
The phase 1/2 trial described by Dr. Page and colleagues included 455 adults at risk of HCV infection because of injection drug use. They were randomized to vaccine, which consisted of a recombinant chimpanzee adenovirus-3 vectored vaccine prime plus a recombinant Modified Vaccinia virus Ankara boost, or to two doses of placebo at days 0 and 56 of the study.
There was no difference in chronic HCV infection at 6 months, the primary endpoint of the study. There were 14 chronically infected participants in the vaccine group, as well as 14 in the placebo group, for an overall incidence of infection of 13.0/100 person-years, Dr. Page and coauthors reported in the abstract.
However, there were significant differences in HCV RNA geometric mean peak at 1 month, which was 193,795 IU/L in the vaccine group and 1,078,092 IU/L in the placebo group, according to investigators. Similarly, geometric mean fold rise after infection was 0.2 in the vaccine group and 13.5 in the placebo group.
A total of 78% of vaccinated individuals had T-cell responses to at least one vaccine antigen pool, investigators said, adding that the vaccine was safe, well tolerated, and not associated with any serious adverse events.
Dr. Page had no disclosures related to the abstract.
SOURCE: Page K et al. The Liver Meeting 2019. Abstract LP17.
REPORTING FROM THE LIVER MEETING 2019
Key clinical point: A prime-boost HCV vaccine altered viral trajectory but did not protect against chronic infection.
Major finding: At 6 months after vaccination, there were 14 chronically infected participants in the vaccine group, and 14 in the placebo group.
Study details: A randomized, placebo controlled phase 1/2 trial including 455 adults at risk of HCV infection.
Disclosures: The first author reported no disclosures.
Source: Page K et al. The Liver Meeting 2019. Abstract LP17.
45-year-old woman • fever and chills • diffuse abdominal pain • shortness of breath • Dx?
THE CASE
A 45-year-old white woman presented to our emergency department (ED) with a 3-day history of fever, chills, diffuse abdominal pain, severe headache, and shortness of breath.
The patient’s medical and surgical history was notable for acromegaly secondary to pituitary microadenoma, pituitary resection, and complete thyroidectomy 4 years earlier. Her medications included lanreotide, levothyroxine, gabapentin, alprazolam, and zolpidem. She had no history of cardiac disease, diabetes mellitus, immunodeficiency, or injection drug use. Three months prior to presenting to the ED, she underwent an outpatient gynecologic procedure for insertion of a levonorgestrel-releasing intrauterine device (IUD) for menorrhagia.
In the ED, the patient had a fever (101.5°F) and an elevated white blood cell count of 13,600/mm3 (reference range, 4,000–10,000/mm3). Cardiac auscultation revealed a regular heart rate and rhythm, with normal S1 and S2 sounds without murmur. Electrocardiogram documented normal sinus rhythm with no abnormalities. The physical examination revealed a diffusely tender lower abdomen without rebound or guarding. A pelvic examination was not conducted, and there was no collection of a vaginal swab sample to test for gonorrhea, chlamydia, or group B Streptococcus (GBS). Further workups for infection, including urinalysis, lumbar puncture, and chest x-ray, all yielded normal results.
Shortly after she was discharged from the ED, the patient was called to return to the hospital after blood cultures grew GBS; she was admitted for treatment.
THE DIAGNOSIS
A diagnosis of sepsis secondary to GBS bacteremia was made. However, the source of the GBS bacteremia and the patient’s abdominal symptoms remained unclear. Further workup included computed tomography (CT) of the abdomen, pelvis, and head, and magnetic resonance imaging of the brain; all imaging revealed no acute findings. Blood work (chem-7 panel, complete blood count, human immunodeficiency virus testing) was unremarkable except for an elevated level of C-reactive protein of 90 mg/L (reference range, 0–10 mg/L).
Radiography confirmed that the IUD was in the correct intrauterine position. However, transesophageal echocardiography (TEE) showed vegetations on the mitral and aortic valves, with preserved cardiac function. A diagnosis of GBS endocarditis was made, and infectious disease specialists were consulted. Because the patient had an anaphylactic allergy to penicillin, she was treated with intravenous vancomycin for 4 weeks. One month later, she had the IUD removed because of persistent abdominal pain.
DISCUSSION
Although the source of GBS bacteremia and endocarditis in our patient remained nondefinitive, the recent insertion of the IUD continued to be the suspected source and leading diagnosis.
Continue to: Other sources of GBS bacteremia...
Other sources of GBS bacteremia were unlikely based on the examination and imaging results. The patient’s abdominal exam was benign, and no intra-abdominal abscess was detected on CT. Although Streptococcus viridans, S bovis, and enterococcus are far more common pathogens for infective endocarditis,1 there was no evidence of dental caries, gastrointestinal pathology, or urinary tract infection to suggest misidentification of bacteria.
Theoretically, GBS bacteremia after a gynecologic procedure is possible since GBS frequently colonizes the vagina.2 However, most reports document transient rather than persistent bacteremia and/or endocarditis.3,4
IUD insertion as a cause of bacteremia. The medical literature offers scant evidence of endocarditis or severe GBS bacteremia related to IUD insertion. Of 124 gynecology-related reports of infective endocarditis between 1946 and 1986, only 3 were associated with IUDs.5 All 3 women had underlying cardiac disease, and 2 of the 3 had identifiable pelvic infections.5
Among 12 case reports of endocarditis related to gynecologic procedures from 1985 to 2003, therapeutic abortion was the most common antecedent event, and no cases were related to IUD insertion.2 Compared with cases reported before 1985, in these cases most patients (64%) did not have underlying valvular disease, and most had a subacute course with low mortality but high morbidity (8 of 11 patients had clinically significant emboli).2 The study authors also mentioned a case of endocarditis following a Pap smear test, suggesting that minimally invasive procedures may result in infective endocarditis.2
THE TAKEAWAY
Our patient presented with fever, fatigue, and abdominal pain in the setting of recent IUD insertion. She was found to have GBS bacteremia with endocarditis based on TEE and positive blood culture growth. Her clinical situation was suspicious for a gynecologic source of bacteremia.
Continue to: There is no definitive way...
There is no definitive way to confirm that IUD insertion 3 months prior caused the GBS bacteremia. However, this case illustrates that it is important to consider a usually benign gynecologic procedure as the source of clinically significant persistent bacteremia.
Evidence is insufficient to recommend prophylactic antibiotic use prior to a gynecologic procedure, and it is not recommended by current practice guidelines of the American College of Obstetricians and Gynecologists or the European Society of Cardiology.6,7
This patient case raises our suspicion for IUD-related bacteremia as an adverse reaction in healthy women with recent IUD insertion who present with fever and diffuse abdominal pain without apparent signs of a pelvic infection. Prompt antibiotic treatment is necessary to prevent significant morbidity and mortality.
CORRESPONDENCE
Lauren Cowen, MD, 777 South Clinton Avenue, Rochester, NY 14620; [email protected]
1. Baddour LM, Wilson WR, Bayer AS, et al; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015;132:1435-1486.
2. Crespo A, Retter AS, Lorber B. Group B streptococcal endocarditis in obstetric and gynecologic practice. Infect Dis Obstet Gynecol. 2003;11:109-115.
3. Murray S, Hickey JB, Houang E. Significant bacteremia associated with replacement of intrauterine contraceptive device. Am J Obstet Gynecol. 1987;156:698-700.
4. Everett ED, Reller LB, Droegemueller W, et al. Absence of bacteremia after insertion or removal of intrauterine devices. Obstet Gynecol. 1976;47:207-209.
5. Seaworth BJ, Durack DT. Infective endocarditis in obstetric and gynecologic practice. Am J Obstet Gynecol. 1986;154:180-188.
6. ACOG Committee on Practice Bulletins–Gynecology. Practice bulletin no. 186: Long-acting reversible contraception: implants and intrauterine devices. Obstet Gynecol. 2017;130:e251-e269.
7. Habib G, Lancellotti P, Antunes MJ, et al; ESC Scientific Document Group. 2015 ESC guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J. 2015;36:3075-3128.
THE CASE
A 45-year-old white woman presented to our emergency department (ED) with a 3-day history of fever, chills, diffuse abdominal pain, severe headache, and shortness of breath.
The patient’s medical and surgical history was notable for acromegaly secondary to pituitary microadenoma, pituitary resection, and complete thyroidectomy 4 years earlier. Her medications included lanreotide, levothyroxine, gabapentin, alprazolam, and zolpidem. She had no history of cardiac disease, diabetes mellitus, immunodeficiency, or injection drug use. Three months prior to presenting to the ED, she underwent an outpatient gynecologic procedure for insertion of a levonorgestrel-releasing intrauterine device (IUD) for menorrhagia.
In the ED, the patient had a fever (101.5°F) and an elevated white blood cell count of 13,600/mm3 (reference range, 4,000–10,000/mm3). Cardiac auscultation revealed a regular heart rate and rhythm, with normal S1 and S2 sounds without murmur. Electrocardiogram documented normal sinus rhythm with no abnormalities. The physical examination revealed a diffusely tender lower abdomen without rebound or guarding. A pelvic examination was not conducted, and there was no collection of a vaginal swab sample to test for gonorrhea, chlamydia, or group B Streptococcus (GBS). Further workups for infection, including urinalysis, lumbar puncture, and chest x-ray, all yielded normal results.
Shortly after she was discharged from the ED, the patient was called to return to the hospital after blood cultures grew GBS; she was admitted for treatment.
THE DIAGNOSIS
A diagnosis of sepsis secondary to GBS bacteremia was made. However, the source of the GBS bacteremia and the patient’s abdominal symptoms remained unclear. Further workup included computed tomography (CT) of the abdomen, pelvis, and head, and magnetic resonance imaging of the brain; all imaging revealed no acute findings. Blood work (chem-7 panel, complete blood count, human immunodeficiency virus testing) was unremarkable except for an elevated level of C-reactive protein of 90 mg/L (reference range, 0–10 mg/L).
Radiography confirmed that the IUD was in the correct intrauterine position. However, transesophageal echocardiography (TEE) showed vegetations on the mitral and aortic valves, with preserved cardiac function. A diagnosis of GBS endocarditis was made, and infectious disease specialists were consulted. Because the patient had an anaphylactic allergy to penicillin, she was treated with intravenous vancomycin for 4 weeks. One month later, she had the IUD removed because of persistent abdominal pain.
DISCUSSION
Although the source of GBS bacteremia and endocarditis in our patient remained nondefinitive, the recent insertion of the IUD continued to be the suspected source and leading diagnosis.
Continue to: Other sources of GBS bacteremia...
Other sources of GBS bacteremia were unlikely based on the examination and imaging results. The patient’s abdominal exam was benign, and no intra-abdominal abscess was detected on CT. Although Streptococcus viridans, S bovis, and enterococcus are far more common pathogens for infective endocarditis,1 there was no evidence of dental caries, gastrointestinal pathology, or urinary tract infection to suggest misidentification of bacteria.
Theoretically, GBS bacteremia after a gynecologic procedure is possible since GBS frequently colonizes the vagina.2 However, most reports document transient rather than persistent bacteremia and/or endocarditis.3,4
IUD insertion as a cause of bacteremia. The medical literature offers scant evidence of endocarditis or severe GBS bacteremia related to IUD insertion. Of 124 gynecology-related reports of infective endocarditis between 1946 and 1986, only 3 were associated with IUDs.5 All 3 women had underlying cardiac disease, and 2 of the 3 had identifiable pelvic infections.5
Among 12 case reports of endocarditis related to gynecologic procedures from 1985 to 2003, therapeutic abortion was the most common antecedent event, and no cases were related to IUD insertion.2 Compared with cases reported before 1985, in these cases most patients (64%) did not have underlying valvular disease, and most had a subacute course with low mortality but high morbidity (8 of 11 patients had clinically significant emboli).2 The study authors also mentioned a case of endocarditis following a Pap smear test, suggesting that minimally invasive procedures may result in infective endocarditis.2
THE TAKEAWAY
Our patient presented with fever, fatigue, and abdominal pain in the setting of recent IUD insertion. She was found to have GBS bacteremia with endocarditis based on TEE and positive blood culture growth. Her clinical situation was suspicious for a gynecologic source of bacteremia.
Continue to: There is no definitive way...
There is no definitive way to confirm that IUD insertion 3 months prior caused the GBS bacteremia. However, this case illustrates that it is important to consider a usually benign gynecologic procedure as the source of clinically significant persistent bacteremia.
Evidence is insufficient to recommend prophylactic antibiotic use prior to a gynecologic procedure, and it is not recommended by current practice guidelines of the American College of Obstetricians and Gynecologists or the European Society of Cardiology.6,7
This patient case raises our suspicion for IUD-related bacteremia as an adverse reaction in healthy women with recent IUD insertion who present with fever and diffuse abdominal pain without apparent signs of a pelvic infection. Prompt antibiotic treatment is necessary to prevent significant morbidity and mortality.
CORRESPONDENCE
Lauren Cowen, MD, 777 South Clinton Avenue, Rochester, NY 14620; [email protected]
THE CASE
A 45-year-old white woman presented to our emergency department (ED) with a 3-day history of fever, chills, diffuse abdominal pain, severe headache, and shortness of breath.
The patient’s medical and surgical history was notable for acromegaly secondary to pituitary microadenoma, pituitary resection, and complete thyroidectomy 4 years earlier. Her medications included lanreotide, levothyroxine, gabapentin, alprazolam, and zolpidem. She had no history of cardiac disease, diabetes mellitus, immunodeficiency, or injection drug use. Three months prior to presenting to the ED, she underwent an outpatient gynecologic procedure for insertion of a levonorgestrel-releasing intrauterine device (IUD) for menorrhagia.
In the ED, the patient had a fever (101.5°F) and an elevated white blood cell count of 13,600/mm3 (reference range, 4,000–10,000/mm3). Cardiac auscultation revealed a regular heart rate and rhythm, with normal S1 and S2 sounds without murmur. Electrocardiogram documented normal sinus rhythm with no abnormalities. The physical examination revealed a diffusely tender lower abdomen without rebound or guarding. A pelvic examination was not conducted, and there was no collection of a vaginal swab sample to test for gonorrhea, chlamydia, or group B Streptococcus (GBS). Further workups for infection, including urinalysis, lumbar puncture, and chest x-ray, all yielded normal results.
Shortly after she was discharged from the ED, the patient was called to return to the hospital after blood cultures grew GBS; she was admitted for treatment.
THE DIAGNOSIS
A diagnosis of sepsis secondary to GBS bacteremia was made. However, the source of the GBS bacteremia and the patient’s abdominal symptoms remained unclear. Further workup included computed tomography (CT) of the abdomen, pelvis, and head, and magnetic resonance imaging of the brain; all imaging revealed no acute findings. Blood work (chem-7 panel, complete blood count, human immunodeficiency virus testing) was unremarkable except for an elevated level of C-reactive protein of 90 mg/L (reference range, 0–10 mg/L).
Radiography confirmed that the IUD was in the correct intrauterine position. However, transesophageal echocardiography (TEE) showed vegetations on the mitral and aortic valves, with preserved cardiac function. A diagnosis of GBS endocarditis was made, and infectious disease specialists were consulted. Because the patient had an anaphylactic allergy to penicillin, she was treated with intravenous vancomycin for 4 weeks. One month later, she had the IUD removed because of persistent abdominal pain.
DISCUSSION
Although the source of GBS bacteremia and endocarditis in our patient remained nondefinitive, the recent insertion of the IUD continued to be the suspected source and leading diagnosis.
Continue to: Other sources of GBS bacteremia...
Other sources of GBS bacteremia were unlikely based on the examination and imaging results. The patient’s abdominal exam was benign, and no intra-abdominal abscess was detected on CT. Although Streptococcus viridans, S bovis, and enterococcus are far more common pathogens for infective endocarditis,1 there was no evidence of dental caries, gastrointestinal pathology, or urinary tract infection to suggest misidentification of bacteria.
Theoretically, GBS bacteremia after a gynecologic procedure is possible since GBS frequently colonizes the vagina.2 However, most reports document transient rather than persistent bacteremia and/or endocarditis.3,4
IUD insertion as a cause of bacteremia. The medical literature offers scant evidence of endocarditis or severe GBS bacteremia related to IUD insertion. Of 124 gynecology-related reports of infective endocarditis between 1946 and 1986, only 3 were associated with IUDs.5 All 3 women had underlying cardiac disease, and 2 of the 3 had identifiable pelvic infections.5
Among 12 case reports of endocarditis related to gynecologic procedures from 1985 to 2003, therapeutic abortion was the most common antecedent event, and no cases were related to IUD insertion.2 Compared with cases reported before 1985, in these cases most patients (64%) did not have underlying valvular disease, and most had a subacute course with low mortality but high morbidity (8 of 11 patients had clinically significant emboli).2 The study authors also mentioned a case of endocarditis following a Pap smear test, suggesting that minimally invasive procedures may result in infective endocarditis.2
THE TAKEAWAY
Our patient presented with fever, fatigue, and abdominal pain in the setting of recent IUD insertion. She was found to have GBS bacteremia with endocarditis based on TEE and positive blood culture growth. Her clinical situation was suspicious for a gynecologic source of bacteremia.
Continue to: There is no definitive way...
There is no definitive way to confirm that IUD insertion 3 months prior caused the GBS bacteremia. However, this case illustrates that it is important to consider a usually benign gynecologic procedure as the source of clinically significant persistent bacteremia.
Evidence is insufficient to recommend prophylactic antibiotic use prior to a gynecologic procedure, and it is not recommended by current practice guidelines of the American College of Obstetricians and Gynecologists or the European Society of Cardiology.6,7
This patient case raises our suspicion for IUD-related bacteremia as an adverse reaction in healthy women with recent IUD insertion who present with fever and diffuse abdominal pain without apparent signs of a pelvic infection. Prompt antibiotic treatment is necessary to prevent significant morbidity and mortality.
CORRESPONDENCE
Lauren Cowen, MD, 777 South Clinton Avenue, Rochester, NY 14620; [email protected]
1. Baddour LM, Wilson WR, Bayer AS, et al; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015;132:1435-1486.
2. Crespo A, Retter AS, Lorber B. Group B streptococcal endocarditis in obstetric and gynecologic practice. Infect Dis Obstet Gynecol. 2003;11:109-115.
3. Murray S, Hickey JB, Houang E. Significant bacteremia associated with replacement of intrauterine contraceptive device. Am J Obstet Gynecol. 1987;156:698-700.
4. Everett ED, Reller LB, Droegemueller W, et al. Absence of bacteremia after insertion or removal of intrauterine devices. Obstet Gynecol. 1976;47:207-209.
5. Seaworth BJ, Durack DT. Infective endocarditis in obstetric and gynecologic practice. Am J Obstet Gynecol. 1986;154:180-188.
6. ACOG Committee on Practice Bulletins–Gynecology. Practice bulletin no. 186: Long-acting reversible contraception: implants and intrauterine devices. Obstet Gynecol. 2017;130:e251-e269.
7. Habib G, Lancellotti P, Antunes MJ, et al; ESC Scientific Document Group. 2015 ESC guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J. 2015;36:3075-3128.
1. Baddour LM, Wilson WR, Bayer AS, et al; American Heart Association Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease of the Council on Cardiovascular Disease in the Young, Council on Clinical Cardiology, Council on Cardiovascular Surgery and Anesthesia, and Stroke Council. Infective endocarditis in adults: diagnosis, antimicrobial therapy, and management of complications: a scientific statement for healthcare professionals from the American Heart Association. Circulation. 2015;132:1435-1486.
2. Crespo A, Retter AS, Lorber B. Group B streptococcal endocarditis in obstetric and gynecologic practice. Infect Dis Obstet Gynecol. 2003;11:109-115.
3. Murray S, Hickey JB, Houang E. Significant bacteremia associated with replacement of intrauterine contraceptive device. Am J Obstet Gynecol. 1987;156:698-700.
4. Everett ED, Reller LB, Droegemueller W, et al. Absence of bacteremia after insertion or removal of intrauterine devices. Obstet Gynecol. 1976;47:207-209.
5. Seaworth BJ, Durack DT. Infective endocarditis in obstetric and gynecologic practice. Am J Obstet Gynecol. 1986;154:180-188.
6. ACOG Committee on Practice Bulletins–Gynecology. Practice bulletin no. 186: Long-acting reversible contraception: implants and intrauterine devices. Obstet Gynecol. 2017;130:e251-e269.
7. Habib G, Lancellotti P, Antunes MJ, et al; ESC Scientific Document Group. 2015 ESC guidelines for the management of infective endocarditis: the Task Force for the Management of Infective Endocarditis of the European Society of Cardiology (ESC). Eur Heart J. 2015;36:3075-3128.
Poll: Clostridium difficile
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The correct answer is a.) 1 to 2
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Measles infection linked to impaired ‘immune memory’
Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.
The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.
“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.
“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”
In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 the children experienced mild measles, and 43 had severe measles.
They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.
This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.
The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.
Dr. Mina and associates wrote.
They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.
In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.
Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).
In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.
The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.
As a result of reduced vaccination, after decades of decline, the number of worldwide cases of measles has increased by nearly 300% since 2018. Epidemiologic evidence has associated measles infections with increases in morbidity and mortality for as long as 5 years after the infection and suggests that, in the prevaccine era, measles virus may have been associated with up to 50% of all childhood deaths, mostly because of nonmeasles infections. Measles replication in immune cells has been hypothesized to impair immune memory, potentially causing what some scientists call “immunological amnesia.”A measles virus receptor, called CD150/ SLAMF1, is highly expressed on memory T, B, and plasma cells. Measles virus gains entry to these immune memory cells using that receptor and kills the cells.
The scientists stated that it could take months or years to return the immune repertoire back to baseline. During the rebuilding process, children would be at increased risk for infectious diseases they had previously experienced.
In a second outstanding paper, Petrova et al. in Science Immunology studied B cells before and after measles infection, and identified two immunologic consequences: The naive B-cell pool was depleted, leading to a return to immunologic immaturity, and the memory B-cell pool was depleted, resulting in compromised immune memory to previously encountered pathogens.
Thus, the link between measles infections and increased susceptibility to other infections and increased deaths from nonmeasles infectious diseases in the aftermath of measles has been revealed. This information adds new data to share with parents who consider refusing measles vaccination. The risks are far greater than getting measles.
Michael E. Pichichero, MD, is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He was asked to comment on the articles. Dr. Pichichero has no conflicts to declare.
As a result of reduced vaccination, after decades of decline, the number of worldwide cases of measles has increased by nearly 300% since 2018. Epidemiologic evidence has associated measles infections with increases in morbidity and mortality for as long as 5 years after the infection and suggests that, in the prevaccine era, measles virus may have been associated with up to 50% of all childhood deaths, mostly because of nonmeasles infections. Measles replication in immune cells has been hypothesized to impair immune memory, potentially causing what some scientists call “immunological amnesia.”A measles virus receptor, called CD150/ SLAMF1, is highly expressed on memory T, B, and plasma cells. Measles virus gains entry to these immune memory cells using that receptor and kills the cells.
The scientists stated that it could take months or years to return the immune repertoire back to baseline. During the rebuilding process, children would be at increased risk for infectious diseases they had previously experienced.
In a second outstanding paper, Petrova et al. in Science Immunology studied B cells before and after measles infection, and identified two immunologic consequences: The naive B-cell pool was depleted, leading to a return to immunologic immaturity, and the memory B-cell pool was depleted, resulting in compromised immune memory to previously encountered pathogens.
Thus, the link between measles infections and increased susceptibility to other infections and increased deaths from nonmeasles infectious diseases in the aftermath of measles has been revealed. This information adds new data to share with parents who consider refusing measles vaccination. The risks are far greater than getting measles.
Michael E. Pichichero, MD, is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He was asked to comment on the articles. Dr. Pichichero has no conflicts to declare.
As a result of reduced vaccination, after decades of decline, the number of worldwide cases of measles has increased by nearly 300% since 2018. Epidemiologic evidence has associated measles infections with increases in morbidity and mortality for as long as 5 years after the infection and suggests that, in the prevaccine era, measles virus may have been associated with up to 50% of all childhood deaths, mostly because of nonmeasles infections. Measles replication in immune cells has been hypothesized to impair immune memory, potentially causing what some scientists call “immunological amnesia.”A measles virus receptor, called CD150/ SLAMF1, is highly expressed on memory T, B, and plasma cells. Measles virus gains entry to these immune memory cells using that receptor and kills the cells.
The scientists stated that it could take months or years to return the immune repertoire back to baseline. During the rebuilding process, children would be at increased risk for infectious diseases they had previously experienced.
In a second outstanding paper, Petrova et al. in Science Immunology studied B cells before and after measles infection, and identified two immunologic consequences: The naive B-cell pool was depleted, leading to a return to immunologic immaturity, and the memory B-cell pool was depleted, resulting in compromised immune memory to previously encountered pathogens.
Thus, the link between measles infections and increased susceptibility to other infections and increased deaths from nonmeasles infectious diseases in the aftermath of measles has been revealed. This information adds new data to share with parents who consider refusing measles vaccination. The risks are far greater than getting measles.
Michael E. Pichichero, MD, is a specialist in pediatric infectious diseases and director of the Research Institute at Rochester (N.Y.) General Hospital. He was asked to comment on the articles. Dr. Pichichero has no conflicts to declare.
Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.
The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.
“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.
“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”
In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 the children experienced mild measles, and 43 had severe measles.
They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.
This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.
The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.
Dr. Mina and associates wrote.
They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.
In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.
Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).
In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.
The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.
Infection with the measles virus appears to reduce immunity to other pathogens, according to a paper published in Science.
The hypothesis that the measles virus could cause “immunological amnesia” by impairing immune memory is supported by early research showing children with measles had negative cutaneous tuberculin reactions after having previously tested positive.
“Subsequent studies have shown decreased interferon signaling, skewed cytokine responses, lymphopenia, and suppression of lymphocyte proliferation shortly after infection,” wrote Michael Mina, MD, from Brigham and Women’s Hospital in Boston, and coauthors.
“Given the variation in the degree of immune repertoire modulation we observed, we anticipate that future risk of morbidity and mortality after measles would not be homogeneous but would be skewed toward individuals with the most severe elimination of immunological memory,” they wrote. “These findings underscore the crucial need for continued widespread vaccination.”
In this study, researchers compared the levels of around 400 pathogen-specific antibodies in blood samples from 77 unvaccinated children, taken before and 2 months after natural measles infection, with 5 unvaccinated children who did not contract measles. A total of 34 the children experienced mild measles, and 43 had severe measles.
They found that the samples taken after measles infection showed “substantial” reductions in the number of pathogen epitopes, compared with the samples from children who did not get infected with measles.
This amounted to approximately a 20% mean reduction in overall diversity or size of the antibody repertoire. However, in children who experienced severe measles, there was a median loss of 40% (range, 11%-62%) of antibody repertoire, compared with a median of 33% (range, 12%-73%) range in children who experienced mild infection. Meanwhile, the control subjects retained approximately 90% of their antibody repertoire over a similar or longer time period. Some children lost up to 70% of antibodies for specific pathogens.
The study did find increases in measles virus–specific antigens in children both after measles infection and MMR vaccination. However the authors did not detect any changes in total IgG, IgA, or IgM levels.
Dr. Mina and associates wrote.
They also noted that controls who received the MMR vaccine showed a marked increase in overall antibody repertoire.
In a separate investigation reported in Science Immunology, Velislava N. Petrova, PhD, of the Wellcome Sanger Institute in Cambridge, England, and coauthors investigated genetic changes in 26 unvaccinated children from the Netherlands who previously had measles to determine if B-cell impairment can lead to measles-associated immunosuppression. Their antibody genes were sequenced before any symptoms of measles developed and roughly 40 days after rash. Two control groups also were sequenced accordingly: vaccinated adults and three unvaccinated children from the same community who were not infected with measles.
Naive B cells from individuals in the vaccinated and uninfected control groups showed high correlation of immunoglobulin heavy chain (IgVH-J) gene frequencies across time periods (R2 = 0.96 and 0.92, respectively) but no significant differences in gene expression (P greater than .05). At the same time, although B-cell frequencies in measles patients recovered to levels before infection, they had significant changes in IgVH-J gene frequencies (P = .01) and decreased correlation in gene expression (R2 = 0.78).
In addition, individuals in the control groups had “a stable genetic composition of B memory cells” but no significant changes in the third complementarity-determining region (CDR3) lengths or mutational frequency of IgVH-J genes (P greater than .05). B memory cells in measles patients, however, showed increases in mutational frequency (P = .0008) and a reduction in CDR3 length (P = .017) of IgVH genes, Dr. Petrova and associates reported.
The study by Mina et al. was supported by grants from various U.S., European, and Finnish foundations and national organizations. Some of the coauthors had relationships with biotechnology and pharmaceutical companies, and three reported a patent holding related to technology used in the study. The study by Petrova et al. was funded by grants to the investigators from various Indonesian and German organizations and the Wellcome Trust. The authors reported no conflicts of interest.
SOURCES: Mina M et al. Science. 2019 Nov 1;366:599-606; Petrova VN et al. Sci Immunol. 2019 Nov 1. doi: 10.1126/sciimmunol.aay6125.
FROM SCIENCE
Oral antibiotics as effective as IV for stable endocarditis patients
Background: Patients with left-sided infective endocarditis often are treated with prolonged courses of intravenous (IV) antibiotics. The safety of switching from IV to oral antibiotics is unknown.
Study design: Randomized, multicenter, noninferiority study.
Setting: Cardiac centers in Denmark during July 2011–August 2017.
Synopsis: The study enrolled 400 patients with left-sided infective endocarditis and positive blood cultures from Streptococcus, Enterococcus, Staphylococcus aureus, or coagulase-negative staph (non–methicillin-resistant Staphylococcus aureus), without evidence of valvular abscess. Following at least 7 days (for those who required surgical intervention) or 10 days (for those who did not require surgical intervention) of IV antibiotics, patients with ongoing fever, leukocytosis, elevated C-reactive protein, or concurrent infections were excluded from the study. Patients were randomized to receive continued IV antibiotic treatment or switch to oral antibiotic treatment. The IV treatment group received a median of 19 additional days of therapy, compared with 17 days in the oral group. The primary composite outcome of death, unplanned cardiac surgery, embolic event, and relapse of bacteremia occurred in 12.1% in the IV therapy group and 9% in the oral therapy group (difference of 3.1%; 95% confidence interval, –3.4 to 9.6; P = .40), meeting the studies prespecified noninferiority criteria. Poor representation of women, obese patients, and patients who use IV drugs may limit the study’s generalizability. An accompanying editorial advocated for additional research before widespread change to current treatment recommendations are made.
Bottom line: For patients with left-sided infective endocarditis who have been stabilized on IV antibiotic treatment, transitioning to an oral antibiotic regimen may be a noninferior approach.
Citation: Iverson K et al. Partial oral versus intravenous antibiotic treatment of endocarditis. N Eng J Med. 2019 Jan 31;380(5):415-24.
Dr. Phillips is a hospitalist at Beth Israel Deaconess Medical Center and instructor in medicine at Harvard Medical School.
Background: Patients with left-sided infective endocarditis often are treated with prolonged courses of intravenous (IV) antibiotics. The safety of switching from IV to oral antibiotics is unknown.
Study design: Randomized, multicenter, noninferiority study.
Setting: Cardiac centers in Denmark during July 2011–August 2017.
Synopsis: The study enrolled 400 patients with left-sided infective endocarditis and positive blood cultures from Streptococcus, Enterococcus, Staphylococcus aureus, or coagulase-negative staph (non–methicillin-resistant Staphylococcus aureus), without evidence of valvular abscess. Following at least 7 days (for those who required surgical intervention) or 10 days (for those who did not require surgical intervention) of IV antibiotics, patients with ongoing fever, leukocytosis, elevated C-reactive protein, or concurrent infections were excluded from the study. Patients were randomized to receive continued IV antibiotic treatment or switch to oral antibiotic treatment. The IV treatment group received a median of 19 additional days of therapy, compared with 17 days in the oral group. The primary composite outcome of death, unplanned cardiac surgery, embolic event, and relapse of bacteremia occurred in 12.1% in the IV therapy group and 9% in the oral therapy group (difference of 3.1%; 95% confidence interval, –3.4 to 9.6; P = .40), meeting the studies prespecified noninferiority criteria. Poor representation of women, obese patients, and patients who use IV drugs may limit the study’s generalizability. An accompanying editorial advocated for additional research before widespread change to current treatment recommendations are made.
Bottom line: For patients with left-sided infective endocarditis who have been stabilized on IV antibiotic treatment, transitioning to an oral antibiotic regimen may be a noninferior approach.
Citation: Iverson K et al. Partial oral versus intravenous antibiotic treatment of endocarditis. N Eng J Med. 2019 Jan 31;380(5):415-24.
Dr. Phillips is a hospitalist at Beth Israel Deaconess Medical Center and instructor in medicine at Harvard Medical School.
Background: Patients with left-sided infective endocarditis often are treated with prolonged courses of intravenous (IV) antibiotics. The safety of switching from IV to oral antibiotics is unknown.
Study design: Randomized, multicenter, noninferiority study.
Setting: Cardiac centers in Denmark during July 2011–August 2017.
Synopsis: The study enrolled 400 patients with left-sided infective endocarditis and positive blood cultures from Streptococcus, Enterococcus, Staphylococcus aureus, or coagulase-negative staph (non–methicillin-resistant Staphylococcus aureus), without evidence of valvular abscess. Following at least 7 days (for those who required surgical intervention) or 10 days (for those who did not require surgical intervention) of IV antibiotics, patients with ongoing fever, leukocytosis, elevated C-reactive protein, or concurrent infections were excluded from the study. Patients were randomized to receive continued IV antibiotic treatment or switch to oral antibiotic treatment. The IV treatment group received a median of 19 additional days of therapy, compared with 17 days in the oral group. The primary composite outcome of death, unplanned cardiac surgery, embolic event, and relapse of bacteremia occurred in 12.1% in the IV therapy group and 9% in the oral therapy group (difference of 3.1%; 95% confidence interval, –3.4 to 9.6; P = .40), meeting the studies prespecified noninferiority criteria. Poor representation of women, obese patients, and patients who use IV drugs may limit the study’s generalizability. An accompanying editorial advocated for additional research before widespread change to current treatment recommendations are made.
Bottom line: For patients with left-sided infective endocarditis who have been stabilized on IV antibiotic treatment, transitioning to an oral antibiotic regimen may be a noninferior approach.
Citation: Iverson K et al. Partial oral versus intravenous antibiotic treatment of endocarditis. N Eng J Med. 2019 Jan 31;380(5):415-24.
Dr. Phillips is a hospitalist at Beth Israel Deaconess Medical Center and instructor in medicine at Harvard Medical School.
HCV testing/awareness successful as part of HIV integrated care
(PWID), according to researchers reporting on a multisite randomized trial of nearly 12,000 HIV-infected individuals in India.
HCV antibody prevalence at these sites ranged from 7.2%-76.6%. Across six integrated care centers (ICCs), 5,263 clients underwent HCV testing, of whom 2,278 were newly diagnosed. At evaluation, PWID in ICC clusters were nearly four times more likely to report being tested for HCV than those in usual care clusters (adjusted prevalence ratio [aPR]: 3.69), according to the report by Sunil Suhas Solomon, MD, of Johns Hopkins University School of Medicine, Baltimore, and colleagues.
PWID in ICC clusters were also seven times more likely to be aware of their HCV status (aPR: 7.11; 95% confidence interval: 1.14, 44.3) and significantly more likely to initiate treatment, (aPR: 9.86; 95% CI: 1.52, 63.8), than individuals in usual care, the authors stated in their report published online ahead of press in the Journal of Hepatology.
“These data provide among the first empirical support of the benefits of integrating HCV testing with HIV prevention and treatment services for PWID. Over a short duration, we observed significant impact on community-level HCV testing and awareness of HCV status among PWID. While additional strategies might be required to improve population awareness levels, integration of HCV testing with HIV programs for PWID particularly given the high burden of HIV/HCV coinfection represents a critical first step,” the researchers concluded.
The study was funded by the National Institutes of Health and the Elton John AIDS Foundation. The authors reported that they had no relevant disclosures.
SOURCE: Solomon, SS et al. J Hepatol. 2019. doi.org/10.1016/j.jhep.2019.09.022.
(PWID), according to researchers reporting on a multisite randomized trial of nearly 12,000 HIV-infected individuals in India.
HCV antibody prevalence at these sites ranged from 7.2%-76.6%. Across six integrated care centers (ICCs), 5,263 clients underwent HCV testing, of whom 2,278 were newly diagnosed. At evaluation, PWID in ICC clusters were nearly four times more likely to report being tested for HCV than those in usual care clusters (adjusted prevalence ratio [aPR]: 3.69), according to the report by Sunil Suhas Solomon, MD, of Johns Hopkins University School of Medicine, Baltimore, and colleagues.
PWID in ICC clusters were also seven times more likely to be aware of their HCV status (aPR: 7.11; 95% confidence interval: 1.14, 44.3) and significantly more likely to initiate treatment, (aPR: 9.86; 95% CI: 1.52, 63.8), than individuals in usual care, the authors stated in their report published online ahead of press in the Journal of Hepatology.
“These data provide among the first empirical support of the benefits of integrating HCV testing with HIV prevention and treatment services for PWID. Over a short duration, we observed significant impact on community-level HCV testing and awareness of HCV status among PWID. While additional strategies might be required to improve population awareness levels, integration of HCV testing with HIV programs for PWID particularly given the high burden of HIV/HCV coinfection represents a critical first step,” the researchers concluded.
The study was funded by the National Institutes of Health and the Elton John AIDS Foundation. The authors reported that they had no relevant disclosures.
SOURCE: Solomon, SS et al. J Hepatol. 2019. doi.org/10.1016/j.jhep.2019.09.022.
(PWID), according to researchers reporting on a multisite randomized trial of nearly 12,000 HIV-infected individuals in India.
HCV antibody prevalence at these sites ranged from 7.2%-76.6%. Across six integrated care centers (ICCs), 5,263 clients underwent HCV testing, of whom 2,278 were newly diagnosed. At evaluation, PWID in ICC clusters were nearly four times more likely to report being tested for HCV than those in usual care clusters (adjusted prevalence ratio [aPR]: 3.69), according to the report by Sunil Suhas Solomon, MD, of Johns Hopkins University School of Medicine, Baltimore, and colleagues.
PWID in ICC clusters were also seven times more likely to be aware of their HCV status (aPR: 7.11; 95% confidence interval: 1.14, 44.3) and significantly more likely to initiate treatment, (aPR: 9.86; 95% CI: 1.52, 63.8), than individuals in usual care, the authors stated in their report published online ahead of press in the Journal of Hepatology.
“These data provide among the first empirical support of the benefits of integrating HCV testing with HIV prevention and treatment services for PWID. Over a short duration, we observed significant impact on community-level HCV testing and awareness of HCV status among PWID. While additional strategies might be required to improve population awareness levels, integration of HCV testing with HIV programs for PWID particularly given the high burden of HIV/HCV coinfection represents a critical first step,” the researchers concluded.
The study was funded by the National Institutes of Health and the Elton John AIDS Foundation. The authors reported that they had no relevant disclosures.
SOURCE: Solomon, SS et al. J Hepatol. 2019. doi.org/10.1016/j.jhep.2019.09.022.
FROM THE JOURNAL OF HEPATOLOGY