Vaccines

The Ervebo vaccine not only reduces the risk for Ebola infection but also halves mortality rates. This is the result of a study published in The Lancet Infectious Diseases.

Rebecca Coulborn, an epidemiologist at Epicentre in Paris, France, and colleagues analyzed data collected during the 10th Ebola epidemic in the Democratic Republic of the Congo. Their analysis revealed that among the 2279 patients with confirmed Ebola who were admitted to an Ebola health facility between July 27, 2018, and April 27, 2020, the mortality risk was 56% for unvaccinated patients. In vaccinated patients, however, it was only 25%. The reduced mortality applied to all patients, regardless of age and gender.

The study was funded by Doctors Without Borders. For data collection, Epicentre, the epidemiological division of Doctors Without Borders, collaborated with the Institut National de Recherche Biomédicale and the Ministry of Health of the Democratic Republic of the Congo.

The study authors focused on the Ervebo vaccine, which is approved for use against Zaire ebolavirus in the European Union, the United States, and some African countries, among others. It is the only Ebola vaccine currently recommended for use during an epidemic. It is administered intramuscularly as a single dose and is approved for adults aged 18 years and older.

The vaccine is primarily recommended for ring vaccination of individuals at a high risk for infection during an epidemic. In studies, the vaccine has been used for ring vaccinations among contacts of diagnosed cases since the end of the Ebola outbreak in West Africa in 2014 and 2015 and since 2018 in the Democratic Republic of the Congo.

The preliminary estimated vaccine effectiveness 10 days after vaccination is 97.5%-100%. The duration of protection is unknown. Individuals who became ill despite vaccination typically experienced a milder course of illness.

Although people should be vaccinated as early as possible during Ebola outbreaks, the results of the Epicentre study showed that the vaccine still protects against the risk for infection even when administered after exposure to the virus.

Furthermore, Dr. Coulborn and her team found no antagonistic effect between vaccination and Ebola treatment in their analysis. “Vaccination following exposure to a person infected with Ebola still provides significant protection against death, even if administered shortly before the onset of symptoms,” said study author Dr. Coulborn in a press release from Doctors Without Borders.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The Ervebo vaccine not only reduces the risk for Ebola infection but also halves mortality rates. This is the result of a study published in The Lancet Infectious Diseases.

Rebecca Coulborn, an epidemiologist at Epicentre in Paris, France, and colleagues analyzed data collected during the 10th Ebola epidemic in the Democratic Republic of the Congo. Their analysis revealed that among the 2279 patients with confirmed Ebola who were admitted to an Ebola health facility between July 27, 2018, and April 27, 2020, the mortality risk was 56% for unvaccinated patients. In vaccinated patients, however, it was only 25%. The reduced mortality applied to all patients, regardless of age and gender.

The study was funded by Doctors Without Borders. For data collection, Epicentre, the epidemiological division of Doctors Without Borders, collaborated with the Institut National de Recherche Biomédicale and the Ministry of Health of the Democratic Republic of the Congo.

The study authors focused on the Ervebo vaccine, which is approved for use against Zaire ebolavirus in the European Union, the United States, and some African countries, among others. It is the only Ebola vaccine currently recommended for use during an epidemic. It is administered intramuscularly as a single dose and is approved for adults aged 18 years and older.

The vaccine is primarily recommended for ring vaccination of individuals at a high risk for infection during an epidemic. In studies, the vaccine has been used for ring vaccinations among contacts of diagnosed cases since the end of the Ebola outbreak in West Africa in 2014 and 2015 and since 2018 in the Democratic Republic of the Congo.

The preliminary estimated vaccine effectiveness 10 days after vaccination is 97.5%-100%. The duration of protection is unknown. Individuals who became ill despite vaccination typically experienced a milder course of illness.

Although people should be vaccinated as early as possible during Ebola outbreaks, the results of the Epicentre study showed that the vaccine still protects against the risk for infection even when administered after exposure to the virus.

Furthermore, Dr. Coulborn and her team found no antagonistic effect between vaccination and Ebola treatment in their analysis. “Vaccination following exposure to a person infected with Ebola still provides significant protection against death, even if administered shortly before the onset of symptoms,” said study author Dr. Coulborn in a press release from Doctors Without Borders.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The Ervebo vaccine not only reduces the risk for Ebola infection but also halves mortality rates. This is the result of a study published in The Lancet Infectious Diseases.

Rebecca Coulborn, an epidemiologist at Epicentre in Paris, France, and colleagues analyzed data collected during the 10th Ebola epidemic in the Democratic Republic of the Congo. Their analysis revealed that among the 2279 patients with confirmed Ebola who were admitted to an Ebola health facility between July 27, 2018, and April 27, 2020, the mortality risk was 56% for unvaccinated patients. In vaccinated patients, however, it was only 25%. The reduced mortality applied to all patients, regardless of age and gender.

The study was funded by Doctors Without Borders. For data collection, Epicentre, the epidemiological division of Doctors Without Borders, collaborated with the Institut National de Recherche Biomédicale and the Ministry of Health of the Democratic Republic of the Congo.

The study authors focused on the Ervebo vaccine, which is approved for use against Zaire ebolavirus in the European Union, the United States, and some African countries, among others. It is the only Ebola vaccine currently recommended for use during an epidemic. It is administered intramuscularly as a single dose and is approved for adults aged 18 years and older.

The vaccine is primarily recommended for ring vaccination of individuals at a high risk for infection during an epidemic. In studies, the vaccine has been used for ring vaccinations among contacts of diagnosed cases since the end of the Ebola outbreak in West Africa in 2014 and 2015 and since 2018 in the Democratic Republic of the Congo.

The preliminary estimated vaccine effectiveness 10 days after vaccination is 97.5%-100%. The duration of protection is unknown. Individuals who became ill despite vaccination typically experienced a milder course of illness.

Although people should be vaccinated as early as possible during Ebola outbreaks, the results of the Epicentre study showed that the vaccine still protects against the risk for infection even when administered after exposure to the virus.

Furthermore, Dr. Coulborn and her team found no antagonistic effect between vaccination and Ebola treatment in their analysis. “Vaccination following exposure to a person infected with Ebola still provides significant protection against death, even if administered shortly before the onset of symptoms,” said study author Dr. Coulborn in a press release from Doctors Without Borders.

This story was translated from the Medscape German edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

Amid an ongoing measles outbreak in Florida possibly sparked by vaccine hesitancy, the state’s surgeon general Joseph Ladapo, MD, is contradicting public health guidance of encouraging quarantine of unvaccinated children. 

Rather than requesting that parents keep children unvaccinated against measles home from school or to get their children vaccinated, both critical tools in containing an outbreak, Dr. Ladapo has advised parents to do whatever they think is best. Pediatricians and infectious disease specialists fear a free-for-all will fuel the spread of the highly infectious virus, including in their own clinics. 

The outbreak has been traced to an elementary school in Weston and has so far sickened at least eight children, one of whom is younger than 5 years. According to the Centers for Disease Control and Prevention, roughly 91% of the 230,000-odd kindergarteners in Florida had received the requisite doses of the MMR vaccine, which also protects against mumps and rubella, for the 2022-2023 school year, below the 95% vaccination level which public health authorities believes confers herd immunity against measles. An estimated 4.5% of kindergarteners in the state have received an exemption for the vaccine, which prevents measles in 97% of the people who get the shots, for a lifetime. The first dose is given around age 13 months and the second when people are age 4 or 5 years and soon to enter school.

“If you’re vaccinated you have a very slim chance of getting the virus,” said Rana Alissa, MD, a pediatrician at University of Florida Health in Jacksonville.

An unvaccinated child has no protection against measles, and could spread it to others merely by sneezing or touching a surface. In a school setting, infection could spread to a teacher who cannot receive the measles vaccine due to a weakened immune system, or the unvaccinated child could spread the virus at a pediatric clinic or hospital when seeking care for measles unless the clinic staff takes rigorous steps to separate the child from other children. Some children at the clinic won’t be able to get the measles vaccine either because of immunodeficiency or perhaps having had a bone marrow transplant. 

Assuming the unvaccinated child is healthy, the measles infection will run its course, and the child will then be immune to the disease, Dr. Alissa said. But meanwhile, the child could pose a significant risk to others. 

“We’re not worried about the unvaccinated kids who are very healthy. We’re worried about the adults who did not get vaccinated and who are very sick,” said Dr. Alissa, vice president of the Florida chapter of the American Academy of Pediatrics (AAP). “We’re worried about the little kids who are less than 13 months old. We’re worried about the kids with immunodeficiency disorders.” The Florida chapter of the AAP encourages parents to get their children vaccinated against measles amid the ongoing outbreak.

“I wish our surgeon general was on the same page as us,” Dr. Alissa added, noting that she thinks misplaced vaccine hesitancy has caused some parents to forego a safe and effective vaccine for their children.
 

Never Too Late to Vaxx

Measles symptoms appear 10-14 days after exposure and can include sore throat, cough, runny nose, inflamed eyes, fever, and blotchy skin rashes. According to the Centers for Disease Control and Prevention (CDC), 20% of people who are unvaccinated against measles will be hospitalized for the virus if they contract it.

Given the incubation period for the virus, clinicians and public health officials recommend unvaccinated children isolate for 21 days after being exposed to measles at school. The advice applies to any unvaccinated child, whether because their parent opted against the vaccine or because they cannot safely receive the immunization.

This is the guidance that Surgeon General Ladapo is flouting.

“We have a public health system. They’re awesome. They’re the experts. Let’s use them,” Dr. Alissa noted. “Their recommendation is to keep the unvaccinated kids at home for 21 days when you have an outbreak.” 

“We’re not calling him doctor anymore,” said Andrew Pavia, MD, chief of the Division of Pediatric Infectious Diseases at the University of Utah in Salt Lake City. 

“Getting your kids immunized before they enter school is so critical,” added Dr. Pavia, because the 21-day quarantine period is onerous for children and parents alike.

In a February 26 statement, Marcus Plescia, MD, MPH, chief medical officer of the Association of State and Territorial Health Officials, said “well-established public health practice recommends that unvaccinated persons exposed to measles stay home for at least 21 days to prevent further growth of the outbreak. While this is undoubtedly disruptive to the persons impacted, imagine how much more disruptive it would be if measles takes hold again in the United States, spreading widely, and impacting children and communities across the entire nation.”

During an outbreak, it’s still possible to give a measles vaccine to a child who has not yet received the shots, Dr. Pavia stressed. But time is of the essence: Vaccination should occur within 72 hours of the first known measles case in a school.

“It’s not perfect, they may still get measles, but it will greatly decrease the severity,” Dr. Pavia said.

If some children won’t get vaccinated during an outbreak, their parents may call a pediatrician or hospital staff for help as measles symptoms take hold. Clinicians should advise everyone in the home who is older than 2 years to begin wearing N95 masks and gloves, Dr. Alissa said. And when the child comes into the clinic he or she should be examined in a separate room, ideally one with negative air pressure and frequent filtration, Dr. Alissa added. If not, any private room will do if nobody else uses the room for at least 2 hours afterward.

“Measles is phenomenally transmissible,” Dr. Pavia said. A person with the virus can infect 12 to 18 others who are not protected against the pathogen. 

Someone with a severe reaction to measles could get an injection of intramuscular immunoglobulin, Dr. Pavia said, although this tends to be uncomfortable and expensive.

“The vaccine works. We almost got rid of measles,” Dr. Alissa said, although parents who choose to send their unvaccinated children to school can do so if they choose to.

“The fear of every pediatrician is to have a child die from this,” she said. “People who are sick, please stay at home.” 

Dr. Pavia reported an advisory relationship with Sanofi Pasteur regarding an RSV vaccine. Dr. Alissa reported no relevant financial conflicts of interest. 
 

A version of this article appeared on Medscape.com.

Amid an ongoing measles outbreak in Florida possibly sparked by vaccine hesitancy, the state’s surgeon general Joseph Ladapo, MD, is contradicting public health guidance of encouraging quarantine of unvaccinated children. 

Rather than requesting that parents keep children unvaccinated against measles home from school or to get their children vaccinated, both critical tools in containing an outbreak, Dr. Ladapo has advised parents to do whatever they think is best. Pediatricians and infectious disease specialists fear a free-for-all will fuel the spread of the highly infectious virus, including in their own clinics. 

The outbreak has been traced to an elementary school in Weston and has so far sickened at least eight children, one of whom is younger than 5 years. According to the Centers for Disease Control and Prevention, roughly 91% of the 230,000-odd kindergarteners in Florida had received the requisite doses of the MMR vaccine, which also protects against mumps and rubella, for the 2022-2023 school year, below the 95% vaccination level which public health authorities believes confers herd immunity against measles. An estimated 4.5% of kindergarteners in the state have received an exemption for the vaccine, which prevents measles in 97% of the people who get the shots, for a lifetime. The first dose is given around age 13 months and the second when people are age 4 or 5 years and soon to enter school.

“If you’re vaccinated you have a very slim chance of getting the virus,” said Rana Alissa, MD, a pediatrician at University of Florida Health in Jacksonville.

An unvaccinated child has no protection against measles, and could spread it to others merely by sneezing or touching a surface. In a school setting, infection could spread to a teacher who cannot receive the measles vaccine due to a weakened immune system, or the unvaccinated child could spread the virus at a pediatric clinic or hospital when seeking care for measles unless the clinic staff takes rigorous steps to separate the child from other children. Some children at the clinic won’t be able to get the measles vaccine either because of immunodeficiency or perhaps having had a bone marrow transplant. 

Assuming the unvaccinated child is healthy, the measles infection will run its course, and the child will then be immune to the disease, Dr. Alissa said. But meanwhile, the child could pose a significant risk to others. 

“We’re not worried about the unvaccinated kids who are very healthy. We’re worried about the adults who did not get vaccinated and who are very sick,” said Dr. Alissa, vice president of the Florida chapter of the American Academy of Pediatrics (AAP). “We’re worried about the little kids who are less than 13 months old. We’re worried about the kids with immunodeficiency disorders.” The Florida chapter of the AAP encourages parents to get their children vaccinated against measles amid the ongoing outbreak.

“I wish our surgeon general was on the same page as us,” Dr. Alissa added, noting that she thinks misplaced vaccine hesitancy has caused some parents to forego a safe and effective vaccine for their children.
 

Never Too Late to Vaxx

Measles symptoms appear 10-14 days after exposure and can include sore throat, cough, runny nose, inflamed eyes, fever, and blotchy skin rashes. According to the Centers for Disease Control and Prevention (CDC), 20% of people who are unvaccinated against measles will be hospitalized for the virus if they contract it.

Given the incubation period for the virus, clinicians and public health officials recommend unvaccinated children isolate for 21 days after being exposed to measles at school. The advice applies to any unvaccinated child, whether because their parent opted against the vaccine or because they cannot safely receive the immunization.

This is the guidance that Surgeon General Ladapo is flouting.

“We have a public health system. They’re awesome. They’re the experts. Let’s use them,” Dr. Alissa noted. “Their recommendation is to keep the unvaccinated kids at home for 21 days when you have an outbreak.” 

“We’re not calling him doctor anymore,” said Andrew Pavia, MD, chief of the Division of Pediatric Infectious Diseases at the University of Utah in Salt Lake City. 

“Getting your kids immunized before they enter school is so critical,” added Dr. Pavia, because the 21-day quarantine period is onerous for children and parents alike.

In a February 26 statement, Marcus Plescia, MD, MPH, chief medical officer of the Association of State and Territorial Health Officials, said “well-established public health practice recommends that unvaccinated persons exposed to measles stay home for at least 21 days to prevent further growth of the outbreak. While this is undoubtedly disruptive to the persons impacted, imagine how much more disruptive it would be if measles takes hold again in the United States, spreading widely, and impacting children and communities across the entire nation.”

During an outbreak, it’s still possible to give a measles vaccine to a child who has not yet received the shots, Dr. Pavia stressed. But time is of the essence: Vaccination should occur within 72 hours of the first known measles case in a school.

“It’s not perfect, they may still get measles, but it will greatly decrease the severity,” Dr. Pavia said.

If some children won’t get vaccinated during an outbreak, their parents may call a pediatrician or hospital staff for help as measles symptoms take hold. Clinicians should advise everyone in the home who is older than 2 years to begin wearing N95 masks and gloves, Dr. Alissa said. And when the child comes into the clinic he or she should be examined in a separate room, ideally one with negative air pressure and frequent filtration, Dr. Alissa added. If not, any private room will do if nobody else uses the room for at least 2 hours afterward.

“Measles is phenomenally transmissible,” Dr. Pavia said. A person with the virus can infect 12 to 18 others who are not protected against the pathogen. 

Someone with a severe reaction to measles could get an injection of intramuscular immunoglobulin, Dr. Pavia said, although this tends to be uncomfortable and expensive.

“The vaccine works. We almost got rid of measles,” Dr. Alissa said, although parents who choose to send their unvaccinated children to school can do so if they choose to.

“The fear of every pediatrician is to have a child die from this,” she said. “People who are sick, please stay at home.” 

Dr. Pavia reported an advisory relationship with Sanofi Pasteur regarding an RSV vaccine. Dr. Alissa reported no relevant financial conflicts of interest. 
 

A version of this article appeared on Medscape.com.

Amid an ongoing measles outbreak in Florida possibly sparked by vaccine hesitancy, the state’s surgeon general Joseph Ladapo, MD, is contradicting public health guidance of encouraging quarantine of unvaccinated children. 

Rather than requesting that parents keep children unvaccinated against measles home from school or to get their children vaccinated, both critical tools in containing an outbreak, Dr. Ladapo has advised parents to do whatever they think is best. Pediatricians and infectious disease specialists fear a free-for-all will fuel the spread of the highly infectious virus, including in their own clinics. 

The outbreak has been traced to an elementary school in Weston and has so far sickened at least eight children, one of whom is younger than 5 years. According to the Centers for Disease Control and Prevention, roughly 91% of the 230,000-odd kindergarteners in Florida had received the requisite doses of the MMR vaccine, which also protects against mumps and rubella, for the 2022-2023 school year, below the 95% vaccination level which public health authorities believes confers herd immunity against measles. An estimated 4.5% of kindergarteners in the state have received an exemption for the vaccine, which prevents measles in 97% of the people who get the shots, for a lifetime. The first dose is given around age 13 months and the second when people are age 4 or 5 years and soon to enter school.

“If you’re vaccinated you have a very slim chance of getting the virus,” said Rana Alissa, MD, a pediatrician at University of Florida Health in Jacksonville.

An unvaccinated child has no protection against measles, and could spread it to others merely by sneezing or touching a surface. In a school setting, infection could spread to a teacher who cannot receive the measles vaccine due to a weakened immune system, or the unvaccinated child could spread the virus at a pediatric clinic or hospital when seeking care for measles unless the clinic staff takes rigorous steps to separate the child from other children. Some children at the clinic won’t be able to get the measles vaccine either because of immunodeficiency or perhaps having had a bone marrow transplant. 

Assuming the unvaccinated child is healthy, the measles infection will run its course, and the child will then be immune to the disease, Dr. Alissa said. But meanwhile, the child could pose a significant risk to others. 

“We’re not worried about the unvaccinated kids who are very healthy. We’re worried about the adults who did not get vaccinated and who are very sick,” said Dr. Alissa, vice president of the Florida chapter of the American Academy of Pediatrics (AAP). “We’re worried about the little kids who are less than 13 months old. We’re worried about the kids with immunodeficiency disorders.” The Florida chapter of the AAP encourages parents to get their children vaccinated against measles amid the ongoing outbreak.

“I wish our surgeon general was on the same page as us,” Dr. Alissa added, noting that she thinks misplaced vaccine hesitancy has caused some parents to forego a safe and effective vaccine for their children.
 

Never Too Late to Vaxx

Measles symptoms appear 10-14 days after exposure and can include sore throat, cough, runny nose, inflamed eyes, fever, and blotchy skin rashes. According to the Centers for Disease Control and Prevention (CDC), 20% of people who are unvaccinated against measles will be hospitalized for the virus if they contract it.

Given the incubation period for the virus, clinicians and public health officials recommend unvaccinated children isolate for 21 days after being exposed to measles at school. The advice applies to any unvaccinated child, whether because their parent opted against the vaccine or because they cannot safely receive the immunization.

This is the guidance that Surgeon General Ladapo is flouting.

“We have a public health system. They’re awesome. They’re the experts. Let’s use them,” Dr. Alissa noted. “Their recommendation is to keep the unvaccinated kids at home for 21 days when you have an outbreak.” 

“We’re not calling him doctor anymore,” said Andrew Pavia, MD, chief of the Division of Pediatric Infectious Diseases at the University of Utah in Salt Lake City. 

“Getting your kids immunized before they enter school is so critical,” added Dr. Pavia, because the 21-day quarantine period is onerous for children and parents alike.

In a February 26 statement, Marcus Plescia, MD, MPH, chief medical officer of the Association of State and Territorial Health Officials, said “well-established public health practice recommends that unvaccinated persons exposed to measles stay home for at least 21 days to prevent further growth of the outbreak. While this is undoubtedly disruptive to the persons impacted, imagine how much more disruptive it would be if measles takes hold again in the United States, spreading widely, and impacting children and communities across the entire nation.”

During an outbreak, it’s still possible to give a measles vaccine to a child who has not yet received the shots, Dr. Pavia stressed. But time is of the essence: Vaccination should occur within 72 hours of the first known measles case in a school.

“It’s not perfect, they may still get measles, but it will greatly decrease the severity,” Dr. Pavia said.

If some children won’t get vaccinated during an outbreak, their parents may call a pediatrician or hospital staff for help as measles symptoms take hold. Clinicians should advise everyone in the home who is older than 2 years to begin wearing N95 masks and gloves, Dr. Alissa said. And when the child comes into the clinic he or she should be examined in a separate room, ideally one with negative air pressure and frequent filtration, Dr. Alissa added. If not, any private room will do if nobody else uses the room for at least 2 hours afterward.

“Measles is phenomenally transmissible,” Dr. Pavia said. A person with the virus can infect 12 to 18 others who are not protected against the pathogen. 

Someone with a severe reaction to measles could get an injection of intramuscular immunoglobulin, Dr. Pavia said, although this tends to be uncomfortable and expensive.

“The vaccine works. We almost got rid of measles,” Dr. Alissa said, although parents who choose to send their unvaccinated children to school can do so if they choose to.

“The fear of every pediatrician is to have a child die from this,” she said. “People who are sick, please stay at home.” 

Dr. Pavia reported an advisory relationship with Sanofi Pasteur regarding an RSV vaccine. Dr. Alissa reported no relevant financial conflicts of interest. 
 

A version of this article appeared on Medscape.com.

The smallpox vaccine effectively induces immunity against mpox virus infection (formerly simian smallpox) in patients with human immunodeficiency virus (HIV) infection, although patients with lymphocyte counts below 500 cells/mm³ require booster doses, according to data from a study published in the Journal of Medical Virology.

The data come from the prospective observational study conducted by researchers at the Infection Biology Laboratory of the Department of Medicine and Life Sciences at Pompeu Fabra University and the HIV Unit of the Hospital del Mar Medical Research Institute in Barcelona, Spain. The investigators analyzed T-cell responses induced by vaccination with JYNNEOS.

Despite the substantial decrease in the reporting frequency of mpox cases from the global peak in August 2022 (30,894 cases) to 804 monthly cases in the last six months of 2023, mpox continues to circulate, and there is no specific vaccine. The JYNNEOS vaccine, with protective cross-reactivity against orthopoxviruses, is approved by the US Food and Drug Administration and the European Medicines Agency for the prevention of smallpox and mpox in adults at high risk for infection.

During the 2022 outbreak in the United States and Europe, vaccine shortages led to the emergency use authorization of a lower intradermal dose. This strategy was aimed at increasing vaccine supply up to fivefold.

Further clinical trials are needed to evaluate responses to JYNNEOS vaccination and compare different administration routes in patients with HIV infection. Protecting this population against mpox is a priority because people with high viral loads or loCD4+ T-lymphocyte counts are especially susceptible to severe disease.
 

Vaccination Responses 

The study assessed the immune response to the JYNNEOS vaccine in patients with HIV who were receiving antiretroviral therapy as outpatients at the Infectious Diseases Unit of Hospital del Mar in Barcelona, Spain. Participants had viral loads controlled by antiretroviral therapy and CD4+ T-lymphocyte counts ≤ 500/mm³ (loCD4 group) or ≥ 500/mm³ (hiCD4 group) in blood. Vaccine responses were compared with those of vaccinated controls without the disease. The study included cases that received the standard subcutaneous vaccine (before August 2022) or the emergency dose-saving intradermal vaccine after its approval in August 2022.

The results demonstrated that the intradermal dose-saving vaccination route is preferable to the subcutaneous route and that patients in the loCD4 group may require at least one booster to generate an efficient response of specific T cells for mpox, wrote the authors.

“This study has two relevant points,” study author Robert Güerri-Fernandez, MD, PhD, head of infectious diseases at the Hospital del Mar Medical Research Institute, told this news organization. “In the subgroup of patients with HIV with effective treatment but without an immune response (ie, loCD4), the vaccine response is worse than in people who have recovered immunity or do not have HIV. Therefore, they need a booster dose.

“The second point is that the intradermal route with one-fifth of the standard subcutaneous dose has a better immune response than the standard subcutaneous route.” He added that it was a good strategy to save doses and be able to vaccinate many more people when vaccine shortages occurred.

“A general conclusion cannot be drawn,” he said. “It needs to be validated with many more subjects, of course, but in some way, it reinforced our confidence in the strategy of health authorities to promote intradermal vaccination. There we had evidence that the patients we were vaccinating intradermally were responding well.”

In Spain, although there is no shortage of vaccines today, they continue to be administered intradermally with a fractionated dose equivalent to one fifth of a standard dose, said Dr. Güerri-Fernandez.

However, in his opinion, observations regarding the two administration routes signal a need for further research. The main message should be that for patients with HIV infection who do not have an immune response, the vaccine response is incomplete, and they need booster doses as well as monitoring of the vaccine immune response, said Dr. Güerri-Fernandez.
 

More Studies Required

The research, which prospectively collected data and blood samples from patients with HIV who received the JYNNEOS vaccine, is small and included only 24 patients with HIV infection, with seven hospital workers who also received the vaccine and seven unvaccinated individuals as controls. “I am one of the control subjects of the study, and intradermal vaccination is not especially pleasant,” said Dr. Güerri-Fernandez. “It is a very innervated area, and the moment of introducing the liquid is uncomfortable. But it is perfectly bearable.”

Outpatient HIV-infected patients from the Infectious Diseases Unit of Hospital del Mar on antiretroviral therapy and with undetectable viral loads were grouped according to their CD4+ T-lymphocyte counts. Those with CD4+ T-lymphocyte counts ≤ 500/mm³ required at least one booster vaccine to exhibit efficient virus-specific T-lymphocyte responses. The magnitude of the T-cell response after this booster correlated directly with the CD4+ T-lymphocyte count of those vaccinated.

For Argentine infectious disease specialist Julián García, MD, clinical researcher at the Huésped Foundation in Buenos Aires, Argentina, who did not participate in the study, it is always productive to know that T-cell responses develop in patients with HIV infection, with CD4+ T-lymphocyte counts > and < 500/mm^3, through an intradermal administration route.

Dr. García emphasized that the most novel aspect is that the JYNNEOS vaccine induces a specific T-cell response in patients with HIV infection that increases with higher CD4+ T-lymphocyte levels. However, he noted that the number of patients was less than 10 in most study groups, and the control group had only intradermal administration, which limits the interpretation of the results. “It will be necessary to verify this in studies with larger groups with control groups from all routes and with a correlate of protection.”

Dr. García referred to this latter point as a significant source of uncertainty. “The study is fundamentally based on the cellular response, but nowadays, there is no immune correlate of real-life protection.” He concluded that the study builds knowledge, which is essential for a vaccine that began to be used for mpox and the effectiveness of which is based on estimates. 

Dr. Güerri-Fernandez and Dr. Garcia declared no relevant financial conflicts of interest. 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The smallpox vaccine effectively induces immunity against mpox virus infection (formerly simian smallpox) in patients with human immunodeficiency virus (HIV) infection, although patients with lymphocyte counts below 500 cells/mm³ require booster doses, according to data from a study published in the Journal of Medical Virology.

The data come from the prospective observational study conducted by researchers at the Infection Biology Laboratory of the Department of Medicine and Life Sciences at Pompeu Fabra University and the HIV Unit of the Hospital del Mar Medical Research Institute in Barcelona, Spain. The investigators analyzed T-cell responses induced by vaccination with JYNNEOS.

Despite the substantial decrease in the reporting frequency of mpox cases from the global peak in August 2022 (30,894 cases) to 804 monthly cases in the last six months of 2023, mpox continues to circulate, and there is no specific vaccine. The JYNNEOS vaccine, with protective cross-reactivity against orthopoxviruses, is approved by the US Food and Drug Administration and the European Medicines Agency for the prevention of smallpox and mpox in adults at high risk for infection.

During the 2022 outbreak in the United States and Europe, vaccine shortages led to the emergency use authorization of a lower intradermal dose. This strategy was aimed at increasing vaccine supply up to fivefold.

Further clinical trials are needed to evaluate responses to JYNNEOS vaccination and compare different administration routes in patients with HIV infection. Protecting this population against mpox is a priority because people with high viral loads or loCD4+ T-lymphocyte counts are especially susceptible to severe disease.
 

Vaccination Responses 

The study assessed the immune response to the JYNNEOS vaccine in patients with HIV who were receiving antiretroviral therapy as outpatients at the Infectious Diseases Unit of Hospital del Mar in Barcelona, Spain. Participants had viral loads controlled by antiretroviral therapy and CD4+ T-lymphocyte counts ≤ 500/mm³ (loCD4 group) or ≥ 500/mm³ (hiCD4 group) in blood. Vaccine responses were compared with those of vaccinated controls without the disease. The study included cases that received the standard subcutaneous vaccine (before August 2022) or the emergency dose-saving intradermal vaccine after its approval in August 2022.

The results demonstrated that the intradermal dose-saving vaccination route is preferable to the subcutaneous route and that patients in the loCD4 group may require at least one booster to generate an efficient response of specific T cells for mpox, wrote the authors.

“This study has two relevant points,” study author Robert Güerri-Fernandez, MD, PhD, head of infectious diseases at the Hospital del Mar Medical Research Institute, told this news organization. “In the subgroup of patients with HIV with effective treatment but without an immune response (ie, loCD4), the vaccine response is worse than in people who have recovered immunity or do not have HIV. Therefore, they need a booster dose.

“The second point is that the intradermal route with one-fifth of the standard subcutaneous dose has a better immune response than the standard subcutaneous route.” He added that it was a good strategy to save doses and be able to vaccinate many more people when vaccine shortages occurred.

“A general conclusion cannot be drawn,” he said. “It needs to be validated with many more subjects, of course, but in some way, it reinforced our confidence in the strategy of health authorities to promote intradermal vaccination. There we had evidence that the patients we were vaccinating intradermally were responding well.”

In Spain, although there is no shortage of vaccines today, they continue to be administered intradermally with a fractionated dose equivalent to one fifth of a standard dose, said Dr. Güerri-Fernandez.

However, in his opinion, observations regarding the two administration routes signal a need for further research. The main message should be that for patients with HIV infection who do not have an immune response, the vaccine response is incomplete, and they need booster doses as well as monitoring of the vaccine immune response, said Dr. Güerri-Fernandez.
 

More Studies Required

The research, which prospectively collected data and blood samples from patients with HIV who received the JYNNEOS vaccine, is small and included only 24 patients with HIV infection, with seven hospital workers who also received the vaccine and seven unvaccinated individuals as controls. “I am one of the control subjects of the study, and intradermal vaccination is not especially pleasant,” said Dr. Güerri-Fernandez. “It is a very innervated area, and the moment of introducing the liquid is uncomfortable. But it is perfectly bearable.”

Outpatient HIV-infected patients from the Infectious Diseases Unit of Hospital del Mar on antiretroviral therapy and with undetectable viral loads were grouped according to their CD4+ T-lymphocyte counts. Those with CD4+ T-lymphocyte counts ≤ 500/mm³ required at least one booster vaccine to exhibit efficient virus-specific T-lymphocyte responses. The magnitude of the T-cell response after this booster correlated directly with the CD4+ T-lymphocyte count of those vaccinated.

For Argentine infectious disease specialist Julián García, MD, clinical researcher at the Huésped Foundation in Buenos Aires, Argentina, who did not participate in the study, it is always productive to know that T-cell responses develop in patients with HIV infection, with CD4+ T-lymphocyte counts > and < 500/mm^3, through an intradermal administration route.

Dr. García emphasized that the most novel aspect is that the JYNNEOS vaccine induces a specific T-cell response in patients with HIV infection that increases with higher CD4+ T-lymphocyte levels. However, he noted that the number of patients was less than 10 in most study groups, and the control group had only intradermal administration, which limits the interpretation of the results. “It will be necessary to verify this in studies with larger groups with control groups from all routes and with a correlate of protection.”

Dr. García referred to this latter point as a significant source of uncertainty. “The study is fundamentally based on the cellular response, but nowadays, there is no immune correlate of real-life protection.” He concluded that the study builds knowledge, which is essential for a vaccine that began to be used for mpox and the effectiveness of which is based on estimates. 

Dr. Güerri-Fernandez and Dr. Garcia declared no relevant financial conflicts of interest. 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The smallpox vaccine effectively induces immunity against mpox virus infection (formerly simian smallpox) in patients with human immunodeficiency virus (HIV) infection, although patients with lymphocyte counts below 500 cells/mm³ require booster doses, according to data from a study published in the Journal of Medical Virology.

The data come from the prospective observational study conducted by researchers at the Infection Biology Laboratory of the Department of Medicine and Life Sciences at Pompeu Fabra University and the HIV Unit of the Hospital del Mar Medical Research Institute in Barcelona, Spain. The investigators analyzed T-cell responses induced by vaccination with JYNNEOS.

Despite the substantial decrease in the reporting frequency of mpox cases from the global peak in August 2022 (30,894 cases) to 804 monthly cases in the last six months of 2023, mpox continues to circulate, and there is no specific vaccine. The JYNNEOS vaccine, with protective cross-reactivity against orthopoxviruses, is approved by the US Food and Drug Administration and the European Medicines Agency for the prevention of smallpox and mpox in adults at high risk for infection.

During the 2022 outbreak in the United States and Europe, vaccine shortages led to the emergency use authorization of a lower intradermal dose. This strategy was aimed at increasing vaccine supply up to fivefold.

Further clinical trials are needed to evaluate responses to JYNNEOS vaccination and compare different administration routes in patients with HIV infection. Protecting this population against mpox is a priority because people with high viral loads or loCD4+ T-lymphocyte counts are especially susceptible to severe disease.
 

Vaccination Responses 

The study assessed the immune response to the JYNNEOS vaccine in patients with HIV who were receiving antiretroviral therapy as outpatients at the Infectious Diseases Unit of Hospital del Mar in Barcelona, Spain. Participants had viral loads controlled by antiretroviral therapy and CD4+ T-lymphocyte counts ≤ 500/mm³ (loCD4 group) or ≥ 500/mm³ (hiCD4 group) in blood. Vaccine responses were compared with those of vaccinated controls without the disease. The study included cases that received the standard subcutaneous vaccine (before August 2022) or the emergency dose-saving intradermal vaccine after its approval in August 2022.

The results demonstrated that the intradermal dose-saving vaccination route is preferable to the subcutaneous route and that patients in the loCD4 group may require at least one booster to generate an efficient response of specific T cells for mpox, wrote the authors.

“This study has two relevant points,” study author Robert Güerri-Fernandez, MD, PhD, head of infectious diseases at the Hospital del Mar Medical Research Institute, told this news organization. “In the subgroup of patients with HIV with effective treatment but without an immune response (ie, loCD4), the vaccine response is worse than in people who have recovered immunity or do not have HIV. Therefore, they need a booster dose.

“The second point is that the intradermal route with one-fifth of the standard subcutaneous dose has a better immune response than the standard subcutaneous route.” He added that it was a good strategy to save doses and be able to vaccinate many more people when vaccine shortages occurred.

“A general conclusion cannot be drawn,” he said. “It needs to be validated with many more subjects, of course, but in some way, it reinforced our confidence in the strategy of health authorities to promote intradermal vaccination. There we had evidence that the patients we were vaccinating intradermally were responding well.”

In Spain, although there is no shortage of vaccines today, they continue to be administered intradermally with a fractionated dose equivalent to one fifth of a standard dose, said Dr. Güerri-Fernandez.

However, in his opinion, observations regarding the two administration routes signal a need for further research. The main message should be that for patients with HIV infection who do not have an immune response, the vaccine response is incomplete, and they need booster doses as well as monitoring of the vaccine immune response, said Dr. Güerri-Fernandez.
 

More Studies Required

The research, which prospectively collected data and blood samples from patients with HIV who received the JYNNEOS vaccine, is small and included only 24 patients with HIV infection, with seven hospital workers who also received the vaccine and seven unvaccinated individuals as controls. “I am one of the control subjects of the study, and intradermal vaccination is not especially pleasant,” said Dr. Güerri-Fernandez. “It is a very innervated area, and the moment of introducing the liquid is uncomfortable. But it is perfectly bearable.”

Outpatient HIV-infected patients from the Infectious Diseases Unit of Hospital del Mar on antiretroviral therapy and with undetectable viral loads were grouped according to their CD4+ T-lymphocyte counts. Those with CD4+ T-lymphocyte counts ≤ 500/mm³ required at least one booster vaccine to exhibit efficient virus-specific T-lymphocyte responses. The magnitude of the T-cell response after this booster correlated directly with the CD4+ T-lymphocyte count of those vaccinated.

For Argentine infectious disease specialist Julián García, MD, clinical researcher at the Huésped Foundation in Buenos Aires, Argentina, who did not participate in the study, it is always productive to know that T-cell responses develop in patients with HIV infection, with CD4+ T-lymphocyte counts > and < 500/mm^3, through an intradermal administration route.

Dr. García emphasized that the most novel aspect is that the JYNNEOS vaccine induces a specific T-cell response in patients with HIV infection that increases with higher CD4+ T-lymphocyte levels. However, he noted that the number of patients was less than 10 in most study groups, and the control group had only intradermal administration, which limits the interpretation of the results. “It will be necessary to verify this in studies with larger groups with control groups from all routes and with a correlate of protection.”

Dr. García referred to this latter point as a significant source of uncertainty. “The study is fundamentally based on the cellular response, but nowadays, there is no immune correlate of real-life protection.” He concluded that the study builds knowledge, which is essential for a vaccine that began to be used for mpox and the effectiveness of which is based on estimates. 

Dr. Güerri-Fernandez and Dr. Garcia declared no relevant financial conflicts of interest. 

This story was translated from the Medscape Spanish edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I want to briefly discuss a critically important topic that cannot be overly emphasized. It is the relevance, the importance, the benefits, and the outcome of HPV vaccination.

The paper I’m referring to was published in Pediatrics in October 2023. It’s titled, “Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety.”

Let me emphasize that we’re talking about a 10-year follow-up. In this particular paper and analysis, 301 boys — I emphasize boys — were included and 971 girls at 40 different sites in 13 countries, who received the 9-valent vaccine, which includes HPV 16, 18, and seven other types.

These investigators demonstrated that the seropositivity rate 10 years after vaccination remained high for all nine types they looked at. Most importantly, there was not a single case. Not one. Let me repeat this: There was not a single case of high-grade intraepithelial neoplasia, or worse, or condyloma in either males or females. There was not a single case in over 1000 individuals with a follow-up of more than 10 years.

It is difficult to overstate the magnitude of the benefit associated with HPV vaccination for our children and young adults on their risk of developing highly relevant, life-changing, potentially deadly cancers.

For those of you who are interested in this topic — which should include almost all of you, if not all of you — I encourage you to read this very important follow-up paper, again, demonstrating the simple, overwhelming magnitude of the benefit of HPV vaccination. I thank you for your attention.
 

Dr. Markman is a professor in the department of medical oncology and therapeutics research, City of Hope, Duarte, California, and president of medicine and science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline; AstraZeneca.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I want to briefly discuss a critically important topic that cannot be overly emphasized. It is the relevance, the importance, the benefits, and the outcome of HPV vaccination.

The paper I’m referring to was published in Pediatrics in October 2023. It’s titled, “Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety.”

Let me emphasize that we’re talking about a 10-year follow-up. In this particular paper and analysis, 301 boys — I emphasize boys — were included and 971 girls at 40 different sites in 13 countries, who received the 9-valent vaccine, which includes HPV 16, 18, and seven other types.

These investigators demonstrated that the seropositivity rate 10 years after vaccination remained high for all nine types they looked at. Most importantly, there was not a single case. Not one. Let me repeat this: There was not a single case of high-grade intraepithelial neoplasia, or worse, or condyloma in either males or females. There was not a single case in over 1000 individuals with a follow-up of more than 10 years.

It is difficult to overstate the magnitude of the benefit associated with HPV vaccination for our children and young adults on their risk of developing highly relevant, life-changing, potentially deadly cancers.

For those of you who are interested in this topic — which should include almost all of you, if not all of you — I encourage you to read this very important follow-up paper, again, demonstrating the simple, overwhelming magnitude of the benefit of HPV vaccination. I thank you for your attention.
 

Dr. Markman is a professor in the department of medical oncology and therapeutics research, City of Hope, Duarte, California, and president of medicine and science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline; AstraZeneca.

A version of this article appeared on Medscape.com.

This transcript has been edited for clarity.

I want to briefly discuss a critically important topic that cannot be overly emphasized. It is the relevance, the importance, the benefits, and the outcome of HPV vaccination.

The paper I’m referring to was published in Pediatrics in October 2023. It’s titled, “Ten-Year Follow-up of 9-Valent Human Papillomavirus Vaccine: Immunogenicity, Effectiveness, and Safety.”

Let me emphasize that we’re talking about a 10-year follow-up. In this particular paper and analysis, 301 boys — I emphasize boys — were included and 971 girls at 40 different sites in 13 countries, who received the 9-valent vaccine, which includes HPV 16, 18, and seven other types.

These investigators demonstrated that the seropositivity rate 10 years after vaccination remained high for all nine types they looked at. Most importantly, there was not a single case. Not one. Let me repeat this: There was not a single case of high-grade intraepithelial neoplasia, or worse, or condyloma in either males or females. There was not a single case in over 1000 individuals with a follow-up of more than 10 years.

It is difficult to overstate the magnitude of the benefit associated with HPV vaccination for our children and young adults on their risk of developing highly relevant, life-changing, potentially deadly cancers.

For those of you who are interested in this topic — which should include almost all of you, if not all of you — I encourage you to read this very important follow-up paper, again, demonstrating the simple, overwhelming magnitude of the benefit of HPV vaccination. I thank you for your attention.
 

Dr. Markman is a professor in the department of medical oncology and therapeutics research, City of Hope, Duarte, California, and president of medicine and science, City of Hope Atlanta, Chicago, and Phoenix. He disclosed ties with GlaxoSmithKline; AstraZeneca.

A version of this article appeared on Medscape.com.

Maria Maio wasn’t the only person in her workplace battling COVID-19 in early December 2023. But while everyone else she knows got better, she got long COVID.

A celebrity makeup artist, the 55-year-old New Yorker had been boosted and vaccinated at every opportunity since vaccines were approved at the end of 2020, until the fall of 2023, when she skipped the shot.

“I really started subscribing to the mindset that you have an immune system and your immune system is supposed to work for you,” she said. “That was the stupidest thing I’ve ever done.”

Maio was not the only person to skip the latest booster: A recent study reported that while nearly 80% of adults in the United States said they’d received their first series of vaccines, barely 20% were up to date on boosters. Nor was Maio alone in getting long COVID 4 years after the start of the deadliest pandemic in a century.

It’s tempting, this far out from the shutdowns of 2020, to think the virus is over, that we’re immune, and nobody’s going to get sick anymore. But while fewer people are getting COVID, it is still very much a part of our lives. And as Maio and others are learning the hard way, long COVID is, too — and it can be deadly.

For those who have recently contracted long COVID, it can feel as if the whole world has moved on from the pandemic, and they are being left behind.
 

Too Easy to Let Our Guard Down

“It’s really difficult to prevent exposure to COVID no matter how careful you are and no matter how many times you are vaccinated,” said Akiko Iwasaki, an immunology professor at Yale School of Medicine, New Haven, Connecticut, and pioneer in long COVID research. Iwasaki was quick to point out that “we should never blame anybody for getting long COVID because there is no bulletproof way of preventing long COVID from happening” — although research shows you can increase your protection through vaccination, masking, and increasing ventilation indoors.

Also, just because you didn’t get long COVID after catching the virus once, doesn’t mean you’ll dodge the bullet if you get sick again, as Maio has now learned twice. She had long COVID in 2022 after her second bout with the virus, with breathing problems and brain fog that lasted for several months.

Subsequent long COVID experiences won’t necessarily mimic previous ones. Although Maio developed brain fog again, this time she didn’t have the breathing problems that plagued her in 2022. Instead, she had headaches so excruciating she thought she was dying of a brain aneurysm.

A Journal of the American Medical Association study released in May identified the 37 most common symptoms of long COVID, including symptom subgroups that occurred in 80% of the nearly 10,000 study participants. But the symptoms that patients with long COVID are experiencing now are slightly different from earlier in the pandemic or at least that’s what doctors are finding at the Post-COVID Recovery Clinic affiliated with the University of Pittsburgh Medical Center.

Michael Risbano, MD, the clinic’s codirector, said fewer patients have pulmonary or lung damage now than in the past, but a steady stream report problems with brain fog, forgetfulness, exercise intolerance (shortness of breath and fatigue with exercise and difficulty performing any kind of exertional activity), and post-exertional malaise (feeling wiped out or fatigued for hours or even days after physical or mental activity).
 

Long COVID Treatments Showing Improvement — Slowly

“There still isn’t a great way to treat any of this,” said Risbano, whose clinic is involved with the National Institute of Health’s RECOVER-VITAL trial, which is evaluating potential treatments including Paxlovid and exercise to treat autonomic dysfunction with similarities to myalgic encephalomyelitis/chronic fatigue syndrome and POTS, exercise intolerance, and neurocognitive effects such as brain fog.

Risbano and colleagues have found that physical therapy and exercise training have helped patients with exercise intolerance and neurocognitive problems. “It’s not a quick thing where they go through one visit and are better the next day,” he stressed. “It takes a little bit of time, a little bit of effort, a little bit of homework — there are no silver bullets, no magic medications.”

A quick fix was definitely not in the cards for Dean Jones, PhD, who could barely move when he developed long COVID in May 2023. A 74-year-old biochemist and professor of medicine at Emory University in Atlanta, Georgia, he’d recovered fully the first time he had COVID, in August 2022, but had a completely different experience the second time. He had been vaccinated four times when he began experiencing chronic fatigue, intense exertion-induced migraines, severe airway congestion, brain fog, and shortness of breath. The symptoms began after Memorial Day and worsened over the next month.

His resting heart rate began racing even when he was sleeping, jumping from 53 to 70 beats per minute. “It was almost as though the virus had hit my heart rather than the lungs alone,” he said.

Doctors prescribed multiple inhalers and glucocorticoids to calm Jones’s immune system. The worst symptoms began to abate after a few weeks. The bad ones continued for fully 2 months, severely limiting Jones’s activity. Although he no longer slept all day, just walking from one room to another was exhausting. A dedicated scientist who typically worked 10-15 hours a day before getting sick, he was lucky to focus on work-related tasks for a fraction of that time.

Although the migraines went away early on, the headaches remained until well into the fall. Jones’s energy level gradually returned, and by Christmas, he was beginning to feel as healthy as he had before getting COVID in May.

Still, he’s not complaining that it took so long to get better. “At 74, there’s a lot of colleagues who have already passed away,” he said. “I respect the realities of my age. There are so many people who died from COVID that I’m thankful I had those vaccines. I’m thankful that I pulled through it and was able to rebound.”
 

Time Helps Healing — But Prompt Care Still Needed

Recovery is the case for most patients with long COVID, said Lisa Sanders, MD, medical director of the Yale New Haven Health Systems Long COVID Consultation Clinic, which opened in March 2023. Although the clinic has a small segment of patients who have had the condition since 2020, “people who recover, who are most people, move on,” she said. “Even the patients who sometimes have to wait a month or so to see me, some of them say, ‘I’m already starting to get better. I wasn’t sure I should come.’”

Maio, too, is recovering but only after multiple visits to the emergency room and a neurologist in late December and early January. The third emergency room trip was prompted after a brief episode in which she lost the feeling in her legs, which began convulsing. A CAT scan showed severely constricted blood vessels in her brain, leading the medical team to speculate she might have reversible cerebral vasoconstriction syndrome (RCVS), which can trigger the thunderclap headaches that had been causing her such misery.

After her third such headache prompted a fourth emergency room visit, further tests confirmed RCVS, which doctors said was related to inflammation caused by COVID. Maio was then admitted to the hospital, where she spent 4 days starting on a regimen of blood pressure medication, magnesium for the headaches, and oxycodone for pain management.

The TV show Maio works on went back into production after the holidays. She went back at the end of January. She’s still having headaches, though they’re less intense, and she’s still taking medication. She was scheduled for another test to look at her blood vessels in February.

Maio has yet to forgive herself for skipping the last booster, even though there’s no guarantee it would have prevented her from getting sick. Her message for others: it’s better to be safe than to be as sorry as she is.

“I’ll never, ever be persuaded by people who don’t believe in vaccines because I believe in science, and I believe in vaccines — that’s why people don’t die at the age of 30 anymore,” she said. “I really think that people need to know about this and what to expect. Because it is horrendous. It is very painful. I would never want anyone to go through this. Ever.”

A version of this article appeared on Medscape.com.

Maria Maio wasn’t the only person in her workplace battling COVID-19 in early December 2023. But while everyone else she knows got better, she got long COVID.

A celebrity makeup artist, the 55-year-old New Yorker had been boosted and vaccinated at every opportunity since vaccines were approved at the end of 2020, until the fall of 2023, when she skipped the shot.

“I really started subscribing to the mindset that you have an immune system and your immune system is supposed to work for you,” she said. “That was the stupidest thing I’ve ever done.”

Maio was not the only person to skip the latest booster: A recent study reported that while nearly 80% of adults in the United States said they’d received their first series of vaccines, barely 20% were up to date on boosters. Nor was Maio alone in getting long COVID 4 years after the start of the deadliest pandemic in a century.

It’s tempting, this far out from the shutdowns of 2020, to think the virus is over, that we’re immune, and nobody’s going to get sick anymore. But while fewer people are getting COVID, it is still very much a part of our lives. And as Maio and others are learning the hard way, long COVID is, too — and it can be deadly.

For those who have recently contracted long COVID, it can feel as if the whole world has moved on from the pandemic, and they are being left behind.
 

Too Easy to Let Our Guard Down

“It’s really difficult to prevent exposure to COVID no matter how careful you are and no matter how many times you are vaccinated,” said Akiko Iwasaki, an immunology professor at Yale School of Medicine, New Haven, Connecticut, and pioneer in long COVID research. Iwasaki was quick to point out that “we should never blame anybody for getting long COVID because there is no bulletproof way of preventing long COVID from happening” — although research shows you can increase your protection through vaccination, masking, and increasing ventilation indoors.

Also, just because you didn’t get long COVID after catching the virus once, doesn’t mean you’ll dodge the bullet if you get sick again, as Maio has now learned twice. She had long COVID in 2022 after her second bout with the virus, with breathing problems and brain fog that lasted for several months.

Subsequent long COVID experiences won’t necessarily mimic previous ones. Although Maio developed brain fog again, this time she didn’t have the breathing problems that plagued her in 2022. Instead, she had headaches so excruciating she thought she was dying of a brain aneurysm.

A Journal of the American Medical Association study released in May identified the 37 most common symptoms of long COVID, including symptom subgroups that occurred in 80% of the nearly 10,000 study participants. But the symptoms that patients with long COVID are experiencing now are slightly different from earlier in the pandemic or at least that’s what doctors are finding at the Post-COVID Recovery Clinic affiliated with the University of Pittsburgh Medical Center.

Michael Risbano, MD, the clinic’s codirector, said fewer patients have pulmonary or lung damage now than in the past, but a steady stream report problems with brain fog, forgetfulness, exercise intolerance (shortness of breath and fatigue with exercise and difficulty performing any kind of exertional activity), and post-exertional malaise (feeling wiped out or fatigued for hours or even days after physical or mental activity).
 

Long COVID Treatments Showing Improvement — Slowly

“There still isn’t a great way to treat any of this,” said Risbano, whose clinic is involved with the National Institute of Health’s RECOVER-VITAL trial, which is evaluating potential treatments including Paxlovid and exercise to treat autonomic dysfunction with similarities to myalgic encephalomyelitis/chronic fatigue syndrome and POTS, exercise intolerance, and neurocognitive effects such as brain fog.

Risbano and colleagues have found that physical therapy and exercise training have helped patients with exercise intolerance and neurocognitive problems. “It’s not a quick thing where they go through one visit and are better the next day,” he stressed. “It takes a little bit of time, a little bit of effort, a little bit of homework — there are no silver bullets, no magic medications.”

A quick fix was definitely not in the cards for Dean Jones, PhD, who could barely move when he developed long COVID in May 2023. A 74-year-old biochemist and professor of medicine at Emory University in Atlanta, Georgia, he’d recovered fully the first time he had COVID, in August 2022, but had a completely different experience the second time. He had been vaccinated four times when he began experiencing chronic fatigue, intense exertion-induced migraines, severe airway congestion, brain fog, and shortness of breath. The symptoms began after Memorial Day and worsened over the next month.

His resting heart rate began racing even when he was sleeping, jumping from 53 to 70 beats per minute. “It was almost as though the virus had hit my heart rather than the lungs alone,” he said.

Doctors prescribed multiple inhalers and glucocorticoids to calm Jones’s immune system. The worst symptoms began to abate after a few weeks. The bad ones continued for fully 2 months, severely limiting Jones’s activity. Although he no longer slept all day, just walking from one room to another was exhausting. A dedicated scientist who typically worked 10-15 hours a day before getting sick, he was lucky to focus on work-related tasks for a fraction of that time.

Although the migraines went away early on, the headaches remained until well into the fall. Jones’s energy level gradually returned, and by Christmas, he was beginning to feel as healthy as he had before getting COVID in May.

Still, he’s not complaining that it took so long to get better. “At 74, there’s a lot of colleagues who have already passed away,” he said. “I respect the realities of my age. There are so many people who died from COVID that I’m thankful I had those vaccines. I’m thankful that I pulled through it and was able to rebound.”
 

Time Helps Healing — But Prompt Care Still Needed

Recovery is the case for most patients with long COVID, said Lisa Sanders, MD, medical director of the Yale New Haven Health Systems Long COVID Consultation Clinic, which opened in March 2023. Although the clinic has a small segment of patients who have had the condition since 2020, “people who recover, who are most people, move on,” she said. “Even the patients who sometimes have to wait a month or so to see me, some of them say, ‘I’m already starting to get better. I wasn’t sure I should come.’”

Maio, too, is recovering but only after multiple visits to the emergency room and a neurologist in late December and early January. The third emergency room trip was prompted after a brief episode in which she lost the feeling in her legs, which began convulsing. A CAT scan showed severely constricted blood vessels in her brain, leading the medical team to speculate she might have reversible cerebral vasoconstriction syndrome (RCVS), which can trigger the thunderclap headaches that had been causing her such misery.

After her third such headache prompted a fourth emergency room visit, further tests confirmed RCVS, which doctors said was related to inflammation caused by COVID. Maio was then admitted to the hospital, where she spent 4 days starting on a regimen of blood pressure medication, magnesium for the headaches, and oxycodone for pain management.

The TV show Maio works on went back into production after the holidays. She went back at the end of January. She’s still having headaches, though they’re less intense, and she’s still taking medication. She was scheduled for another test to look at her blood vessels in February.

Maio has yet to forgive herself for skipping the last booster, even though there’s no guarantee it would have prevented her from getting sick. Her message for others: it’s better to be safe than to be as sorry as she is.

“I’ll never, ever be persuaded by people who don’t believe in vaccines because I believe in science, and I believe in vaccines — that’s why people don’t die at the age of 30 anymore,” she said. “I really think that people need to know about this and what to expect. Because it is horrendous. It is very painful. I would never want anyone to go through this. Ever.”

A version of this article appeared on Medscape.com.

Maria Maio wasn’t the only person in her workplace battling COVID-19 in early December 2023. But while everyone else she knows got better, she got long COVID.

A celebrity makeup artist, the 55-year-old New Yorker had been boosted and vaccinated at every opportunity since vaccines were approved at the end of 2020, until the fall of 2023, when she skipped the shot.

“I really started subscribing to the mindset that you have an immune system and your immune system is supposed to work for you,” she said. “That was the stupidest thing I’ve ever done.”

Maio was not the only person to skip the latest booster: A recent study reported that while nearly 80% of adults in the United States said they’d received their first series of vaccines, barely 20% were up to date on boosters. Nor was Maio alone in getting long COVID 4 years after the start of the deadliest pandemic in a century.

It’s tempting, this far out from the shutdowns of 2020, to think the virus is over, that we’re immune, and nobody’s going to get sick anymore. But while fewer people are getting COVID, it is still very much a part of our lives. And as Maio and others are learning the hard way, long COVID is, too — and it can be deadly.

For those who have recently contracted long COVID, it can feel as if the whole world has moved on from the pandemic, and they are being left behind.
 

Too Easy to Let Our Guard Down

“It’s really difficult to prevent exposure to COVID no matter how careful you are and no matter how many times you are vaccinated,” said Akiko Iwasaki, an immunology professor at Yale School of Medicine, New Haven, Connecticut, and pioneer in long COVID research. Iwasaki was quick to point out that “we should never blame anybody for getting long COVID because there is no bulletproof way of preventing long COVID from happening” — although research shows you can increase your protection through vaccination, masking, and increasing ventilation indoors.

Also, just because you didn’t get long COVID after catching the virus once, doesn’t mean you’ll dodge the bullet if you get sick again, as Maio has now learned twice. She had long COVID in 2022 after her second bout with the virus, with breathing problems and brain fog that lasted for several months.

Subsequent long COVID experiences won’t necessarily mimic previous ones. Although Maio developed brain fog again, this time she didn’t have the breathing problems that plagued her in 2022. Instead, she had headaches so excruciating she thought she was dying of a brain aneurysm.

A Journal of the American Medical Association study released in May identified the 37 most common symptoms of long COVID, including symptom subgroups that occurred in 80% of the nearly 10,000 study participants. But the symptoms that patients with long COVID are experiencing now are slightly different from earlier in the pandemic or at least that’s what doctors are finding at the Post-COVID Recovery Clinic affiliated with the University of Pittsburgh Medical Center.

Michael Risbano, MD, the clinic’s codirector, said fewer patients have pulmonary or lung damage now than in the past, but a steady stream report problems with brain fog, forgetfulness, exercise intolerance (shortness of breath and fatigue with exercise and difficulty performing any kind of exertional activity), and post-exertional malaise (feeling wiped out or fatigued for hours or even days after physical or mental activity).
 

Long COVID Treatments Showing Improvement — Slowly

“There still isn’t a great way to treat any of this,” said Risbano, whose clinic is involved with the National Institute of Health’s RECOVER-VITAL trial, which is evaluating potential treatments including Paxlovid and exercise to treat autonomic dysfunction with similarities to myalgic encephalomyelitis/chronic fatigue syndrome and POTS, exercise intolerance, and neurocognitive effects such as brain fog.

Risbano and colleagues have found that physical therapy and exercise training have helped patients with exercise intolerance and neurocognitive problems. “It’s not a quick thing where they go through one visit and are better the next day,” he stressed. “It takes a little bit of time, a little bit of effort, a little bit of homework — there are no silver bullets, no magic medications.”

A quick fix was definitely not in the cards for Dean Jones, PhD, who could barely move when he developed long COVID in May 2023. A 74-year-old biochemist and professor of medicine at Emory University in Atlanta, Georgia, he’d recovered fully the first time he had COVID, in August 2022, but had a completely different experience the second time. He had been vaccinated four times when he began experiencing chronic fatigue, intense exertion-induced migraines, severe airway congestion, brain fog, and shortness of breath. The symptoms began after Memorial Day and worsened over the next month.

His resting heart rate began racing even when he was sleeping, jumping from 53 to 70 beats per minute. “It was almost as though the virus had hit my heart rather than the lungs alone,” he said.

Doctors prescribed multiple inhalers and glucocorticoids to calm Jones’s immune system. The worst symptoms began to abate after a few weeks. The bad ones continued for fully 2 months, severely limiting Jones’s activity. Although he no longer slept all day, just walking from one room to another was exhausting. A dedicated scientist who typically worked 10-15 hours a day before getting sick, he was lucky to focus on work-related tasks for a fraction of that time.

Although the migraines went away early on, the headaches remained until well into the fall. Jones’s energy level gradually returned, and by Christmas, he was beginning to feel as healthy as he had before getting COVID in May.

Still, he’s not complaining that it took so long to get better. “At 74, there’s a lot of colleagues who have already passed away,” he said. “I respect the realities of my age. There are so many people who died from COVID that I’m thankful I had those vaccines. I’m thankful that I pulled through it and was able to rebound.”
 

Time Helps Healing — But Prompt Care Still Needed

Recovery is the case for most patients with long COVID, said Lisa Sanders, MD, medical director of the Yale New Haven Health Systems Long COVID Consultation Clinic, which opened in March 2023. Although the clinic has a small segment of patients who have had the condition since 2020, “people who recover, who are most people, move on,” she said. “Even the patients who sometimes have to wait a month or so to see me, some of them say, ‘I’m already starting to get better. I wasn’t sure I should come.’”

Maio, too, is recovering but only after multiple visits to the emergency room and a neurologist in late December and early January. The third emergency room trip was prompted after a brief episode in which she lost the feeling in her legs, which began convulsing. A CAT scan showed severely constricted blood vessels in her brain, leading the medical team to speculate she might have reversible cerebral vasoconstriction syndrome (RCVS), which can trigger the thunderclap headaches that had been causing her such misery.

After her third such headache prompted a fourth emergency room visit, further tests confirmed RCVS, which doctors said was related to inflammation caused by COVID. Maio was then admitted to the hospital, where she spent 4 days starting on a regimen of blood pressure medication, magnesium for the headaches, and oxycodone for pain management.

The TV show Maio works on went back into production after the holidays. She went back at the end of January. She’s still having headaches, though they’re less intense, and she’s still taking medication. She was scheduled for another test to look at her blood vessels in February.

Maio has yet to forgive herself for skipping the last booster, even though there’s no guarantee it would have prevented her from getting sick. Her message for others: it’s better to be safe than to be as sorry as she is.

“I’ll never, ever be persuaded by people who don’t believe in vaccines because I believe in science, and I believe in vaccines — that’s why people don’t die at the age of 30 anymore,” she said. “I really think that people need to know about this and what to expect. Because it is horrendous. It is very painful. I would never want anyone to go through this. Ever.”

A version of this article appeared on Medscape.com.

Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.

“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
 

Papillomavirus and Cancer

One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.

However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.

“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.

In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.

It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
 

Time of Infection

Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.

However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.

It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.

Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.

“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
 

Protecting One’s Partner

Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.

The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”

So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
 

Clearing the Virus

There are treatments for cervical lesions but not for papillomavirus infection.

“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.

“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.

“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
 

Papillomavirus and Cancer

One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.

However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.

“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.

In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.

It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
 

Time of Infection

Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.

However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.

It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.

Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.

“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
 

Protecting One’s Partner

Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.

The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”

So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
 

Clearing the Virus

There are treatments for cervical lesions but not for papillomavirus infection.

“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.

“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Faced with a positive human papillomavirus (HPV) test, patients are quickly overwhelmed by anxiety-inducing questions. It is crucial to provide them with adequate responses to reassure them, emphasized Jean-Louis Mergui, MD, president of the International Federation for Colposcopy, during the press conference of the Congress of the French Society of Colposcopy and Cervico-Vaginal Pathology.

“Do I have cancer? When did I catch this papillomavirus? Is it dangerous for my partner? How do I get rid of it?” “Not everyone is equipped to answer these four questions. However, it is extremely important that healthcare professionals provide correct answers to patients so that they stop worrying,” Dr. Mergui explained.
 

Papillomavirus and Cancer

One of the first instincts of patients who receive a positive HPV test is to turn to the Internet. There, they read about “high-risk HPV, which is potentially oncogenic,” and become completely panicked, said Dr. Mergui.

However, among women, the probability of having a high-grade CIN3 lesion or higher on the cervix when the HPV test is positive is about 7%, according to the ATHENA study. “About 93% of patients do not have a severe lesion on the cervix. That’s why colposcopy is not performed on all patients. They need to be reassured,” said Dr. Mergui. When the papillomavirus persists, there is a risk for a cervical lesion. After 11 years, between 20% and 30% of patients develop a high-grade lesion on the cervix. However, on average, a high-risk HPV is spontaneously eliminated within 1-2 years. “After 14 months, 50% of women will test negative for their papillomavirus,” Dr. Mergui noted.

“High-risk HPV does not mean there is a lesion; it means there is a risk of developing a lesion on the cervix one day. That’s why these patients need to be monitored and explored,” he added.

In practice, when a patient aged between 30 and 65 years has a positive HPV test, cytology is performed to look for lesions. Only in the case of an abnormal smear, ASC-US, is colposcopy recommended. In the absence of a lesion, a control HPV test is conducted 1 year later to monitor virus persistence.

It should be noted that patients who have been treated for a cervical lesion have a five times higher risk of developing invasive cervical, vaginal, or vulvar cancer. Therefore, treated patients must be monitored once every 3 years for life.
 

Time of Infection

Many patients ask, “When did I catch this papillomavirus?” In response, Dr. Mergui first emphasized that HPV infection is common. “Between ages 15 and 30 years, most of us are infected with a high-risk HPV. When we look at the incidence between ages 15 and 25 years, every year, 20% of all young girls are infected with HPV, including 17% with high-risk HPV. The virus is usually caught within the first 5 years of sexual activity, and typically disappears after about a year,” he explained.

However, the most disturbing scenario for patients is when their last examination was negative, and there is no apparent reason for having caught the virus since then. Suspicion often falls on the partner. Once again, the gynecologist seeks to reassure.

It is possible that the last time screening was conducted, the virus was not sought (HPV test), but rather cervical lesions were sought by smear. However, a normal smear does not mean that the papillomavirus is not present. A negative cytology does not mean a negative HPV test. As we have seen, the virus is not always associated with the presence of a lesion, explained Dr. Mergui.

Also, having had a negative HPV test a few years earlier does not mean that one was not already infected. The HPV test determines the quantity of virus. Therefore, it is possible that the virus was present in small quantities that were without clinical significance (hence, a negative test). However, a few years later, the virus may have multiplied, and the HPV test became positive.

“Sometimes, the virus re-emerges 40, 50 years after infection due to age-related immune decline,” said Dr. Mergui. “So, just because the smear was negative or the HPV test was negative at the last examination does not mean that one was infected between the two.” Moreover, only 15% of couples have the same virus present on the penis or vagina, he pointed out.
 

Protecting One’s Partner

Once the diagnosis is made, it is often too late to protect the partner because they have already been infected. “It is certain that the partner will be infected or has already been infected because when the patient comes to you with a positive HPV test, she has already had sexual intercourse. It is worth noting that the virus can be transmitted through digital touching, and condoms are not very effective in preventing virus transmission,” said Dr. Mergui.

The speaker further clarified that the risk for men is much lower than that for women. “In women, about 40,000 lesions linked to high-risk HPV types, precancerous or cancerous, are observed every year. In men, this number is 1900. So, this represents 20 times fewer neoplastic lesions in men. The problem in men is oropharyngeal lesions, which are three times more common than in women. However, there is no screening for oropharyngeal cancer.”

So, when should the partner consult? Dr. Mergui advised consulting when there are clinically visible lesions (small warts, bumps, or ear, nose, and throat symptoms). “I do not recommend systematic examination of male or female partners,” he added.
 

Clearing the Virus

There are treatments for cervical lesions but not for papillomavirus infection.

“The only thing that can be suggested is quitting smoking, which increases viral clearance, thus reducing viral load. Also, the use of condoms helps improve viral clearance, but when women have a stable relationship, it seems unrealistic to think they will constantly use condoms. Finally, the prophylactic vaccine has been proposed, but it does not treat the infection. In fact, the real solution is to tell patients that they need to continue regular monitoring,” said Dr. Mergui.

“It should be noted that an ongoing study at the European level seems to show that when women who have undergone surgical treatment for a high-grade cervical lesion are vaccinated at the time of treatment or just after treatment, it reduces the risk of recurrence by 50%. So, the risk of recurrence is around 7%-8%. This strategy could be interesting, but for now, there is no official recommendation,” Dr. Mergui concluded.
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Cases of menstrual disorders, particularly unusually heavy menstrual bleeding, have been reported following RNA vaccination against COVID-19.

In France, this safety signal has been confirmed and added to the product characteristics summaries and vaccine leaflets for mRNA vaccines in October 2022. However, few studies have accurately measured this risk to date.

To address this gap in research, the French scientific interest group in the epidemiology of health products, ANSM-Cnam EPI-PHARE, conducted a study to assess the risk for heavy menstrual bleeding requiring hospitalization after COVID-19 vaccination in France.

“This study provides new evidence supporting the existence of an increased risk for heavy menstrual bleeding following COVID-19 vaccination with mRNA vaccines,” wrote the authors.
 

Study Details

The study included all women aged 15-50 years who were diagnosed with heavy menstrual bleeding in the hospital between May 12, 2021, and August 31, 2022. Participants were identified in the National Health Data System, and the study population totaled 4610 women.

Each participant was randomly matched with as many as 30 women who had not been hospitalized for abnormal genital bleeding and had similar characteristics in terms of age, department of residence, social deprivation index of the commune of residence, and contraceptive method.

Women who had a recent pregnancy, hysterectomy, or coagulation disorder within the specified time frames were excluded.

At the time of the study, 71% of cases and 70% of controls had received at least one dose of the COVID-19 vaccine. Among vaccinated participants, 68% and 66%, respectively, received a vaccination dose (first or second dose). An mRNA vaccine (Comirnaty or Spikevax) was the last vaccine for 99.8% of the population.
 

Increased Risk 

Compared with control women, those hospitalized for heavy menstrual bleeding were more likely to have received their last dose of mRNA vaccine (Comirnaty or Spikevax) in the previous 1-3 months. This association was observed for vaccination doses (odds ratio [OR], 1.20), indicating a 20% increased risk, but it was not found for booster doses (OR, 1.07).

This association was particularly notable for women residing in socially disadvantaged communities (OR, 1.28) and women not using hormonal contraception (OR, 1.28).

The risk did not appear to be increased beyond 3 months after vaccination. Researchers noted that the increased risk may have occurred earlier, considering the likely interval between initial symptoms and hospitalization.

Assuming a causal relationship, the estimated number of cases attributable to vaccination was 8 cases per million vaccinated women, totaling 103 cases among all women aged 15-50 years who were vaccinated in France between May 12, 2021, and August 31, 2022.

As of the study date and in the 3 years before the study, none of the authors had any conflicts of interest with pharmaceutical companies. 
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Cases of menstrual disorders, particularly unusually heavy menstrual bleeding, have been reported following RNA vaccination against COVID-19.

In France, this safety signal has been confirmed and added to the product characteristics summaries and vaccine leaflets for mRNA vaccines in October 2022. However, few studies have accurately measured this risk to date.

To address this gap in research, the French scientific interest group in the epidemiology of health products, ANSM-Cnam EPI-PHARE, conducted a study to assess the risk for heavy menstrual bleeding requiring hospitalization after COVID-19 vaccination in France.

“This study provides new evidence supporting the existence of an increased risk for heavy menstrual bleeding following COVID-19 vaccination with mRNA vaccines,” wrote the authors.
 

Study Details

The study included all women aged 15-50 years who were diagnosed with heavy menstrual bleeding in the hospital between May 12, 2021, and August 31, 2022. Participants were identified in the National Health Data System, and the study population totaled 4610 women.

Each participant was randomly matched with as many as 30 women who had not been hospitalized for abnormal genital bleeding and had similar characteristics in terms of age, department of residence, social deprivation index of the commune of residence, and contraceptive method.

Women who had a recent pregnancy, hysterectomy, or coagulation disorder within the specified time frames were excluded.

At the time of the study, 71% of cases and 70% of controls had received at least one dose of the COVID-19 vaccine. Among vaccinated participants, 68% and 66%, respectively, received a vaccination dose (first or second dose). An mRNA vaccine (Comirnaty or Spikevax) was the last vaccine for 99.8% of the population.
 

Increased Risk 

Compared with control women, those hospitalized for heavy menstrual bleeding were more likely to have received their last dose of mRNA vaccine (Comirnaty or Spikevax) in the previous 1-3 months. This association was observed for vaccination doses (odds ratio [OR], 1.20), indicating a 20% increased risk, but it was not found for booster doses (OR, 1.07).

This association was particularly notable for women residing in socially disadvantaged communities (OR, 1.28) and women not using hormonal contraception (OR, 1.28).

The risk did not appear to be increased beyond 3 months after vaccination. Researchers noted that the increased risk may have occurred earlier, considering the likely interval between initial symptoms and hospitalization.

Assuming a causal relationship, the estimated number of cases attributable to vaccination was 8 cases per million vaccinated women, totaling 103 cases among all women aged 15-50 years who were vaccinated in France between May 12, 2021, and August 31, 2022.

As of the study date and in the 3 years before the study, none of the authors had any conflicts of interest with pharmaceutical companies. 
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

Cases of menstrual disorders, particularly unusually heavy menstrual bleeding, have been reported following RNA vaccination against COVID-19.

In France, this safety signal has been confirmed and added to the product characteristics summaries and vaccine leaflets for mRNA vaccines in October 2022. However, few studies have accurately measured this risk to date.

To address this gap in research, the French scientific interest group in the epidemiology of health products, ANSM-Cnam EPI-PHARE, conducted a study to assess the risk for heavy menstrual bleeding requiring hospitalization after COVID-19 vaccination in France.

“This study provides new evidence supporting the existence of an increased risk for heavy menstrual bleeding following COVID-19 vaccination with mRNA vaccines,” wrote the authors.
 

Study Details

The study included all women aged 15-50 years who were diagnosed with heavy menstrual bleeding in the hospital between May 12, 2021, and August 31, 2022. Participants were identified in the National Health Data System, and the study population totaled 4610 women.

Each participant was randomly matched with as many as 30 women who had not been hospitalized for abnormal genital bleeding and had similar characteristics in terms of age, department of residence, social deprivation index of the commune of residence, and contraceptive method.

Women who had a recent pregnancy, hysterectomy, or coagulation disorder within the specified time frames were excluded.

At the time of the study, 71% of cases and 70% of controls had received at least one dose of the COVID-19 vaccine. Among vaccinated participants, 68% and 66%, respectively, received a vaccination dose (first or second dose). An mRNA vaccine (Comirnaty or Spikevax) was the last vaccine for 99.8% of the population.
 

Increased Risk 

Compared with control women, those hospitalized for heavy menstrual bleeding were more likely to have received their last dose of mRNA vaccine (Comirnaty or Spikevax) in the previous 1-3 months. This association was observed for vaccination doses (odds ratio [OR], 1.20), indicating a 20% increased risk, but it was not found for booster doses (OR, 1.07).

This association was particularly notable for women residing in socially disadvantaged communities (OR, 1.28) and women not using hormonal contraception (OR, 1.28).

The risk did not appear to be increased beyond 3 months after vaccination. Researchers noted that the increased risk may have occurred earlier, considering the likely interval between initial symptoms and hospitalization.

Assuming a causal relationship, the estimated number of cases attributable to vaccination was 8 cases per million vaccinated women, totaling 103 cases among all women aged 15-50 years who were vaccinated in France between May 12, 2021, and August 31, 2022.

As of the study date and in the 3 years before the study, none of the authors had any conflicts of interest with pharmaceutical companies. 
 

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

When infants are born, they have nearly a clean slate with regard to their immune systems. Virtually all their immune cells are naive. They have no immunity memory. Vaccines at birth, and in the first 2 years of life, elicit variable antibody levels and cellular immune responses. Sometimes, this leaves fully vaccinated children unprotected against vaccine-preventable infectious diseases.

Newborns are bombarded at birth with microbes and other antigenic stimuli from the environment; food in the form of breast milk, formula, water; and vaccines, such as hepatitis B and, in other countries, with BCG. At birth, to avoid immunologically-induced injury, immune responses favor immunologic tolerance. However, adaptation must be rapid to avoid life-threatening infections. To navigate the gauntlet of microbe and environmental exposures and vaccines, the neonatal immune system moves through a gradual maturation process toward immune responsivity. The maturation occurs at different rates in different children. A major factor affecting immune development is the microbiome of the newborn and the first 100 days of life.
 

Reassessing Vaccine Responsiveness

Vaccine responsiveness is usually assessed by measuring antibody levels in blood. Until recently, it was thought to be “bad luck” when a child failed to develop protective immunity following vaccination. The bad luck was suggested to involve illness at the time of vaccination, especially illness occurring with fever, and especially common viral infections. But studies proved that notion incorrect. About 10 years ago I became more interested in variability in vaccine responses in the first 2 years of life. In 2016, my laboratory described a specific population of children with specific cellular immune deficiencies that we classified as low vaccine responders (LVRs).¹ To preclude the suggestion that low vaccine responses were to be considered normal biological variation, we chose an a priori definition of LVR as those with sub-protective IgG antibody levels to four (≥ 66 %) of six tested vaccines in DTaP-Hib (diphtheria toxoid, tetanus toxoid, pertussis toxoid, pertactin, and filamentous hemagglutinin [DTaP] and Haemophilus influenzae type b polysaccharide capsule [Hib]). Antibody levels were measured at 1 year of age following primary vaccinations at child age 2, 4, and 6 months old. The remaining 89% of children we termed normal vaccine responders (NVRs). We additionally tested antibody responses to viral protein and pneumococcal polysaccharide conjugated antigens (polio serotypes 1, 2, and 3, hepatitis B, and Streptococcus pneumoniae capsular polysaccharides serotypes 6B, 14, and 23F). Responses to these vaccine antigens were similar to the six vaccines (DTaP/Hib) used to define LVR. We and other groups have used alternative definitions of low vaccine responses that rely on statistics.

I recently reviewed the topic of the determinants of vaccine responses in early life, with a focus on the infant microbiome and metabolome: a.) cesarean section versus vaginal delivery, b.) breast versus formula feeding and c.) antibiotic exposure, that impact the immune response² (Figure). In the review I also discussed how microbiome may serve as natural adjuvants for vaccine responses, how microbiota-derived metabolites influence vaccine responses, and how low vaccine responses in early life may be linked to increased infection susceptibility (Figure).

Courtesy Dr. Pichichero

Multiple studies strongly support the notion that breastfeeding has a favorable impact on immune development in early life associated with better vaccine responses, mediated by the microbiome. The mechanism of favorable immune responses to vaccines largely relates to the presence of a specific bacteria species, Bifidobacterium infantis. Breast milk contains human milk oligosaccharides that are not digestible by newborns. B. infantis is a strain of bacteria that utilizes these non-digestible oligosaccharides. Thereby, infants fed breast milk provides B. infantis the essential source of nutrition for its growth and predominance in the newborn gut. Studies have shown that Bifidobacterium spp. abundance in early life is correlated with better immune responses to multiple vaccines. Bifidobacterium spp. abundance has been positively correlated with antibody responses measured after 2 years, linking the microbiome composition to the durability of vaccine-induced immune responses.

Antibiotic exposure in early life may disproportionately damage the newborn and infant microbiome compared with later childhood. The average child receives about three antibiotic courses by the age of 2 years. My lab was among the first to describe the adverse effects of antibiotics on vaccine responses in early life.³ We found that broader spectrum antibiotics had a greater adverse effect on vaccine-induced antibody levels than narrower spectrum antibiotics. Ten-day versus five-day treatment courses had a greater negative effect. Multiple antibiotic courses over time (cumulative antibiotic exposure) was negatively associated with vaccine-induced antibody levels.

Over 11 % of live births worldwide occur preterm. Because bacterial infections are frequent complications of preterm birth, 79 % of very low birthweight and 87 % of extremely low birthweight infants in US NICUs receive antibiotics within 3 days of birth. Recently, my group studied full-term infants at birth and found that exposure to parenteral antibiotics at birth or during the first days of life had an adverse effect on vaccine responses.⁴
 

Microbiome Impacts Immunity

How does the microbiome affect immunity, and specifically vaccine responses? Microbial-derived metabolites affect host immunity. Gut bacteria produce short chain fatty acids (SCFAs: acetate, propionate, butyrate) [115]. SCFAs positively influence immunity cells. Vitamin D metabolites are generated by intestinal bacteria and those metabolites positively influence immunity. Secondary bile acids produced by Clostridium spp. are involved in favorable immune responses. Increased levels of phenylpyruvic acid produced by gut and/or nasopharyngeal microbiota correlate with reduced vaccine responses and upregulated metabolome genes that encode for oxidative phosphorylation correlate with increased vaccine responses.

In summary, immune development commences at birth. Impairment in responses to vaccination in children have been linked to disturbance in the microbiome. Cesarean section and absence of breastfeeding are associated with adverse microbiota composition. Antibiotics perturb healthy microbiota development. The microbiota affect immunity in several ways, among them are effects by metabolites generated by the commensals that inhabit the child host. A child who responds poorly to vaccines and has specific immune cell dysfunction caused by problems with the microbiome also displays increased infection proneness. But that is a story for another column, later.

Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (N.Y.) General Hospital. He has no conflicts of interest to declare.

References

1. Pichichero ME et al. J Infect Dis. 2016 Jun 15;213(12):2014-2019. doi: 10.1093/infdis/jiw053.

2. Pichichero ME. Cell Immunol. 2023 Nov-Dec:393-394:104777. doi: 10.1016/j.cellimm.2023.104777.

3. Chapman TJ et al. Pediatrics. 2022 May 1;149(5):e2021052061. doi: 10.1542/peds.2021-052061.

4. Shaffer M et al. mSystems. 2023 Oct 26;8(5):e0066123. doi: 10.1128/msystems.00661-23.

When infants are born, they have nearly a clean slate with regard to their immune systems. Virtually all their immune cells are naive. They have no immunity memory. Vaccines at birth, and in the first 2 years of life, elicit variable antibody levels and cellular immune responses. Sometimes, this leaves fully vaccinated children unprotected against vaccine-preventable infectious diseases.

Newborns are bombarded at birth with microbes and other antigenic stimuli from the environment; food in the form of breast milk, formula, water; and vaccines, such as hepatitis B and, in other countries, with BCG. At birth, to avoid immunologically-induced injury, immune responses favor immunologic tolerance. However, adaptation must be rapid to avoid life-threatening infections. To navigate the gauntlet of microbe and environmental exposures and vaccines, the neonatal immune system moves through a gradual maturation process toward immune responsivity. The maturation occurs at different rates in different children. A major factor affecting immune development is the microbiome of the newborn and the first 100 days of life.
 

Reassessing Vaccine Responsiveness

Vaccine responsiveness is usually assessed by measuring antibody levels in blood. Until recently, it was thought to be “bad luck” when a child failed to develop protective immunity following vaccination. The bad luck was suggested to involve illness at the time of vaccination, especially illness occurring with fever, and especially common viral infections. But studies proved that notion incorrect. About 10 years ago I became more interested in variability in vaccine responses in the first 2 years of life. In 2016, my laboratory described a specific population of children with specific cellular immune deficiencies that we classified as low vaccine responders (LVRs).¹ To preclude the suggestion that low vaccine responses were to be considered normal biological variation, we chose an a priori definition of LVR as those with sub-protective IgG antibody levels to four (≥ 66 %) of six tested vaccines in DTaP-Hib (diphtheria toxoid, tetanus toxoid, pertussis toxoid, pertactin, and filamentous hemagglutinin [DTaP] and Haemophilus influenzae type b polysaccharide capsule [Hib]). Antibody levels were measured at 1 year of age following primary vaccinations at child age 2, 4, and 6 months old. The remaining 89% of children we termed normal vaccine responders (NVRs). We additionally tested antibody responses to viral protein and pneumococcal polysaccharide conjugated antigens (polio serotypes 1, 2, and 3, hepatitis B, and Streptococcus pneumoniae capsular polysaccharides serotypes 6B, 14, and 23F). Responses to these vaccine antigens were similar to the six vaccines (DTaP/Hib) used to define LVR. We and other groups have used alternative definitions of low vaccine responses that rely on statistics.

I recently reviewed the topic of the determinants of vaccine responses in early life, with a focus on the infant microbiome and metabolome: a.) cesarean section versus vaginal delivery, b.) breast versus formula feeding and c.) antibiotic exposure, that impact the immune response² (Figure). In the review I also discussed how microbiome may serve as natural adjuvants for vaccine responses, how microbiota-derived metabolites influence vaccine responses, and how low vaccine responses in early life may be linked to increased infection susceptibility (Figure).

Courtesy Dr. Pichichero

Multiple studies strongly support the notion that breastfeeding has a favorable impact on immune development in early life associated with better vaccine responses, mediated by the microbiome. The mechanism of favorable immune responses to vaccines largely relates to the presence of a specific bacteria species, Bifidobacterium infantis. Breast milk contains human milk oligosaccharides that are not digestible by newborns. B. infantis is a strain of bacteria that utilizes these non-digestible oligosaccharides. Thereby, infants fed breast milk provides B. infantis the essential source of nutrition for its growth and predominance in the newborn gut. Studies have shown that Bifidobacterium spp. abundance in early life is correlated with better immune responses to multiple vaccines. Bifidobacterium spp. abundance has been positively correlated with antibody responses measured after 2 years, linking the microbiome composition to the durability of vaccine-induced immune responses.

Antibiotic exposure in early life may disproportionately damage the newborn and infant microbiome compared with later childhood. The average child receives about three antibiotic courses by the age of 2 years. My lab was among the first to describe the adverse effects of antibiotics on vaccine responses in early life.³ We found that broader spectrum antibiotics had a greater adverse effect on vaccine-induced antibody levels than narrower spectrum antibiotics. Ten-day versus five-day treatment courses had a greater negative effect. Multiple antibiotic courses over time (cumulative antibiotic exposure) was negatively associated with vaccine-induced antibody levels.

Over 11 % of live births worldwide occur preterm. Because bacterial infections are frequent complications of preterm birth, 79 % of very low birthweight and 87 % of extremely low birthweight infants in US NICUs receive antibiotics within 3 days of birth. Recently, my group studied full-term infants at birth and found that exposure to parenteral antibiotics at birth or during the first days of life had an adverse effect on vaccine responses.⁴
 

Microbiome Impacts Immunity

How does the microbiome affect immunity, and specifically vaccine responses? Microbial-derived metabolites affect host immunity. Gut bacteria produce short chain fatty acids (SCFAs: acetate, propionate, butyrate) [115]. SCFAs positively influence immunity cells. Vitamin D metabolites are generated by intestinal bacteria and those metabolites positively influence immunity. Secondary bile acids produced by Clostridium spp. are involved in favorable immune responses. Increased levels of phenylpyruvic acid produced by gut and/or nasopharyngeal microbiota correlate with reduced vaccine responses and upregulated metabolome genes that encode for oxidative phosphorylation correlate with increased vaccine responses.

In summary, immune development commences at birth. Impairment in responses to vaccination in children have been linked to disturbance in the microbiome. Cesarean section and absence of breastfeeding are associated with adverse microbiota composition. Antibiotics perturb healthy microbiota development. The microbiota affect immunity in several ways, among them are effects by metabolites generated by the commensals that inhabit the child host. A child who responds poorly to vaccines and has specific immune cell dysfunction caused by problems with the microbiome also displays increased infection proneness. But that is a story for another column, later.

Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (N.Y.) General Hospital. He has no conflicts of interest to declare.

References

1. Pichichero ME et al. J Infect Dis. 2016 Jun 15;213(12):2014-2019. doi: 10.1093/infdis/jiw053.

2. Pichichero ME. Cell Immunol. 2023 Nov-Dec:393-394:104777. doi: 10.1016/j.cellimm.2023.104777.

3. Chapman TJ et al. Pediatrics. 2022 May 1;149(5):e2021052061. doi: 10.1542/peds.2021-052061.

4. Shaffer M et al. mSystems. 2023 Oct 26;8(5):e0066123. doi: 10.1128/msystems.00661-23.

When infants are born, they have nearly a clean slate with regard to their immune systems. Virtually all their immune cells are naive. They have no immunity memory. Vaccines at birth, and in the first 2 years of life, elicit variable antibody levels and cellular immune responses. Sometimes, this leaves fully vaccinated children unprotected against vaccine-preventable infectious diseases.

Newborns are bombarded at birth with microbes and other antigenic stimuli from the environment; food in the form of breast milk, formula, water; and vaccines, such as hepatitis B and, in other countries, with BCG. At birth, to avoid immunologically-induced injury, immune responses favor immunologic tolerance. However, adaptation must be rapid to avoid life-threatening infections. To navigate the gauntlet of microbe and environmental exposures and vaccines, the neonatal immune system moves through a gradual maturation process toward immune responsivity. The maturation occurs at different rates in different children. A major factor affecting immune development is the microbiome of the newborn and the first 100 days of life.
 

Reassessing Vaccine Responsiveness

Vaccine responsiveness is usually assessed by measuring antibody levels in blood. Until recently, it was thought to be “bad luck” when a child failed to develop protective immunity following vaccination. The bad luck was suggested to involve illness at the time of vaccination, especially illness occurring with fever, and especially common viral infections. But studies proved that notion incorrect. About 10 years ago I became more interested in variability in vaccine responses in the first 2 years of life. In 2016, my laboratory described a specific population of children with specific cellular immune deficiencies that we classified as low vaccine responders (LVRs).¹ To preclude the suggestion that low vaccine responses were to be considered normal biological variation, we chose an a priori definition of LVR as those with sub-protective IgG antibody levels to four (≥ 66 %) of six tested vaccines in DTaP-Hib (diphtheria toxoid, tetanus toxoid, pertussis toxoid, pertactin, and filamentous hemagglutinin [DTaP] and Haemophilus influenzae type b polysaccharide capsule [Hib]). Antibody levels were measured at 1 year of age following primary vaccinations at child age 2, 4, and 6 months old. The remaining 89% of children we termed normal vaccine responders (NVRs). We additionally tested antibody responses to viral protein and pneumococcal polysaccharide conjugated antigens (polio serotypes 1, 2, and 3, hepatitis B, and Streptococcus pneumoniae capsular polysaccharides serotypes 6B, 14, and 23F). Responses to these vaccine antigens were similar to the six vaccines (DTaP/Hib) used to define LVR. We and other groups have used alternative definitions of low vaccine responses that rely on statistics.

I recently reviewed the topic of the determinants of vaccine responses in early life, with a focus on the infant microbiome and metabolome: a.) cesarean section versus vaginal delivery, b.) breast versus formula feeding and c.) antibiotic exposure, that impact the immune response² (Figure). In the review I also discussed how microbiome may serve as natural adjuvants for vaccine responses, how microbiota-derived metabolites influence vaccine responses, and how low vaccine responses in early life may be linked to increased infection susceptibility (Figure).

Courtesy Dr. Pichichero

Multiple studies strongly support the notion that breastfeeding has a favorable impact on immune development in early life associated with better vaccine responses, mediated by the microbiome. The mechanism of favorable immune responses to vaccines largely relates to the presence of a specific bacteria species, Bifidobacterium infantis. Breast milk contains human milk oligosaccharides that are not digestible by newborns. B. infantis is a strain of bacteria that utilizes these non-digestible oligosaccharides. Thereby, infants fed breast milk provides B. infantis the essential source of nutrition for its growth and predominance in the newborn gut. Studies have shown that Bifidobacterium spp. abundance in early life is correlated with better immune responses to multiple vaccines. Bifidobacterium spp. abundance has been positively correlated with antibody responses measured after 2 years, linking the microbiome composition to the durability of vaccine-induced immune responses.

Antibiotic exposure in early life may disproportionately damage the newborn and infant microbiome compared with later childhood. The average child receives about three antibiotic courses by the age of 2 years. My lab was among the first to describe the adverse effects of antibiotics on vaccine responses in early life.³ We found that broader spectrum antibiotics had a greater adverse effect on vaccine-induced antibody levels than narrower spectrum antibiotics. Ten-day versus five-day treatment courses had a greater negative effect. Multiple antibiotic courses over time (cumulative antibiotic exposure) was negatively associated with vaccine-induced antibody levels.

Over 11 % of live births worldwide occur preterm. Because bacterial infections are frequent complications of preterm birth, 79 % of very low birthweight and 87 % of extremely low birthweight infants in US NICUs receive antibiotics within 3 days of birth. Recently, my group studied full-term infants at birth and found that exposure to parenteral antibiotics at birth or during the first days of life had an adverse effect on vaccine responses.⁴
 

Microbiome Impacts Immunity

How does the microbiome affect immunity, and specifically vaccine responses? Microbial-derived metabolites affect host immunity. Gut bacteria produce short chain fatty acids (SCFAs: acetate, propionate, butyrate) [115]. SCFAs positively influence immunity cells. Vitamin D metabolites are generated by intestinal bacteria and those metabolites positively influence immunity. Secondary bile acids produced by Clostridium spp. are involved in favorable immune responses. Increased levels of phenylpyruvic acid produced by gut and/or nasopharyngeal microbiota correlate with reduced vaccine responses and upregulated metabolome genes that encode for oxidative phosphorylation correlate with increased vaccine responses.

In summary, immune development commences at birth. Impairment in responses to vaccination in children have been linked to disturbance in the microbiome. Cesarean section and absence of breastfeeding are associated with adverse microbiota composition. Antibiotics perturb healthy microbiota development. The microbiota affect immunity in several ways, among them are effects by metabolites generated by the commensals that inhabit the child host. A child who responds poorly to vaccines and has specific immune cell dysfunction caused by problems with the microbiome also displays increased infection proneness. But that is a story for another column, later.

Dr. Pichichero is a specialist in pediatric infectious diseases, Center for Infectious Diseases and Immunology, and director of the Research Institute, at Rochester (N.Y.) General Hospital. He has no conflicts of interest to declare.

References

1. Pichichero ME et al. J Infect Dis. 2016 Jun 15;213(12):2014-2019. doi: 10.1093/infdis/jiw053.

2. Pichichero ME. Cell Immunol. 2023 Nov-Dec:393-394:104777. doi: 10.1016/j.cellimm.2023.104777.

3. Chapman TJ et al. Pediatrics. 2022 May 1;149(5):e2021052061. doi: 10.1542/peds.2021-052061.

4. Shaffer M et al. mSystems. 2023 Oct 26;8(5):e0066123. doi: 10.1128/msystems.00661-23.

TOPLINE:

The vaccine Cervarix was effective in protecting women from cervical cancer when administered between ages 12 and 13 years, according to a new study published in Journal of the National Cancer Institute.

METHODOLOGY:

• Cervical cancer is the fourth most common cancer among women worldwide.
• Programs to provide Cervarix, a bivalent vaccine, began in the United Kingdom in 2007.
• After the initiation of the programs, administering the vaccine became part of routine care for girls starting at age 12 years.
• Researchers collected data in 2020 from 447,845 women born between 1988 and 1996 from the Scottish cervical cancer screening system to assess the efficacy of Cervarix in lowering rates of cervical cancer.
• They correlated the rate of cervical cancer per 100,000 person-years with data on women regarding vaccination status, age when vaccinated, and deprivation in areas like income, housing, and health.

TAKEAWAY:

• No cases of cervical cancer were found among women who were immunized at ages 12 or 13 years, no matter how many doses they received. 
• Women who were immunized between ages 14 and 18 years and received three doses had fewer instances of cervical cancer compared with unvaccinated women regardless of deprivation status (3.2 cases per 100,00 women vs 8.4 cases per 100,000). 

IN PRACTICE:

“Continued participation in screening and monitoring of outcomes is required, however, to assess the effects of changes in vaccines used and dosage schedules since the start of vaccination in Scotland in 2008 and the longevity of protection the vaccines offer.”

SOURCE:

The study was led by Timothy J. Palmer, PhD, Scottish Clinical Lead for Cervical Screening at Public Health Scotland.

LIMITATIONS:

Only 14,645 women had received just one or two doses, which may have affected the statistical analysis. 

DISCLOSURES:

The study was funded by Public Health Scotland. A coauthor reports attending an advisory board meeting for HOLOGIC and Vaccitech. Her institution received research funding or gratis support funding from Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis, Seegene, Roche, Hologic, and Vaccitech in the past 3 years.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The vaccine Cervarix was effective in protecting women from cervical cancer when administered between ages 12 and 13 years, according to a new study published in Journal of the National Cancer Institute.

METHODOLOGY:

• Cervical cancer is the fourth most common cancer among women worldwide.
• Programs to provide Cervarix, a bivalent vaccine, began in the United Kingdom in 2007.
• After the initiation of the programs, administering the vaccine became part of routine care for girls starting at age 12 years.
• Researchers collected data in 2020 from 447,845 women born between 1988 and 1996 from the Scottish cervical cancer screening system to assess the efficacy of Cervarix in lowering rates of cervical cancer.
• They correlated the rate of cervical cancer per 100,000 person-years with data on women regarding vaccination status, age when vaccinated, and deprivation in areas like income, housing, and health.

TAKEAWAY:

• No cases of cervical cancer were found among women who were immunized at ages 12 or 13 years, no matter how many doses they received. 
• Women who were immunized between ages 14 and 18 years and received three doses had fewer instances of cervical cancer compared with unvaccinated women regardless of deprivation status (3.2 cases per 100,00 women vs 8.4 cases per 100,000). 

IN PRACTICE:

“Continued participation in screening and monitoring of outcomes is required, however, to assess the effects of changes in vaccines used and dosage schedules since the start of vaccination in Scotland in 2008 and the longevity of protection the vaccines offer.”

SOURCE:

The study was led by Timothy J. Palmer, PhD, Scottish Clinical Lead for Cervical Screening at Public Health Scotland.

LIMITATIONS:

Only 14,645 women had received just one or two doses, which may have affected the statistical analysis. 

DISCLOSURES:

The study was funded by Public Health Scotland. A coauthor reports attending an advisory board meeting for HOLOGIC and Vaccitech. Her institution received research funding or gratis support funding from Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis, Seegene, Roche, Hologic, and Vaccitech in the past 3 years.
 

A version of this article appeared on Medscape.com.

TOPLINE:

The vaccine Cervarix was effective in protecting women from cervical cancer when administered between ages 12 and 13 years, according to a new study published in Journal of the National Cancer Institute.

METHODOLOGY:

• Cervical cancer is the fourth most common cancer among women worldwide.
• Programs to provide Cervarix, a bivalent vaccine, began in the United Kingdom in 2007.
• After the initiation of the programs, administering the vaccine became part of routine care for girls starting at age 12 years.
• Researchers collected data in 2020 from 447,845 women born between 1988 and 1996 from the Scottish cervical cancer screening system to assess the efficacy of Cervarix in lowering rates of cervical cancer.
• They correlated the rate of cervical cancer per 100,000 person-years with data on women regarding vaccination status, age when vaccinated, and deprivation in areas like income, housing, and health.

TAKEAWAY:

• No cases of cervical cancer were found among women who were immunized at ages 12 or 13 years, no matter how many doses they received. 
• Women who were immunized between ages 14 and 18 years and received three doses had fewer instances of cervical cancer compared with unvaccinated women regardless of deprivation status (3.2 cases per 100,00 women vs 8.4 cases per 100,000). 

IN PRACTICE:

“Continued participation in screening and monitoring of outcomes is required, however, to assess the effects of changes in vaccines used and dosage schedules since the start of vaccination in Scotland in 2008 and the longevity of protection the vaccines offer.”

SOURCE:

The study was led by Timothy J. Palmer, PhD, Scottish Clinical Lead for Cervical Screening at Public Health Scotland.

LIMITATIONS:

Only 14,645 women had received just one or two doses, which may have affected the statistical analysis. 

DISCLOSURES:

The study was funded by Public Health Scotland. A coauthor reports attending an advisory board meeting for HOLOGIC and Vaccitech. Her institution received research funding or gratis support funding from Cepheid, Euroimmun, GeneFirst, SelfScreen, Hiantis, Seegene, Roche, Hologic, and Vaccitech in the past 3 years.
 

A version of this article appeared on Medscape.com.

If a pregnant woman contracts rubella in the first 17 weeks of pregnancy, then the risk for congenital rubella in the newborn — which may entail spontaneous abortion, intrauterine death, or severe fetal malformations — is as high as 80%. This risk once frightened patients and clinicians in Italy. Thanks to widespread population vaccination, however, the World Health Organization declared the elimination of endemic transmission of rubella in Italy in 2021. The Italian National Institute of Health took note, and the recent update of the Guidelines for the Management of Physiological Pregnancy no longer recommends offering rubella screening to all pregnant women.

The Rubeo Test

The rubeo test, an analysis for detecting antibodies in the blood produced by vaccination or a past rubella infection, traditionally forms part of the examination package that every doctor prescribes to expectant patients at the beginning of pregnancy. If the test shows that the woman is not vaccinated and has never encountered the virus, making her susceptible to the risk for infection, according to the previous edition of the Guidelines, then the test should be repeated at 17 weeks of gestation. The purpose is to detect any rubella contracted during pregnancy and offer the woman multidisciplinary counseling in the case of a high risk for severe fetal damage. Infection contracted after the 17th week, however, poses only a minimal risk for congenital deafness. There is no treatment to prevent vertical transmission in case of infection during pregnancy.

For women at risk for infection, the old Guidelines also recommended planning vaccination postnatally, with the prospect of protecting future pregnancies. Rubella vaccination is contraindicated during pregnancy because the vaccine could be teratogenic.

Recommendation Update

In the early ‘90s, universal vaccination against rubella for newborns was introduced in Italy. It became one of the 10 mandatory pediatric vaccinations in 2017. In June 2022, the Ministry of Health reported a vaccination coverage of 93.8% among children aged 24 months, a coverage of 93.3% for the first dose, and a coverage of 89.0% for the second dose in the 2003 birth cohort.

“Rubella is a notifiable disease, and in 2013, the newly activated national surveillance system detected one case of congenital rubella per 100,000 newborns. From 2018 onward, no cases have been reported,” said Vittorio Basevi, a gynecologist of the Perinatal Technical-Scientific Advisory Commission in the Emilia Romagna Region and coordinator of the Technical-Scientific Committee that developed the updated Guidelines. “Thanks to extensive vaccination coverage, the infection no longer circulates in Italy. Based on these data, we decided not to offer screening to pregnant women anymore.”

The recommendation to offer rubella vaccination post partum to women without documentation of two doses or previous infection remains confirmed.

Patients Born Abroad 

How should one handle the care of a pregnant woman born in a country where universal rubella vaccination is not provided? The likelihood that she is susceptible to infection is higher than the that of the general Italian population. “On the other hand, since the virus no longer circulates in our country, the probability of contracting the virus during pregnancy is negligible, unless she has recently traveled to her country of origin or come into contact with family members who recently arrived in Italy,” said Dr. Basevi. “The Guidelines refer to offering screening to all pregnant women. In specific cases, it is up to the treating physician to adopt the conduct they deem appropriate in science and conscience.”

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

If a pregnant woman contracts rubella in the first 17 weeks of pregnancy, then the risk for congenital rubella in the newborn — which may entail spontaneous abortion, intrauterine death, or severe fetal malformations — is as high as 80%. This risk once frightened patients and clinicians in Italy. Thanks to widespread population vaccination, however, the World Health Organization declared the elimination of endemic transmission of rubella in Italy in 2021. The Italian National Institute of Health took note, and the recent update of the Guidelines for the Management of Physiological Pregnancy no longer recommends offering rubella screening to all pregnant women.

The Rubeo Test

The rubeo test, an analysis for detecting antibodies in the blood produced by vaccination or a past rubella infection, traditionally forms part of the examination package that every doctor prescribes to expectant patients at the beginning of pregnancy. If the test shows that the woman is not vaccinated and has never encountered the virus, making her susceptible to the risk for infection, according to the previous edition of the Guidelines, then the test should be repeated at 17 weeks of gestation. The purpose is to detect any rubella contracted during pregnancy and offer the woman multidisciplinary counseling in the case of a high risk for severe fetal damage. Infection contracted after the 17th week, however, poses only a minimal risk for congenital deafness. There is no treatment to prevent vertical transmission in case of infection during pregnancy.

For women at risk for infection, the old Guidelines also recommended planning vaccination postnatally, with the prospect of protecting future pregnancies. Rubella vaccination is contraindicated during pregnancy because the vaccine could be teratogenic.

Recommendation Update

In the early ‘90s, universal vaccination against rubella for newborns was introduced in Italy. It became one of the 10 mandatory pediatric vaccinations in 2017. In June 2022, the Ministry of Health reported a vaccination coverage of 93.8% among children aged 24 months, a coverage of 93.3% for the first dose, and a coverage of 89.0% for the second dose in the 2003 birth cohort.

“Rubella is a notifiable disease, and in 2013, the newly activated national surveillance system detected one case of congenital rubella per 100,000 newborns. From 2018 onward, no cases have been reported,” said Vittorio Basevi, a gynecologist of the Perinatal Technical-Scientific Advisory Commission in the Emilia Romagna Region and coordinator of the Technical-Scientific Committee that developed the updated Guidelines. “Thanks to extensive vaccination coverage, the infection no longer circulates in Italy. Based on these data, we decided not to offer screening to pregnant women anymore.”

The recommendation to offer rubella vaccination post partum to women without documentation of two doses or previous infection remains confirmed.

Patients Born Abroad 

How should one handle the care of a pregnant woman born in a country where universal rubella vaccination is not provided? The likelihood that she is susceptible to infection is higher than the that of the general Italian population. “On the other hand, since the virus no longer circulates in our country, the probability of contracting the virus during pregnancy is negligible, unless she has recently traveled to her country of origin or come into contact with family members who recently arrived in Italy,” said Dr. Basevi. “The Guidelines refer to offering screening to all pregnant women. In specific cases, it is up to the treating physician to adopt the conduct they deem appropriate in science and conscience.”

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.

If a pregnant woman contracts rubella in the first 17 weeks of pregnancy, then the risk for congenital rubella in the newborn — which may entail spontaneous abortion, intrauterine death, or severe fetal malformations — is as high as 80%. This risk once frightened patients and clinicians in Italy. Thanks to widespread population vaccination, however, the World Health Organization declared the elimination of endemic transmission of rubella in Italy in 2021. The Italian National Institute of Health took note, and the recent update of the Guidelines for the Management of Physiological Pregnancy no longer recommends offering rubella screening to all pregnant women.

The Rubeo Test

The rubeo test, an analysis for detecting antibodies in the blood produced by vaccination or a past rubella infection, traditionally forms part of the examination package that every doctor prescribes to expectant patients at the beginning of pregnancy. If the test shows that the woman is not vaccinated and has never encountered the virus, making her susceptible to the risk for infection, according to the previous edition of the Guidelines, then the test should be repeated at 17 weeks of gestation. The purpose is to detect any rubella contracted during pregnancy and offer the woman multidisciplinary counseling in the case of a high risk for severe fetal damage. Infection contracted after the 17th week, however, poses only a minimal risk for congenital deafness. There is no treatment to prevent vertical transmission in case of infection during pregnancy.

For women at risk for infection, the old Guidelines also recommended planning vaccination postnatally, with the prospect of protecting future pregnancies. Rubella vaccination is contraindicated during pregnancy because the vaccine could be teratogenic.

Recommendation Update

In the early ‘90s, universal vaccination against rubella for newborns was introduced in Italy. It became one of the 10 mandatory pediatric vaccinations in 2017. In June 2022, the Ministry of Health reported a vaccination coverage of 93.8% among children aged 24 months, a coverage of 93.3% for the first dose, and a coverage of 89.0% for the second dose in the 2003 birth cohort.

“Rubella is a notifiable disease, and in 2013, the newly activated national surveillance system detected one case of congenital rubella per 100,000 newborns. From 2018 onward, no cases have been reported,” said Vittorio Basevi, a gynecologist of the Perinatal Technical-Scientific Advisory Commission in the Emilia Romagna Region and coordinator of the Technical-Scientific Committee that developed the updated Guidelines. “Thanks to extensive vaccination coverage, the infection no longer circulates in Italy. Based on these data, we decided not to offer screening to pregnant women anymore.”

The recommendation to offer rubella vaccination post partum to women without documentation of two doses or previous infection remains confirmed.

Patients Born Abroad 

How should one handle the care of a pregnant woman born in a country where universal rubella vaccination is not provided? The likelihood that she is susceptible to infection is higher than the that of the general Italian population. “On the other hand, since the virus no longer circulates in our country, the probability of contracting the virus during pregnancy is negligible, unless she has recently traveled to her country of origin or come into contact with family members who recently arrived in Italy,” said Dr. Basevi. “The Guidelines refer to offering screening to all pregnant women. In specific cases, it is up to the treating physician to adopt the conduct they deem appropriate in science and conscience.”

This article was translated from Univadis Italy, which is part of the Medscape Professional Network. A version of this article appeared on Medscape.com.