Burden of asymptomatic pertussis in infants is greater than previously thought

New study challenges long-standing assumptions about disease severity in infants, and suggests that standard qPCR interpretations underestimate the true burden of other highly contagious diseases, such as COVID-19 and influenza.

Pertussis, also known as "whooping cough," remains a significant cause of death in infants and young children around the world and, despite global vaccination programs, many countries are experiencing a resurgence of this highly contagious disease.

A new study by Boston University School of Public Health and the University of Georgia's Odum School of Ecology presents evidence that could help explain this resurgence: asymptomatic individuals. Lots of them.

Published in the journal eLife, the study suggests that most adults and many children who contract pertussis display no symptoms at all–a reversal of what many experts have long believed about an infection that can cause months of violent coughing fits and "whooping" sounds.

The paper builds upon a 2015 study in which the researchers discovered a series of weakly positive pertussis infections after collecting nasal swab samples from 2,000 mother/infant pairs in Zambia every 2-3 weeks for several months, using quantitative PCR (qPCR) diagnosis. In a standard qPCR analysis, these low-intensity signals would be discounted as false-positive results. But the repeated clusters of mother/infant cases, which illustrated a natural arc of infection as the infection ran its course, suggested that these weak PCR signals provided important information about disease.

The fact that we found concordance within the mother/infant pairs told us that, in all likelihood, even the weakly affected mothers are contagious at close range, and are probably infecting their babies."

Dr. Christopher Gill, co-lead author of the study and associate professor of global health at BUSPH

Asymptomatic spread is not a unique phenomenon with infectious diseases, he says, but as the world has seen with COVID-19, the ability to detect asymptomatic infections early and accurately through qPCR can provide vital information about the epidemiology and burden of diseases.

"This was a quest to understand weakly positive qPCR and then determine what proportion of pertussis transmissions are coming from asymptomatic people," Gill says.

To confirm that these weak signals were accurate and relevant, the researchers conducted a closer analysis for the eLife study, and discovered additional evidence supporting the likelihood of asymptomatic transmission. The cluster of weak signals aligned with stronger signals, indicating that they occurred during an outbreak; the clusters reflected the natural rise and fall of an epidemic; signals were strongly clustered within mother/infant pairs; and the stronger the qPCR signal, the more likely individuals were to experience symptoms.

Confident in their findings, the researchers then compared the symptomatic cases to the asymptomatic cases and discovered that about 70% of infected mothers displayed no symptoms, and about 25% of infected babies displayed no symptoms. And infants with only mild symptoms (cough or runny nose) comprised over 50% of infections.

"We expected this in mothers, since pertussis becomes less severe with age and repeat exposure," says co-lead author Dr. Christian Gunning, post-doctoral researcher at UGA's School of Ecology. "But mild and asymptomatic infection in infants was assumed to be quite rare. And what we see here is the opposite–severe pertussis in infants is the exception rather than the rule."

The findings underscore the need for a shift in the way qPCR tests are interpreted, Gill says.

"Using a 'line in the sand' approach to interpret results is too simplistic and leads us to discard true and useful information," he says. "If one were trying to map a flu season, it would make more sense to use the weakly positive PCR results as an early warning of impending flu outbreaks, rather than waiting for symptomatic patients with very strong PCR results to start showing up in the ER."

Gunning agrees, saying disease surveillance plays an important role in preventing and responding to disease outbreaks. "Our results differ from traditional approaches that medical doctors use to diagnose and treat patients," he says. "When we tested many people many times, we could 'peer under the hood' and see a lot of hidden infections in this population."

Gunning says that a similar approach could help monitor for outbreaks of COVID. "To control disease outbreaks, we need to know when and where the disease has spread. New strategies like wastewater monitoring could leverage weak qPCR signals to give us a better, fasteridea of who's at risk, and allow us to more quickly intervene. And if you only look at sick people, you're going to miss a lot."


Boston University School of Medicine

Journal reference:

Gill, C.J., et al. (2021) Asymptomatic Bordetella pertussis infections in a longitudinal cohort of young African infants and their mothers. eLife. doi.org/10.7554/eLife.65663.

Posted in: Child Health News | Medical Research News

Tags: Children, Cough, Coughing, Education, Epidemiology, Flu, Infectious Diseases, Influenza, Pertussis, Public Health, Research, Whooping Cough

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Should 12-year-olds get the COVID-19 vaccine?

Kids as young as 12 can now receive the Pfizer-BioNTech COVID-19 vaccine, yet some parents are hesitant to get their children vaccinated. Parents might worry about giving a 12-year-old a vaccine that has not yet been approved for even younger kids. So we asked doctors who specialize in infectious diseases in children a question many parents have been wondering about: Should 12-year-olds get the COVID-19 vaccine? 

The answer from experts is a resounding yes. “I absolutely think they should get the vaccine, just like I think anyone who’s vaccine-eligible, which goes down to 12 now, should get vaccinated,” said Dr. Aaron Milstone, a pediatric infectious diseases specialist at Johns Hopkins Children’s Center in Baltimore. “Because it is, one, the best way they can protect themselves against this infection, and, two, it’s the best way to help protect the community from the spread of the virus.” 

The U.S. Centers for Disease Control and Prevention (CDC) recommends that people ages 12 and older get a COVID-19 vaccine, as does the American Academy of Pediatrics (AAP). Indeed, the CDC recently urged parents to encourage their teens to get vaccinated, after an increase in hospitalizations was reported in this age group in March and April.

“At some point, parents will have to decide whether they want to get their kids a vaccine or whether they want them to get COVID,” Milstone said. “I know some people are nervous and they’re anxious. And hopefully, as more and more children are safely vaccinated, it will reassure them that this is a safer approach than risking your child having a complication from the infection itself.” 

On May 10, the U.S. Food and Drug Administration (FDA) extended the emergency use authorization (EUA) for use of the Pfizer-BioNTech COVID-19 vaccine in kids ages 12 to 15, Live Science previously reported. The FDA had already granted an EUA for use of the same vaccine in people ages 16 and older on Dec. 11, 2020. 

The vaccine is 100% effective in preventing COVID-19 in 12- to 15-year-olds, according to a Phase 3 clinical trial with 2,260 participants, the results of which were published May 27 in The New England Journal of Medicine. Approximately half of the participants received the vaccine, and half received a placebo. There were no cases of confirmed COVID-19 in the participants who received the vaccine and 18 cases in those who received the placebo. 

The vaccine also has a “favorable safety and side-effect profile,” the authors wrote in their study. None of the vaccine recipients in the trial had any serious vaccine-related adverse events. Further, in a statement about the EUA, the FDA said it had determined that the benefit of the vaccine to children 12 and older outweighed the “known and potential risks, supporting the vaccine’s use in this population.”

Benefits of vaccination

Severe COVID-19 is uncommon in children, but that’s not to say COVID-19 hasn’t affected kids. By the end of April, there had been more than 3.7 million cases of COVID-19 in children in the United States, 15,456 child hospitalizations due to COVID-19 and 303 child deaths from COVID-19, according to a report by the AAP and the Children’s Hospital Association. Many of those hospitalizations involved intensive care, added Dr. Yvonne Maldonado, chair of the AAP Committee on Infectious Diseases and chief of Stanford University School of Medicine’s division of pediatric infectious diseases.

“We really do think that to protect children themselves, it’s really important to get vaccinated and also to protect people in the community where children live from getting infections transmitted by children. So for both the children’s good and the good of the community, it is important,” said Maldonado, who is also one of the investigators on the trial of the Pfizer-BioNTech COVID-19 vaccine in kids under 12. 

Another reason to get vaccinated is for protection against the long-term consequences of COVID-19, which remain to be determined, Milstone said. An example of a long-term consequence that has already been observed is multisystem inflammatory syndrome in children (MIS-C), which can develop in kids a month or two after infection with SARS-CoV-2, the virus that causes COVID-19, he said. MIS-C is characterized by the inflammation of multiple organs, Live Science previously reported

“We don’t know whether there could be other late effects from this virus that just emerged a year and a half ago,” Milstone said. “So for right now, I think the surest way to protect ourselves is to get vaccinated.”

Furthermore, vaccination offers kids the chance to go about many of their activities without wearing masks. “The social benefits are important,” Maldonado said, adding that the new mask guidelines from the CDC indicate that vaccinated people can go without masks in most situations. “And it really would be helpful for children to have that opportunity,” Maldonado said.

‘Millions of kids’

Within a week following FDA approval of the Pfizer-BioNTech vaccine for kids ages 12 to 15, 600,000 kids within that age group had received their first doses, CDC Director Rochelle Walensky told members of the media May 18, Reuters reported. As of that date, 4 million people 17 and under had been vaccinated, Walensky said. 

“Hopefully, the fact that millions of kids have gotten these vaccines safely in the United States will reassure people that this is a safe thing to do for their child,” Milstone said.

In a survey reported in the Kaiser Family Foundation’s May Vaccine Monitor, 41% of parents of kids ages 12 to 17 said that their children have either gotten at least one dose or that they will get vaccinated right away. 

Yet not all parents are eager for their kids to get vaccinated. In the same survey, 14% of parents said they would get their child vaccinated only if their school required it, and another 20% said they would “definitely not” get their 12- to 17-year-old vaccinated. Many parents said they are worried about vaccine side effects. 

Side effects and risks

The most common side effects of the Pfizer-BioNTech vaccine in kids ages 12 to 15 are “tiredness, headache, chills, muscle pain, fever and joint pain,” according to the FDA statement about the EUA. These side effects are similar to those reported by vaccine recipients ages 16 and up, according to the statement. 

In a May 17 statement, the CDC said it had been investigating a few cases of myocarditis (heart inflammation), primarily in adolescents, within four days of receiving a vaccine, Live Science previously reported. And recently, data from the U.S. Vaccine Adverse Event Reporting System (VAERS) showed a higher than expected number of myocarditis cases in older adolescents and young adults, ages 16 to 24, within a month after receiving their second shot of either the Pfizer or Moderna vaccine, according to the CDC’s Advisory Committee on Immunization Practices (ACIP). Researchers will continue to monitor this link as more young people are vaccinated to determine whether the vaccine is really the cause of these myocarditis cases, the ACIP said. It will be important to determine if there really are more cases among vaccinated people, Milstone said, because only then would it make sense to attribute the heart inflammation to the COVID-19 vaccine.

Given the large number of infections, hospitalizations and deaths from COVID-19 in children, “we do think that the benefits of the vaccine will outweigh the risks, and that if people are concerned about myocarditis, they should know that the CDC and others are still investigating a potential relationship, but if there is a relationship, it will be rare,” Maldonado said. Out of millions of vaccinations given to people under 18, there have been just a few cases of heart inflammation. Those cases have been mild and have resolved quickly, she said. 

—Is the COVID-19 vaccine causing rare myocarditis cases?

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—Could the novel coronavirus one day become a common cold?

Currently, the Pfizer-BioNTech vaccine is the only COVID-19 vaccine approved for use in people under 18. However, Moderna announced in a May 25 statement that its vaccine is safe and effective in kids ages 12 to 17, based on the results of a Phase 2/3 clinical trial, and that it plans to submit its data to the FDA in June.

Originally published on Live Science.

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The two surprising first symptoms of COVID explained – and it’s not the ‘classic’ three

COVID-19 is an infectious disease that has been confirmed in more than 30 million people across the world. If you develop any of the key coronavirus symptoms, you should get tested for the infection straight away.

The UK has seen a steady rise in the number of coronavirus cases over the past few weeks.

Almost 10 million people across the country have been put into local lockdowns, in a bid to stop the rising spread of the infection.

Prime Minister Boris Johnson has now ordered all pubs and restaurants to shut at 10pm, while nobody should meet with more than five other people for the foreseeable future.

The most common early symptoms of coronavirus have now been revealed.

Most people that have COVID-19 develop a bad headache, and persistent fatigue, according to the COVID Symptom Study app.

More than 80 percent of all patients reported a headache as one of their first symptoms, whereas 72 percent reported fatigue.

All age groups were most likely to experience a headache and fatigue, it added.

But the three most common signs of coronavirus – fever, cough and loss of smell – are still absolutely key to the infection.

Coronavirus symptoms: A coronavirus cough [ANALYSIS]
Coronavirus UK: Gastrointestinal symptoms of COVID-19 [RESEARCH]
The hidden sign of COVID on your lips – how to reveal your risk [STUDY]

“Our data shows that the most commonly experienced early symptoms are actually headache (82 percent) and fatigue (72 percent) – and this is the case for all age groups,” it said.

“Only nine percent of COVID-positive adults aged 18-65 didn’t experience headache or fatigue.

“Of course, headache and fatigue commonly occur in other conditions which is why they don’t trigger a test on their own.

“In fact, only one percent of people who reported fatigue and/or headache on our app ended up testing positive for COVID.”

Headaches are very common, and aren’t necessarily indicative of a coronavirus infection.

They usually go away by themselves without requiring any extra treatment, but drinking plenty of water and taking paracetamol may help to relieve the pain.

Fatigue, meanwhile, may be caused by a number of medical conditions.

You should consider speaking to a doctor about your fatigue if it lasts longer than a few weeks, and you can’t think of any obvious reason for it.

A high fever, a new cough, and a change to your sense of smell or taste are the most crucial coronavirus symptoms, according to the NHS.

In the UK, you should only get tested for the infection if you develop any of these symptoms.

Some patients have also reported a sore throat, diarrhoea, and even hiccups, on top of the more common signs.

More than 41,000 people have died from coronavirus in the UK.

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