Yesterday in Emerging Infectious Diseases, Centers for Disease Control and Prevention (CDC) researchers described the cases of eight US children who died of acute hepatitis of unknown cause—half of whom tested positive for adenovirus—from October 2021 to June 2023.

A total of 392 pediatric hepatitis cases of unknown origin were reported during the period. Of the eight who died, two had weakened immune systems, and one of the four who tested positive for adenovirus had no underlying medical conditions. Adenoviruses typically cause mild flu- or cold-like symptoms.

Hepatitis is an inflammation of the liver caused by genetic, drug-related, metabolic, infectious, or immune-mediated conditions. Before these cases, adenovirus had been associated with hepatitis only in people with impaired immune systems. Another 1,010 similar cases were later reported by other countries.

In April 2022, the CDC issued a healthy advisory that recommended testing affected children younger than 10 years for adenovirus.

Two children required liver transplant

The median patient age was 2.4 years, 62.5% were boys, and 62.5% were Hispanic. Emergency department or hospital admission occurred after a median 7 days of symptoms. Seven of eight children had received at least two doses of hepatitis B vaccine, and five had been given one or two doses of hepatitis A vaccine.

Investigation into whether Hispanic/Latino children are at higher risk for diseases and death is needed.

The median length of hospitalization was 14 days. Seven children had acute liver failure as noted on their medical abstraction form, and two received a liver transplant. The causes of death for seven children with available information were liver-related, cardiopulmonary causes, cerebral herniation (displacement of part of the brain due to increased intercranial pressure), and multiorgan failure. Of the four children who tested positive for adenovirus, three had adenovirus noted in their death certificate or autopsy report. 

"Our findings emphasize the importance of continued investigation to determine the mechanism of liver injury and appropriate treatment," the researchers wrote. "Testing for adenovirus in similar cases could elucidate the role of the virus. Investigation into whether Hispanic/Latino children are at higher risk for diseases and death is needed."

Pharmaceutical company Merck said yesterday that results from phase 3 clinical studies and real-world evidence indicate that an investigational, 21-valent (21-strain) pneumococcal conjugate vaccine produces an immune response for all 21 serotypes covered and is protective against the pneumococcal serotypes responsible for most pneumococcal disease in adults 50 and older.

At the annual meeting of the International Society of Pneumonia and Pneumococcal Diseases, company officials said data from multiple phase 3 studies showed that V116, which was specifically designed to prevent pneumococcal disease and pneumococcal pneumonia in adults, was immunogenic for all 21 serotypes covered by the vaccine in a variety of adult populations 50 and older. That includes those with increased risk of pneumococcal disease and both pneumococcal vaccine-naïve and pneumococcal vaccine-experienced adults.

V116 also elicited higher immune response than the pneumococcal 15-valent conjugate vaccine (PCV15) and the polyvalent pneumococcal vaccine (PPSV23) for the eight unique Streptococcus pneumoniae serotypes it covers.  

Real-world data

In addition, preliminary data from the real-world Pneumococcal Pneumoniae Epidemiology, Urine Serotyping, and Mental Outcomes study showed that, of the 242 serotypes found among 2,065 adults aged 50 and over who had community-acquired pneumonia from 2018 through 2022, about 84% were covered by V116. Roughly 25% of those serotypes were covered only by V116 and not by PCV15 or PCV20.

"The extensive data presented this week reaffirm our confidence in the potential clinical value V116 could provide to a range of adult populations," Eliav Barr, MD, senior vice president, chief medical officer, and head of global development at Merck Research Laboratories, said in a company press release. "We are encouraged by the results of these studies showing that V116 has generated immune responses to the serotypes responsible for the majority of adult invasive pneumococcal disease."

The Food and Drug Administration (FDA) granted Merck priority review of its application for approval of V116 in December 2023. The FDA has set a target action date of June 17, 2024.

We are encouraged by the results of these studies showing that V116 has generated immune responses to the serotypes responsible for the majority of adult invasive pneumococcal disease.

The World Health Organization (WHO) said today in an outbreak notice that 13 countries in Africa have reported confirmed or probable yellow fever cases since the start of 2023. It urged countries to increase surveillance because of the potential for onward transmission through travel and the presence of mosquitoes in neighboring countries that are capable of spreading the disease.

The countries are Burkina Faso, Cameroon, the Central African Republic, Chad, Republic of the Congo, Ivory Coast, the Democratic Republic of the Congo (DRC), Guinea, Niger, Nigeria, South Sudan, Togo, and Uganda. During the last quarter of 2023 through February 25, eight of the countries have reported active yellow fever transmission and have started response planning: Cameroon, Chad, Congo, DRC, Guinea, Niger, Nigeria, and South Sudan.

Niger and Nigeria reported cases in January, and investigations are still under way. An outbreak in South Sudan, first reported in December 2023 and centered in West Equatoria state, has grown to 64 cases that fit the case definition, of which 6 were fatal.

Urban spread in Cameroon's biggest city

The WHO also warned that Aedes mosquitoes in urban areas can amplify outbreaks. It said that, of Cameroon's nine lab-confirmed cases, six were from a densely populated area of Douala, the country's largest city.

Preliminary information for 2023 shows a case-fatality rate of 11%.

Though progress has been made with vaccination, suboptimal vaccine coverage in some areas and persistent population immunity gaps pose a high risk and threaten progress toward elimination. The WHO put the regional risk at moderate and kept the global risk low.