Research maps the causes of hospitalizations for childhood diarrhea

Despite vaccine availability, rotaviruses still account for the majority of severe cases of diarrhea in children under 5 years of age in low- and middle-income countries, causing more than 200,000 deaths each year. This is what has been pointed out by a large study conducted by the Global Pediatric Diarrhea Surveillance Network, coordinated by the World Health Organization (WHO) with the participation of the Oswaldo Cruz Institute (IOC/Fiocruz).

Conference of genetic analysis results: IOC/Fiocruz laboratory receives samples from different parts of the country and Latin America (photo: Gutemberg Brito)

Published in the scientific journal BMJ Global Health, the research presents data from the monitoring conducted between 2017 and 2019 in sentinel hospitals in 28 countries encompassing the regions of the Americas, Africa, Europe, Asia, and Oceania. The results of the work reinforce the importance of immunization. Considering the set of countries, rotavirus accounted for 33% of hospitalizations. However, the impact of the pathogen has halved in places where immunization is offered.

“This result illustrates the positive impact of the rotavirus vaccine and the need to strengthen and expand this immunization. WHO recommends that all countries offer the immunizer. However, less than half of the children born in 2018 have been vaccinated”, emphasizes virologist José Paulo Gagliardi Leite, a researcher at the Laboratory of Comparative and Environmental Virology of the IOC/Fiocruz and one of the authors of the study.

Besides rotaviruses, the research identified other pathogens that caused a significant portion of children's hospitalizations: the Shigella bacteria (accounting for 10% of the cases), norovirus (detected in 6.5% of the cases), and adenovirus (confirmed in 5.5% of the cases).

From the data collected, the researchers estimated the number of deaths of children under 5 years of age caused annually by each of the microorganisms in low- and middle-income countries: 208,000 by rotavirus; 63,000 by Shigella; 37,000 by adenovirus; and 36,000 by norovirus.

“Diarrhea is one of the five leading causes of death of children under five years of age in the world. There are more than a thousand deaths a day. Knowing the microorganisms that cause the disease is important to design more effective prevention and control strategies”, states the virologist Tulio Fumian, also a researcher at the Laboratory of Comparative and Environmental Virology of the IOC/Fiocruz and one of the authors of the work.

“Regarding new vaccines, there are already studies underway to develop immunizers against Shigella and norovirus. From the data, we can see that adenoviruses can also be considered in these initiatives”, adds José Paulo.

The situation in the Americas

The American continent was the only region surveyed where rotavirus was not the main cause of hospitalizations. In South America, most hospitalizations were due to the norovirus. In Central America, on the other hand, the Shigella bacteria was more prevalent.

The study highlights that the six countries in the region with sentinel hospitals included in the research (Honduras, Nicaragua, Bolivia, Ecuador, Peru, and Paraguay) offer the rotavirus vaccine in their national immunization programs since 2010.

According to the researchers, the data observed in the research are compatible with the analyses conducted in Brazil by the Laboratory of Comparative and Environmental Virology of the IOC/Fiocruz, which acts as a regional reference center for rotaviruses for the Ministry of Health and for the Pan-American Health Organization (PAHO/WHO), receiving near a thousand samples each year from 11 states in the South, Southeast, and Northeast regions of the country, in addition to samples from Latin American countries (Bolivia, Ecuador, Paraguay, and Peru).

“As a reference, we analyze not only the severe cases that require hospitalization, but also outpatient occurrences, especially in outbreak situations. In Brazil, in our last studies, we have detected approximately twice as many norovirus infections compared to rotaviruses”, clarifies Tulio.

On the map, the countries with sentinel hospitals included in the survey, in the different regions. The graphs show the percentage of cases attributed to each of the pathogens. Source: article 'Aetiology and incidence of diarrhea requiring hospitalization in children under 5 years of age in 28 low-income and middle-income countries: findings from the Global Pediatric Diarrhea Surveillance network'

The researcher warns: It is necessary to increase vaccination coverage in the country. “In the 2022 analyses, we have observed an increase in rotavirus infections. Besides, as the country presents low vaccination coverage in 2020 and 2021, it is essential to reverse this decline”, points out the researcher.

Introduced in the National Immunization Program (PNI) in March 2006, the rotavirus vaccine is administered orally, at 2 and 4 months of age, to protect against acute gastroenteritis caused by the pathogen. In 2015, the vaccination rate reached 95% of children under one year of age. However, it began to decline in 2016 and the situation worsened during the COVID-19 pandemic. In 2021, only 71% of the children were immunized. “In general, coverage is lower in the North and Northeast regions”, points out José Paulo.

In addition to vaccination, the researchers highlight other important measures to prevent cases of diarrhea. “Sanitation is essential and has a big impact on cases of bacterial diarrhea. Regarding rotaviruses, noroviruses, and adenoviruses, due to their biological characteristics, they can remain infectious for long periods in the environment. Hand hygiene and the cleaning and disinfection of places liable to be contaminated by feces and vomit are very important. Children with diarrhea should also be kept away from the daycare center in order to prevent outbreaks”, lists Leite.

Real-time monitoring perspective

Funded by the Bill & Melinda Gates Foundation and the Global Vaccine Alliance (Gavi), the Global Pediatric Diarrhea Surveillance Network has been conducting ongoing monitoring of diarrhea-related hospitalizations of children under 5 years of age in the 33 established sentinel hospitals since 2017.

Samples selected for analysis are sent to one of eight WHO Rotavirus Regional Reference Laboratories, among them, the Laboratory of Comparative and Environmental Virology of the IOC/Fiocruz. The identification of the pathogens is performed through genetic analysis, by the real-time PCR methodology.

“The test can simultaneously identify 16 pathogens, including bacteria, parasites, and viruses, which are causes of acute diarrhea. It also detects subtypes of microorganisms, such as different bacterial species or viral genotypes, totaling 73 variations”, explains the biologist Irene Araújo Maciel, the technologist in charge of the project's analyses at the Laboratory of the IOC/Fiocruz. The results obtained are sent to the University of Virginia in the United States, where the test (called the ‘Tac Array Card’) was developed and where scientists perform the statistical analyses of the study.

The publication of the first research results was delayed by the pandemic, as health centers and laboratories had to turn their efforts to the fighting against COVID-19. Currently, scientists are analyzing the samples for 2020, but the goal is to perform real-time analyses in the next few years. “At that moment, we are still dealing with the effects of the pandemic. But in the near future, we hope that we are able to perform real-time diagnostics. This will allow a panoramic and geographical view of the dissemination of microorganisms in the five continents, to monitor outbreaks and compare what occurs in different regions”, states José Paulo.