Study pinpoints pathogens causing biggest diarrhea burden in kids

May 14, 2013 (CIDRAP News) – While many pathogens cause serious diarrhea in children in developing countries, four stand out as culprits in most of the infections, a finding that could drive new prevention strategies, an international research team reported today.

The group spent 3 years in seven developing countries, collecting health information, lab samples, and outcome data on 3,439 youngsters who had moderate-to-severe diarrhea. They published their findings today in an early online release from The Lancet.

On a global scale each year, diarrheal diseases kill about 800,000 children under age 5, most of them in sub-Saharan Africa and southern Asia, according to the report.

Though interventions such as rotavirus vaccines are starting to have an impact on deaths and disease incidence, scientific data to guide other strategies to curb the diseases are scarce, especially in regions where child deaths are the highest, the group wrote.

To fill the gap, the team focused their analysis on kids under age 5 who did and didn't have moderate-to-severe diarrhea in selected cities in Bangladesh, Gambia, India, Kenya, Mali, Mozambique, and Pakistan. The study included 13,129 matched controls.

The researchers collected clinical and epidemiologic information, took anthropometric measurements, and took fecal samples to identify pathogens. For each child they made a follow-up home visit 60 days later to assess health status, clinical outcome, and growth measures.

Four pathogens were the most common causes of diarrhea across all sites: rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli (ETEC) producing heat-stable toxin (ST), and Shigella, according to the study.

Other pathogens played important roles in some of the countries. For example, Aeromonas was a frequent cause of childhood diarrhea in Pakistan and Bangladesh, while Vibrio cholerae O1 frequently caused disease in all of the Asian sites, as well as in Mozambique.

When researchers compared health outcomes in kids with and without diarrhea, they found that the odds of death were 8.5 fold higher in those with diarrheal infections. Most of the deaths occurred within the first 2 years of life. The group's analysis of kids who did and didn't die from their infections found that the ones who died were more likely to be infected with ST-producing ETEC.

The most common cause of serious diarrhea at every site during the first year of life was rotavirus, according to the study. The team said that finding raises hopes that the GAVI Alliance decision to make rotavirus vaccine available to the world's poorest countries will yield important benefits for children's health.

One surprising finding was that Cryptosporidium was an important pathogen at all sites, the group wrote. They noted that the pathogen is a frequent cause of life-threating illness in people with HIV/AIDS and is linked to diarrhea and malnutrition in young children in sub-Saharan Africa.

"These findings highlight the need to develop resources to diagnose, treat, and prevent cryptosporidiosis in resource-poor settings," the team wrote.

Focusing prevention efforts on the four most common causes of diarrhea and resulting malnutrition could reduce disease and its effects by 40% during the first 2 years of life, researchers suggested.

Urgent steps include speeding the introduction of interventions that are already having an impact, such as the rotavirus vaccine, promoting treatment of acute diarrhea with zinc, developing new vaccines, and revising diarrhea case management in ways that have been shown to reduce malnutrition, they wrote.

In an accompanying editorial in the The Lancet, two pediatric health experts from India commended the researchers for collecting and analyzing microbial data from such a large number of children on two continents. The authors are Uma chandra mouli Natchu, MD, and Shinjini Bhatnagar, PhD, with the Pediatric Biology Centre at the Translational Health Science and Technology institute in Haryana.

The two experts also said a similar study design should be used to explore the causes of other high-burden infections.

They wrote that the Cryptosporidium finding deserves attention, because of how common it was in children younger than 2 years old. "The first 2 years of life is a crucial period when most mortality and growth faltering occurs; pathogens with high burden in this period are therefore important to target," the two wrote.

The study group found pathogens and growth failure even in the control-group kids, suggesting the possibility that gut changes due to the pathogens could impair growth, a potential linkage that should studied further, according to Natchu and Bhatnagar.

Kotloff KL, Nataro JP, Blackwelder WC, et al. Burden and aetiology of diarrhoeal disease in infants and young children in developing countries (the Global Enteric Multicenter Study, GEMS): a prospective, case-control study. Lancet 2013 May 14 [Abstract]

Natchu U, Bhatnagar S. Diarrhoea in children: identifying the cause and burden (Editorial). Lancet 2013 May 14 [Extract]

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