It is a 3-year, prospective, age-stratified, matched case-control study of moderate-to-severe diarrhoea in children aged 0-59 months residing in censused populations at four sites in Africa and three in Asia.
The researchers said that recruited children with moderate-to-severe diarrhoea seeking care at health centres along with one to three randomly selected matched community control children without diarrhoea.
From patients with moderate-to-severe diarrhoea and controls, they said they obtained clinical and epidemiological data, anthropometric measurements, and a faecal sample to identify enteropathogens at enrolment.
One follow-up home visit was made about 60 days later to ascertain vital status, clinical outcome, and interval growth.
They enrolled 9439 children with moderate-to-severe diarrhoea and 13 129 control children without diarrhoea.
By analysing adjusted population attributable fractions, they found that most attributable cases of moderate-to-severe diarrhoea were due to four pathogens: rotavirus, Cryptosporidium, enterotoxigenic Escherichia coli producing heat-stable toxin (ST-ETEC; with or without co-expression of heat-labile enterotoxin), and Shigella.
Other pathogens were important in selected sites (eg, Aeromonas, Vibrio cholerae O1, Campylobacter jejuni).
They also found that odds of dying during follow-up were 8.5-fold higher in patients with moderate-to-severe diarrhoea than in controls.
Pathogens associated with increased risk of case death were ST-ETEC and typical enteropathogenic E coli in infants aged 0-11 months, and Cryptosporidium in toddlers aged 12-23 months.
The researchers noted that interventions targeting five pathogens (rotavirus, Shigella, ST-ETEC, Cryptosporidium, typical enteropathogenic E coli) could substantially reduce the burden of moderate-to-severe diarrhoea.
New methods and accelerated implementation of existing interventions (rotavirus vaccine and zinc) are needed to prevent disease and improve outcomes, they added.
The research was published in Lancet.