Global Study on Diarrhoea Finds New Culprit in Pakistan, Recommends Fresh Interventions

The Global Enteric Multicenter Study, GEMS, an extensive, ground-breaking study in the developing world, has come up with the clearest picture yet of the most common causes and impact of diarrheal diseases — the second leading killer of young children globally after pneumonia.

The study reveals that while the germs, rotavirus, Shigella and E. Coli are notorious for causing the majority of moderate-to-severe diarrhoea cases, Cryptosporidiumand Aeromonas are two pathogens that have been underestimated for their ability to cause the disease.

At the same time, GEMS recommends going beyond the current safe hand and hygiene practices to treat diarrhoea, and that National immunisation programmes should include vaccinations for rotavirus and other bacteria for which inoculations are available.

The results of GEMS have been published in this week’s edition of The Lancet. 

“When it comes to childhood disease and deaths, diarrhoea remains a leading culprit,” said Dr Anita Zaidi, principal investigator at the Pakistan study site of GEMS and Chair, Department of Paediatrics, Aga Khan University. “The GEMS data are the most conclusive evidence we have to date of the bacteria we must target and the prevention and treatment practices that need to be improved.”       

The three-year-long GEMS enrolled more than 20,000 children from seven sites across Asia and Africa; in Pakistan, the study was conducted in four peri-urban field sites in Bin Qasim Town in Karachi. 

“The University has been working at these field sites for the past few years and had basic data on the population. So it was easy for us to build on it,” Dr Zaidi elaborated. “To really know if something was causing diarrhoea, we included an equal number of controls. When we collected a stool sample from a sick child, we also collected one from a well child  for comparison. Each stool sample was tested for 40 different diarrhoea causing pathogens. Many of these bugs were being tested for the first time in Pakistan." 

Each child was followed up at home after 60 days to assess the effect on his or her growth after standard treatment was given.

Similar to other sites in the study, AKU researchers found that rotavirus, Shigella, Cryptosporidium and Enterotoxigenic E. Coli (ETEC) were the leading causes of diarrheal disease; prior to GEMS, Cryptosporidium was not considered a major cause of the disease.

Uniquely, in the Pakistan and Bangladesh sites, Aeromonas, another type of bacteria, was the second leading cause of moderate-to-severe diarrhoea, confirming its regional importance.

The researchers also found concrete evidence that the effects of diarrhoea were far more than immediate: height delays were significant among children under 5 in Pakistan in the two months following the diarrheal episode as compared to children in the control group without diarrhoea.

Worse, children with diarrhoea were 13 times more likely to die over the course of the two-month follow-up period, with most of these deaths happening at home.

“And this was despite WHO-recommended standard management practices for diarrhoea being followed: each child in the community was given rehydration therapy – orally and IV as needed – as well as zinc supplementation, and antibiotics for dysentery. Yet the chance of death was high with underlying malnutrition probably paying a significant role ,” Dr Zaidi revealed.

“GEMS strongly indicates that follow-up care after the initial diarrheal episode is critical to protect the health and wellbeing of children,” added Professor George Griffin, Senior Co-Chair of the GEMS International Strategic Advisory Committee and Professor at St. George’s, University of London. “By focusing only on the acute diarrhoea that brings children to hospitals, we overlook a significant portion of diarrheal diseases’ burden.”

Dr Thomas Brewer, deputy director of the Enteric & Diarrheal Diseases team at the Bill & Melinda Gates Foundation, which funded the study, added: “Vaccines and treatments available today can save thousands of children right now, and targeted research to develop new tools to combat severe diarrhoea could save many more lives in the future.”

Hence, Dr Zaidi hopes that the findings of this study, particularly with regards torotavirus vaccination would be taken into consideration by the government of Pakistan and international donors.

“In addition to water and sanitation interventions,  we need vaccines becauserotavirus is a widely occurring infection that is not related to hygiene standards. It took us many years to introduce pneumococcal vaccine in our national immunization programme, and I hope rotavirus vaccine becomes a part of our immunization programme soon as well. Right now a single dose of rotavirusvaccine costs Rs. 4,500 but if it comes under the EPI cover then it will be free for all children,” Dr Zaidi added.

She also commented on the frequent presence of cholera in the Karachi communities. “We usually hear of cholera in gastroenteritis outbreaks, but in fact GEMS has revealed that cholera germs are commonly isolated for children older than 1 year of age even in non-outbreak settings. There is a good cholera vaccine available and we should consider it for cholera prevention in Pakistan”

 “GEMS is a landmark study for the child health community,” said Professor Fred Binka, Co-Chair of the GEMS International Strategic Advisory Committee and Vice-Chancellor at the University of Health and Allied Sciences, Ghana. “By using consistent methods across countries, GEMS sites generated data that can guide evidence-based decision making at both the local and global level."