Trial with 4,500 Babies in Odisha Finds Breakthrough Weapon Against Sepsis

The infection is believed to be responsible for almost one in four neonatal deaths in India every year. The new intervention promises to bring this rate down by 40% at about $1 per baby.

Sreelatha Menon is a freelance journalist.

Update, August 24: The Indian Council of Medical Research (ICMR) has shown keen interest in the study and has said it would like to recreate it in six states, Sailajanandan Parida, a member of the research team, told The Wire. Odisha is one of them; investigators have yet to finalise the other five. He added that the ICMR version would be more challenging because it plans to include low birth-weight babies, whom the Odisha study had excluded.

Pinaki Panigrahi, who led the team, said, “ICMR is not planning to replicate our studies; [they plan to] use a different probiotic combination, which is fine. A lot of research needs to be done in this domain. A time will come where multiple preparations can be compared for their efficacy. We are at ground zero now.”

According to Parida, he and his colleagues will help with the Odisha chapter of the ICMR initiative since they have a lot of experience.

A large field-based trial performed in Odisha has found that feeding newborn babies a cocktail of healthy bacteria can bring down deaths caused by sepsis by 40%. The researchers say the supplement is safe and ready for use. They want to replicate the findings in other locations in India, and abroad, next to formulate consensus guidelines.

Sepsis is one of the infections responsible for 33% of the two million neonatal deaths that occur in India every year. By itself, it is thought to be responsible for a quarter of all neonatal deaths in India and that of over 600,000 infant deaths globally. Moreover, a 2016 article in the journal Lancet Global Health had also stated that “56,524 neonates die each year from resistance-attributable neonatal sepsis deaths caused by bacteria resistant to first-line antibiotics in India.”

It is then heartening that in the new study, the researchers found that sepsis can be prevented to a great extent if a synbiotic supplement is fed to babies within the first two weeks of their births. A synbiotic supplement is a mix of prebiotic bacteria and bacteria beneficial to human health, a.k.a. probiotic bacteria.

The study was led by Pinaki Panigrahi, a doctor and researcher at the University of Nebraska Medical Center, Omaha. It covered 4,556 babies from 149 villages in Odisha; the trials began in in 2008 and concluded in 2012. The findings were published in the journal Nature on August 16.

During a trial, infants were randomly assigned to one of two groups. One was given the synbiotic supplement, a concoction of fructooligosaccharide, a commonly used sweetener, and Lactobacillus plantarum, a strain of bacteria selected for being effective at colonising the human gut. The supplements were provided for a week while the other group was given a placebo in the same period. Sixty days after the course concluded, the researchers conducted follow-up checks. They found that sepsis and death had occurred in 5.4% of the infants in the treatment arm versus 9% in the placebo arm. The total cost for a week’s course of the synbiotic supplement is $1 (about Rs 70) per baby.

“These findings suggest that a large proportion of neonatal sepsis in developing countries could be effectively prevented using a synbiotic,” the authors wrote in their paper.

No effective prevention for sepsis is currently available, Panigrahi told The Wire. “Exclusive breastfeeding helps, but in spite of best efforts neonatal sepsis rates have not come down.” The most unfortunate part of it, he said, “is that in spite of chanting this for decades, there has not been a single effort to try something different, something new. Why should you expect sepsis rates to go down if no intervention [specifically] targeting sepsis has been implemented?’’

Panigrahi has been working in India for the last 20 years. “In 2002 we started the first and large-scale community-based surveillance for neonatal infection,” he said. “Then, we spent time setting up the research infrastructure, and then the actual trial took four to five years, plus post-study monitoring and finally analysis and communication of the paper.” In 2008, he helped establish India’s first full fledged institute of public health in Bhubaneswar, called the Asian Institute of Public Health, in 2008.

During the trial, Panigrahi was assisted by a large team of physicians, microbiologists, lab personnel, managers, community health workers and data management personnel – totally about 300 – all funded by the NIH.

They had been working with the full approval of the state and central governments as well as the the ICMR. “All were waiting to see the results of this large study. It is time now for us, and the media, to get engaged to take it to the next step,” Panigrahi said.

According to Rajiv Bahl, of the R&D department of the maternal, newborn, child and adolescent health at the World Health Organisation, “This is an important study that adds to our knowledge of the potential role of probiotics in newborn health.” However, he also cautioned that “a single study cannot be used as the basis of making a recommendation. The overall body of evidence, including the current trial, will have to be carefully evaluated to decide if a universal or conditional recommendation should be made.”

The existing set of interventions to prevent sepsis have been recommended by WHO. They include early and exclusive breastfeeding, applying a chlorhexidine solution to the umbilical cord stump and preventing and treating maternal peripartum infections early.

According to Bahl, “Lack of access to the [current recommended] interventions is an important reason for the high number of deaths that occur due to newborn sepsis” – and so “expanding the repertoire of interventions against sepsis is important.”

Sailajanandan Parida, a coauthor of the study and former professor and head of neonatology at the SCB Medical College, Cuttack, said that the methods of sepsis prevention emphasised by WHO and other bodies “have not been able to produce a remarkable dent on the neonatal mortality rate.”

“Though sepsis is a major cause of death in India and elsewhere, till now, it has been quite impossible to prevent it altogether because of the varied etiology of sepsis-producing organisms, the timing, the route of invasion,” etc., he told The Wire, adding that he and his colleagues had addressed the issue to a “great” extent. “We have demonstrated the route of invasion through the gastrointestinal tract and the process of colonisation by L. plantarum in the babies’ guts for a very long period and its role in preventing the late onset of sepsis, which has been happening in our community.”

“We would like to replicate our study and its impact in multiple sites in India and abroad so that consensus guidelines can be evolved.”

The synbiotic supplement in question can be procured or manufactured locally without any difficulty. It can also be in the first week of a baby’s life without any complications, as the study demonstrated. “Some training imparted to community-level health workers would help them to administer the probiotic safely,” Parida explained.

Additionally: “It would be much easier to administer the preparation in a community setting as robust follow-up mechanisms are already in place in our country, [thanks to] various programmes taken up by the National Health Mission. As the incidence of [babies delivered in hospitals] is rising, it would also be easier to consult with the mother for synbiotic feeding two or three days after discharge.”

The research team also stands ready to assist the state and central governments, should they be called upon, Parida finished.