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Oral Cholera Vaccine (Shancol) That Is Two Doses and Low Cost Protects Against Endemic Disease in Highly Populated Urban Setting, Lancet Study Shows; Trial in Bangladesh Funded by Bill & Melinda Gates Foundation

In an announcement published on July 9, 2015, the International Centre for Diarrheal Disease Research in Dhaka, Bangladesh (ICDDR,B) reported that The Lancet had published an article online on July 8, 2015, by ICDDR,B scientists, demonstrating that a double-dose, low-cost oral cholera vaccine can substantially reduce hospitalizations and deaths from cholera in densely populated urban settings. The article is titled “Feasibility and Effectiveness of Oral Cholera Vaccine in an Urban Endemic Setting in Bangladesh: A Cluster Randomized Open-Label Trial.” This Lancet article is accompanied by a commentary that is titled “Oral Cholera Vaccines in Endemic Countries.” Links to these articles in The Lancet are provided below, as are links to many of the popular press stories on this major advance. While oral cholera vaccines have previously been shown to be effective in trial settings, this is the first study to prove their effectiveness and feasibility in a real-life situation. The findings lend support to the vaccine’s use in routine mass vaccination programs to help to control cholera in endemic countries. Cholera exacts a tremendous toll on public health globally – 91,000 deaths and 2.8 million cases of cholera are reported every year and over 1 billion people are estimated to be at risk. Approximately half the deaths occur in children under 5 years of age. The burden of cholera is greatest in the developing countries of Africa and South Asia where a large number of people live in unsanitary conditions without access to clean water, factors which are critical to the spread of cholera. While environmental factors can take a long time to improve, an oral cholera vaccine can provide a much-needed alternative in these settings. The study by Dr. Firdausi Qadri, Director of the ICDDR,B’s Centre for Vaccine Sciences, and colleagues took place over two years, between 2011 and 2013, in the urban slums of Mirpur in Dhaka city, an area with a high rate of hospitalization for severe dehydrating cholera. The study sample included 267,270 residents of this area who are considered to be at ‘high risk’ because of factors such as living in overcrowded quarters, unsafe sources of water, poor sanitation, and unhygienic living conditions.

The researchers aimed to assess the level of protection provided by a two-dose regimen of the oral cholera vaccine Shanchol against severe dehydrating cholera that leads to hospitalization. The vaccine was administered through routine government services in the densely populated urban area. Shanchol is a low-cost oral cholera vaccine – just US $1.85 per dose – that has been prequalified for vaccination programs by the World Health Organization (WHO) as it was proven to be safe and effective in field trials.

The study took a cluster-randomized trial approach in which participants were randomly assigned to one of three groups: those who received Shanchol vaccine, those who received Shanchol and an intervention that encouraged handwashing and drinking water treatment with chlorine, and those who received no intervention at all, the control group.

The results show that at 65% vaccination coverage level the incidence of severely dehydrating cholera was reduced by 37% in the overall study population, irrespective of their vaccination status. The incidence of cholera decreased by 45% in the group that received both vaccination and handwashing-water treatment intervention.

For participants who received the full two doses of the vaccine, the rate of hospitalization decreased by more than 50%. For individuals who were vaccinated, it was shown to confer 53% protection two years after the vaccine was administered, a finding consistent with previous field trials.

The vaccine was well tolerated with no serious adverse effects reported. The majority of adverse events were mild or moderate—the most common were acute watery diarrhoea, vomiting, abdominal pain, and fever.

Dr. Qadri says that “our findings show that a routine oral cholera vaccination program in cholera-endemic countries could substantially reduce the burden of disease and greatly contribute to cholera control efforts. The vaccine is cheap – two doses cost around a third of the price of the other licensed vaccine Dukoral.”

She adds, “Ultimately, the key to controlling cholera is clean water, improved hygiene practices, and adequate sanitation facilities, which half the developing world – around 2.5 billion people – lack. These improvements require large investments for major infrastructural changes, which remain a rather difficult reality for the world’s poorest nations, as well as those affected by climate change, war, and natural disasters.”

The researchers noted that adding the handwashing-water treatment component to vaccination improved the level of protection conferred by the vaccine, but to a limited extent. However, they stressed that further efforts to improve water quality and make handwashing easier for low-income communities with poor infrastructure should be pursued to reduce the incidence of cholera. These are critical components of global cholera control efforts.

Dr Leanne Unicomb, former Head of the ICDDR.B’s Water, Sanitation and Hygiene Research Group, says that “The handwashing-water treatment component was only able to reduce cholera cases to a small degree in this study. Washing hands with soap and treating water with chlorine are low-cost means of reducing diarrhoea, yet they are difficult behaviors to practice frequently in low-income settings where water can be limited and crowding is common. We need to further work with the community to make these practices more convenient to reduce diarrhea, including that caused by cholera.”

The study was funded by the Bill & Melinda Gates Foundation and done in collaboration with Bangladesh’s Ministry of Health and Family Welfare. Additional support was provided from core grants to the ICDDR,B from the governments of Australia, Bangladesh, Canada, Sweden, and the United Kingdom.

[ICDDR.B announcement] [The Lancet abstract] [The Lancet Comment abstract]

[NY Times article] [Fox News article] [Science Magazine news article] [Reuters article] [Voice of America news article] [BBC News article] [Bangladesh News article]