12:32am Friday 24 November 2017

Vaccine will be crucial in fight against dysentery, study suggests

Dysentery is a diarrhoeal infection primarily associated with low-income countries and poor water quality. Although most people have heard about the disease, few know about the bacteria that causes it, Shigella.

Shigella is relatively understudied, and little is known about its population structure or its origins. Yet more than one million people, mostly young children, are estimated to die from dysentery caused by strains of Shigella bacteria each year.

Traditionally, Shigella flexneri has been the most common strain of Shigella to cause dysentery in low-income countries, and Shigella sonnei is more prevalent in high-income countries. As low-income countries become more industrialised, the number of S. flexneri infections is known to decline, which is associated with improved health, different lifestyles and – perhaps most importantly – access to clean water. At the same time, however, the incidence of S. sonnei actually increases, suggesting that the disease is unlikely to be resolved by providing access to clean water.

The international team of researchers sequenced the genome of 132 globally distributed isolates of S. sonnei to find out more information about its origins and the reasons for its rapid spread through high-income countries.

Their findings indicate that S. sonnei was first established in Europe just a few centuries ago but has spread to the rest of the world in the past few decades. They also found that a key factor in the spread of this pathogen was a rise in multidrug resistance – the ability to survive exposure to a wide array of antibiotics.

Because S. sonnei is easily transmitted and has high levels of drug resistance, the researchers suggest that drug treatment and better sanitation alone will not be sufficient for controlling the disease. Vaccine development will be crucial.

Dr Kathryn Holt, first author from the University of Melbourne, explains: “Although S. sonnei is a relatively new species of bacterium, during its spread it has diversified into an array of different distinguishable clones or strains found right across the world. This is hard to see using traditional methods, but by sequencing the genomes of over 100 different forms of the bacteria, we were able to get a glimpse into its past and really start to understand how it is evolving and moving around the world.

“We compared the S. sonnei family tree and geographical locations of the different strains to determine when and where this bacterium first emerged and why it has become such a problem in industrialised countries with increasing access to clean water. Traditionally, we associate dysentery with contaminated water and lack of industrialisation.”

To investigate why the bacterium was spreading so effectively, the team looked at the genetic evolution of S. sonnei and found that only a few types of genes were selectively evolving over time, particularly those involved with drug resistance. This suggests that a major driver in the spread of this bacterium was its apparent ability to become resistant to drug treatment.

Dr Stephen Baker, a senior author from the Oxford University Clinical Research Unit in Vietnam, said: “Our data is consistent with antibiotic resistance as being a main driver of the spread and persistence of S. sonnei around the world, stressing that antibiotics are not a long-term solution for the elimination of this global health problem.”

“One of the Millennium Development Goals is to improve drinking water and reduce water-borne diseases, an undeniably important aim,” says Professor Nicholas Thomson, lead author from the Wellcome Trust Sanger Institute. “This may have the unforeseen result of increasing the incidence of S. sonnei dysentery in transitional countries.

“Our research emphasises the importance of a vaccine against Shigella. The combination of increased incidence and antibiotic resistance of S. sonnei means that a vaccine will be increasingly important for the long-term control and prevention of dysentery.”

Image: Shigella flexneri invading an embryonic stem cell. Credit: David Goulding, Wellcome Trust Sanger Institute, Wellcome Images.

Reference

Holt KE et al. Out of Europe: the recent global dissemination of Shigella sonnei. Nat Genet 2012 (epub ahead of print).

Wellcome Trust, Gibbs Building, 215 Euston Road, London NW1 2BE, UK T:+44 (0)20 7611 8888

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