Monday, October 1, 2012

HIV could be turning salmonella nastier

A nastier kind of salmonella infection has emerged alongside the HIV epidemic in Africa. The finding is the first evidence that HIV might be allowing new human pathogens to evolve in immunosuppressed people.

Most people who get salmonella contract it from eating contaminated meat, leading to an unpleasant but brief gut upset. But in Africa, the bacteria escapes into the blood of people with suppressed immune systems, causing a fever called invasive, non-typhoidal salmonella (iNTS) that can kill in up to 45 per cent of cases. The main victims used to be children who have immune deficiency as a result of malnutrition or malaria, but iNTS is also a classic complication of HIV.

Chinyere Okoro of the Wellcome Trust Sanger Institute in Hinxton, UK, and colleagues fully sequenced the DNA of iNTS samples from Africa, then used that to analyse the family trees of the bacteria sampled across the continent. The team found they nearly all clustered in one of two closely related lineages.

One arose in Malawi in 1960 and spread across eastern and central Africa in the 1980s. It was recently replaced by a second lineage that arose in central Africa in the late 1970s and spread in distinct waves across sub-Saharan Africa. The second seems to have replaced the first because it resists chloramphenicol, the antibiotic widely used to treat the first lineage.

Crucially, the timing and locations of the spread of the bacteria coincide closely with the spread of HIV across the continent, says Robert Kingsley of the Sanger Institute, a senior author of the study. Before HIV became widespread, iNTS mainly affected children, who rarely travelled. HIV created adult carriers who move around more. The salmonella they carried now dominates these infections across Africa.

This represents more than a case of one set of bacteria taking over from another. The salmonella strain associated with HIV may also be adapting to us. Another kind of salmonella, which causes typhoid fever, has completely adapted to people, to the extent that we catch it from other people rather than from the environment. The African strain of iNTS seems to be undergoing similar genetic changes to the typhoid bacteria, and may also be spreading between people.

"These adaptations confer a selective advantage on this lineage in an immune-compromised host," says Kingsley. The question is, are the bacteria doing well because they resist many antibiotics, or because in adapting to a new niche ? people infected with HIV ? they are evolving into a new human pathogen? To settle that, Kingsley says, we need to know more about how the bacteria spread.

"This is a really important question," says Andrew Read of Pennsylvania State University in University Park, who studies pathogen evolution. "Does a large novel reservoir of immunosuppressed people with HIV create a portal for new pathogens to invade humanity?"

This could be happening with salmonella, he says. "We have to watch for this possibility in a whole range of infectious diseases."

Reference: Nature Genetics, DOI: 10.1038/ng.2423

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