Study: Intra-Continental Spread of Invasive Non-Typhoidal Salmonella

 

 Salmonella typhimurium bacteria – Credit CDC PHIL

 

 

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You might not think there’d be much of a connection between an emergent serotype of Salmonella and the HIV epidemic in Sub-Saharan Africa - but if researchers from the Wellcome Trust Sanger Institute have it right - this highly pathogenic bacterial strain may have had a powerful viral ally.

 

There are more than 2500 serovars of Non-Typhoidal Salmonella (NTS) that can produce gastroenteritis or other infections in humans. Taken together, these Gram negative, anaerobic bacteria are believed to be the second most common source of food poisoning in the United States.

 

Those infected often develop diarrhea, fever, vomiting, and abdominal cramps that may persist for several days.

 

In the western world most recover without treatment, although the CDC estimates that nearly 400 people infected die each year in the United States (Cite  CDC Food borne Illness Estimates).

 

In developing countries, Non-typhoidal Salmonella can (and does) exact a much higher toll, particularly among those who may be malnourished or suffer from chronic ailments such as malaria and HIV.

 

In recent years researchers have also noted a much more virulent form of NTS, spreading across sub-Saharan Africa, that they’ve dubbed  Invasive Non-Typhoidal Salmonella (iNTS). 

 

Not only is it a multi-drug resistant strain, it is fatal in about 25% of those who contract it.

 

Today, we’ve a study that appears in Nature Genetics that links the Intracontinental spread and evolution of this invasive and severe form of Salmonella to the emergence and spread of HIV.

 

Intracontinental spread of human invasive Salmonella Typhimurium pathovariants in sub-Saharan Africa

Chinyere K Okoro,Robert A Kingsley,Thomas R Connor,Simon R Harris,Christopher M Parry,Manar N Al-Mashhadani,Samuel Kariuki,Chisomo L Msefula,Melita A Gordon,Elizabeth de Pinna,John Wain,Robert S Heyderman,Stephen Obaro,Pedro L Alonso,Inacio Mandomando,Calman A MacLennan, Milagritos D Tapia,Myron M Levine,Sharon M Tennant,Julian Parkhill & Gordon Dougan

Published online 30 September 2012

 

While the bulk of the study is behind a pay wall, the Abstract is available, as is this press release from the Wellcome Trust Sanger Institute.

 

New pathogen epidemic identified in sub-Saharan Africa

Researchers track the spread of human invasive non-Typhoidal Salmonella in sub-Saharan Africa

A new study out today (Sunday 30 September) reveals that the emergence and spread of a rapidly evolving invasive intestinal disease, that has a significant mortality rate (up to 45%) in infected people in sub-Saharan Africa, seems to have been potentiated by the HIV epidemic in Africa.

 

The team found that invasive non-Typhoidal Salmonella (iNTS) disease is caused by a new form of the bacteria Salmonella Typhimurium that has spread from two different focal hubs in Southern and Central Africa beginning 52 and 35 years ago, respectively. They also found that one of the major contributing factors for the successful spread of iNTS was the acquisition of genes that afford resistance to several front line drugs used to treat blood-borne infection such as iNTS.

 

iNTS is a blood-borne infection that kills approximately one of four people in sub-Saharan Africa who catch it. Yet, in the rest of the world, NTS is a leading cause of acute inflammatory diarrhoea that is self-limiting and tends to be fatal in less than 1 per cent of people infected. The disease is more severe in sub-Saharan Africa than the rest of the world because of factors such as malnutrition, co-infection with malaria or HIV and potentially the novel genotype of the Salmonella bacteria.

 

"The immune system susceptibility provided by HIV, malaria and malnutrition at a young age, may provide a population in sub-Saharan Africa that is large enough for this detrimental pathogen to enter, adapt, circulate and thrive," says Chinyere Okoro, joint first author from the Wellcome Trust Sanger Institute. "We used whole genome sequencing to define a novel lineage of Salmonella Typhimurium that is causing a previously unrecognised epidemic across the region. Its genetic makeup is evolving into a more typhoid like bacteria, able to efficiently spread around the human body"

 

<SNIP>

 

"There has been some evidence that this disease can be passed from human to human. Now the race is on to discover how NTS is actually transmitted in sub-Saharan Africa so that effective intervention strategies can be implemented."

 

(Continue . . . )

 

 

And for more on all of this, here’s Debra McKenzie’s article for New Scientist.

 

 

HIV could be turning salmonella nastier

 

18:00 30 September 2012 by Debora MacKenzie

 

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.

 

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When Pig Viruses Fly

 

 

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Being of swine origin, the pandemic producing 2009 H1N1 virus – to no great surprise – moved easily from human hosts back into pig populations around the globe.

 

By the fall of 2009 we’d seen reports of pigs in Canada, the US, Japan, Ireland, Norway, Australia, Argentina, Iceland, and China  showing infection with the humanized H1N1 virus. 

 

Since humans are far more traveled than your average pig, a virus that might have remained confined to swine herds in one region of the world for years soon spread to every continent via international travel.

 

Each year, more than 17 million commercial airline flights transport hundreds of millions of people across the globe (see Pathological Flyers).

 

You can literally travel from just about any two cities (with airports) anywhere in the world in 24 hours or less. No longer are the oceans, or distance, a protection against diseases normally seen only in remote areas of the world.

 

Which is why the pandemic of 2009 spread so quickly around the globe.

 

Given the very limited animal testing and surveillance in the United States and around the world (see Swine Flu: Don’t Test, Don’t Tell) the true scope of the spread of the H1N1 virus back into the pig population remains unknown.

 

The concern is that once `humanized’, and then reintroduced back into the swine population, the virus will have enhanced opportunities to meet up with – and reassort with – other flu viruses. 

 

Reassortment happens when two different influenza viruses co-infect the same host, swap genetic material, and produce a hybrid virus. 

 

 

We’ve already seen multiple reports of pdmH1N1 reassortments, although none have emerged that pose a renewed pandemic threat. 

 

With global pig production growing rapidly to meet the demands of a hungry world, each year we add millions more `mixing vessels’ to natures laboratory.  And the bulk of the predicted growth in hog farming is expected in developing countries where testing is pretty much non-existent.

 

Credit – FAO

 

 

Illustrating the problem is a report yesterday from UCLA on the prevalence of the pandemic H1N1 virus among pigs in Cameroon.

 

In one village, nearly all of the pigs tested showed evidence of current or past infection.

 

 

I’ve a small excerpt from a much longer UCLA Newsroom background article, along with a link to the study.

 

 

UCLA scientists find H1N1 flu virus prevalent in animals in Africa

By Stuart Wolpert September 22, 2011

 

UCLA life scientists and their colleagues have discovered the first evidence of the H1N1 virus in animals in Africa. In one village in northern Cameroon, a staggering 89 percent of the pigs studied had been exposed to the H1N1 virus, commonly known as the swine flu.

 

"I was amazed that virtually every pig in this village was exposed," said Thomas B. Smith, director of UCLA's Center for Tropical Research and the senior author of the research. "Africa is ground zero for a new pandemic. Many people are in poor health there, and disease can spread very rapidly without authorities knowing about it."

(Continue . . . )

 

The study appears (behind a pay wall) in Veterinary Microbiology.

 

Pandemic A/H1N1/2009 influenza virus in Swine, Cameroon, 2010

Kevin Y. Njabo,  Trevon L. Fuller, Anthony Chasar, John P. Pollinger, Giovanni Cattoli, Calogero Terregino, Isabella Monne, Jean-Marc Reynes, Richard Njouom, Thomas B. Smith

 

 

The viruses detected in Cameroon were  reportedly `virtually identical’ to the H1N1 viruses detected early in the pandemic in San Diego. Thomas B. Smith, the senior author of the research is quoted as saying:

 

"When different strains of influenza are mixed in pigs, such as an avian strain with a human strain, you can get new hybrid strains that may affect humans much more severely and can potentially produce a pandemic that can allow human-to-human infection. This is how a pandemic can arise; we need to be very vigilant.

 

 

Of course, it isn’t just the 2009 H1N1 virus in swine that we concern ourselves with. In recent years we’ve seen a variety of reassorted H1N1 and H3N2 viruses in pigs, and on rare occasions these have been passed on to humans.

 

Pigs in Indonesia have also been found to have contracted the H5N1 bird flu virus (see EID Journal: Asymptomatic H5N1 In Pigs).

 

 

Most recently, four cases of a reassorted H3N2 virus with the M gene from H1N1 turned up in children in Pennsylvania and Indiana (see CDC Update On Recent Novel Swine Flu Cases).

 

While the epidemiological investigation continues, so far we’ve no evidence of sustained human transmission.

 

It is likely that limited infection by novel influenza reassortments such as these occur occasionally (and largely unnoticed) all over the world. Since only a tiny fraction of influenza flu viruses are ever sequenced, we really don’t know how often these types of novel infections occur.

 

But it’s probably more often than we think.

 

These rare SOIV infections are important to monitor and analyze, and may give us an early warning about the next pandemic threat. But for now they pose a very low public health threat.

 

Admittedly, it may be years or even decades before another pandemic emerges and threatens the human population. The timing of these events is impossible to predict.

 

But surveillance studies like the one above show that flu viruses will literally go to the ends of the earth looking for new hosts and an evolutionary advantage.

 

 

 

For more on the reassortment potential of avian, swine, and human flu viruses, you can’t do better than  Helen Branswell’s excellent Scientific American article from last December called Flu Factories, or her SciAm Podcast interview.

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Uganda: Unidentified Hemorrhagic Outbreak

 

 

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In December of 2007 I wrote several blogs about an Ebola outbreak in Bundibugyo, located in western Uganda.  

 

A brief excerpt from one of those posts follows:

 

Ugandan Nightmare

 

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The picture above gives a pretty good indication of how the Ebola virus is spreading in Uganda. Notice the lack of gloves on the attendant's hands, the lack of goggles, and the use of only a simple surgical mask.

 

Disposables, like gloves, are in very short supply even in the hospitals, and this has led to the deaths of 5 health care workers.

 

(Continue . . . )

 

We didn’t realize it at the time, but what they were seeing was a new – previously unidentified strain – of ebola.   A strain which would eventually be named Bundibugyo ebolavirus after its place of discovery.

 

While less deadly (34% Case Fatality Rate) than other strains of ebola (excluding Ebola Reston), the emergence of this new strain was a sober reminder that a year rarely passes when we don’t discover a new zoonotic disease capable of jumping to humans.

 

A year later (2008) doctors in Zambia and South Africa ran across a mysterious, previously unclassified virus that caused hemorrhagic symptoms in its victims similar to Ebola.

 

It appeared to be highly contagious, and was fatal in 4 of the 5 identified victims.    Like most other infectious disease bloggers, I covered the story a bit, although the amount of information available then was pretty thin.

 

WHO Update On South African `Mystery Disease'

South African `Mystery Virus' Identified

 

On October 13th, 2008 the virus was tentatively identified as a new arenavirus, but since that time more exacting studies have been done.   In 2009, this virus was named the Lujo Virus, and detailed in the PloS Pathogens report.

 

Genetic Detection and Characterization of Lujo Virus, a New Hemorrhagic Fever–Associated Arenavirus from Southern Africa

 

 

Today, again from western Uganda, we are seeing reports of a new hemorrhagic disease outbreak – cause unknown – that has reportedly killed 13 people so far.

 

This report courtesy of Shiloh on FluTrackers, indicates that preliminary testing by the Uganda Virus Research Institute has ruled out Ebola, Marburg, and Lassa.  Samples have been sent to the CDC in Atlanta for analysis.

 

 

13 dead, as strange disease spreads

Monday, 15th November, 2010

 

By David Labeja and Sam Oboke
THIRTEEN people have been reported dead in Abim and Agago districts, following an outbreak of a strange disease in Abim.

 

Twenty cases have been reported in Abim district, out of whom eight have already died.

 

In neighouring Agago district, five cases have been reported in the sub counties of Omiya P’Chua and Paimol, which border Abim district.

(Continue . . . )

 

Additional reports will most certainly be posted on this FluTrackers Thread.

 

Hemorrhagic viruses, while horrific, are usually self-limiting and generally only pose a threat to the area where they emerge. 

 

Most are believed initially contracted by eating (or preparing) bush meat, and are subsequently spread via bodily fluids.

 

Health care workers – particularly in areas where personal protective equipment is unavailable – are at particularly high risk of contracting the illness.

 

When we know more about this particular outbreak, I’ll update this story.

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