Archive for March, 2011

Bacterial Superpowers

By Rebecca Kreston | March 20, 2011 9:00 pm

The emergence of the New Delhi Metallo-Beta Lactamase (NDM-1) gene in bacteria commonly associated with nosocomial, or hospital-borne, infections this past summer has sparked the latest fears of a “superbug” waging war in hospitals around the world. It may sound like talking about nosocomial infections tends to the hyperbole, with an abundance of unnecessary war-associated terminology. Indeed, there does seem to be an “arms race” of sorts in that the weapons that we have long used again microbes, typically antibiotics and antivirals, are becoming less effective in the face of evolving microbial antibiotic resistance. Penicillin was deemed the “magic bullet” upon its introduction in medicine in XXX; unfortunately, we are rapidly running out of such panacea. NDM-1 is just the latest antibiotic-resistance gene and seems poised to do the most damage to our already beleaguered arsenal of antibiotics.

The narrative of the spread of NDM-1 warrants special interest in particular due to its association with a unique medical trend that has recently emerged in the past few years. Medical tourism has  quickly evolved into a viable alternative for Western consumers seeking cheap medical treatment options (1). In addition, there are also the unlucky few who have fallen ill overseas and returned with unwelcome bacterial souvenirs. The global dissemination of the NDM-1 gene in such an extraordinarily short timespan is attributed to these global travelers. As such, the gene has been found in clinical isolates ranging from India, Pakistan, Bangladesh, Iraq, the United Kingdom, France, and Canada, and research strongly implicates patient carriage of this gene with having received recent medical treatment in the Indian subcontinent (2).

As to the discovery of this novel gene, a Swedish patient of Indian origin returned to Sweden  following a trip to New Delhi after which he had been hospitalized with a large gluteal abscess. In this case, this patient had unfortunately fallen gravely ill from previously existing medical conditions, not as a result of cosmetic surgery. He returned home with an unwelcome souvenir, a urinary tract infection (UTI), that yielded a clinical isolate of Klebsiella pneumoniae. The UTI was unremarkable in that the bacterial load in a urine culture was quite low, but the bacterial isolate truly was unique.

Molecular typing of the isolate indicated that it carried a novel metallo-beta-lactamase (MBL) gene through strangely lacked other common MBL genes. Most unnerving was the isolate’s wide-spread broad resistance to antibiotics upon completion of drug susceptibility profiles. A host of commonly used antibiotics targeting the beta-lactamase systems, including the heavy hitting cephalosporins Ceftazidime, Cefotaxime and Cefepime, were shown to be ineffective against against the Klebsiella pneumoniae clinical isolate of this patient. The isolate was highly resistant not only to beta-lactams but also to aminoglycosides, quinolones, tetracycline, nitrofurantoin, and cotrimoxazole (3).

As of now, the gene is limited to bacteria within the Enterobacteriaceae family, including  the pathogens Klebsiella pneumoniae, Escherichia coli and Enterobacter spp. Regrettably, it is these very organisms that are the source of the majority of nosocomial infections causing considerable morbidity and mortality (4). These opportunistic bacteria tend to cause secondary infections in urinary and respiratory tracts as well as in wounds, and they happen to do so very well.

The international travels of a previously localized pathogen, disease vector or even a pathogenic gene is not uncommon. Globalization has been quite the agreeable force in the spread of disease. The ease of international travel, the necessity of migrating for one’s economic livelihood and the global food trade are just a few examples of the incredible effect that globalization has had upon the geographical spread and introduction of infectious diseases, as well as antibiotic resistance. Diseases previously confined to specific locales are suddenly global travelers, as was the case with hookworm and malaria in Africa prior to their introduction to the Americas during the slave trade (5). The importance of establishing and maintaining rigorous syndromic surveillance sites, such as ProMed, to monitor emerging disease outbreaks, proliferation of antibiotic resistance genes, traveling of disease vectors, and their diffusion across country borders is more crucial than ever.

References

(1) Konrad W. (2009, Mar 20)  Going Abroad to Find Affordable Health Care. New York Times. Retrieved February 26th, 2011 from http://www.nytimes.com/2009/03/21/health/21patient.html
(2) Kumarasamy et al. (2010) Emergence of a new antibiotic resistance in India, Pakistan, and the UK: a molecu- lar, biological, and epidemiological study. Lancet Infect Dis.10: 597–602
(3) Tijet et al. (2011) New Delhi Metallo- ?-Lactamase, Ontario, Canada. EID Journal Online. 17(2): http://www.cdc.gov/eid/content/17/2/306.htm
(4) Fraser et al. (2010) Enterobacter Infections. Retrieved February 26, 2011 from http://emedicine.medscape.com/article/216845-overview
(5 ) Palmer P and Reeder MM. The Imaging of Tropical Diseases: With Epidemiological, Pathological and Clinical Correlation Volume 2. 2nd ed. Birkhäuser, 2001. Accessed here.

CATEGORIZED UNDER: Bacteria, Vaccines & drugs

Beating around the Bush: Bushmeat & Emerging Diseases

By Rebecca Kreston | March 18, 2011 3:36 am

Many diseases so familiar to those of us in the study of infectious disease (ID) are of zoonotic, or animal, origin. It’s a long, chilling list – AIDs, SARs, Ebola, West Nile Virus, and dengue hemorrhagic fever are just a few well-known examples. What’s worse is that those just listed have only emerged in the past two decades (1). Frightening stuff. Here’s another alarming statistic: a staggering 75% of novel emerging diseases are of zoonotic origin (2).

One of the most exciting work in the studies of emerging infectious diseases (EID) and, in particular, zoonotic diseases is the work of Nathan Wolfe and his team at the Global Viral Forecasting Initiative. Their pioneering research has primarily focused on the origin and evolution of major IDs amongst mankind, many of which can be traced to originating with animals of different species. The wild animal and human interface seems to be a very rich source of new travel destinations for microbes.

As such, the best place for examining the “who, what, how and why” of novel EIDs, this so-called “viral chatter”, is to venture into regions where this real-life experiment is on-going. For Wolfe and his team, that means examining communities in African forests that rely on the bushmeat trade as a livelihood. By looking at anthropoid primates and their homegrown diseases, Wolfe’s team may give us greater insight into the latest zoonotic disease that may visit a closely related primate, the human. If you’re into gambling, maybe we could even predict a disease that’ll make a lasting jump from a previously wild reservoir into human civilization.

Wolfe’s most seminal research looks at a virus  endemic in most Old World primates native to Africa and Asia. The virus, simian foamy virus (SFV), is a blood-borne, non-fatal virus that is genetically similar to HIV. Wolfe and his team have looked at the presence SFV of in humans as a transmission marker to examine the potential of other such similar viral transmission events between humans and primates. As expected, the more contact people have with primates, especially that of blood and bodily fluids as a result of meat butchering, the greater the likelihood is that they have antibodies to SFV, an indication of immunological exposure to the virus (3).

Previous research examining the phylogenies of HIV-1 and HIV-2, as well as the closely related simian immunodeficiency viruses (SIVs), indicate that the viruses had on the order of eight separate transmission between African monkeys and apes (3). Wolfe’s research gives as a bit of an idea of what the plot background was with those eight separate transmissions, in which these viruses were metaphorically hopscotching between primates and humans and prior to their permanent entry into mankind.

A bushmeat hunter & his kill: a still from Wolfes TED talk

Wolfe’s team is also engaged in viral monitoring in which they track zoonotic viruses with the assistance of bushmeat hunters in Cameroon. Trained hunters take blood samples from their kill by dripping small drops of blood into prepared filter papers that will later serve as samples for their fantastic investigate work into the transmission history between retroviruses (4). Blood samples are also taken from the hunters themselves so as to monitor any evidence of cross-species viral infection with their prey. This surveillance research complements their molecular and phylogenetic based work in that they can monitor the current catalog of viruses in the wild and any potential real-time transmissions between wild animals and bushmeat hunters. Already they have discovered several new retroviruses genetically similar to HIV (5). You can check out his genuinely inspiring talk on TED and get a better idea of the project.

Asking just these kinds of questions is of the utmost importance in the public health field. ID’s already account for 16% of global deaths as is and there are more lurking in the jungles just waiting for some human-wild animal interface (2). Remember the SARS pandemic in 2002? That’s a great example of the sticky, tangled interactions between zoonoses, the bushmeat trade and international travel. An unfamiliar member of the coronavirus family (the common cold is also a member), Severe Acute Respiratory Syndrome (SARS-CoV) virus had never been seen before in humans and it was quite the introduction. In the span of over six months, the extraordinarily infectious virus had infected more than 8,000 people and killed 774 people around the world, 347 of those on the Chinese mainland (6). The virus has the ignoble title of initiating the first pandemic of the 21st century.

As the virus swept China and started appearing in nearby countries, blame focused upon the civet cat, whose meat is considered a great delicacy in Southern China. Many of the earliest cases of SARS were professionals with heavy involved in the bushmeat trade in the Guangdong Province, ranging from breeding, butchering, selling and even preparing and serving civet cat meat (7). Immediate culling of the carnivores, along with two other suspects, the raccoon dog and Chinese ferret badger, commenced in the hope that with the elimination of the primary source, transmission rates would plummet and end the pandemic (8). However, recent research has implicated bats of the genus Rhinolophus as the natural, unaffected reservoir of the SARS virus, not the civet cat (7). Indeed, the SARS pandemic showcased just how rapidly viral evolution can occur. A mutation in the receptor-binding domain (RBD) of a gene known as the spike protein appears to have enhanced the virus’ ability to infect humans (7); indeed this very gene has been implicated before in the ability of viruses to adopt to novel hosts. In the case of this virus, the civet cat was an unwitting intermediate host of a viral spillover from bats that made the transition to humans.

From MSNBC: A civet cat at a wild-game market in Guangzhou, capital of the Guangdong province

It seems like a random fluke, just an evolutionary anomaly in the viral world. A small mutation and a viral protein is suddenly able to bind just a little bit better to a human cell receptor and slink into our cells. And perhaps it would remain just a stroke of bad luck in the viral immunology world except that this isn’t the first time it’s happened. And if the history of infectious diseases is anything to go by, nor will it be the first – just last year we were introduced to influenza H5N1, the ignominiously named “swine flu”. Probably best to stick with a street-meat hot dog as opposed to bushmeat wild dog for the time being.

There is a lot of really fantastic research exploring this issue and much more, including how man-made problems such as deforestation, climate-change, logging, agriculture and even civil conflict have increased contact between humans and wild life. Indeed, bushmeat plays just a small role in zoonotic EIDs. There are complex ecological, biological and social factors involved in disease transmission beyond simply human-animal contact; the host, vector and the pathogen itself are at the whim of the environment, the diversity of human cultures and behaviors, and, as previously mentioned, sheer luck.

Check out these great reviews for more info if you’re interested!

Wild Primate Populations in Emerging Infectious Disease Research:  The Missing Link?

Nathan Wolfe’s talk on his research at TED in 2009

References

(1) Wolfe ND et al. (1998) Wild Primate Populations in Emerging Infectious Disease Research:  The Missing Link? Emerging Infectious Diseases. 4(2): 149-58.
(2) Karesh, WB & Noble, E. (2009) The Bushmeat Trade: Increased Opportunities for Transmission of Zoonotic Disease. Mount Sinai Journal of Medicine. 76(5):429–434.
(3) Wolfe ND. (2004) Naturally acquired simian retrovirus infections in central African hunters. Lancet. 363(9413): 932-7.
(4) Wolfe ND. “Nathan Wolfe’s jungle search for viruses” (video). TED Conference Website. http://www.ted.com/talks/nathan_wolfe_hunts_for_the_next_aids.html. Accessed February 25, 2011
(5) Svoboda, E. “Deep in the Rain Forest, Stalking the Next Pandemic.” New York Times, October 20, 2008. Accessed February 25, 2011.? http://www.nytimes.com/2008/10/21/health/research/21prof.html?_r=2&ref=science&oref=slogin.
(6) “Civet cat crackdown reported in China.” International Herald Tribune, February 19, 2007. Accessed February 25, 2011. http://www.nytimes.com/2007/02/19/world/asia/19iht-sars.4644110.html
(7) Wang L and Eaton B. (2007) Bats, Civets and the Emergence of SARS. Wildlife and Emerging Zoonotic Diseases: The Biology, Circumstances and Consequences of Cross-Species Transmission. Current Topics in Microbiology and Immunology. 315: 325-344.
(8) Childs JE. (2007) Pre-spillover Prevention of Emerging Zoonotic Diseases: What Are the Targets and What Are the Tools? Wildlife and Emerging Zoonotic Diseases: The Biology, Circumstances and Consequences of Cross-Species Transmission. Current Topics in Microbiology and Immunology315: 389-443
ResearchBlogging.org
Wolfe, N. (1998). Wild Primate Populations in Emerging Infectious Disease Research: The Missing Link? Emerging Infectious Diseases, 4 (2), 149-158 DOI: 10.3201/eid0402.980202

Hello!

By Rebecca Kreston | March 2, 2011 3:55 am

My name is Rebecca and I’m currently a student of Tropical Medicine at Tulane’s School of Public Health. I’ve long been interested in gross human diseases that usually make people shudder and luckily I’ve been able to study them academically and out in the “real world”. This is my latest adventure/experiment. Ultimately, I want to use this blog to explore the intersections of human behavior and infectious diseases, which is, in my opinion, one of the more interesting aspects of public health. Instead of trapping people at cocktail parties and yakking about intestinal parasites, I’m hoping that I can do this in a more socially acceptable manner online.

I hope ya’ll have as much fun reading my posts as I do researching, writing and sharing them with you!

CATEGORIZED UNDER: Emerging Diseases
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