Tuesday, March 20, 2018

mBio: The Gathering Storm: Is Untreatable Typhoid Fever on the Way?


Roughly three weeks ago a team of British and Pakistani researchers published a study in the American Society For Microbiology Journal mBio - which detailed the first large outbreak of extensively drug-resistant (XDR) typhoid - which emerged in the Sindh region of Pakistan (includes Karachi & Hyderbad) in late  2016.

You can read the full paper at the link below, or read CIDRAP's excellent summary of Feb 20th (see Study: XDR typhoid in Pakistan carries added resistance genes).

Emergence of an Extensively Drug-Resistant Salmonella enterica Serovar Typhi Clone Harboring a Promiscuous Plasmid Encoding Resistance to Fluoroquinolones and Third-Generation Cephalosporins 
Elizabeth J. Klemma, Sadia Shakoorb, Andrew J. Pagea, Farah Naz Qamarb, Kim Judgea, Dania K. Saeedb, Vanessa K. Wongc, Timothy J. Dallmand, Satheesh Naird, Stephen Bakere,f,g, Ghazala Shaheenb, Shahida Qureshib, Mohammad Tahir Yousafzaib, Muhammad Khalid Saleemb, Zahra Hasanb, Gordon Dougana,c, Rumina Hasanb
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Although XDR, this particular strain of Typhoid is not yet completely resistant; it remains susceptible to oral azithromycin.  Other strains in Southeast Asia have already shown resistance to azithromycin, leading to concerns that susceptibility to this last oral antibiotic may eventually fall.

While we've been watching the inroads made by a growing array of antibiotic resistant organisms around the globe for years, for the most part, human infections have been sporadic, and thus far, very few `pan-resistant' infections have emerged.

The past couple of years, however, we've seen an increase in the number and variety of resistant organisms, many exhibiting even broader resistance than before.  A few recent blogs include:

Global AMR Threat: Centrally Approved & Unapproved Antibiotic Formulations Sold In India
WHO: First Global Antimicrobial Surveillance System (GLASS) Report
MMWR: Fatal Pan-Drug Resistant CRE - Nevada 2016
mBio: 1st Colistin & Carbapenem Resistant E. Coli Infection In A U.S. Patient
And last fall CIDRAP reported on a Hypervirulent, highly resistant Klebsiella identified in China, one which a week later was described as New Klebsiella strains 'worst-case scenario,' experts say.
Of particular concern, the enzymes that convey antibiotic resistance can be carried by a plasmid – a snippet of portable DNA  - that can be horizontally transferred to other types of bacteria (see Study: Adaptation Of Plasmids To New Bacterial Species). 
This provides bacteria with a great advantage, as resistance need not develop independently in individual pathogens; it can be shared and passed along to other organisms.
If we're in a war against antibiotic resistance, then the news from the front isn't good.
Salmonella Typhi, the causative agent of Typhoid Fever, is a bacterium that has no known natural reservoir outside of humans. It is usually acquired via the fecal-oral route, often by consuming food or drink that has been handled by someone who is shedding the Salmonella Typhi bacteria.

While still common in some developing countries, Typhoid fever is rarely seen anymore in the United States. The CDC’s Typhoid Fever FAQ states the U.S. sees only about 400 cases of Typhoid each year, of which 3/4ths are brought into this country via international travel.   
Today mBio carries a commentary on last month's study, which the authors describe as `momentous'.  I've only included the abstract, so you'll want to follow the link and read it in its entirety.
When you return, I'll have a postscript.
The Gathering Storm: Is Untreatable Typhoid Fever on the Way?
Myron M. Levinea, Raphael Simona


Klemm et al. (mBio 9:e00105-18, 2018, https://doi.org/10.1128/mBio.00105-18) present comprehensive antibiotic sensitivity patterns and genomic sequence data on Salmonella enterica serovar Typhi blood culture isolates from typhoid fever cases during an epidemic in Pakistan. Microbiologic and genomic data pinpoint the identities and locations of the antimicrobial resistance genes and the outbreak strain’s lineage.
They propose that Salmonella enterica serovar Typhi be added to the list of bacterial pathogens of public health importance that have become extensively drug resistant (XDR). This paper portends possible dire scenarios for typhoid fever control if XDR strains disseminate globally. Since the outbreak strain is of the H58 haplotype, known for its ability to spread worldwide and displace endemic S. Typhi, this concern is well-founded. 
The report of Klemm et al. forewarns the global community to address control of typhoid fever more aggressively through prevention, should therapeutic options disappear. This Commentary frames the Klemm et al. findings within a historic perspective.
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Once a major scourge around the world, deaths from Typhoid Fever have declined greatly since the chlorination of water supplies in industrialized nations began early in the last century, along with the development of effective antibiotic treatments. 

While modern sanitation methods - at least in industrialized nations - may limit the impact of AMR (antimicrobial resistant) Typhoid, the reality is this is just one of a growing array of AMR threats in the wings.
Short of a 1918-style (or worse) pandemic, the rise of antibiotic (and anti-fungal) resistant organisms is likely the greatest public health threat we will face in the next couple of decades.
While I cover AMR topics from time to time, I can heartily recommend CIDRAP's Antimicrobial Stewardship Project as the best place to learn about this looming global threat of AMR.

You'll also want to check out the CIDRAP-ASP Youtube Channel, which has more than 20 hours of lectures and webinars on Antimicrobial stewardship.