A persistent epidemic of extensively drug-resistant (XDR) typhoid in Pakistan is just a small genetic step away from becoming untreatable – and health experts expect it to spread worldwide.
“It’s a global concern right now,” Dr. Eric Mintz, an epidemiologist at the Centers for Disease Control and Prevention. The New York Times. “Everything indicates that this species will survive well and spread easily – and acquiring resistance to azithromycin is only a matter of time.” Azithromycin is currently the only remaining antibiotic that treats the infection.
Typhoid fever, caused by: Salmonella enterica serovar Typhi bacteria, is endemic to Pakistan, parts of which suffer from poor infrastructure, congested urban areas and insufficient access to health care. The epidemic caused by the XDR strain – the first of its kind – has been unfolding there since November 2016. It has now affected at least 850 people in 14 districts, according to the latest figures from the National Institute of Health in Islamabad and first reported. By the Time. Prior to this epidemic, there were only four known, unrelated cases of such heavily drug-resistant typhus, occurring in Iraq, Bangladesh, India and Pakistan.
The XDR strain has already started to spread outside of Pakistan, with a travel-related case in the UK.
In a recent report on the emergence of the species in the journal mBio, infectious disease experts have determined that it can withstand attacks from five classes of antibiotics used to treat typhoid fever. They concluded that the evolution of the species was a “surprising demonstration” of how easy S. Typhi may pick up genetic elements that confer drug resistance, “turning it on to XDR and further limiting treatment options.”
Antibiotics are the only effective treatment for typhoid fever, a systemic infection of varying severity that can become life-threatening. The infection is generally characterized by fever, headache, nausea, loss of appetite and constipation or sometimes diarrhea. The highest number of deaths occurs in children under the age of four. About 2 to 5 percent of those infected can become chronic asymptomatic carriers and shed the bacteria in their stool. The Salmonella Typhi bacteria are usually spread through food or water contaminated with feces.
Researchers estimate that there are between 10 million and 20 million cases per year worldwide, leading to between 130,000 and 210,000 deaths. And that’s the case of antibiotic treatments are largely still available and working.
“Most clinicians and clinical microbiologists do not appreciate the lethality that typhoid fever showed in the pre-antibiotic era,” say Myron Levine and Raphael Simon. The vaccine researchers, both from the University of Maryland School of Medicine, recently wrote a commentary on the “rising storm” of XDR typhoid in Pakistan.
During the epidemic, researchers suspect that leaking sewage pipes were the cause of the genesis and spread of the XDR strain. According to the Time, early disease maps showed cases clustering around sewer lines in the city of Hyderabad. Researchers speculate that, in that seeping sewage, the aggressive MDR typhoid strain H58 met and picked up a circular piece of DNA (a plasmid) containing genes encoding additional drug resistance, likely from a E coli strain or other gut bacteria. This waste rendezvous created the XDR strain.
With the epidemic in full swing, health authorities have already launched a campaign to ramp up sanitation and hygiene efforts, such as getting people to boil drinking water and wash more hands. Health authorities are also trying to get children vaccinated against the harmful germs.
As Levine and Simon comment in their commentary: “We know how to hinder the enhanced transmission of typhoid in most areas of endemicity, i.e. to treat the water supply and make it widely available and to improve sanitation and personal hygiene so that human do not contaminate faeces, water and food.” But, they note, such efforts “are expensive and take time to deploy, even if political will and funding are available.”
The recent spread of the XDR H58 is a “clarion storm,” they conclude.
“Now is the time for global action to prevent a ‘gathering storm’ from becoming a ‘perfect storm’ and a massive public health crisis.”