Drug-resistance makes a bug extremely worrying
TYPHOID affects some 21m people each year, and about 1% of cases are fatal. Before antibiotics were used to treat the disease 70 years ago, death rates were much higher. If left unchecked, typhoid can cause internal bleeding, perforation of the gut and, in up to a fifth of cases, death. Researchers are now concerned that an “extensively drug resistant” (XDR) strain of Salmonella enterica serotype Typhi (S. typhi), the bacterium that causes the disease, could see a return to those dangerous days.
Since November 2016 the XDR strain has led to 858 reported cases of the disease and four deaths in the Sindh province of Pakistan, according to the latest figures from Pakistan’s National Institute of Health. Together with their colleagues, Elizabeth Klemm of the Wellcome Sanger Institute near Cambridge and Rumina Hasan of the Aga Khan University in Karachi have analysed the pathogen. Their study, published recently in mBio, showed that its genome contains resistance genes for five types of antibiotic, making the Sindh epidemic the first known to be caused by an XDR strain. That, in effect, leaves doctors in Pakistan with just one oral antibiotic, azithromycin, with which to treat patients suffering from the disease.
If that was not worrying enough, the researchers showed that the Sindh S. typhi was of a lineage known as H58. Since emerging on the Indian subcontinent around 30 years ago, H58, which is resistant to as many as four classes of antibiotic, has spread to much of South-East Asia and, more recently, to sub-Saharan Africa and Oceania. The researchers found that S. typhi had gained more resistance genes by acquiring a plasmid, a circular piece of DNA, from another bacterium (a process known as horizontal gene transfer). Similarities in DNA sequences between this plasmid and those of other bacteria suggest that the culprit was probably Escherichia coli, which is commonly found in the human gut. Troublingly, H58 has in the past absorbed other antibiotic-resistance genes into its chromosome, where they can become more “hard wired” than plasmids, which can just as easily be lost as gained.
There is no reason why S. typhi should not also become resistant to azithromycin. Indeed, many experts believe it is simply a matter of time before it does so. That would mean the only treatments left would be “antibiotics of last resort”, such as carbapenems, which are expensive and have to be injected by trained staff. In poor countries, where such treatment is unlikely, it means an epidemic may be nearly impossible to contain.
In the long term, the solution is straightforward. The bacterium is found in the faeces of those infected, as well as a small proportion of people who have recovered but remain asymptomatic carriers. The disease spreads through water or food contaminated with infected faeces. Effective sanitation and access to clean water has largely eliminated typhoid from rich countries. It could, in time, do so in poorer ones, too. More careful use of antibiotics could help avoid a near-untreatable strain of S. typhi emerging. There are also ongoing efforts to find new antibiotics.
In the short term, however, vaccination, monitoring and treatment remain the best options. Unfortunately, vaccines do not provide lasting immunity, require multiple doses or are only approved for children older than two. A new vaccine from Bharat Biotech, a firm based in Hyderabad, protects for at least three years with a single dose and can be administered to children as young as six months. GAVI, an international public-private alliance that provides vaccines to poor countries, has agreed to pay $85m for vaccinating children in countries where the disease is rife. The race is on to contain typhoid before it evolves into an even deadlier threat.