A highly drug-resistant strain of typhoid is spreading in Pakistan, killing four and affecting around 850 others.

The “extensively drug-resistant” bug was first identified in November 2016 in Hyderabad but has since spread to other parts of the country. According to the Pakistani National Institute of Health Islamabad four people have died and 858 people have become infected with the resistant strain of the disease.

Because typhoid spreads quickly via food and water – and in places where there is poor sanitation – doctors are worried about the drug-resistant bug's potential to threaten vast numbers of people in Pakistan and beyond.

In December, the strain was identified in a patient who came to the UK from Pakistan. The patient, who was isolated and treated successfully, was one of around 300 diagnosed with typhoid in the UK every year, the majority of whom are infected in India, Pakistan and Bangladesh.

Antibiotic resistance is a growing problem in lower and middle-income countries such as Pakistan and India, where drugs are poorly regulated and it is easy to buy antibiotics over the counter. There have also been reports of superbugs in countries such as Yemen and Syria, where the health infrastructure has been damaged after years of unrest.

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Sadia Shakoor, assistant professor of pathology and laboratory medicine, and her colleagues at Aga Khan University in Karachi, were the first doctors to identify the strain of typhoid resistant to the antibiotic ceftriaxone in the current large outbreak of the disease. She said that because so many people have already been affected it is likely to spread even further.

“We've also learnt from history that once the typhoid bug acquires a resistance gene it holds on to it and just spreads within geographical regions where sanitation measures are poor,” she said.

For patients who do not need to be hospitalised doctors are using the antibiotic azithromycin but if patients are seriously ill and require admission to hospital they are given an intravenous antibiotic called meropenem.

Dr Shakoor said azithromycin was a commonly used and effective drug for typhoid.

This is the first time we have seen an outbreak of extensively drug-resistant typhoid

"We can use this drug but azithromycin is the last resort. Many regions of the world have reported resistance to this drug. There is no resistance yet in Pakistan but if we lose this drug we will have no drugs left for patients to take orally," she said.

Those most affected by the drug resistant strain are children under the age of five, however there have also been cases of the bug in adolescents.

Last year, Dr Shakoor and her colleagues asked geneticists at the Wellcome Sanger Institute in the UK to genetically analyse the outbreak. The scientists performed whole genome sequencing of the typhoid samples from Pakistan and found that this outbreak was caused by an extra strand of bacterial DNA – a plasmid – which had possibly been picked up from E. coli.

Elizabeth Klemm, one of the the researchers who sequenced the typhoid isolate, said antibiotic resistance in typhoid has been a mounting problem for decades. However, because this strain acquired an extra piece of DNA it was classified as "extensively drug resistant".

“This is the first time we have seen an outbreak of extensively drug-resistant typhoid,” she said.

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Researchers at the Aga Khan University in collaboration with the provincial government of Sindh launched an emergency vaccination programme to contain the current outbreak of typhoid but experts have been lobbying the World Health Organization and the Pakistani government to initiate a large-scale typhoid vaccination programme across the whole country.

In March WHO pre-qualified a new typhoid vaccine, Typbar-TCV, which can be used in children as young as six months old and which is more effective than other vaccines. Dr Shakoor said that the only way to eradicate infectious diseases was through vaccination.

"We have eradicated smallpox and we are on the way to eradicating polio because we have an effective vaccine," she said.

Raw sewage leaking from a faulty pipe into the drinking water supply is believed to have sparked the current outbreak and Dr Shakoor said infrastructure improvements were also needed.

"There is a huge infrastructure problem here. There is a lack of planning, people just build on top of each other and we have had large-scale urbanisation," she said.

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