24.09.24 Global Superbugs

‘The final warning sign’: drug-resistant typhoid is spreading across Pakistan

From his sickbed, eight-year-old Ukasha watched through heavy eyes as his siblings played with a ball in the courtyard. His head hurt and his body felt too heavy to move. Ukasha had typhoid fever – an illness he should typically have recovered from in days. It had been a month.

At its worst, typhoid can kill. Ukasha’s family were anxious to see signs of recovery, even moving his bed outside to give him fresh air and sunlight. And now, he could sit up, smile at the sight before him and even feel some of his appetite return. He was finally able to eat his favourite food, eggs.

Across the road, his classmate, 12-year-old AbuZar, had also been stuck in bed for months with typhoid. At the height of his infection, he woke up in the middle of the night, drenched in sweat and his forehead running hot.

They were not the only ones. Ukasha’s father noticed that children across the entire village – on the outskirts of Peshawar, northern Pakistan – had been falling ill.

Typhoid, also known as enteric fever, is an infection that is often caused by faeces-contaminated food or water. If left untreated, it kills one in five. But the treatment is simple: a course of antibiotics. Most people, if they get their drugs promptly, should start recovering within a few days.

But the drugs that used to cure the fever are now, in many cases, failing. The bacteria that cause the infection, salmonella typhi, have developed resistance to the antibiotics meant to kill them. It’s a pattern repeated across the world; the problem of resistant infections is global and borderless.

At the height of his illness, Ukasha’s father took him to a hospital in Peshawar. On the children’s ward, each single bed held four or five patients. Ukasha’s typhoid was soon diagnosed, and it was contagious.

“Typhoid was once treatable with a set of pills and now ends up with patients in hospital,” says Dr Jehanzeb Khan, the clinical pharmacist at the hospital.

With the hospital rammed, his father took him home for the rest of his treatment.

A superbug strain

Ukasha’s infection wasn’t caused by an ordinary strain of typhoid. It was XDR-typhoid, short for extensively drug-resistant typhoid – a strain of “superbug” that emerged in Pakistan in 2016. XDR-typhoid is resistant to almost all of the antibiotics that are supposed to treat the disease, so options are limited and death rates are higher.

Of the roughly 9 million people around the world who get sick from typhoid each year, the vast majority are infected by a drug-resistant strain. Pakistan has the worst rate of typhoid in south Asia, a problem that has only escalated since the emergence of XDR-typhoid. More than 15,000 cases of XDR-typhoid have been reported in Pakistan – and some outbreaks, like the one in Ukasha’s village, go unrecorded.

Laboratory testing was crucial to Ukasha’s recovery TBIJ/BSAC/Saiyna Bashir

The risk of typhoid is higher where a community lacks safe water and sanitation. A neglected sewage system, for instance, can contaminate water and compound the problem.

In Pakistan, water is a critical issue. It has one of the lowest rankings in the world for access to clean water near homes, and contaminated water is thought to be the cause of about 80% of diseases in the country.

“There is no reason we should have typhoid fever today if we have proper access to safe water and sanitation,” says Dr Maria Neira, a director at the World Health Organization’s department of environment, climate change and health.

Ukasha’s father was convinced that a contaminated water tank in the boys’ school had led to the typhoid outbreak in their village. When TBIJ contacted the school, it said that nothing had been reported.

“Access to safe water is one of the public health fundamentals that should not be denied to anyone,” Dr Neira said. “Wherever you have a lack of hand hygiene and the [lack of] possibility in the healthcare facilities to wash your hands, you will see an overlap with cases of drug-resistant typhoid.

“Drug-resistant typhoid is unique in the challenge that it represents,” she added. “It is preventable and it is very much related to poverty – the vulnerability of people, and lack of access to water and sanitation.”

Typhoid can also be prevented with a childhood vaccine. Pakistan has vaccinated more than 30 million children since 2019, but these efforts have been mostly concentrated in the south of the country, where XDR-typhoid first emerged. There are more than 100 million children in Pakistan and the infection has since spread north.

Two-tier testing

Laboratory testing was crucial to Ukasha’s recovery. The doctors were able to identify the strain causing the infection, which can be treated with only three antibiotics. The variant was resistant to all other antibiotics that are usually recommended for typhoid.

Ukasha needed meropenem – a “last-resort” drug reserved for the most serious illnesses. He was given 22 injections, two a day, at home. Each shot took a significant financial toll on the family.

How did such an extensively drug-resistant typhoid strain emerge?

Overuse of antibiotics is one of the biggest contributors to drug-resistant bacteria TBIJ/BSAC/Saiyna Bashir

Over time, bacteria are able to develop the ability to defend themselves against the antibiotics that are meant to kill them. The more the bacteria are exposed to antibiotics, the more this ability can spread.

Overuse of antibiotics is one of the biggest contributors to drug-resistant bacteria. Global consumption of antibiotics has increased by almost half between 2000 and 2018. The greatest rises have been in countries in south Asia, like Pakistan, where the proportion of people receiving antibiotics on a given day has more than doubled.

This overuse is in part down to typhoid having similar symptoms to other illnesses, such as malaria, dengue or even Covid-19. All of those diseases are caused by viruses and microbes that can’t be fought with antibiotics. But if proper testing isn’t available, doctors may prescribe antibiotics "just in case", particularly in rural parts of the country where access to healthcare is limited.

Rapid tests for typhoid can also throw up false positives. Without follow-up lab tests, the rapid tests can lead to overdiagnosis of typhoid, and more patients being given pointless antibiotics.

Experts in Pakistan have gone so far as to blame these tests – commonly known as Typhidot and Widal – for driving cases of drug-resistant typhoid. Health authorities have banned the tests, but they remain widely available.

When AbuZar was admitted to hospital, he was treated with azithromycin, one of the few antibiotics that can still work against XDR-typhoid. However, doctors are now seeing strains of typhoid that no longer respond to it. Another last line of defence is failing.

AbuZar was treated with azithromycin, one of the few antibiotics that works against XDR-typhoid TBIJ/BSAC/Saiyna Bashir

Global problem

Superbugs like XDR-typhoid are not confined by borders. Cases have been identified in 16 other countries due to international travel from Pakistan, including in India, China, Qatar, the UK and US. The US Centers for Disease Control has warned all travellers to Pakistan to take precautions against the superbug.

This month, world leaders will meet at the United Nations to address drug-resistant infections. The aim of the meeting is to negotiate a political declaration for member states to curb the impact on health, the environment and development.

“XDR-typhoid is the final warning sign. After this we will enter a stage where the superbug won’t respond to any drugs at all. That means we will go back to when typhoid was a more deadly disease. And that really worries us,” Dr Khan said.

In Pakistan, Ukasha and AbuZar both felt well enough to return to school. Within a few days, they had fevers again.

Top picture: Ukasha watches on from his bed in the courtyard. Credit: TBIJ/BSAC/Saiyna Bashir

Reporter: Misbah Khan
Global Health editor: Fiona Walker
Deputy editors: Chrissie Giles and Katie Mark
Editor: Franz Wild
Production editor: Frankie Goodway
Fact checker: Somesh Jha

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