What's new

Pakistan is racing to combat the world’s first extensively drug-resistant typhoid outbreak

Abdullah719

T20I Captain
Joined
Apr 16, 2013
Runs
44,825
When Qaurat al-Ain brought her fever-stricken daughter Mariam to a doctor in this city 90 miles east of Karachi, she assumed the one-year-old had a chest cold. The doctor prescribed antibiotics and sent her on her way, but the fever persisted. Another doctor tried antimalarial drugs, also to no avail. That’s when al-Ain got really worried—the fever had already lasted two weeks.

She sought a third opinion, and finally doctors at a specialized maternal and child care hospital in Hyderabad said her child likely had typhoid. That made sense: Pakistan is one of the few places where the bacterial infection remains endemic. Just over half a million people a year contract it here, often by consuming feces-contaminated food or water. Its hallmark symptom is a persistently high fever, and when left untreated it can cause intestinal perforation and fatal sepsis. “I remember having typhoid as a kid,” al-Ain says. “I just remember being out of school for a week, and other kids in my class having it, too.” But Mariam’s illness did not seem typical. “She would shake with fever chills for hours,” al-Ain recalls. “Seeing my baby like that was terrifying. It didn’t help that the doctors seemed so anxious, too.”

Mariam’s doctors, it turned out, had reason to be concerned: A blood test revealed the typhoid strain Mariam carried was resistant to five classes of antibiotics typically used to treat the infection. Although resistance to three classes of typhoid medication—formally known as “multidrug-resistant” typhoid—had become common in Pakistan in recent decades, this extreme level of resistance was much worse. Mariam’s infection was designated “extensively drug resistant,” or XDR—meaning it would only respond to one powerful, broad-spectrum class of antibiotics: azithromycin, which is considered the last line of defense against typhoid.

Mariam, who fell ill in November 2016, had the dubious distinction of becoming the second confirmed case of XDR typhoid in an outbreak that would soon roil much of southern Pakistan. Around the time Mariam was admitted to a hospital, another child was brought to the same ward and testing revealed the same affliction. The next week there were two more cases, and by the end of 2016 Hyderabad’s doctors had seen more than a dozen people with the extensively drug-resistant strain. Since then there have been more than 800 lab-confirmed cases, according to tracking by Aga Khan University (A.K.U.) in Karachi. And that number is widely considered an underestimate; many cases likely go undiagnosed or uncounted.

Infectious disease experts say Pakistan is in the grip of the world’s first outbreak of XDR typhoid, and they suspect the country’s abysmal sewage and water systems are the root cause for its spread. In most poor neighborhoods sewage lines do not exist, and where they do they are often faulty or broken, leaving potable water supplies vulnerable to contamination. Open sewage pools in areas throughout Hyderabad, even in the poshest neighborhoods in this sprawling city of six million people.

The XDR typhoid outbreak has crept across southern Pakistan and reached its largest city, Karachi. At first, government officials hoped it would remain small and burn out on its own. But it soon became clear they would need to launch an extensive vaccination campaign to battle the spread of the mutated strain.


A SHAKY START

A new typhoid vaccine, produced in neighboring India, was approved by the World Health Organization last year. It is more effective than its earlier counterparts and only requires a single dose. Health care workers have rushed to bring it to Hyderabad. Last month they kicked off a long-awaited campaign to vaccinate all children under age five in the city’s hardest-hit neighborhoods; the disease most often kills young kids who have not developed immunological defenses against it.

At the same time, researchers have been racing to understand the biological underpinnings of the XDR typhoid pathogen in the hopes of unraveling how it became so drug-resistant. A team of scientists from A.K.U. and colleagues from the Wellcome Sanger Institute in England have pored over Hyderabad’s typhoid-causing bacterium, and recently reported it developed its “superbug” powers by picking up DNA from another microbe—likely Escherichia coli. The team mapped cases and found the biggest clusters around the city’s sewage lines. Sadia Shakoor, an A.K.U. microbiology professor and co-author of the study, believes the pathogen likely mutated in those lines and spread when it seeped into the water supply.

But even though researchers have uncovered the “how” behind this outbreak, controlling its day-to-day spread remains a problem. At the beginning of this year 250,000 vials of vaccine reached Hyderabad, thanks to a Bill and Melinda Gates Foundation grant in collaboration with the U.S. Agency for International Development, which provided syringes. The vaccination effort has been underway for a little over a month, but Tahir Yousafzai, an infectious disease expert at A.K.U. and lead organizer of the vaccination campaign, says the work has run up against community opposition. Rumors are circulating about the vaccine itself, including talk that it is part of a foreign plot to poison Pakistan’s children, and vaccinators face refusals almost every day.

Suspicions surrounding public inoculation campaigns are not new in this country—years ago the Pakistani Taliban declared vaccination efforts part of a Western conspiracy against Islam. And in 2011, when it was discovered that a team of hepatitis vaccinators had aided U.S. intelligence efforts to locate Osama bin Laden, those rumors suddenly gained new credence in the eyes of many. Subsequently, distrust of vaccinators has become common across the country.

Midway into their daily rounds, vaccinators Baktawar Memon and Jannath Rind recently knocked on doors in one Hyderabad neighborhood—only to be repeatedly turned away by parents. “This is medicine! It will help protect your children,” they yelled through the door at one home, but no one answered. They marked the house as a “refusal” on their clipboards, and by chalking a series of letters and numbers on the door.

Frequent migration in the region also means the XDR typhoid bacterium could potentially spread beyond areas contaminated with the raw sewage. But even without spread beyond southern Pakistan, Yousafzai says he is worried about the months and years ahead. Unless the vaccine’s use is standardized beyond an emergency campaign, he cautions, XDR typhoid could become endemic in Pakistan in the way multidrug-resistant typhoid was in decades past. “Our fear is that the mutant gene will prevail—that the antibiotics we have left will be rendered useless,” he says.

As for Mariam, she finally recovered from the resistant-typhoid strain weeks after being diagnosed. One recent afternoon al-Ain watched the toddler play on a tricycle. “I wouldn’t want any mother to watch her baby suffer like I did,” she says. Yet as XDR continues to spread, she knows many will.

https://www.scientificamerican.com/...-extensively-drug-resistant-typhoid-outbreak/
 
Drug resistance is the next major public health crisis. We desperately need more investment in developing new classes of antibiotics, and stop unnecessary overprescribing of existing antibiotics.
 
Drug resistance is the next major public health crisis. We desperately need more investment in developing new classes of antibiotics, and stop unnecessary overprescribing of existing antibiotics.

Drug resistance could turn into a problem of alarming proportions esp in countries like India and Pakistan where spending on healthcare as a percentage of GDP is abysmally low. There have been cases of drug resistance TB lately in India and although the Govt has taken a stern attitude on the whole issue, their methods are unsurprisingly same old ineffective which won't yield much in the long run.

Again simply spending on Infrastructure and R&D wont suffice since the problem has behavioural roots as well.
In Subcontinent, people prefer to buy medicine over the counter leading to rampant misuse of antibiotics. Also, many don't even finish the full dose whenever they start feeling little better since it'sexpensive to complete it, this results in a few better adapted bacteria surviving inside that person and eventually developing resistance against the said drug.

It's mind blowing that we have cases of drug resistance against last resort antibiotics such as Colistin.
 
MDR Typhoid: S Typhi resistant to Ampicillin,chloramphenicol,and sulphamthaxole/trimethoprim.

Now i have not seen these antibiotics used to treat typhoid for years in India.

Quinolones are used and then cephalosporins. Now quinolone resistance in some cases but havent heard much about Cephalosporin resistant Typhoid.

Any idea?
[MENTION=131701]Mamoon[/MENTION]
[MENTION=140234]DRsohail[/MENTION]
[MENTION=43242]Dr_Bassim[/MENTION]
[MENTION=133135]kaayal[/MENTION]
 
I haven't heard of Cephalosporin resistant Typhoid. I don't know what to give if such a situation arises....
 
MDR Typhoid: S Typhi resistant to Ampicillin,chloramphenicol,and sulphamthaxole/trimethoprim.

Now i have not seen these antibiotics used to treat typhoid for years in India.

Quinolones are used and then cephalosporins. Now quinolone resistance in some cases but havent heard much about Cephalosporin resistant Typhoid.

Any idea?

[MENTION=131701]Mamoon[/MENTION]
[MENTION=140234]DRsohail[/MENTION]
[MENTION=43242]Dr_Bassim[/MENTION]
[MENTION=133135]kaayal[/MENTION]

Cephalosporins are quite effective ehre.....but 20% resistant has been reported to quinilones which is alarming.
I have never seen a single case yet not responding to 3rd generation cephalosporins.
 
Drug resistance could turn into a problem of alarming proportions esp in countries like India and Pakistan where spending on healthcare as a percentage of GDP is abysmally low. There have been cases of drug resistance TB lately in India and although the Govt has taken a stern attitude on the whole issue, their methods are unsurprisingly same old ineffective which won't yield much in the long run.

Again simply spending on Infrastructure and R&D wont suffice since the problem has behavioural roots as well.
In Subcontinent, people prefer to buy medicine over the counter leading to rampant misuse of antibiotics. Also, many don't even finish the full dose whenever they start feeling little better since it'sexpensive to complete it, this results in a few better adapted bacteria surviving inside that person and eventually developing resistance against the said drug.

It's mind blowing that we have cases of drug resistance against last resort antibiotics such as Colistin.

I agree we need to change behaviour not only on the part of patients but also prescribers. In the UK, there was a recent study reporting at least a fifth of antibiotic prescriptions are unnecessary. There are some doctors who prescribe antibiotics for minor ailments like coughs, colds and other Respiratory Tract Infections to "be on the safe side" when in reality, these symptoms are self-limiting and caused by viruses which don't respond to antibiotics !

One of the good things that's happening here is that the NHS is trying to fund more pharmacists to work in primary care in GP surgeries through their Pharmacy Integration Fund. As a pharmacist we are educated on "antimicrobial stewardship" and so are equipped to promote judicious use of antibiotics in the community where there is a huge amount of antibiotic overprescribing.

What would also be enormously beneficial is rapid diagnostic tests in primary care so we can get test results quicker.

There's overuse of antibiotics in agriculture too which contributes to resistance and requires tougher regulation. In the developing world, there needs to be further investment in clean drinking water and sanitation to minimise the risk of bacterial infections in the first place.

This resistance issue is huge and needs more media coverage and public policy action otherwise even routine surgeries 20-30 years from now could become high risk.
 
But shouldnt we be careful in using macrolides in our part of the world. Azithro is second line for MDR TB.

YEs that is but what we can do,we have very limited choices available.floroquinilones are not wrokinng.u cant always put the patient on iv cephalosporins.And people are prescribing azithro even for pharingitis.
I usually prescribe azithro when i am not sure about the diagnosis as it cover gram positives as welland even works in UTI.
In diabetes we have only one option now in ward and that is cefoperazone plus sulbactum combination.....the resistance of E,Coli in diabetics is alarming,
 
I agree we need to change behaviour not only on the part of patients but also prescribers. In the UK, there was a recent study reporting at least a fifth of antibiotic prescriptions are unnecessary. There are some doctors who prescribe antibiotics for minor ailments like coughs, colds and other Respiratory Tract Infections to "be on the safe side" when in reality, these symptoms are self-limiting and caused by viruses which don't respond to antibiotics !

One of the good things that's happening here is that the NHS is trying to fund more pharmacists to work in primary care in GP surgeries through their Pharmacy Integration Fund. As a pharmacist we are educated on "antimicrobial stewardship" and so are equipped to promote judicious use of antibiotics in the community where there is a huge amount of antibiotic overprescribing.

What would also be enormously beneficial is rapid diagnostic tests in primary care so we can get test results quicker.

There's overuse of antibiotics in agriculture too which contributes to resistance and requires tougher regulation. In the developing world, there needs to be further investment in clean drinking water and sanitation to minimise the risk of bacterial infections in the first place.

This resistance issue is huge and needs more media coverage and public policy action otherwise even routine surgeries 20-30 years from now could become high risk.
While the resistance by Bacteria against the different class of antibiotics due to their indiscriminate widespread is well known, You would be surprised to know that antibiotics cause damage to non target species as well, so these too tend to evolve immunity. For instance the resistance developed by harmless gut bacteria. Since most antibiotics are administered orally, these peaceful bacteria are particularly susceptible to evolutionary pressures.

I was reading a study published in Nature which revealed that gut Bacteria also often tend to develop resistance against drugs such as painkillers which are not intended to harm them. Coincidentally, these same bacteria which are most resistant to these type of drugs are also most resistant to antibiotics. This implied that these Bacteria were using similar means to defend themselves against both sorts of medicine.

Basically the study reported that the proteins which protected bacteria from non antibiotic drugs such as Omeprazole, antihistamines, painkillers etc were ones already known to make them resistant to antibiotics. Now this suggests that bacteria often use similar mechanisms to evade all classes of drug.
Now these can be spread by these Bacteria to other harmful Bacteria through conjugation by which they transfer DNA to each other.

This means the gut bacteria of patients consuming (say) painkillers might evolve a resistance that they then passed on to a pathogen that subsequently infected the body. This is quite worrisome since drug resistant infections could, by some estimates, become responsible for 10 million deaths a year by 2050.
 
YEs that is but what we can do,we have very limited choices available.floroquinilones are not wrokinng.u cant always put the patient on iv cephalosporins.And people are prescribing azithro even for pharingitis.
I usually prescribe azithro when i am not sure about the diagnosis as it cover gram positives as welland even works in UTI.
In diabetes we have only one option now in ward and that is cefoperazone plus sulbactum combination.....the resistance of E,Coli in diabetics is alarming,

How often is Carbapenems used? What is the cost?

Is Pipercillin Tazobactam used in UTI?

Usage of Azithro for pharyngitis is common in India as well. even though Amox plus Clavulanic acid covers it.
 
How often is Carbapenems used? What is the cost?

Is Pipercillin Tazobactam used in UTI?

Usage of Azithro for pharyngitis is common in India as well. even though Amox plus Clavulanic acid covers it.

We have never used pipercilin tazo and carbapinems in Enteric .
 
We have never used pipercilin tazo and carbapinems in Enteric .

No we don't use that for enteric fever either. I guess he is asking about the use of carbapenems in general and esp in regard to the Complicated Urinary Tract Infections.
 
We have never used pipercilin tazo and carbapinems in Enteric .

No we don't use that for enteric fever either. I guess he is asking about the use of carbapenems in general and esp in regard to the Complicated Urinary Tract Infections.

Yes this.
[MENTION=133135]kaayal[/MENTION]

Whats the situation at your end regarding carbapenems,PipTaz,Teicoplanin etc?
 
Yes this.

[MENTION=133135]kaayal[/MENTION]

Whats the situation at your end regarding carbapenems,PipTaz,Teicoplanin etc?

They are using this extensively in big private hospitals. But in Govt hospitals it's a bit controlled.
 
Cool Man. Did the transition go smooth?
Lord knows we need more doctors in this country.

Initially it was tough. Taking orders and instruction from senior consultants in the hospital. I am still junior here. I was about to quit in 3-4 months.But slowly it improved and i got used to not being the ultimate decision maker. Now preparing for my MD.
 
Initially it was tough. Taking orders and instruction from senior consultants in the hospital. I am still junior here. I was about to quit in 3-4 months.But slowly it improved and i got used to not being the ultimate decision maker. Now preparing for my MD.

Good luck.
 
Initially it was tough. Taking orders and instruction from senior consultants in the hospital. I am still junior here. I was about to quit in 3-4 months.But slowly it improved and i got used to not being the ultimate decision maker. Now preparing for my MD.

Good.:)
 
Surgery people use it too often but here in medicine we usually not use it rather i will say no.

[MENTION=133135]kaayal[/MENTION]

See this. Hardly any use of carbapenems and piptaz etc. Something to learn.
 
Drug resistance is a major global issue and it is one that big pharma is more than happy to accommodate, because there is little money is developing new antibiotics, so much more is put into developing/selling long term medication, for those with everything from heart disease to diabetes.

To put it plainly, infections are not cost effective.
 
How can Typhoid Fever persist beyond 20 days without perforation ? Plus some other things in OP that negate medical facts.
 
Back
Top