Typhoid lurks in India’s water. Why are antibiotics failing to stop it?

A mild fever. Constipation. The fever increases by a degree. Diarrhoea. The fever plateaus. A profound fatigue. The fever rises again. A headache, as severe as ever. The fever plateaus again.

Probably a viral infection, right? Maybe, maybe not. That’s the problem with typhoid. It’s so commonplace, so unassuming in the way it presents that you’d hardly suspect it means trouble.

Typhoid has had a lot of practice hoodwinking us. It has accompanied humanity through most of its evolution—from the time we migrated out of Africa, to be precise. For years, we mistook it to be the same as typhus (typhoid literally translates to typhus-like). In the 1860s, it was confirmed that typhoid only spreads when we consume food or water contaminated by the bacteria that causes it, usually a result of sewage water contaminating drinking water supplies. Only in the 1880s, over a decade after the germ theory (the theory that microorganisms cause diseases) was widely accepted, was the offending organism isolated: Salmonella typhi.

This spurred the invention of diagnostic tools like the Widal test and even a vaccine over the next decade and a half, but nothing that could effectively fight the disease. The bacteria continued to weaken hosts through month-long fevers, and kill 10–20% of those it infected. The discovery of chloramphenicol in 1947 changed that. The antibiotic drastically reduced the duration of the fever and brought down the mortality rate to under 1%. It was nothing short of miraculous. The failure of this miracle is staring us in the face today.

Typhoid has had a lot of practice hoodwinking us. It has accompanied humanity through most of its evolution.

Typhoid continues to be endemic to (consistently present in) over 75 countries across Asia, Africa, and Oceania, contributing to around 9.3 million cases annually, and 107,500 deaths. India, shockingly, accounts for 58% of the world's typhoid burden, distantly followed by Pakistan (8%) and Bangladesh (5%). Data also suggests that children below 15 years of age make up the lion’s share of India’s typhoid burden. The frightening truth? Almost 70% of these cases have stopped responding to the safest, most accessible antibiotics prescribed. A crisis is reaching its boiling point across these countries, but especially in India—and we may miss our window to act.

Also read: How drug-resistant tuberculosis is bringing life to a halt in India

Shot in the dark

There is a textbook definition of how typhoid presents in patients: a step ladder fever, a slightly enlarged liver, plaque on the molar teeth, and rose spots (pink lesions on the chest and abdomen). Dr. Jacob John, a PhD in Infectious Disease Epidemiology who co-authored a 2026 Lancet paper on India’s typhoid burden, says that only about 30% of India’s current cases present with these classical symptoms. Doctors now report seeing patients with cough, or chills—symptoms that they have not been trained to associate with typhoid. “Fever is the only consistent symptom,” says Dr. John. “So, anything that can be dengue, can be typhoid.” 

Even if a doctor suspects typhoid, confirming it via diagnostics is no easy task. A diagnostic test can take one of two routes: detect the pathogen (the Salmonella bacteria) or the antibody (our body’s disease-specific defense). Pathogen-based tests require the bacteria to be present in large quantities in the bloodstream for the test to pick up on it.

Even if a doctor suspects typhoid, confirming it via diagnostics is no easy task.

Antibody tests only work well in countries where the typhoid burden is low; in ours, it might return false positives, i.e. wrongly diagnose patients with typhoid. This happens because repeated exposure to unsanitary water (and thus, traces of the typhoid bacteria) results in low levels of antibodies in the general population. Though this drawback is well-known, antibody tests are still used as a preliminary test because they give speedy results, and can be paired with a basic blood test (CBC) to diagnose typhoid, shares internist Dr. Rakesh Saigaonkar.

Another way to ensure that someone doesn’t get wrongly diagnosed is to make the cut-off for antibody concentration higher. “If a patient’s antibody count is more than 1:160, then we consider that they have typhoid. Or else we check their antibody count again after 3 days, and if the count has increased, they are more likely to have typhoid,” says Dr. Saigaonkar. 

Blood culture is the reference or gold standard for typhoid testing, especially since it can also test for antibiotic resistant strains. That said, it is rarely, if ever, used in typhoid detection outside of scientific studies because of the sheer time taken for results, the price involved, and that the test correctly identifies only 60% of the cases that come its way.

Diagnostic realities reveal worrying patterns. Firstly, any statistics we have on typhoid are likely underestimating the typhoid burden. The bacteria also has a tendency to persist in 1-6% of recovered patients, making them chronic asymptomatic carriers. Secondly, the variable symptoms and the lack of a point-of-care diagnostic test make both diagnosis and—as a result—treatment shots in the dark for doctors.

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Cyclical antibiotic resistance

Typhoid is sticky, devious, and skilled at stationing itself in your intestines. By impacting your capacity to digest food, it weakens your access to the energy needed to fight it. If you are unvaccinated, your body does not even have prior experience recognising or fighting this bacteria, and is on the back foot. Antibiotics are the only medicines that can step in at this point and fight the battle for you. Given how stubbornly the bacteria occupies the body, antibiotics have to be prescribed for a minimum of 14 days, and, if severe, for up to 6 weeks. The last thing you want is for the medicine to not work and instead make the bacteria stronger.

By the 1990s, none of the first-line drugs were any good, and a second line of defence evolved.

But, in what Dr. John describes as a “cat and mouse game,” that is exactly what has happened. Shortly after chloramphenicols were introduced for typhoid treatment, two other classes of antibiotics were also found to be effective: cotrimoxazole, and penicillin derivatives like ampicillin and amoxicillin. Together, these 3 form the first-line drugs, or the first set of antibiotics prescribed to help the body fight typhoid.

It took only about two decades of antibiotic use before the earliest case of drug-resistant typhoid was reported in Mexico. By the 1990s, none of the first-line drugs were any good, and a second line of defence evolved: fluoroquinolones and third-generation cephalosporins. Fluoroquinolones were widely prescribed since they were cheaper and faster than the first-line drugs, and reduced chances of relapse. Unfortunately, this has meant a steady increase in fluoroquinolone resistance (FQR), which accounted for 94% of the total number of cases in 2017. Although this is worrying, the number of cases, both overall and drug-resistant ones, have fallen in the past 6 years. These antibiotics are being prescribed with far more caution now, which have most likely cut down the cases, but it is still early to tell.

By 2024, only 63% of India’s typhoid strains were fluoroquinolone-resistant, but still accounted for 82% of the hospitalisations associated with the disease. Moreover, only 3% of cases are unresponsive to cephalosporins, and an additional 3% are resistant to azithromycin, but no strain (so far) is resistant to both.

Typhoid’s ‘luggage limit’

Currently, antibiotics are administered intravenously only for patients with severe typhoid. Growing drug-resistance in typhoid is forcing doctors to resort to stronger antibiotics like carbapenems, which can only be given intravenously. A shift towards IV antibiotics threatens to strain an already overburdened health system and the patient’s finances. A modelling study from 2023 suggests that 91% of typhoid-related expenses in India are borne by patients, and only 9% by the government. These costs spike when hospitalisation and fluoroquinolone resistance are involved. Some studies also associate IV antibiotics with higher mortality due to the risk of infection. Luckily, XDR strains are a rare occurrence in India.

But India has its own challenges. The data so far suggests a loose hierarchy to antibiotic resistant typhoid: first-line drugs first, then second-line drugs, and then azithromycin and carbapenems as the last line of defence. In reality, the drug-resistance patterns are far more messy and unpredictable. There are cases where fluoroquinolones and azithromycin are both powerless but the old first-line drug ampicillin works. There are cases where fluoroquinolones and ampicillin don’t work but chloramphenicol works. What is really happening here?

Dr. John cites the plasmid theory as a possible explanation. Essentially, bacteria store DNA in two suitcases (of sorts)—a big one for chromosomal DNA, which is essential for the bacteria to reproduce, and a small one with some non-essential but nice-to-have DNA. This small suitcase is called the plasmid. Genes related to antibiotic resistance are usually stored here since they provide a competitive edge to the bacteria but are not indispensable. Thankfully for us, plasmids have a luggage limit; they cannot carry the genes for ampicillin-resistance and cephalosporin-resistance and azithromycin-resistance all together. Over a period of time, they have to choose which genes to keep, and which to discard. If ampicillin is not used for a long time, the bacteria has no practical reason to store genes that evade the drug. 

This sounds exciting, because it suggests that typhoid’s drug resistance is cyclical. But there are two caveats to this cyclicity: first, even if the antibiotic is not used to treat typhoid, but to treat other illnesses, drug-resistance will continue to develop. Secondly, antibiotics like chloramphenicol were abandoned because they had negative side-effects. Though it occasionally works again now, it is not a preferred antibiotic for treatment.

What is the right way to fight typhoid then? The complexities of diagnosing and treating typhoid make the use of broad-spectrum antibiotics unavoidable. With the time it takes to detect antibiotic resistance through laboratories, doctors are forced to make decisions empirically, often prescribing a combination of antibiotics to increase the chances of successful treatment. While it must be stressed that patients finish their antibiotic courses, prescription itself cannot be streamlined until more precise diagnostic tools are invented.

In reality, the drug-resistance patterns are far more messy and unpredictable.

Government guidelines are constantly observing and adjusting to national patterns in drug-resistance. The Indian government’s July 2025 guidelines exclude fluoroquinolones and recommend third-generation cephalosporins and azithromycin as the primary drugs. The guidelines also reinstated one of the first-line drugs, cotrimoxazole, since S. typhi has become susceptible to it again. Aligning treatment practices with these guidelines is an important first step in controlling drug-resistance.

Also read: Recycled water helps meet India’s cleaning needs. But can it quench our thirst? 

A two-pronged solution

At an individual level, small traces of antibiotics (like those left in your body when you don’t finish the prescribed antibiotic course) teach bacteria to evolve to survive the antibiotic. Your gut bacteria are among these, and through a process called horizontal gene transfer, they can pass on this genetic information to pathogens, enabling the bacteria to develop resistance after entering your body.

These individual cases add up, and the S. typhi evolves. It becomes a matter of survival for the bacteria to learn to fight, say, azithromycin, and the strain of bacteria that can fight azithromycin survives. And thus, (for the sake of this example) azithromycin-resistant typhoid becomes the predominant strain of typhoid. This means that even if a small child who has never had antibiotics before happens to eat the wrong paani puri, they will ingest an antibiotic-resistant strain of typhoid and the medicine they are given will not work.

There are two ways to work around this, both involving prevention rather than cure. First: teach your body to fight. Vaccination teaches your body to identify and defeat the typhoid bacteria without depending on an antibiotic. Not depending on antibiotics is useful for many reasons, including that antibiotic discovery is difficult, underfunded and time-consuming, and that S. typhi will eventually develop resistance against any new antibiotic. Vaccines have the potential to immediately reduce case load, and build an internal self-defence system that functions regardless of whether a strain is resistant to antibiotics or not. Vaccines are especially important for typhoid because getting the illness does not provide patients with natural immunity for more than a year or two. 

Until recently, typhoid vaccines offered only temporary and moderately effective protection. In 2018, the WHO approved the Typhoid Conjugate Vaccine (TCV) that is far more effective in only one dose. Though manufactured in India, the vaccine has not yet been introduced into India’s Universal Immunisation Programme despite the National Technical Advisory Group on Immunisation’s (NTAGI) recommendation to introduce it around 9–12 months of age.While this recommendation has not been formalised in the national immunisation schedule yet, the Indian Academy of Pediatrics recommends administering the TCV vaccine when a child is 6 months old. A Lancet study from 2026 also endorses catch-up vaccination campaigns for children under 15, since that is the age group with the highest typhoid burden in India. The vaccine is available in most private clinics for Rs. 2,000-2,500.

This means that even if a small child who has never had antibiotics before happens to eat the wrong paani puri, they will ingest an antibiotic-resistant strain of typhoid and the medicine they are given will not work.

Second: fix sanitation and sewage disposal. Typhoid is not just a waterborne disease. It spreads only from faecal-oral routes, meaning that it only leaves the body as faeces and only enters the body through the mouth. “If you can ensure no contamination occurs, it is guaranteed that typhoid will disappear,” says Dr. John. “But it is not an easy thing to do because we have unplanned cities. Where do you put your sewage? Under the road in front of your house. Where is your water line flowing? Under the same road.” The architecture of the sewage system—poorly planned, with sewage pipes laid close to clean pipes—must be addressed. Even a single typhoid case is a failure in sanitation, but being the country with the largest typhoid burden is an indictment of India’s water supply infrastructure. Sanitation workers, especially those involved in cleaning toilets, manholes, or septic tanks are especially at risk of coming in contact with faecal pathogens. 

Even a single typhoid case is a failure in sanitation, but being the country with the largest typhoid burden is an indictment of India’s water supply infrastructure.

Sanitary reforms have been directly linked to the reduction in typhoid cases in Oxford in the late 1800s. The reason that vaccination is championed as a more urgent solution in landmark studies on typhoid is that we believe that our poorly planned cities cannot change. It raises a question: should our solutions be restricted to the realities of the world we occupy, or should they carry the radical belief of what we could become?

Edited by Anushka Mukherjee and Neerja Deodhar

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