A curious case of hidden, dangerous typhoid: It's time to take action now

In 2017, when clinician scientist Gagandeep Kang and her colleagues started an extensive typhoid surveillance study across India, the general perception among the scientific community was that typhoid was significantly declining based on the data reported by big hospitals in India. But when Kang’s team began to closely study people at the community level, it found about 20-fold increase in typhoid cases, mostly children, at most study centres in comparison to the numbers reported by the hospitals. 

Researchers find about 800 typhoid patients for every 100,000 people. These numbers are comparable with typhoid cases reported in 1990s from Delhi slums. Typhoid cases over 100 for every 100,000 people qualify for high disease burden in a country. “Typhoid never went away, we had stopped looking,” says Kang who heads Transnational Health Science and Technology Institute in Faridabad.

While scientists continue to find more typhoid patients (exact numbers would be in by mid- next year), what’s worrying the scientists even more is that treating the patients is getting incredibly difficult and could complicate further in future. That is because a typhoid bacterial strain in India’s neighbour Pakistan has become resistant to second-last line of antibiotics and caused an outbreak there. 
 

If the strain travels to India, “which it will sooner or later,” says Kang, we could end up in a similar situation.

Although the second last-line of antibiotics still works on Indian typhoid patients, the bacterial strains in India have also begun to show resistance against some of them. Spread by consuming water and food contaminated with feces, typhoid affects upto 14.3 million people worldwide. 

As many as 72 per cent of the patients are in South Asia because of poor sanitation conditions. Typhoid, which has symptoms of fever, kills 75,000 patients in South Asia every year, and this is likely an underestimate because of poor disease reporting systems, according to scientists.

In 2016, a study showed a significant decline in typhoid cases reported from big hospitals in India. For example, in New Delhi’s All India Institute of Medical Sciences the number of confirmed typhoid patients dropped from 103 in 2000 to just 31 in 2015. If you look at those numbers, which policy makers also look at, you’d think that typhoid is declining, says Jacob John who is leading the national typhoid surveillance study. But when his team began to investigate fever patients in the communities from where some of them go to hospitals, researchers found high typhoid burden. “It’s a network paradox,” says John, a specialist in community medicine at the Christian Medical College or CMC in Vellore. World Health Organization recommends vaccination in countries with high typhoid burden.

The paradox persists because in most cases when a child gets fever, he or she either takes antibiotics over the counter from a chemist or is taken to a nearby private or government hospital where the doctor prescribes antibiotics but doesn’t send the blood sample for testing to know whether or not it is typhoid. 

In either case, the child goes back to the community, takes the antibiotics and probably recovers without getting diagnosed for typhoid. Meanwhile, the child sheds typhoid bacteria in the feces, which through leaky sewers lines gets mixed with the community’s drinking water supply and infects many others. Those who get the disease then probably repeat what the child did. Some patients continue to shed bacteria even after typhoid symptoms go away. This way the typhoid strain keeps circulating in the community and patients don’t get diagnosed.

Indiscriminate use of antibiotics has compounded the problem. Typhoid bacterial strains in India are already resistant to the cheapest first and second line of antibiotics. Doctors here use the third or second last line of antibiotics such as Azithromycin (given orally) and Ceftriaxone (given through veins).  

The bacterial strain in Pakistan has become resistant to both of them leading to outbreak. So, doctors in Pakistan now use the last available line of antibiotics — carbapenems. The per person cost of treating typhoid fever with carbapenems is about Rs 10,000 excluding hospitalisation and other costs, says Balaji Veeraraghavan, scientist working on anti-microbial resistance in CMC Vellore. Currently typhoid costs about Rs 1000-1500 per patient.

What scientists fear is that Indian doctors might have to resort to carbapenems if the strains here become resistant to both the second-last line of drugs or if the resistant strain from Pakistan travels here. Researchers in India have picked up strains in Mumbai that show some resistance to Azithromycin (one of the second-last line antibiotics). 

If the strain from Pakistan marries with the Mumbai strains, “then we are done for,” says Kang.

Due to restricted travel between India and Pakistan, it is more likely for the strain from Pakistan to reach India through West Asia where people from both India and Pakistan travel for Haj and business, says Veeraraghavan. The Ceftriaxone resistant strain has already been reported in Saudi Arabia. India would need really good disease reporting system to pick up those strains, which means doctors routinely testing patients’ blood samples. That often doesn’t happen, is costly for poor patients, and even if it is done there is no guarantee that the first test would pick up the strain if the patient has already taken antibiotics. 

Inadequate diagnostic tests complicate the management of typhoid, wrote scientists in a paper led by Christopher M Parry, a clinician scientist with Liverpool School of Tropical Medicine in United Kingdom. Investments in newer diagnostics that do not require sophisticated lab infrastructure is critical to improve management of typhoid, the paper recommends.

Treating typhoid is already a problem. Some of Jacob’s typhoid patients have been in hospitals for 15-20 days when they should have recovered between three and five days. The ongoing typhoid surveillance study along with ongoing studies to estimate how much national typhoid vaccination might cost would help scientists evaluate whether or not the Indian government should include typhoid vaccine in the national vaccination program. Numbers so far tell there is a case, and definitely in urban slums, says Jacob. 
 

Although clean water is the real solution, it is unclear when India might achieve that. Increasing anti-microbial resistance and delaying vaccination could mean loss of more lives and more money in treating typhoid patients. The question is, scientists ask, whether we want to wait for a situation like in Pakistan where the government has to now mass vaccinate people in response of the outbreak or act now.