In Gorakhpur, no one knew why the kids were dying. It was 2014, and various explanations were doing the rounds. None was convincing enough, though. In August that year, at a meeting of the Indian Council of Medical Research to deliberate on the matter, it was decided that Dr G. Arunkumar, a virologist, and his team from the Manipal Centre for Virus Research, Manipal University, would be roped in to investigate the 'mystery' fever.
The conundrum, said Arunkumar, who is head of department of virus research at Manipal University, was that the children in Gorakhpur and adjoining districts have been affected by the Japanese Encephalitis Virus (JEV) since the 1980s. The JEV is a mosquito-borne flavivirus that causes fever, headache, vomiting and altered sensorium. In its advanced stages, the virus can cause seizures. It can also leave the patient in a coma, and can cause death. Japanese encephalitis has no cure. “Back then, about 20 to 25 per cent of cases of encephalitis that were being tested were attributed to the JE virus,” said Arunkumar. “Subsequently, the government followed up with an aggressive vaccination campaign. In a few years, encephalitis deaths because of JEV came down.”
But, though JE-related deaths reduced, cases of encephalitis did not. In about 90 per cent of the cases that came to the Baba Raghav Das Medical College and Hospital—also the site of the recent crisis of infant deaths—the doctors had no diagnosis, said Arunkumar. By 2010-11, the Gorakhpur unit of the National Institute of Virology held that encephalitis in the region was caused by enteroviruses found in respiratory secretions and faeces of infected people. According to the NIV, the water table in Gorakhpur was high, and due to open defecation, faecal matter found its way to water bodies, and ultimately, to the intestine of kids. To rectify this, the government dug a few deep wells so that water was not contaminated, said Arunkumar. Despite these measures, the total number of cases of acute encephalitis syndrome (AES) were not reducing, especially from August to November. By mid-August 2014, Arunkumar and his team had reached Gorakhpur. “We found that these cases did not display symptoms of JE,” he said. “Besides the fever, their liver and heart were affected, too.” This, he said, was unlike JE, which affects the brain. “The enteroviruses explanation was also ruled out because while those viruses may or may not affect the heart, they usually don't affect the liver,” he said.
Dr G. Arunkumar
Based on the tell-tale skin lesions or eschar, Arunkumar and his team suspected something other than JE. A few tests later, they had zeroed in on the culprit and it was not a virus, but a bacteria—Orientia tsutsugamushi. The bacteria causes scrub typhus, a disease in which children have cough, rashes and skin lesions, and multiple organ failure. The disease, caused by the bite of mite larvae, progresses rapidly and can be fatal, unless detected and treated early. “In the rainy season, the eggs hatch, and the microscopic larvae bite the children playing in the soil and in the scrub vegetation in their backyard,” said Arunkumar. Out of 250 cases, 62 per cent had tested positive for scrub typhus, and only 3 per cent for JEV.
After Gorakhpur recently came under the scanner, experts said the deaths there were a result of a mixed bag of infections. This has led to the discussion over scrub typhus, a reemerging disease in India, gaining prominence. Dr Soumya Swaminathan, director general, ICMR, said scrub typhus was suspected in many cases of encephalitis this year. While the death of infants at the hospital cannot be termed as due to scrub typhus, there is enough confusion each year, said Arunkumar. “At the BRD College all febrile [fever] illnesses get clubbed under AES. AES is only a clinical term, it is not a diagnosis,” he said. “And that is where the problem in Gorakhpur lies. Most of these cases get mixed up, causing confusion, and every year, the story repeats itself.”
Beyond Gorakhpur also, scrub typhus has “reemerged” as a huge public health concern. A mite-borne rickettsiosis (a disease caused by intracellular bacteria), scrub typhus continues to be “under-diagnosed, neglected, with lethal consequences”, according to a 2016 report in the Indian Journal of Medical Research. The authors retrace the origins of the disease in India—initial reports of scrub typhus appeared in the 1930s, and a large number of cases were identified during World War II. “Scrub typhus was first reported in Kumaon hills in 1938, while in Uttar Pradesh it was confirmed in 1945. In Uttarakhand, it was reported in 1992 and 2009... since 2012, when the National Centre for Disease Control confirmed a multi-state outbreak, an increased number of patients have been seen in several states.”
“Of late, cases have been reported from large hospitals in virtually all states including Delhi, Goa, Rajasthan, Himachal and even in Bhutan,” said Dr Anurag Bhargava, professor of medicine at Yenepoya Medical College, Mangaluru, and the lead author of the report. “The disease is not restricted to rural areas, but has also been reported in urban areas including its affluent parts.” Bhargava said that while those engaged in activities such as cutting grass, or those who have proximity to shrubs and dense vegetation are more prone to the disease, people walking barefoot in their lawns or indulging in similar activities are also at risk. “It is also a misconception that the disease affects people in the hills, or those who go for trekking. We are seeing cases from Kerala now, and have seen over a 100 cases from agricultural plains of Uttar Pradesh, ” he said.
Dr Anurag Bhargava
Recent years have seen a few reemerging diseases in India such as chikungunya, and even monkey fever. Scrub typhus, according to experts, is probably the “most neglected, under-recognised, severe but easily treatable disease in the world”. According to Dr George M. Varghese, department of medicine and infectious diseases, Christian Medical College, Vellore, each year, about 1 million cases occur, of which 1.5 lakh deaths are reported in southeast Asia. These are worrying numbers for a disease that can be treated easily with antibiotics such as doxycycline, if diagnosed early.
While statistics for the disease in India are not available, according to Varghese, it has spread to more than 25 states. “Although reporting of the disease is improving, it is still a grossly under-recognised public health concern,” he said. “More than 3,000 cases have been reported at CMC, Vellore, and the disease is very much prevalent in the southern states. Earlier, community sampling showed around 5 per cent serological prevalence of past infection, but now, the prevalence is as high as 30 per cent.” So how did a disease that can be treated easily and at a low cost slip off the radar? Doctors said it is because earlier, patients with fever were prescribed common antibiotics like tetracycline and chloramphenicol that treat scrub typhus, too. “Now, the commonly used antibiotics such as cephalosporins are ineffective against scrub typhus,” said Varghese. “Clearing of forests/vegetation, increasing rodent population, climate change could also be additional factors contributing to the reemergence.”
According to experts, the confusing symptoms of the disease can throw doctors off the track. “The disease is a great mimic of dengue, typhoid and pneumonia,” said Bhargava. “While in Uttarakhand, our work over the years has led to better awareness and access to diagnostic techniques, that is not the story in other states.” He adds that the Army, which used to test for the disease after it was reported during World War II, also stopped testing, causing it to be forgotten in the medical discourse. Better testing techniques are needed to detect the spread of the disease across the country. Serological tests may present false positivity because of the cross reaction with other viral diseases, said Varghese. More advanced tests such as PCR-DNA may not solve the problem either. The test, though highly sensitive, works only in the first week, when the bacteria is in enough concentration in the blood culture, said Bhargava. “The best way for doctors to diagnose it is to look for skin lesions,” he said. “And then, instead of waiting for the results of a diagnostic test, they should start the treatment. The disease progresses very fast and spreads to other organs, if crucial time is lost.” Medical education also needs to focus on the disease. “For MBBS students, scrub typhus is only a paragraph, that will earn them five marks in the exam,” said Arunkumar. “Also, after we alerted the authorities of the ground situation in Gorakhpur, they haven't taken enough action.” Unless better diagnostic labs are set up at community health centres and district hospitals, and doctors and even patients vulnerable to the disease are made aware, a disease that can be treated easily will continue to confound doctors. And each year, Gorakhpur will continue to battle a 'mystery' fever.
