A university project caught India’s fourth Zika case – not the government’s surveillance programme

India’s fourth reported case of infection by the Zika virus, detected in early July in Tamil Nadu, was picked up first by a public health project conducted by Manipal University and then passed on to the national surveillance programme for communicable diseases. If not for Manipal University’s project on fever diagnosis, the case might have gone unreported.

The Manipal Centre for Virus Research launched a project called the Hospital Based Acute Febrile Illness Surveillance in India in 2013. The aim of the project is to characterise the infectious causes of Acute Febrile Illness or AFI among patients in district and sub-district hospitals and in primary health centres across India, by identifying pathogens including the malaria parasite and bacterial, viral and other causes of fevers.

The project operates in 13 districts across 12 states – Karnataka, Kerala, Goa, Tamil Nadu, Assam, Tripura, Odisha, Jharkhand, Gujarat, Punjab, Uttar Pradesh and Bihar – from where samples of fever patients are collected at any of 27 designated sentinel hospitals, which may be district hospitals or primary health centres. Private doctors can also send in samples of their patients who have tested negative for dengue and chikungunya. The samples are sent to the Manipal Centre for Virus Research to be testing.

One of the project sites happens to be the primary health centre in N Puttur village in Krishnagiri, where the blood samples of India’s fourth Zika patient were first collected.

The 27-year-old man went to the primary health centre with fever and redness in his eyes. He also complained of pain behind his eyes, a headache and joint pains. These symptoms are indicative of both dengue and chikungunya and his blood and urine samples were tested for antibodies for both illnesses.

When the tests did not show dengue or chikungunya infections, the team at the Manipal Centre for Virus Research ran a real-time polymerase chain reaction test for Zika. Dr G Arunkumar, professor and head of the department of virus research, was not expecting to find the Zika virus in the samples. His team has tested about 20,000 samples of fever patients till then, all of which were negative.

However, the N Puttur resident’s test results on July 1 showed the presence of the Zika virus. The research team quickly reconfirmed the results. “We took the samples again on July 2,” said Arunkumar. “This time the blood showed the presence of the virus. The urine did not have the virus.”

The laboratory immediately alerted the Indian Council of Medical Research, the union health ministry and the Tamil Nadu government. Another set of the man’s samples were sent to the National Institute of Virology. On July 5, the institute also confirmed that the man had Zika.

The purpose of Manipal’s AFI project is to provide early and accurate diagnosis and treatment of fever-related illnesses even to people in remote parts of the country who do not have easy access to laboratory testing.

Therefore, the question that this case of Zika detection throws up is whether there are Zika cases in areas where the AFI project is not operating that are also being missed by the national surveillance programme for communicable diseases.

Cases getting missed?

Senior health officials agreed that if this patient had belonged to another district where the AFI project was not operating, his blood and urine samples may not have been tested for Zika.

Along with the AFI project, the Manipal Centre for Virus Research is also one of 25 laboratories associated with the Indian Council of Medical Research, the apex agency leading the national surveillance programme.

The national surveillance programme for communicable diseases coordinates testing of samples of fever patients for dengue and chikungunya. If these initial tests are negative, then the samples are tested for Zika. Twenty five laboratories across the country have been equipped to test for Zika. Government and private hospitals have been notified that they can send patient samples to these laboratories to be checked for Zika.

There is no active case finding and health workers are not looking for possible infections within communities. The 25 laboratories mostly end up testing samples of those patients who are admitted at hospitals that they are attached to.

“Most of the labs are located in medical colleges and they receive samples from there for testing,” said Arunkumar, who said that most of the samples that the Manipal Centre for Virus Research tests come from cities. The only samples that they get from rural areas come in as part of the AFI project.

“Less than 1,000 samples came from the [national] surveillance,” he added.

At the same time, not all the 25 laboratories linked with the national surveillance programme have started testing for Zika. “We are waiting for some reagents and other materials to begin testing,” said an official at the Haffkine Institute in Mumbai. The Central Research Institute at Kausali also confirmed to Scroll.in that it had not started testing patient samples for Zika.

However, Dr AC Dhariwal, director of the National Centre for Disease Control said that the system is robust. “Every laboratory is given a region from where they can get and test samples,” he said.

Meanwhile, the real burden of Zika in India remains unknown.

“We are trying to ensure a geographic coverage so that all states are covered,” said Dr Soumya Swaminathan, director general of Indian Council of Medical Research, about the national surveillance programme. “There are more labs in Tamil Nadu and Karnataka. About 50% of 40,000 samples tested for Zika were tested at Manipal.”

Of the 40,000 samples tested only 10% have come from private hospitals, even though most people in India go to private hospitals first for treatment, suggesting that many ever cases being treating at private facilities are not being tested for Zika. There is an even smaller chance, then, that Zika infections that are not showing up as fever are being detected.

“We are testing samples of those with fever and the detection is best if done within first week of symptoms,” said Swaminathan. “About 80% of Zika infected individuals will have no symptoms. It is not possible to screen thousands of asymptomatic people.

Unknown neurological conditions?

Apart from actively looking for Zika cases, the surveillance programme is also conducting tests to check how similar the Zika virus strain found in India is to the strain that caused Zika infections in Brazil through 2015 and 2016. The World Health Organisation declared Zika a Public Health Emergency of International Concern after several reports of women infected with Zika giving birth to babies with microcephaly, a condition in which the brain is small and underdeveloped.

The four Zika cases reported so far in India have all been caused by the Asian strain of the Zika virus, the same strain that caused the Zika outbreak in Brazil. But, the Indian Council of Medical Research is looking closer.

“Even a smaller mutation may make the virus less or more neurotopic,” said Swaminathan, referring to the virus’s ability to attack the nervous system.

Meanwhile, the health ministry has identified 50 hospitals, both government and private and mostly in cities, where all newborns will be screened for Zika infections. The blood samples collected from infants within one week of their birth or their umbilical cord blood will be tested.

“It is not just microcephaly, newer evidence is coming up every day about various neurological conditions [associated with Zika] which can cause developmental delays,” said Swaminathan.