Controversy exists in the Zika virus mutation and microcephaly

On 3 Nov 2018, a press release from the Ministry of Health and Family Welfare cited the Indian Council of Medical Research's (ICMR) findings to say that the Zika strain -- which had earlier caused an outbreak in Rajasthan -- did not have "known mutations" for microcephaly. M.P.'s health officials are now waiting for the ICMR to genetically sequence the local Zika strain, as they believe it may also lack those mutations, and so, may not be dangerous to fetuses. But Zika researches say all Zika strains can probably cause birth defects. Contrary to the belief, it seems there is no “known mutation” for microcephaly. . "People have got to stop saying this," says Nathan Grubaugh, an epidemiologist at the Yale School of Public Health. "It's going to drive complacency within the general population if they don't believe Zika can cause birth defects," he adds. Grubaugh studied the Brazil and U.S. Zika epidemics in 2015. Yet, there are several questions about whether the outbreaks in Rajasthan and M.P. have truly been extinguished. Zika cases typically rise and drop with the seasonal prevalence of the Aedes mosquito, which means the drop in November 2018 may have as much to do with the weather as with antilarval activity. Says Grubagh: "Control of an outbreak is quite hard to define. 1st, not detecting Zika cases doesn't necessarily mean that transmission stopped, because the vast majority of cases are asymptomatic."

The ICMR's surveillance system relies on RT-PCR, which looks for Zika's genetic signature in patient blood samples. But RT-PCR tends to throw up false-negatives when there is too little virus in the patient's blood, something that happens frequently with Zika, says Grubaugh. Such barriers mean that the best of surveillance systems catch only a fraction of the incidence. After an outbreak in Salvador, Brazil during 2015, researchers found that the number of people who had Zika antibodies -- indicating that they had been infected in the past -was roughly 40 times the number of detected cases. If the same multiple is applied to MP, then, given its 127 detected cases, the potential number of infections could be as high as 5080.

Why did the press release suggest that the Rajasthan strain had no known mutations for microcephaly? Responding to a questionnaire, Nivedita Gupta, a virologist at the ICMR, referred to a Science study in 2017 to support the claim. Here, Chinese researchers found that when they infected new-born mice with a Zika strain that contained a mutation called S139N, the mice had more damaged brain cells when compared to animals infected with other strains. This suggested that the mutation had a role to play in making the Zika virus more virulent to foetal brain cells. When the ICMR sequenced the virus that triggered the Rajasthan outbreak, they did not find the S139N mutation. This led to the Health Ministry announcing that the Rajasthan virus did not have "known mutations" for microcephaly.

The problem, according to Grubaugh and other researchers, is that the hypothesis of the Science study has not stood the test of time. Later studies have found microcephaly cases associated with strains that lacked the S139N mutation. Meanwhile, researchers who repeated the mouse experiments did not get the same results.This is why the ICMR's claim about "known mutations" is misleading, according to him. Other scientists agree. "It is still too early to conclude that any particular strain cannot cause microcephaly," says Scott C. Weaver, a microbiologist at the University of Texas, who worked on the Brazilian outbreak. When asked if the ICMR would issue a clarification, Gupta responded that there were no errors in the press release.

It is tough to say how big a risk Zika will be to Indians in the coming days. For now, the 2 outbreaks, in Rajasthan and Madhya Pradesh, appear to be relatively small, with 154 and 127 detected cases, respectively. But given the number of asymptomatic cases, it is difficult to rule out the possibility of Zika cases elsewhere in India. "I would not be surprised if the Zika virus were already present in other parts of the region but has remained undetected due to the lack of active surveillance in the absence of an overt outbreak," says Weaver.