More than 50 years after the infectious pathogen, rubella virus, was identified as the cause of an epidemic of congenital defects, the Centres for Disease Control and Prevention (CDC) in the United States confirmed on April 13 that >Zika virus infection during pregnancy causes microcephaly and other severe foetal brain defects.
The confirmation of causal relationship did not arise from a single definitive piece of evidence. Instead, it was from “various lines of evidence, each of which suggests, but does not on its own prove, that prenatal Zika virus infection can cause adverse outcomes”. Of the nine criteria used to find a causal relationship between Zika virus and microcephaly, the only criterion that was not met was the absence of experimental studies on animal models. The confirmation was published as a special report, again on April 13, in the journal, The New England Journal of Medicine ( NEJM ).
An increase in the number of babies born with microcephaly in Brazil was first noticed in September 2015 and a similar spike in French Polynesia seen after a Zika virus outbreak in 2013-2014. As of February 13, 2016, Brazil notified 5,280 cases of microcephaly but only 1,345 have been investigated and classified. According to the government, only 508 cases have been diagnosed as microcephaly.
A body of scientific evidence linking microcephaly to Zika virus infection during pregnancy was available as early as January this year. One of the reasons the World Health Organisation (WHO) declared Zika virus a public health emergency of international concern on February 1, 2016 was that a causal relationship was “strongly suspected” and hence required international efforts to investigate and understand it. Even in its last Zika situation report of April 7, the WHO stressed that there is scientific consensus that the virus causes microcephaly and Guillain-Barré syndrome (a disorder in which the body’s immune system attacks part of the peripheral nervous system).
Moving with caution As the paper notes, despite the growing body of evidence, the scientific community acted cautiously as no flavivirus has so far been linked to birth defects and no adverse pregnancy outcomes were reported from countries that had experienced Zika outbreaks in the past. Also, no infectious pathogen after the rubella virus has been associated with birth defects in the last 50 years. In addition, alternative explanations to link Zika virus infection during pregnancy and microcephaly were simply absent. Several hypotheses, ranging from the use of genetically modified mosquitoes to keep the wild male Aedes aegypti mosquitoes under check and adding pyriproxyfen larvicide to drinking water, were put out to explain the link. But these came from panicked residents and not from the scientific community and, as expected, did not stand scientific scrutiny.
Moving from a hypothesis to confirming the causal relationship marks a “turning point” in the Zika outbreak. All research efforts can now be directed at understanding the full spectrum of birth defects caused by the infection. As the director of the CDC, Dr. Tom Frieden, said, microcephaly could be the “tip of the iceberg of what we could see in damaging effects on the brain and other developmental problems”.
Rightly, a recent study found that Zika virus may be associated with an autoimmune disorder that attacks the brain’s myelin, similar to multiple sclerosis. A study published on April 13 in The BMJ (formerly the British Medical Journal) , found “severe” brain damage with a range of abnormalities in 23 babies with microcephaly who were for the first time examined using computed tomography and magnetic resonance imaging. The abnormalities ranged from brain calcification, malformation of cortical development, incomplete development of the brain, particularly the cerebellum, ventriculomegaly (abnormal enlargement of the brain cavities) and, finally, delayed myelination. These findings confirm what the director of the National Institute of Allergy and Infectious Diseases, U.S., Dr. Anthony Fauci, said about Zika: “The more and more we learn, the more you get concerned about the scope of what this virus is doing.”
As the NEJM paper notes, besides understanding the entire range of abnormities, concerted efforts can now be directed at quantifying the relative and absolute risk among infants born to mothers who had the infection during pregnancy. They can see if other factors like confection with another virus and/or a pre-existing immune response to another flavivirus are responsible for some babies born to mother infected with Zika virus developing microcephaly.
Makes awareness easier Confirming the causal relationship makes it easier to raise awareness both at the clinical and community levels and communicate the risks to women who are pregnant or planning to get pregnant soon. This is all the more important as awareness levels are low even in the U.S. where the virus is spreading to more States. A poll in March by researchers at the Harvard T.H. Chan School of Public Health, Boston, Massachusetts, found that nearly 25 per cent of 1,275 adults were unaware of the association between Zika virus and microcephaly and 42 per cent did not know that the virus can be transmitted sexually. And four in 10 mistakenly believe Zika virus infection in women is likely to harm future pregnancies, not knowing that the virus takes just one week to clear from the blood of an infected person.
Since the infection remains asymptomatic in a majority of people and not specific even when present, efforts have to be redoubled to develop diagnostic methods and vaccines even as measures to intensify mosquito population are undertaken. With Aedes mosquitoes present in the country and the peak mosquito season a few months away, India has much to do to prevent a Zika outbreak.
prasad.ravindranath@thehindu.co.in
