Zika: ‘The More We Know, the Worse Things Look’

A summary of recent updates.

A firefighter involved in a sanitation drive to protect against mosquito-borne diseases in Brasilia. Credit: agenciabrasilia/Flickr, CC BY 2.0

A firefighter involved in a sanitation drive to protect against mosquito-borne diseases in Brasilia. Credit: agenciabrasilia/Flickr, CC BY 2.0

On March 22, the World Health Organisation’s Director-General Margaret Chan issued a statement updating the media on the Zika virus situation. “In less than a year, the status of Zika has changed from a mild medical curiosity to a disease with severe public health implications,” she said. Chan acknowledged that our knowledge base is quickly expanding as well but also that “the more we know, the worse things look”. This is where we are today with the Zika outbreak and related research developments.

Where has it spread to?

According to WHO’s latest statement, the virus is currently circulating in 38 countries/territories. The US’s Centers for Disease Control and Prevention (CDC) lists 39 countries/territories with active Zika transmission while the European Center for Disease Prevention and Control (ECDC) says that 43 countries/territories have experienced local transmission in the past nine months.

Many of the affected regions seem to experience a similar pattern of events where three weeks after the detection of virus circulation, an increase in number of Guillain-Barré Syndrome (GBS) cases is reported. Cases of foetal malformations like microcephaly emerge months later when infected pregnant women give birth.

So far, according to WHO, 12 countries/territories have reported rise in GBS cases with an apparent Zika-link. Two countries – Brazil and Panama – have reported microcephaly while Colombia, Puerto Rico and Cabo Verde are still investigating their first suspected Zika-linked microcephaly cases. The virus has not been circulating long enough in the other affected countries for their pregnancies to come to term so more microcephaly cases could yet be on the horizon.

Earlier this month, CDC chief Thomas R. Frieden visited the economically troubled Puerto Rico and expressed alarm over the situation there; the frequency of cases is doubling every week and the virus is expected to infect a quarter of the 3.5 million population within a year.

A PTI news report from March 3 quoted Indian Council of Medical Research (ICMR) Director-General Soumya Swaminathan as confirming no Zika case has been found in India so far and the priority right now was to up our surveillance game by equipping labs to test suspected cases.

What has research told us so far?

WHO concedes that there is still no scientific proof that the Zika virus can cause foetal malformations like microcephaly and neurological disorders like GBS, but an increasing body of research correlating them has resulted in a scientific consensus that there is a link. In the light of the pace of the spread and the public health emergency, WHO recommends that urgent action is required and cannot wait for definitive proof. It is now also acknowledged that the virus can be sexually transmitted, though the specifics of this mode of transmission is remains a mystery.

Among the more recent additions to the Zika knowledge base is the finding of Zika viruses in the brains of foetuses with microcephaly. Many questions persist, however: Which stages of pregnancy are most vulnerable? Do all affected mothers pass on the virus? What percentage of infected babies show developmental defects, etc.?

Also, this month, two independent studies for the first time provided observational evidence for the Zika-microcephaly link. The first study showed how Zika viruses more readily infected neural stem cells (precursors to neurons) than compared to other types of cells. The infected cells grew and divided much more slowly, an effect that possibly manifests itself as microcephaly. The second study demonstrated that the development of neural stem cells called neurospheres into mini human brains was severely hampered when the cells were infected with Zika. The resultant organoid was less than half of their normal size.

The case of a 15-year-old Zika infected girl in the Caribbean island cluster of Guadeloupe, who contracted acute myelitis (inflammation of the spinal cord), has also been recorded. She recovered in a couple of weeks but the high concentrations of Zika virus in her serum and cerebrospinal fluid have further bolstered Zika’s reputation as a neurological nightmare.

India, too, is hoping to chip in with Zika research as soon as ICMR receives strains of Zika virus from CDC as requested. Hindustan Times reported on March 12 that the strains were expected to arrive in a week. The priority will be make sure our testing kits are efficient enough in case of a future outbreak in the country.

How can we deal with this emergency?

WHO has held three high-level meetings this month of which two were focused on management of the outbreak. It was agreed that the highest priority was to establish a reliable diagnostic test. Chan said that at this point more than 30 companies are working on such tests. Fourteen vaccine developers around the world, including in India, have Zika vaccine projects under way, said Chan in her statement.

Hyderabad-based Bharat Biotech (the same company whose rotavirus vaccine is being launched nationally on March 26) announced their Zika vaccine projects in February 2016. They began work on their inactivated vaccine in late 2014 and have been named by a WHO official as one of the two front-runners, along with the US NIH’s DNA vaccine. However, the timing of their announcement as well as allegations that they may not have followed standard procedure for importing the virus has raised some suspicion, as reported by a news analysis in Business Standard. Moreover, as The Wire recently wrote, it remains unclear what Bharat Biotech’s plans regarding getting a suitable animal model or clinical trials in India are.

A few of the projects around the world might commence clinical trials by the end of the year, said Chan, but it may take several years for a vaccine to be available after testing and licensing. As these vaccines need to be used on pregnant women, they must meet high standards of safety. On a separate note, highly encouraging results from a dengue virus vaccine trial have sparked hope that a similar technique might work with the closely related Zika virus too.

The other strategy against Zika being given weightage is mosquito control. At the WHO meeting, experts evaluated the potential impact of five different tools for mosquito control. None were declared ready for full-scale implementation but they recommended that two of them be deployed on a pilot basis: microbial control (infecting mosquitoes with Wolbachia bacteria which render them disease-free and releasing them into the wild to replace disease-carrying populations), and genetic manipulation (releasing male mosquitoes inserted with OX513A gene into the wild so that they mate with females and produce offspring that will die before they can breed). The latter technology was developed by Oxitec Ltd. and was also recently cleared by the FDS for field trials.

How has Zika changed the nature of research?

There has been an encouraging repercussion of the Zika debacle on the way research is done. Reacting to the urgency of the public health situation and in the spirit of collaboration and co-operation, many scientists have begun to openly release their data. In February, several global health bodies and journals released a statement supporting the decision to make all Zika content available freely. However, there has been dispute over the etiquette of using public data with one group expressing displeasure that their data was used by another without adequate credit. Nevertheless, such mistakes and debates are probably inevitable and a small price to pay for a faster solution to global health crisis.