Following press reports, the Zika epidemic in Singapore has expanded rapidly since it was first reported in the news 6 days ago. There are now 153 cases reported as of yesterday, including two pregnant women. There is also a separate cluster of Zika infections outside of the original Sims Drive/Aljunied Crescent area, at Bedok North Avenue 3. The Ministry of Health and National Environment Agency appear to have pulled out all stops in order to try to contain the outbreak, although the prime minister has warned just today that the Zika virus could very well have spread outside of the two zones listed above. This is a reasonable assumption, given that the incubation period of the Zika virus in humans is up to 12 days, and there is a further 5-10 days of incubation within an infected mosquito (after it takes a blood meal) before the virus can be detected from the mosquito’s saliva – at which point it becomes infectious.

I was forwarded the following reference, which answered one of my previous questions as to whether there was any transovarial transmission (mother mosquito to offspring) of Zika virus. In a study by Texan investigators that is still in press, they were able to show that the minimum filial injection rate was 1:290, which means that approximately 0.3% of eggs from an infected female Aedes aegypti mosquito will hatch out Zika-infected offspring. This figure is quite similar to other flaviviruses such as dengue, Japanese encephalitis, and yellow fever, suggesting that transovarial spread will be a minor but perhaps important way for the Zika virus to be maintained in the local Aedes aegypti population. A female Aedes mosquito will lay anywhere between 500-1,000 eggs in an uninterrupted lifetime.

We now also have a part answer as to how Zika may cause brain damage and microcephaly in fetuses. In a study published in Journal of Virology last year, investigators from France showed that one of the main receptors used by the Zika virus to enter cells was the AXL receptor tyrosine kinase (RTK), which is part of the TAM family of RTKs (interested persons can download this article which is unfortunately behind a paywall). This rather interesting RTK is associated with several cancers when overproduced in adults (colon cancer, melanoma, chronic myeloid leukaemia), including glioblastoma – a brain cancer. However, it is highly expressed in radial glial cells, which are primary progenitor cells which ultimately differentiate into all the other brain cells. Investigators from University of California San Francisco cleverly showed that radial glial cells and other developing brain cells were susceptible to Zika virus infection, at the same time demonstrating that mature neurons were much less susceptible to infection. This may also explain why microcephaly is rare after the first trimester of pregnancy, and involvement of the brain by the Zika virus in both adults and children appears at present to have negligible effects.

In other news, we also appear to have exported Zika to Malaysia. The patient had returned to Malaysia from Singapore, and came down with symptoms a week later. Her daughter had just been diagnosed with Zika fever, so she was able to inform her doctor who promptly put two and two together. A good thing this case was detected early.