Francesca Tomasi received her B.A. from the University of Chicago and is now a microbiologist.
On February 1, the World Health Organization declared Zika virus and its suspected link to neurological birth defects an international public health emergency. The virus is native to parts of Africa, Southeast Asia, and the Pacific Islands, but it recently made the jump to North and South America and has taken up residence in local Aedes aegypti mosquitoes. It was first detected in Brazil in May 2015 and has since then infiltrated over twenty countries. Even more countries have reported travel-related and sexually-transmitted cases. On February 8, the same day that the CDC raised its Zika response efforts to Level 1 activation (the highest response at the agency), President Obama requested more than $1.8 billion in emergency funding to fight the virus.
The link between Zika and microcephaly, abnormal smallness of the head that results from incomplete fetal brain development, was first hypothesized when the Brazilian Health Ministry reported a skyrocket of microcephaly in newborns that occurred in the same time frame and location as a new outbreak of Zika. And though this was speculation, it was a very serious one that immediately warranted attention, especially as it turned out the virus was rapidly infiltrating almost every mosquito-rich pocket of the Americas.
Finally, researchers have had some time to seriously examine the link between Zika virus and neurological symptoms, and it’s not looking good for the virus. One study, published in The Lancet on February 29, retrospectively studied blood samples from 42 patients who were diagnosed with Guillain-Barré syndrome during an outbreak of Zika virus in French Polynesia that occurred between October 2013 and April 2014. Guillain-Barré syndrome (GBS for short) is a disorder that affects the immune and nervous systems. Symptoms include pain and weakness in the arms and legs, and they quickly progress to paralysis. In 20-30% of cases, GBS can be particularly severe, resulting in respiratory failure and, rarely, death. Most people recover though, despite the frightening paralysis.
During the Zika outbreak in French Polynesia, a rise in GBS was reported. Usually, GBS occurs in 1 or 2 people out of 100,000 per year following an infection like herpes, influenza, or dengue virus. During the 2013-2014 Zika outbreak, though, 32,000 patients consulted physicians about a potential Zika infection, and 42 of these were diagnosed with GBS within the time frame of the outbreak. Scientists from the Institut Pasteur in Paris, France, performed a retrospective analysis of blood samples from these 42 cases and compared them to two control groups – one contained individuals who were at the same hospital as the GBS patients but did not have a fever, and the other group included patients who tested positive for Zika virus but did not develop neurological symptoms.
After studying the blood samples, the authors concluded that Zika virus might cause Guillain-Barré syndrome. They estimated that out of 100,000 people who contract Zika, 24 will develop GBS. Before jumping to any conclusions, however, it is important to note that we do not yet know whether the current Zika virus in the Americas is identical to the strain that spread in French Polynesia two years ago. Two different strains of the same virus can behave differently – look at Ebola virus, which has multiple different strains and a range of fatality rates. When considering the pathogenesis of an infectious disease, it is also important to take into account differences in patient backgrounds with regards to their genetics and immune systems – furthermore, it is always possible that a co-infection or co-morbidity may exacerbate an otherwise mild infection. Notwithstanding these points, this study does link Zika virus with Guillain-Barré syndrome as the medical community attempts to unravel the mysteries of the emerging virus.
While researchers at the Pasteur Institute were studying blood samples from a Zika outbreak in French Polynesia, microbiologists at Johns Hopkins were culturing different kinds of fetal cells and infecting them with Zika to assess any ensuing cellular damage. In these experiments, an alarming 90% of neural progenitor cells – the cells that form the outer layer of the brain – were damaged and often killed. Meanwhile, other fetal cells were significantly less affected. The Johns Hopkins team and their collaborators concluded that neural progenitor cells are targets for Zika virus. Limitations of the study include the in vitro nature of the experiments; that is, these were lab-grown cells cultured outside of the human body and could therefore have displayed different behavior from their environment in a fetus. Furthermore, such exposed cells are naturally more susceptible to infections. Nonetheless, a significant difference in the impact of Zika on neural cells compared to non-neural cells points yet another accusatory finger straight at the virus. Defects in fetal brain development lead to unusually small brains, which manifests as microcephaly in newborns.
While we’re collecting evidence, how about one more study? Researchers from the David Geffen Medical School at UCLA and collaborators in Brazil have been following the pregnancies of 88 women who tested positive for Zika virus in Rio de Janeiro, Brazil. 29% of these women ultimately had abnormal ultrasounds; conditions such as shrunken placentas, brain calcification, retarded brain growth, and unusually small heads were noted. Fetal death occurred in some cases as well. There did not seem to be a definite link between time of Zika infection during pregnancy and these somber outcomes, though doctors in Brazil previously reported that the worst and most frequent fetal damage occurred when mothers were infected during their first trimester. This makes sense, since most essential neurogenesis – early brain development – occurs in the first trimester of pregnancy. Once again, it is important to play devil’s advocate for a minute and point out any study limitations – in this case, the small sample size may have contributed to skewed results.
Barely a month after the WHO declared Zika virus a public health emergency, the scientific evidence is mounting in the case against Zika. Infective Perspective will be on constant lookout for more new studies as this worrying story unfolds.