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Infectious Cause of Microcephaly May Not be Zika

Notably, although the prevalence of congenital CMV infection in high-income countries is estimated to be 0.7% of all live births (versus 1% to 5% in low-income countries), the risk of mother-to-fetus transmission increases with advancing gestational age, from 35% in the first trimester to 65% in the third.

Conversely, the authors of The Lancet review write that HSV has been shown to “infect multiple brain cell types,” but how infection results in microcephaly remains unknown, though animal studies suggest the virus may induce “an immune response that stimulates neural stem cell proliferation” to cause the defect. Thankfully, they note, primary microcephaly is a relatively rare complication of perinatal HSV infection (with in-utero infection accounting for 5% of cases). Similarly, they add, rubella’s role in the pathogenesis of microcephaly remains unknown, even as research suggests that “brain vessels have been found to degenerate following… infection,” indicating that “a neurodegenerative mechanism could be a potential underlying cause.” Although most countries have vaccination programs in place for rubella, nearly 10% of pregnant women worldwide are seronegative, and incidence of congenital rubella syndrome in the developing world (where vaccine programs are typically not fully implemented) is as high as 300 per 100,000 live births.

Finally, the global incidence of congenital toxoplasmosis (T. gondii) is approximately 1.5 per 1,000 live births, with the highest incidence in South America. Dr. Devakumar and colleagues note that research suggests that mother-to-child transmission occurs during pregnancy following primary infection.

“In any differential diagnosis of microcephaly, these infections should be considered, [but] the degree to which a clinician would see one of these causes depends on the setting they are working in,” Dr. Devakumar explained. “When a clinician is faced with a case, the broad differential should be remembered, and that infection should be investigated and treated appropriately. Certainly, communication with parents is [also] important. In every situation, a decision has to be made about how much information to give, when to give it, and in what way. As we have highlighted a diagnosis of microcephaly itself and an infectious cause is often not straightforward, so this can be complicated.”
Brian P. Dunleavy is a medical writer and editor based in New York. His work has appeared in numerous healthcare-related publications. He is the former editor of Infectious Disease Special Edition.
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