Risk of microcephaly after Zika virus infection in Brazil, 2015 to 2016

Abstract

ObjectiveTo estimate the risk of microcephaly in babies born to women infected by the Zika virus during pregnancy in Brazil in an epidemic between 2015 and 2016.MethodsWe obtained data on the number of notified and confirmed microcephaly cases in each Brazilian state between November 2015 and October 2016 from the health ministry. For Pernambuco State, one of the hardest hit, weekly data were available from August 2015 to October 2016 for different definitions of microcephaly. The absolute risk of microcephaly was calculated using the average number of live births reported in each state in the corresponding time period between 2012 and 2014 and assuming two infection rates: 10% and 50%. The relative risk was estimated using the reported background frequency of microcephaly in Brazil of 1.98 per 10 000 live births.FindingsThe estimated absolute risk of a notified microcephaly case varied from 0.03 to 17.1% according to geographical area, the definition of microcephaly used and the infection rate. Assuming a 50% infection rate, there was an 18–127 fold higher probability of microcephaly in children born to mothers with infection during pregnancy compared with children born to mothers without infection during pregnancy in Pernambuco State. For a 10% infection rate, the probability was 88–635 folds higher.ConclusionA large variation in the estimated risk of microcephaly was found in Brazil. Research is needed into possible effect modifiers, reliable measures of Zika virus infection and clear endpoints for congenital malformations.

Epidemiological and ecological determinants of Zika virus transmission in an urban setting

“…We used the estimated attack rate of approximately 65% from 2015 (Figure 4A) and varied the local birth rate and the theoretical risk of MC to obtain an expected number of cases. In agreement with other reports (de Araújo et al, 2016; Cauchemez et al, 2016; Jaenisch et al, 2016; Johansson et al, 2016), our model predicted a relatively low risk for MC given ZIKV infection during pregnancy (Figure 5B,C). In particular, using a conservative total of 21 confirmed MC cases in FSA, i.e.…”

Zika virus infection of first-trimester human placentas: utility of an explant model of replication to evaluate correlates of immune protection ex vivo

“…Multiple reports of success in vaccine and passive transfer studies in animal models suggest an effective ZIKV vaccine could soon be developed, but efficacy in preventing congenital disease may not be known for years to come. In the interim, sporadic outbreaks will likely occur in seronegative communities [51,52]. Immune sera from vaccine trials [78**] and passive immune therapies [41**,86], as well as candidate therapeutic compounds [87], could be tested in explant models of the human placenta and decidua for their ability to specifically prevent virus dissemination, as indicated by infection of Hofbauer cells and other surrogate markers of fetal infection [88*].…”

“…Of particular interest is the question of whether the timing of prior exposure to dengue virus could contribute to regional differences in the frequency of microcephaly associated with ZIKV infection [51,52]. Improved serological methods should help uncover these relationships: non-cross-reactive ZIKV NS1-specific monoclonal antibodies have recently been identified in a screen of human memory B cells and have been used to develop new ZIKV-specific serologic diagnostic tests [41**,53**].…”

Establishing Mouse Models for Zika Virus-induced Neurological Disorders Using Intracerebral Injection Strategies: Embryonic, Neonatal, and Adult

“…A recent study from the CDC on ZIKV cases in the United States suggests that maternal ZIKV infection results in a 20-fold increased risk for a child to develop microcephaly compared to uninfected individuals, and 4% of ZIKV infected mothers from the USA have resulted in children with microcephaly 11 . The rate of microcephaly-associated birth defects during pregnancy from ZIKV infection in Brazil have been reported to have affected up to 17% of babies in infected mothers, indicating that other factors in Latin America may be contributing to the increased risk 13 . While we know that the ZIKV can cause microcephaly and pathogenesis in the neural progenitor cell (NPC) population 7,8,14 , the complete pathogenesis of ZIKV in the developing brain remains elusive.…”