Protecting Women and Infants from Zika

In 2016, the Zika epidemic – along with infant congenital birth defects and adult Guillain Barre syndrome – exploded across Latin America. SSI rapidly pivoted to address urgent questions about Zika by incorporating this new virus into its existing cohort studies, and initiating a community-based study engaging Managua’s women to reduce Zika transmission. SSI collaborated with research institutions globally to understand the fundamentals of Zika — its modes of transmission, means of accurate diagnosis, clinical manifestations, and methods of prevention and treatment.

To correctly diagnose a Zika infection, SSI worked with South American and European laboratories to develop and evaluate new molecular and serological diagnostic tests, including the Zika NS1 BOB (blockade-of-binding) assay, to distinguish between the Zika virus and its close relative, the dengue virus (Balmaseda et al., 2017). Armed with new diagnostic tools, the SSI team conducted a seroprevalence study of Zika virus antibodies in Nicaragua which revealed that 46% of the population had been infected during the 2016 epidemic, and that females are at higher risk for infection (Zambrana et al., 2018).

Females’ greater risk for Zika infection is largely due to gender-based differences in family roles and household responsibilities. The implications for maternal, sexual and reproductive health are critical and highlight the importance of understanding women’s experiences, knowledge, perceptions, and attitudes towards Zika. To that end, SSI and AMOS collaborated to obtain USAID funding to launch the project “Innovative Use of the Care Group Model and mHealth to Reduce Zika Virus Transmission”

SSI participated in multiple studies assessing the effects of the Zika epidemic on women and infants. The largest was the International Cohort Study of Zika in Infants and Pregnancy (ZIP) funded by the National Institutes of Health to better understand the risk that Zika poses to pregnant women and their infants. The ZIP study enrolled approximately 10,000 women in Zika-endemic regions of Brazil, Colombia, Guatemala, Nicaragua, Puerto Rico and Peru. https://www.nih.gov/news-events/videos/zip-study

In Nicaragua, SSI collaborated with the Univ. of California Berkeley (Dr. Eva Harris), the Univ. of North Carolina (Dr. Elizabeth Stringer), and RTI International (Dr. Jill Lebov) to recruit and consent approximately 2,000 women in their first or early second trimester of pregnancy. They were followed through their pregnancies to 6 weeks post-partum, and their infants were followed from to 1 to 5 years of age, depending on the specific study. Women were tested monthly for Zika infection: 59% tested positive for antibodies, and 21% experienced a Zika infection during pregnancy. Among these women, 17% had birth complications and 1.5% of their infants had congenital Zika syndrome. Adverse birth outcomes did not correlate with the timing of the Zika infection. A beneficial study result was the development of a simple algorithm for identifying women likely to be infected with Zika during pregnancy which could be implemented by other prenatal care systems (Collins et al., 2020).

An infant follow-up study, excluding those with congenital Zika syndrome, found that at 24 months of age the infants exposed in utero to the Zika virus had significantly lower cognitive test scores compared to those who had not been exposed. There were no differences in maternal demographic characteristics between the two groups (Stringer et al., 2021).

A study of Nicaraguan children infected with Zika virus during the 2016 epidemic monitored the children and a matched control group for 3 to 5 years post infection. These children’s infections were unrelated to their mothers’ exposure. Assessing their neurological symptoms, researchers found that, compared to the control group, cranial nerve abnormalities were significantly more frequent among Zika infected children, but they did not observe a meaningful link between the Zika infection and subsequent outcomes (Lebov et al., 2024).

SSI’s and UC Berkeley’s researchers have contributed greatly to understanding the interaction effects of dengue and zika viral infections on the human immune system, and the risk of severe disease. Their studies show that antibody-dependent enhancement of disease occurs at a specific range of antibody concentrations. Low level titers of antibody do not enhance disease, intermediate levels exacerbate disease, and high levels protect against severe disease. This knowledge is crucial for preparedness measures and the development of vaccines against both these viruses (Katzelnick, L. et al., 2020).

Balmaseda, A. et al, 2017. Antibody-based assay discriminates Zika virus infection from other flaviviruses. Proceedings of the National Academy of Sciences. July 17, 2017; 114(31), pp. 8384-8389.

Zambrana, J.V. et al., 2018. Seroprevalence, risk factor, and spatial analyses of Zika virus infection after the 2016 epidemic in Managua, Nicaragua. Proceedings of the National Academy of Sciences. Sept 11, 2018; 115(37), pp. 9294-9299.

Collins, M. H. et al., 2020. Serological surveillance of maternal Zika infection in a prospective cohort in Leon, Nicaragua during the peak of the Zika epidemic. PLoS One. Apr 3, 2020; 15(4): e0230692.

Stringer, E. et al., 2021. Neurodevelopmental outcomes of children following in utero exposure to Zika in Nicaragua. Clinical Infectious Diseases. Mar 1, 2021; 72(5), pp. e146-e1453.

Lebov, J. et al., 2024. Cohort study: Neurological and cognitive-behavioral sequelae of acquired Zika virus infection among Nicaraguan children. Pediatric Research. Jul 2, 2024.

Katzelnick, L. et al., 2020. Zika virus infection enhances future risk of severe dengue disease. Science. Aug 28, 2020; 369(6507), pp. 1123-1128.