Seroprevalence, risk factor, and spatial analyses of Zika virus infection after the 2016 epidemic in Managua, Nicaragua

Abstract

In 2015, a Zika epidemic in Brazil began spreading throughout the Americas. Zika virus (ZIKV) entered Managua, Nicaragua, in January 2016 and caused an epidemic that peaked in July-September 2016. ZIKV seropositivity was estimated among participants of pediatric (n = 3,740) and household (n = 2,147) cohort studies, including an adult-only subset from the household cohort (n = 1,074), in Managua. Seropositivity was based on a highly sensitive and specific assay, the Zika NS1 blockade-of-binding ELISA, which can be used in dengue-endemic populations. Overall seropositivity for the pediatric (ages 2-14), household (ages 2-80), and adult (ages 15-80) cohorts was 36, 46, and 56%, respectively. Trend, risk factor, and contour mapping analyses demonstrated that ZIKV seroprevalence increased nonlinearly with age and that body surface area was statistically associated with increasing seroprevalence in children. ZIKV seropositivity was higher in females than in males across almost all ages, with adjusted prevalence ratios in children and adults of 1.11 (95% CI: 1.02-1.21) and 1.14 (95% CI: 1.01-1.28), respectively. No household-level risk factors were statistically significant in multivariate analyses. A spatial analysis revealed a 10-15% difference in the risk of ZIKV infections across our 3-km-wide study site, suggesting that ZIKV infection risk varies at small spatial scales. To our knowledge, this is the largest ZIKV seroprevalence study reported in the Americas, and the only one in Central America and in children to date. It reveals a high level of immunity against ZIKV in Managua as a result of the 2016 epidemic, making a second large Zika epidemic unlikely in the near future.

Keywords: Zika virus; cohort; risk factor; seroprevalence; spatial analysis.

Fig. 1.

Flowchart of study design and sample size of the participating pediatric, household, and adult groups in Managua, Nicaragua, 2017. The PDCS and the HICS participants reside in the catchment area of the HCSFV in District II of Managua, Nicaragua. For both cohort studies, a routine blood sample was collected from healthy participants between February and July of 2017. The pediatric group (2–14 y old) consisted of the PDCS annual samples (n = 3,740). HICS participants were split into (a) the full HICS cohort (2–80 y old), referred to as the household group, to conduct analyses across the full spectrum of age within a single population (n = 2,147) defined by membership in 433 households and (b) an adult-only subset consisting of HICS participants aged 15–80, referred to as the adult group (n = 1,074), to complement analyses of the pediatric group. Of the latter, 125 children are enrolled only in the HICS cohort, while 948 children are in the PDCS. HH, households.

Fig. 2.

Overall and sex-specific ZIKV seroprevalence trend lines by age. ZIKV seroprevalence was graphed based on GAM trend curves, with 95% confidence bands estimated from cluster bootstrapping 10,000 at the household level for the pediatric (A and B), adult (C and D), and household (E and F) groups. Overall (pink) as well as sex-specific (blue and purple) trend lines are presented.

Fig. 3.

Three-dimensional sex-specific contour maps (a.k.a. risk surfaces) for ZIKV seroprevalence as a function of estimated BSA and age. The underlying GAM was adjusted for an SES proxy, hours without water, and location of the water faucet. Combinations of age and BSA that synergistically increased or decreased the conditional probability of ZIKV infection would appear as quadratic peaks or troughs on the 3D risk surface, respectively. No such quadratic peaks were observed in any population. The contour maps for females and males in the pediatric group were nearly planar (A and B). In the household group, ZIKV seroprevalence increased linearly with BSA for both females and males, conditional on age (C and D).

Fig. 4.

Map of neighborhood-specific ZIKV seroprevalence estimates for the pediatric and adult groups. The ZIKV seroprevalence estimates for each neighborhood were mapped for the pediatric group (A) and the adult group (B). The shade of each neighborhood corresponds to its ZIKV seroprevalence (darker shading corresponding to higher seroprevalence). Neighborhoods shaded in gray represent those in which the point estimate may be statistically inconsistent as a result of a low sample size. The red cross signifies the location of the HCSFV.