Exhaustive TORCH Pathogen Diagnostics Corroborate Zika Virus Etiology of Congenital Malformations in Northeastern Brazil

Abstract

The Latin American Zika virus (ZIKV) outbreak had a major impact on reproductive health worldwide. The reasons for the massively increased reports of neonatal microcephaly in northeastern Brazil are still unclear. Beyond the technical limitations of laboratory diagnostics, unambiguous diagnosis of ZIKV as the cause of congenital malformations is hampered by similar clinical pictures elicited by other pathogens known as TORCH pathogens. We performed a case-control study comparing mothers of children with congenital malformations to age-matched controls from Salvador, Brazil, one of the areas most extensively affected by the ZIKV outbreak. The ZIKV and Chikungunya virus seroprevalence rates differed significantly, whereas the levels of maternal exposure to TORCH pathogens were similar between cases and controls. Our data support a link between maternal ZIKV infection and congenital malformations and suggest the occurrence of predominantly vector-borne ZIKV transmission in these cases. In addition, some highly prevalent TORCH pathogens may be misinterpreted as representative of ongoing ZIKV activity in the absence of exhaustive diagnostics in northeastern Brazil.

Leveraging multiple data types to estimate the size of the Zika epidemic in the Americas

“…However, that analysis also estimated the IAR for each location included in their study and estimated lower IARs for Bahia, Brazil (0.02), Salvador, Brazil (0.08), Colombia (0.09), El Salvador (0.15), and Honduras (0.04) than our model. Their IAR estimates for Bahia State and Salvador in Brazil were also much lower than seroprevalence estimates from three studies [17,25,26] that more closely matched our IAR estimates for Bahia State. Underestimating the number of ZIKV infections would lead to an overestimate of GBS incidence per infection.…”

“…One potential reason for the discrepancy between our IAR estimates and serosurvey-based estimates is a mismatch in the spatial scale of the region that the IAR estimate covers. For example, our estimate for the Brazilian state of Bahia (0.514; 95% CrI: 0.388-0.631), was slightly lower than the seroprevalence estimates of 0.63 (95% CI: 0.595-0.671),0.68 (95% CI: 0.600-0.744), and 0.73 (95% CI: 0.70-0.76) from Salvador, the largest city in Bahia [17,25,26]. However, the overall IAR in Bahia might be lower than the IAR in Salvador if rural areas outside of Salvador experienced a lower infection attack rate.…”

“…Estimates of ZIKV infections from blood donors in Puerto Rico through 2016 suggest that almost 470,000 people might have been infected in Puerto Rico alone [23]. High ZIKV seroprevalence estimates from several major cities with populations of more than one million-46% in Managua, Nicaragua [24], 63-68% in Salvador, Brazil [25,26], and 64% in Recife, Brazil [27]-also suggest that the 806,928 suspected and confirmed cases reported by PAHO represent only a small fraction of the total number of ZIKV infections.…”

Descriptive study of suspected congenital Zika syndrome cases during the 2015-2016 epidemic in Brazil

“…Only one child in this study had a laboratory confirmation of a ZIKV infection using an enzymelinked immunosorbent assay (ELISA) IgM detection. An ELISA test can exhibit a cross reaction with other arboviruses, such as those causing dengue fever and yellow fever; however, the CZS diagnosis in this case was determined by the clinical and epidemiological features 20 . According to their medical records, RT-PCR was performed using the serum of six newborns, and none of the samples tested positive for the viral genome.…”

“…Some of the patients in our study did not present with microcephaly, although encephalic injury was reflected by microcalcifications, lissencephaly, ventriculomegaly, white substance hypodensity, myelination defects, and corpus callosum dysgenesis, which corroborates early reports. It is important to highlight that all these forms of CNS impairment are commonly observed in CZS but are not pathognomonic, and they can be observed in other congenital syndromes 20 . In addition, isolated HC measurement is an ambiguous parameter for determining the presence of microcephaly; other CNS imaging findings associated with craniofacial disproportion should be also considered.…”