Cryptic Zika virus infections unmasked from suspected malaria cases in Northeastern Nigeria

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Abstract
Introduction: Although environmental and human behavioral factors in countries with Zika virus (ZIKV) outbreaks are also common in Nigeria, such an outbreak has not yet been reported probably due to misdiagnosis. The atypical symptoms of malaria and ZIKV infections at the initial phase could leverage their misdiagnosis. This study randomly recruited 496 malaria-suspected patients who visited selected health institutions in Adamawa, Bauchi, and Borno states for malaria tests. These patients’ sera were analyzed for ZIKV antibodies using ELISA and plaque reduction neutralization tests (PRNT) at 90% endpoint. About 13.8% of Zika virus-neutralizing antibodies (nAb) did not cross-react with dengue, yellow fever, and West Nile viruses suggesting possible monotypic infections. However, 86% of the sera with ZIKV nAb also neutralized other related viruses at varied degrees: dengue viruses (60.7%), West Nile viruses (23.2%), yellow fever virus (7.1%) and 39.3% were co-infections with chikungunya viruses. Notably, the cross-reactions could also reflect co-infections as these viruses are also endemic in the country. The serum dilution that neutralized 90–100% ZIKV infectivity ranged from 1:8 to 1:128. Also, our findings suggest distinct protection against the ZIKV between different collection sites studied. As indicated by nAb, acute ZIKV infection was detected in 1.7% of IgM-positive patients while past infections occurred in 8.5% of IgM-negatives in the three states. In Borno State, 9.4% of IgG neutralized ZIKV denoting past infections while 13.5% were non-neutralizing IgM and IgG indicating other related virus infections. The age, gender, and occupation of the patients and ZIKV nAb were not significantly different. ZIKV nAb from samples collected within 1–7 days after the onset of symptoms was not significantly different from those of 7–10 days. A wider interval with the same techniques in this study may probably give better diagnostic outcomes. ZIKV nAb was significantly distinct among recipients and non-recipients of antibiotic/antimalaria treatments before seeking malaria tests. The inhibiting effect of these drugs on ZIKV infection progression may probably contribute to the absence of neurological disorders associated with the virus despite being endemic in the environment for several decades. Also, protection against ZIKV as marked by the nAb was different among the vaccinated and unvaccinated YF vaccine recipients. Thus, the YF vaccine may be a good alternative to the Zika vaccine in resource-constrained countries. Conclusion: The cryptic ZIKV infections underscore the need for differential diagnosis of malaria-suspected febrile patients for arboviruses, especially the Zika virus. The absence of systemic surveillance for the virus is worrisome because of its association with neurological disorders in newborns. Co-infections with other arboviruses may impact adversely on the management of these diseases individually.
Funding Information
  • International Center for Genetic Engineering and Biotechnology (CRP/16/010, Reference No. CRP/NGA 16-03)

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