Clinical Manifestations Associated With RT‐PCR–Confirmed Zika Virus Infection Among Adults With Acute Rash in the Brazilian Amazon: A Cross‐Sectional Study

Abstract

Zika virus (ZIKV) infection remains a diagnostic challenge in regions where multiple arboviruses co‐circulate, particularly when laboratory testing is limited. Identifying distinguishing clinical features is therefore relevant for early case recognition. We conducted a cross‐sectional study including 1124 adults presenting with acute exanthema at a reference center in the Brazilian Amazon (2017–2022). Clinical features were assessed at the initial consultation. Diagnostic performance measures, including sensitivity, specificity, positive and negative predictive values, and accuracy, were calculated using RT‐qPCR as the reference standard. A multivariable logistic regression model including clinical, demographic, and hematological variables was constructed, and its diagnostic performance was assessed using ROC curve analysis. Among participants, 319 (28.4%) had RT‐qPCR–confirmed ZIKV infection. Pruritus (94%) and conjunctivitis (73%) were more frequent among individuals with confirmed infection. Lymphadenopathy showed the highest positive predictive value (90.9%), while pruritus had the highest negative predictive value (95.9%). Conjunctivitis demonstrated the highest diagnostic accuracy (73.3%). The multivariable model showed high apparent discrimination in the analyzed dataset (AUC = 0.94; 95% CI: 0.90–0.98), although this estimate should be interpreted cautiously because the model was not validated. Pruritus and conjunctivitis were the manifestations most consistently associated with RT‐qPCR–confirmed ZIKV infection and may support syndromic clinical suspicion in settings with limited laboratory capacity, although they do not replace laboratory confirmation. Other clinical features, including edema and arthralgia, were common but did not retain independent associations after adjustment.