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Background. Pediatric Zika remains an understudied topic. The World Health Organization (WHO) and Pan American Health Organization (PAHO) Zika case definitions have not been assessed in children. We aimed to characterize clinical profiles and evaluate the diagnostic performance of the WHO and PAHO case definitions in a large cohort of pediatric Zika cases. Methods. We prospectively followed a cohort of ~3,700 healthy children aged 2–14 years old in Managua, Nicaragua, from January 2016 to February 2017, encompassing the major 2016 Zika epidemic. We characterized acute clinical findings (signs, symptoms, and complete blood counts) and tested participants with a broad range of clinical profiles suspected of Zika using molecular and serological assays. Findings. We analyzed 556 laboratory-confirmed Zika and 548 non-Zika cases. The WHO and PAHO case definitions captured 176 and 109 confirmed Zika cases, respectively, who presented with the most clinical findings and a dengue-like clinical profile. The remaining sixty percent of Zika cases, principally characterized by undifferentiated fever or afebrile rash, were missed. Among Zika cases, rash (n=440) – particularly generalized erythematous rash (n=334), fever (n=333), leukopenia (n=217), and headache (n=203) were most common and peaked within three days of illness onset. The most common Zika presentation over the first week of illness was rash only (n=80). The sensitivity of Zika case definitions increased across pediatric age (from 11% to 56% for the WHO case definition and from 6% to 37% for the PAHO case definition), as the prevalence of most clinical findings (particularly arthralgia) increased with age, irrespective of prior dengue virus infection. Interpretation. We provide the most thorough description of pediatric Zika to date. Most pediatric Zika cases go undetected under the WHO and PAHO case definitions, suggesting current standards for Zika case ascertainment require revision. Zika manifests with mild but differing clinical profiles across pediatric age, presenting major challenges to diagnosis, surveillance, and efforts to control future Zika epidemics.
TL;DRMost pediatric Zika cases go undetected under the WHO and PAHO case definitions, suggesting current standards for Zika case ascertainment require revision. (Semantic Scholar)