Symptomatic Zika Virus Infection in Infants, Children, and Adolescents Living in Puerto Rico

Abstract

IMPORTANCE Little information is available regarding Zika virus (ZIKV) infection in children. OBJECTIVE To describe patients younger than 18 years who were infected with ZIKV and were enrolled in the Sentinel Enhanced Dengue and Acute Febrile Illness Surveillance System (SEDSS). DESIGN, SETTING, AND PARTICIPANTS Children infected with ZIKV with 7 or fewer days of fever or emancipated minors aged 14 to 17 years with a generalized maculopapular rash, arthritis or arthralgia, or nonpurulent conjunctivitis were eligible for enrollment on or before December 31, 2016, in Puerto Rico. Patients were evaluated using ZIKV polymerase chain reaction testing at 7 or fewer days after the onset of symptoms. Available ZIKV polymerase chain reaction-positive specimens were evaluated to determine viral loads. EXPOSURES Confirmed polymerase chain reaction-positive ZIKV infection. MAIN OUTCOMES AND MEASURES Clinical characteristics and viral loads of symptomatic children with confirmed ZIKV infection. RESULTS Of 7191 children enrolled in SEDSS on or before December 31, 2016, only those with confirmed ZIKV infection (351 participants) were included in this study. Participants who had confirmed ZIKV infection included 25 infants (7.1%), 69 children (19.7%) aged 1 to 4 years, 95 (27.1%) aged 5 to 9 years, and 162 (46.1%) aged 10 to 17 years. Among these, 260 patients (74.1%) presented for evaluation of ZIKV infection at fewer than 3 days after the onset of symptoms, 340 (96.9%) were discharged to home after evaluation, and 349 (99.4%) had fever, 280 (79.8%) had a rash, 243 (69.2%) had facial or neck erythema, 234 (66.7%) had fatigue, 223 (63.5%) had headache, 212 (60.4%) had chills, 206 (58.7%) had pruritus, and 204 (58.1%) had conjunctival hyperemia. Of 480 specimens collected (317 serum and 163 urine specimens) from 349 children, the median number of days after the onset of symptoms was lower for children who had serum specimens (1 day [interquartile range (IQR), 1-2 days]) than for children who had urine specimens (2 [1-3] days) (P < .001). Of 131 children who had both serum and urine specimens collected on the same day, the median viral load was higher in serum than in urine (median [IQR], 23 098 [8784-88 242] copies/mL for serum vs 9966 [2815-52 774] copies/mL for urine; P = .02). When a single serum sample from each of 317 patients was analyzed, there were no statistically significant differences in median viral loads according to age, sex, or disposition. However, the median serum viral load varied significantly according to the number of days after the onset of symptoms (0 days, 106 778 [IQR, 9772-1 571 718] copies/mL; 1 day, 46 299 [10 663-255 030] copies/mL; 2 days, 20 678 [8763-42 458] copies/mL; and Ն3 days, 15 901 [5135-49 248] copies/mL; P = .001). CONCLUSIONS AND RELEVANCE This study represents the largest study to date of ZIKV infection in the pediatric population. Most children infected with ZIKV had fever, rash, and conjunctival hyperemia. The children usually presented for evaluation at fewer than 3 days after the on...

Age-dependent manifestations and case definitions of paediatric Zika: a prospective cohort study

“…12,13 Because Zika manifests differentially across childhood, and standard case definitions include clinical findings rarely observed in our large paediatric population, symptomatic ZIKV infection could manifest differently across the lifespan. This hypothesis is supported by the age-varying prevalence of various Zika clinical findings, observed in comparisons of younger children with older children (in our study and others) 8,9 and in comparisons of children with adults. 9 A comparison of Zika clinical findings in paediatric and general population studies provides further evidence in support of this hypothesis (appendix pp 28-30).…”

“…The increasing prevalence of arthralgia, rash, and fever across paediatric age has been previously noted. 8,9 The WHO and PAHO case definitions are likely based on adult data, as mostly adult data from Yap Island 26 and French Polynesia 27 were available when the case definitions were created 1 and updated. 12,13 Because Zika manifests differentially across childhood, and standard case definitions include clinical findings rarely observed in our large paediatric population, symptomatic ZIKV infection could manifest differently across the lifespan.…”

“…Most of what is known about Zika derives from adult studies. Clinical studies of paediatric Zika are relatively scarce and feature modest sample sizes, [6][7][8][9][10] precluding a full understanding of the disease in children. Using the largest clinical dataset of laboratory-confirmed paediatric Zika cases to date, 11 this study characterises the acute clinical profile of Zika and assesses the diagnostic performance of the WHO 12 and PAHO 13 case definitions in children.…”

Presence of Flavivirus Antibodies Does Not Lead to a Greater Number of Symptoms in a Small Cohort of Canadian Travelers Infected with Zika Virus

“…As noted in Table 1, the mean time between symptom onset and sample collection was similar for both groups. This was important as it is known that ZIKV viremia decreases over the course of disease [20,21]. Viremia was determined in each group using the Altona ZIKV PCR assay [16], and as shown in Figure 1, Ct values (35.87 vs. 35.14, p = 0.2050) and PFU equivalents (p = 0.11) were similar between both groups.…”

Maternal antibodies provide partial protection from postnatal Zika viremia in nonhuman primates

“…It’s not entirely clear what fraction of pregnant women that become infected with ZIKV during pregnancy transmit the virus to their developing fetus but consequences to the fetus can range from mild to severe. Additionally, nonhuman primate studies suggest that infants may remain susceptible to ZIKV induced disease even if infected after birth [32], but the frequency and disease severity postnatal ZIKV infections in human infants remains to be fully examined [37, 38].…”