Zika Virus Disease Comparing Children and Adults in a Dengue-Endemic Setting

Abstract

Acute Zika virus (ZIKV) infection may mimic dengue virus (DENV) infection. We aimed to study the clinical difference of ZIKV disease among suspected non-severe DENV patients comparing children and adults. Patients with acute illness suspected of DENV disease plus no evidence of plasma leakage at the Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand, were enrolled from December 2016 to September 2018. Clinical data including DENV rapid diagnostic test (RDT) results were collected. Zika virus diagnosis was confirmed by real-time reverse transcription PCR on urine. Of 291 (180 pediatric and 111 adult) cases enrolled, 27 (10 pediatric and 17 adult) confirmed ZIKV cases were found. Rash was more frequent among pediatric ZIKV than pediatric non-ZIKV cases (100% versus 60%, P = 0.01). Rash, arthralgia, and conjunctivitis were more frequent among adult ZIKV than adult non-ZIKV cases (100% versus 29.8%, 64.7% versus 26.6%, 52.9% versus 9.7%, all P < 0.01, respectively). The median (interquartile range [IQR]) duration of rash was 4.5 (3.0, 7.25) days and 6.0 (4.5, 7.0) days in pediatric and adults ZIKV cases, respectively. Pediatric ZIKV cases had more fever (100% versus 58.5%, P = 0.03) but less arthralgia (20% versus 64.7%, P = 0.04) and less conjunctivitis (10% versus 52.9%, P = 0.04) than adult ZIKV cases. No ZIKV cases with DENV RDTs performed around day 3 of illness were positive for dengue nonstructural protein 1 (NS1) antigen. In dengue-endemic settings, rash and fever in children, and rash, arthralgia, and conjunctivitis in adults, particularly if rash persists for ≥ 3 days, plus negative dengue NS1 Ag during early febrile phase should prompt ZIKV diagnostic testing.

Serological Differences after Acute Zika Virus Infections between Children and Adults: Implication for Use of a Serological Test

“…The serum samples were collected from a cohort of patients enrolled in a prospective study of ZIKV disease among suspected non-severe DENV cases during December 2016 to September 2018 at the Bamrasnaradura Infectious Diseases Institute, Nonthaburi, Thailand. 11 The patient-enrollment criteria were all children (aged # 15 years) and adults (aged . 15 years) both presenting with acute illness suspected of DENV disease without evidence of plasma leakage (no rising of hematocrit $ 20% over baseline).…”

“…8 Recent studies have also revealed varied clinical features of ZIKV disease according to their age; which pediatric ZIKV cases reported milder symptoms than adult ones. [9][10][11] Hence, most pediatric ZIKV cases were not properly diagnosed under the current World Health Organization's ZIKV case definitions because their symptoms were nonspecific, particularly in young children. 10,11 No clear explanation for this age-dependent clinical features has been documented; and information regarding age-specific serological responses following ZIKV infections has also been lacking.…”

“…[9][10][11] Hence, most pediatric ZIKV cases were not properly diagnosed under the current World Health Organization's ZIKV case definitions because their symptoms were nonspecific, particularly in young children. 10,11 No clear explanation for this age-dependent clinical features has been documented; and information regarding age-specific serological responses following ZIKV infections has also been lacking. To date, controversy still exists regarding whether a previous infection by ZIKV or DENV protects against or enhances a secondary infection by a heterologous flavivirus.…”

Seroprevalence of Zika Virus in Amphawa District, Thailand, after the 2016 Pandemic

“…The majority of ZIKV infections are asymptomatic or mild and self-limiting. Common symptoms include rash, arthralgia, mild fever, conjunctivitis, headache, and myalgia, which are similar to those of Aedes mosquito-borne viral infections, e.g., dengue fever [ 4 , 9 , 10 ]. Thus, clinical assessment alone is insufficient to diagnose ZIKV infection, posing a challenge to the surveillance system.…”