Short Clinical and laboratory profiles of children with severe chikungunya infection

Introduction: Chikungunya infection presents with distinct clinical features depending on the patient age group. Methods: Medical records of children with positive IgM for the chikungunya virus who were hospitalized in a pediatric ward in Fortaleza, Ceará, Brazil were analyzed. Results: Fourteen children with a median age of 4 months (36 days to 15 years) were included. All patients presented with fever persisting for an average of 5 days. The joints were involved in 6 (42.8%) children, and 8 (57.1%) children presented with bullous rash. Conclusions: Systemic involvement and atypical clinical manifestations characterize severe forms of chikungunya infection in children.

Chikungunya fever is an infectious disease caused by the chikungunya arbovirus (CHIKV) and transmitted to humans through insect bites of Aedes mosquitoes (Aedes aegypti and A. albopictus). CHIKV belongs to the genus alphavirus and the family Togaviridae. The acute phase of the disease is characterized by the sudden onset of high fever and polyarthralgia accompanied by skin rash, headache, and fatigue 1 .
The first autochthonous cases were reported in Brazil in the Northern state of Amapá in 2014. Almost at the same time, other autochthonous cases were reported in the state of Bahia in Northeastern Brazil, and the disease rapidly spread to other Northeastern states 2 . By 2017, a total of 185,854 suspected cases of CHIKV had been reported by epidemiological week (EW) 52 in Brazil, with an incidence of 90.1 cases/100 thousand inhabitants 3 . The state of Ceará (Northeastern Brazil) had the highest number of notifications of CHIKV infections in 2017. In EW 45, 138,836 suspected cases were reported, of which 104,880 (75.5%) were confirmed cases 4 .
Most descriptions of CHIKV infection are based on data obtained in adults during epidemic outbreaks. Uncommon clinical features of chikungunya fever were observed particularly in the elderly and in patients with underlying comorbidities during a CHIKV outbreak in Polynesia 5 . Studies evaluating the clinical and laboratory manifestations of severe CHIKV infection in the pediatric population are limited. Therefore, this study aimed to describe and characterize the clinical and laboratory profiles of children hospitalized with severe acute CHIKV infection in a referral hospital for infectious diseases in the state of Ceará, Brazil. This is a case series report analyzing the medical records of children with chikungunya fever admitted to the pediatric ward of the Hospital São José de Doenças Infecciosas (HSJ) in Fortaleza, Ceará state, Brazil. All patients aged <16 years with positive IgM for CHIKV that were hospitalized between May 2016 and April 2017 were included. Clinical and laboratory data   were obtained from medical records. Serological tests were reviewed using the Laboratorial Environment Manager System of the Central Laboratory (LACEN) of the state of Ceará. Data was collected according to a standardized method and included epidemiological, clinical (symptoms and physical examination findings), and laboratory variables, as well as diagnostic test results and outcomes. The study was approved by the Research Ethics Committee of HSJ (Protocol number: 2.405.527).
Fourteen children were included in the study, with a gender distribution of 1:1. The mean age was 4.6 years, with a standard deviation (SD) of 6.6 years and a median of 4 months. The youngest age was 1 month and 6 days and the oldest was 15 years ( Table 1). All children presented with fever persisting for an average of 5 days (SD: 3 days). Rash was present in 13 cases (92,8%). Cutaneous lesions varied from maculopapular to vesicular-bullous exanthema (Figure 1). Eight children (57.1%) developed vesicular-bullous exanthema, with 7 of these patients aged <1 year. Exanthema were predominantly distributed across the lower and upper limbs and less frequently across the thorax and abdomen.
Six children (42.8%) showed joint involvement as arthralgia in the acute phase, with polyarthralgia involving knees, ankles, wrists, elbows, and hips observed in 4 of these patients. Joint edema was In terms of laboratory findings, hemoglobin levels below the reference values (RV, 11.5 g/dL) were detected in 10 (71.4%) children. According to the leukogram, 5 children (35.7%) had leukopenia, which was accompanied by leukocytosis in 1 child (7.1%) and by lymphopenia in another child (7.1%). Eight children (57.1%) presented with thrombocytopenia (RV: <150,000/mm³), with a mean thrombocyte count of 125,553/ mm³ (SD: 36,337/mm³). Analysis of hepatic enzymes revealed that 11 patients (78.5%) had aspartate aminotransferase levels above the reference limit (mean: 160 U/L, SD: 71.9 U/L, RV: 0-50 U/L) and alanine aminotransferase levels were elevated in 5 patients (35.7%, mean: 158 U/L, SD: 121.7 U/L, RV: 0-50 U/L, Table 2). Cerebrospinal analysis was only performed in 2 children, showing increased cellularity and neutrophil predominance in both cases. Results of the other tests were within the normal range. The average length of stay in the hospital was 5 days and all 14 patients were discharged.
The present study describes clinical and laboratory characteristics of pediatric patients with CHIKV infection who were hospitalized due to a severe clinical presentation of the disease. The most common clinical manifestations were fever and skin rash, followed by arthralgia, myalgia, headache, vomiting, and abdominal pain.
Laboratory analyses revealed an altered liver function in CHIKV-infected patients, suggesting a hepatic involvement of the virus in this age group. The number of patients with anemia was also significant, which is consistent with previous studies 7, 10 . There were no fatalities in our study in contrast to previous studies reporting similar cases 10,11 .
The limitations of the present study should be acknowledged. For once, this was a retrospective study conducted by secondary analysis of data from a relatively small sample. Nonetheless, studies on pediatric cases of severe chikungunya fever resulting in hospitalization are limited. In contrast to other studies 7 , differences between infants and adolescents were not determined in our study, which could be relevant because a study in India showed distinct clinical manifestations in infants and older children 8 .
Despite these limitations, this study provides relevant data pertaining to CHIKV infection. The results demonstrate the possibility of systemic involvement of CHIKV in the pediatric 4/4 population. Studies with a larger sample size involving different populations are needed to further characterize the more severe forms and atypical manifestations of CHIKV infection in children.