Incidence of chikungunya virus infections among Kenyan children with neurological disease, 2014–2018: A cohort study

Abstract

Background Neurological complications due to chikungunya virus (CHIKV) infection have been described in different parts of the world, with children being disproportionately affected. However, the burden of CHIKV-associated neurological disease in Africa is currently unknown and given the lack of diagnostic facilities in routine care it is possible that CHIKV is an unrecognized etiology among children with encephalitis or other neurological illness. Methods and findings We estimated the incidence of CHIKV infection among children hospitalized with neurological disease in Kilifi County, coastal Kenya. We used reverse transcriptase polymerase chain reaction (RT-PCR) to systematically test for CHIKV in cerebrospinal fluid (CSF) samples from children aged <16 years hospitalized with symptoms of neurological disease at Kilifi County Hospital between January 2014 and December 2018. Clinical records were linked to the Kilifi Health and Demographic Surveillance System and population incidence rates of CHIKV infection estimated. There were 18,341 pediatric admissions for any reason during the 5-year study period, of which 4,332 (24%) had CSF collected. The most common clinical reasons for CSF collection were impaired consciousness, seizures, and coma (47%, 22%, and 21% of all collections, respectively). After acute investigations done for immediate clinical care, CSF samples were available for 3,980 admissions, of which 367 (9.2%) were CHIKV RT-PCR positive. Case fatality among CHIKV-positive children was 1.4% (95% CI 0.4, 3.2). The annual incidence of CHIKV-associated neurological disease varied between 13 to 58 episodes per 100,000 person-years among all children <16 years old. Among children aged <5 years, the incidence of CHIKV-associated neurological disease was 77 per 100,000 person-years, compared with 20 per 100,000 for cerebral malaria and 7 per 100,000 for bacterial meningitis during the study period. Because of incomplete case ascertainment due to children not presenting to hospital, or not having CSF collected, these are likely minimum estimates. Study limitations include reliance on hospital-based surveillance and limited CSF sampling in children in coma or other contraindications to lumbar puncture, both of which lead to under-ascertainment of incidence and of case fatality. Conclusions In this study, we observed that CHIKV infections are relatively more common than cerebral malaria and bacterial meningitis among children hospitalized with neurological disease in coastal Kenya. Given the wide distribution of CHIKV mosquito vectors, studies to determine the geographic extent of CHIKV-associated neurological disease in Africa are essential.

Detection of acute dengue virus infection, with and without concurrent malaria infection, in a cohort of febrile children in Kenya, 2014–2019, by clinicians or machine learning algorithms

“…Thus, without laboratory testing, passive clinical reporting of DENV infection is not a reliable means for public health surveillance for this re-emerging infection. A similar study to ours uncovered a large burden of chikungunya virus infection among Kenyan children [ 29 ]. The high prevalence and force of infection of malaria, in combination with lack of routine surveillance for arboviruses such as DENV or chikungunya virus, contribute towards under-recognition of alternate or concomitant causes for AFI and over-diagnosis of malaria [ 30 ].…”

Characteristics of acute chikungunya virus infection in children: an epidemiological study in the Department of Caaguazú, Paraguay

“…We found that school-age stage accounts for a disproportionately large number of cases. The school-age stage has been identified as a demographic group of great significance in contributing to a higher incidence of CHIKV cases, as reported in several studies [21][22][23][24] . These studies have demonstrated a negative correlation between age and the incidence of CHIKV infection, suggesting that the school-age population may be particularly vulnerable to CHIKV.…”

Pathophysiology of chikungunya virus infection associated with fatal outcomes

“…However, since this mutation was identified in both fatal and survival cases, it is unlikely to be responsible for fatal outcomes. Indeed, CNS infection and fatal CHIK do not appear to be restricted to a particular CHIKV lineage and have been reported in patients from several regions affected by different CHIKV lineages, such as Asian, 15 , 59 ECSA, 11 , 12 , 41 and the Indian Ocean lineage. 60 , 61 Nevertheless, the effects of E2-R242 mutation on CHIKV infection should be further investigated.…”

“… 8 , 9 Other complications, such as ophthalmologic, cardiac, and neurological involvement, have also been described in CHIK patients. 1 , 7 , 10 , 11 …”