Characterizing the endemicity and disease burden of chikungunya virus infections among children in coastal Kenya

Chikungunya fever (CHIKF) is a viral illness of significant public health concern characterised by acute, often chronic, debilitating joint pain and polyarthritis. CHIKF is caused by the mosquito-borne chikungunya virus (CHIKV) that was first discovered in Tanzania in 1952. CHIKV re-emerged in coastal Kenya in 2004 causing the largest CHIKF epidemic on record. The epidemic affected millions of people, with rapid geographic spread to other countries in Africa, India, southeast Asia and Europe. Descriptions of this and other more recent epidemics outside Africa have informed most of what we know about CHIKF. However, very little is known regarding the burden, distribution, risk factors and clinical manifestation of CHIKV infections in Africa especially among the paediatric population. In this DPhil project I aimed to estimate the burden of CHIKF among children in coastal Kenya over a five-year period, 2014-2018. First, this thesis presents a comprehensive review of available literature on CHIKF, CHIKV and epidemiology (Chapter 1) and a report on the methods used (Chapter 2). It then describes a systematic literature review and meta-analysis of data on childhood CHIKV infections published between 1983-2021 (Chapter 3). I show that CHIKF is a significantly under-recognised and underreported health problem among children globally, with infants under 1 year of age being at highest risk of severe disease. To determine the prevalence and incidence of CHIKV infections among children in coastal Kenya, I used RT-PCR to test: i) children presenting with fever at two primary health facilities in Kilifi county (described in Chapter 4), ii) children admitted with neurological illness at the referral Kilifi County Hospital (KCH; Chapter 5), iii) newborns at the KCH maternity ward (Chapter 6). During the five-year study period, I found that CHIKF was endemic in coastal Kenya, associated with 12.7% (95% CI 11.6, 13.8) of all febrile presentations at the primary healthcare facilities, and accounted for 9.2% (95% CI 8.3, 10.2) of children admitted with neurological illness. A community survey of 435 asymptomatic children in the same study location estimated a prevalence of 0.7% (95% CI 0.2, 2.1) asymptomatic CHIKV infections in 2016 (a year when a CHIKF epidemic was reported in the country). CHIKF incidence was highest in young children and infants, implying acquisition of immunity. However, recurrent CHIKF episodes, associated with fever and viraemia, were observed among 19 of 170 children with multiple febrile episodes during the study period, suggesting imperfect immunity. This is the first time that recurrent CHIKV infections have been observed. 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, suggesting that CHIKV may now be the single most important pathogen associated with neurological illness in coastal Kenya. In summary, this thesis reveals that CHIKF is endemic in coastal Kenya, a common cause of acute febrile illness and neurological disease among children. Sub-clinical CHIKF is rare and recurrent infections do occur. Maternal transmission of CHIKV to the neonate occurs in coastal Kenya and should be considered in obstetric and paediatric protocols. Further studies to enhance knowledge on the geographical distribution of CHIKF, transmission dynamics and associated clinical outcomes should help determine the wider public health significance of CHIKF and inform development of effective prevention and control measures.