Ebola virus transmission and disease severity in Sierra Leone 2013-2016

BACKGROUND The 2013-2016 Ebolavirus Disease (EVD) epidemic in West Africa emphasised critical gaps in the knowledge of Ebolavirus, including the age distribution, true burden, transmission dynamics and risk factorsin households. Against this background this research, undertaken during the epidemic, worked with a large cohort of Sierra Leonean survivors and their households to ask: 1. What is the true age distribution of Ebola virus infection and case/infection fatality? 2. To what extent do asymptomatic and unrecognised ‘mild’ Ebola virus infections exist? 3. What impact do age, type of exposure and other factors have on risk of contracting and dying from Ebola infection? 4. What characterises transmission in households and what is the extent of household secondary transmission? METHODS The study population were survivors discharged from Kerrytown Ebola Treatment Centre, Sierra Leone between November 2014 and March 2015 and their households. Semi-structured household interviews and a novel exposure hierarchy were used to obtain detailed information on individual and household-level risk factors, exposures, transmission and outcomes, and uncover unnotified cases and deaths. A new IgG immunoassay using non-invasive oral fluid samples was used to detect unreported infection: sensitivity and specificity of the novel assay was established using PCR-confirmed survivor samples and community controls. Risk of EVD was calculated by age, sex and exposure level. adjusted for confounding and clustering, and relative risks estimated using logistic regression. Likely transmissions chains were constructed from the detailed exposure narratives and household secondary attack rates were estimated: negative binomial regression was used to assess the determinants of intrahousehold spread. All survivors were followed-up 6-13 months after discharge and verbal autopsy of subsequent deaths conducted to assess the frequency of fatal recrudescence and ‘late’ deaths related to EVD. RESULTS The study involved 933 people, including 168 survivors and 238 deaths, from 94 households, and 339 community controls. Risk of ebolavirus infection was strongly correlated with exposure and with age, with the lowest risk in children aged 5 to 19, even after adjustment for exposure. There was no consistent trend between case fatality rate and increasing exposure. Based on complete follow-up of all survivors over a mean 10 months post-discharge, the first estimates of frequency of viral recrudescence (0.7%) and of ‘late’ deaths (those associated with EVD occurring after discharge, 2.6%) were established. The oral fluid assay was found to be highly sensitive (95.9%) and specific (100%), well-accepted by participants. It showed that 2.6% of asymptomatic household members had been infected, as were 12.0% of household members who recalled experiencing any symptoms but who were not investigated or diagnosed. The estimated household attack rate was 28% and the household secondary attack rate 18%, giving a reproductive number (R) of 1.2. Larger household size, cases aged over 45 years, and cases with more severe disease were important drivers of household transmission. CONCLUSION The extent of undiagnosed symptomatic (and potentially infectious) cases represent a substantial risk to epidemic control and indicate the needed to improve diagnosis. The relatively low household secondary attack rate and R, plus the finding that only one third of cases caused onward transmission suggest it should be possible to curtail spread faster with interventions which empower households to prevent transmission Immunological research is needed to identify what protects young children and teenagers from infection – information which may assist development of vaccine and therapeutics.