Seroprevalence of anti-Lassa Virus IgG antibodies in three districts of Sierra Leone: A cross-sectional, population-based study

Abstract

Background: Lassa virus (LASV), the cause of the acute viral hemorrhagic illness Lassa fever (LF), is endemic in West Africa. Infections in humans occur mainly after exposure to infected excrement or urine of the rodent-host, Mastomys natalensis. The prevalence of exposure to LASV in Sierra Leone is crudely estimated and largely unknown. This cross-sectional study aimed to establish a baseline point seroprevalence of IgG antibodies to LASV in three administrative districts of Sierra Leone and identify potential risk factors for seropositivity and LASV exposure.

Methodology and principal findings: Between 2015 and 2018, over 10,642 participants from Kenema, Tonkolili, and Port Loko Districts were enrolled in this cross-sectional study. Previous LASV and LF epidemiological studies support classification of these districts as "endemic," "emerging," and "non-endemic", respectively. Dried blood spot samples were tested for LASV antibodies by ELISA to determine the seropositivity of participants, indicating previous exposure to LASV. Surveys were administered to each participant to assess demographic and environmental factors associated with a higher risk of exposure to LASV. Overall seroprevalence for antibodies to LASV was 16.0%. In Kenema, Port Loko, and Tonkolili Districts, seroprevalences were 20.1%, 14.1%, and 10.6%, respectively. In a multivariate analysis, individuals were more likely to be LASV seropositive if they were living in Kenema District, regardless of sex, age, or occupation. Environmental factors contributed to an increased risk of LASV exposure, including poor housing construction and proximity to bushland, forested areas, and refuse.

Conclusions and significance: In this study we determine a baseline LASV seroprevalence in three districts which will inform future epidemiological, ecological, and clinical studies on LF and the LASV in Sierra Leone. The heterogeneity of the distribution of LASV and LF over both space, and time, can make the design of efficacy trials and intervention programs difficult. Having more studies on the prevalence of LASV and identifying potential hyper-endemic areas will greatly increase the awareness of LF and improve targeted control programs related to LASV.

Fig 1. Sampling method, participant selection, and district locations.

(A). Process for randomized 2-stage cluster sampling method for participant selection. (B) Map of districts visited and included in recruitment and enrollment in Sierra Leone. Base-layer map provided by Esri, OpenStreetMap contributors, HERE, Garmin, FAO, NOAA, USGS openstreetmap.org and https://cdn.arcgis.com/sharing/rest/content/items/291da5eab3a0412593b66d384379f89f/resources/styles/root.json.

Fig 2. Distribution of LASV IgG Seroprevalence in Sierra Leone.

(A) Mean LASV IgG seroprevalence over all three districts, stratified by village*; (B) Proportion of households with >1 LASV IgG seropositive individual by village and mean LASV IgG seroprevalence stratified by chiefdom in the endemic district (Kenema District); (C) Proportion of households with >1 LASV IgG seropositive individual by village and mean LASV IgG seroprevalence stratified by chiefdom in the emerging district (Tonkolili District); (D) Proportion of households with >1 LASV IgG seropositive individual by village and mean LASV IgG seroprevalence stratified by chiefdom in the non-endemic district (Port Loko District). Base-layer map provided by Esri, OpenStreetMap contributors, HERE, Garmin, FAO, NOAA, USGS openstreetmap.org and https://cdn.arcgis.com/sharing/rest/content/items/291da5eab3a0412593b66d384379f89f/resources/styles/root.json. *Some villages on the map are geographically close to one another. The number of villages over 20% seroprevalence can also be found in Table A in S1 Text for further reference.

Fig 3. Variables of interest (y-axis) and their odds ratio values (x-axis).

(A) Overall pairwise comparisons of LASV IgG seropositivity of individuals; (B) Comparing LASV IgG seropositivity of individuals in Kenema District with those in Tonkolili District; (C) Comparing LASV IgG seropositivity of individuals in Kenema District with those in Port Loko District; (D) Comparing LASV IgG seropositivity of individuals in Tonkolili District with those in Port Loko District.

Fig 4. LASV %IgG Seropositivity of individuals by age category.

Categories presented in 10-year age groups. A join-point regression analysis revealed no significant trend in the data. The sample size for each age group category is listed above each bar (n =).

Fig 5. Percentage of households’ proximity to environmental factors, comparing household level LASV IgG seroprevalence (n = 903).

The distance of the household to the bushes or wild land, the garbage pits or refuse pile for the household, the household’s main water source, the household’s main toilet facility, and the household’s farmland or cultivated vegetation was measured in meters by a LFOT fieldworker. Each household was categorized by the percentage of their seroprevalence. Households with more than 50% seroprevalence were categorized as high. Households with 25–50% were moderate and households less than 25% were low. The likelihood of a household having greater than 50% seroprevalence was determined in a multivariate analysis.