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Cycle 1

Principal Investigator: Donald Grant, Kenema Government Hospital (KGH)
NIH-Supported Collaborator: Robert Garry, Tulane University School of Medicine 
Title of NIH Award: Preclinical Development of Recombinant Antigen Diagnostics for Lassa Fever
Project Dates: October 2013 - October 2017

Project Overview:

Eastern Sierra Leone, particularly the Kenema District, has the highest incidence of Lassa Fever, a severe and often fatal viral hemorrhagic disease transmitted by the rodent Mastomys natalensis, in the world. The rodents are commonly found in homes and transmission occurs from contact with the rodents. Lassa Fever (LF) disproportionately impacts pregnant women and children. Case fatality rates for LF can reach 70% in children under age 5 and 90% in third trimester pregnancies for both the mother and the fetus. The prevalence and true impact of LF is not well understood.This study will address key gaps in knowledge of the epidemiology and natural history of Lassa fever. The goals of the study are to: 1) characterize and contrast the age and sex distribution of Lassa virus (LASV) exposure in endemic and non-endemic areas and 2) elucidate risk factors for LASV infection in pregnant women and children. The target population will consist of the entire Eastern Province of Sierra Leone and women and children in the Kenema District of Sierra Leone. The age and sex distribution of LASV exposure will be determined in a point prevalence study comparing endemic and non-endemic areas. This project will also elucidate risk factors for LASV infection in a case-control study of pregnant women and children, which will identify points in LF transmission. The proposed study will employ field epidemiology, hospital-based surveillance, and advanced laboratory techniques. These efforts will provide informed approaches for treating and controlling LF that can guide evidence-based investments for public health programming and policy.
 PH 1-17 Sierra Leone photo 2 PH 1-17 Sierra Leone photo 1
 Traveling to remote communities.  Engaging the community school children. (photo courtesy of PI Donald Grant)
Overall Project Outcomes and Activities:

This project addressed transmission and treatment of LF. The focus was on children and pregnant women who are impacted more severely by LF than any other group. Through determination of the age and sex distribution of LASV exposure we expect to be able to elucidate of risk factors for LASV infection we will identify points for interventions to effectively prevent LASV infection.

The team carried out a point prevalence study in a group of 50 communities that differ according to exposure to LASV. These communities will consist of 20 endemic villages (from Kenema District), 15 emerging villages (from Tonkolili District), and 15 non-endemic villages (from Port Loko District). Over 11,000 samples from 20+ houises per village distributed among 5 age groups have been collected from these villages. Dried blood spots were used to perform Lassa-specific IgG by ELISA for the detection of past LASV exposure. This effort is ongoing with an interim analysis.

Multiple variables (qualitative and quantitative) will be collected in the questionnaire administered to cases and controls. In addition, the level of rodent infestation in case and control houses will be a key outcome. These variables will be the outcome(s) of interest and will compare cases (exposed) and controls (unexposed) using odds ratios. GPS data for each house in each village has also been collected. An interim analysis of Lassa seroprevalence has been completed for Kenema District. The seroprevalence ranges from 10 to 62%.

The team also performed an interim analysis of Lassa seroprevalence by age in Kenema District. In moderate to high prevalence villages Lassa fever seroprevalence increases with age. There is an increase in incidence in preteens and another increase in young adults. In these villages adults >45 years of age have the high or the highest seroprevalence. Villages with a lower seroprevalence show a distinct pattern with lower seroprevalence in older adults. The team performed an interim analysis of Lassa seroprevalence by sex in Kenema District. With the exception of one village Meleh, there was no significant difference in Lassa seroprevalence by sex.

Electronic databases with coded patient diagnostic designations and demographic, clinical, and laboratory data are being finalized using Microsoft Access. The databases contain demographic and clinical data, and laboratory findings. Manual curation of the databases is also in process, with each entry in the electronic databases cross-checked and confirmed to be consistent with the original clinical and laboratory records. Data linkage is performed using the SAS System (version 9.1; SAS Institute, Cary, NC) and an algorithm has been written to link and query from all of the available data sources.

The data set generated is being carefully and thoroughly integrated with the wealth of clinical data that will be obtained on each patient throughout their stay in the KGH Lassa Ward. Efficient analysis, transfer, integration, monitoring, and quality control of data collected will be essential to the success of the study. The datasets generated are large and we are committed to rigorous statistical analyses which are ongoing.

Overall, Kenema District has long been considered to have the world’s highest LF incidence rate and is an established hotspot for carrying out surveillance and LF-related research. Many districts to the north and west of Kenema are believed to have limited LASV circulation, but it is unknown if this is a consequence of limited efforts for detecting the virus, inability of clinical staff to recognize the disease, or if there is truly no virus circulating in the area. This seroprevalence study suggests that LF incidence may be underestimated in certain historically non-endemic areas. This study also uncovered the age and gender distributions of LF in these areas. Further analysis of data will determine if the age and gender distributions of LASV exposure differ between endemic and non-endemic areas and the team plans to finish this analysis over the next six months. This data will inform Lassa fever vaccine clinical trials conducted by our partners in the VHFC as well as new efforts by CEPI.

Health Cycle 1 Recipients