The largest-ever Lassa fever research programme in West Africa

Background

Lassa fever, a zoonotic acute viral haemorrhagic disease caused by the Lassa virus, has persisted as an endemic threat in Western Africa since its discovery in 1969. While most cases are asymptomatic or mild, severe cases require hospitalisation and often result in death due to organ failure. Survivors may suffer from permanent hearing issues, known as sensorineural hearing loss (SNHL). Current primary treatments for patients involve early supportive care (e.g. fluids & pain relief) and the administration of the anti-viral drug ribavirin; however, the effectiveness of the latter remains debated. Therefore, the need persists for a tailored preventive intervention against Lassa fever infection – leading to the pursuit of an effective vaccine.

Leveraging its unique position as a global partnership between public, private, philanthropic, and civil society organisations, CEPI is a driving force behind these collaborative efforts to combat Lassa fever, setting the stage for ongoing vaccine development and epidemiological research. To address knowledge gaps identified by the World Health Organization for informing the design of future Lassa virus vaccine trials and delivery strategies, CEPI launched a prospective multi-site cohort study and research capacity strengthening effort named the “Enable Lassa Research Programme” in 2019.

Enable 1.0

In Enable 1.0 over 23,000 participants were followed up in 2019–2023 to estimate the incidence of Lassa fever infection and disease across five West African countries (Benin, Guinea, Liberia, Nigeria, and Sierra Leone). Preliminary results indicate that Lassa fever baseline seroprevalence — a measure of the proportion of people who have antibodies against Lassa virus at a given time, indicating previous exposure — was around 30%, ranging from 2% in Benin to 48% in Liberia. During the study, 39 cases of symptomatic Lassa fever were observed. The results of this study are soon to be published. Notable successes of the programme include the high retention rates of participants due to active local engagement, the collection of extensive data to inform future work, going beyond Lassa infection and disease incidence, the establishment of valuable regional partnerships, and the building of community trust for vaccine research and development.

Despite the wealth of collected data, persistent gaps in our understanding of the epidemiology of the disease remain. For example, the disease burden in infants remains ill-defined — as under 2s were excluded in Enable 1.0 — and the frequently observed co-infections with malaria and Lassa fever need further examination. Furthermore, mounting evidence of mild or subclinical Lassa fever cases with different disease expressions suggests that some non-febrile Lassa fever disease cases may have been missed by the study, which hinged its case definition on fever lasting for at least 48h. Lastly, we observed in some study sites a lack of appreciation of vaccines and health system hesitancy, posing challenges for future Lassa fever vaccine trials.

Enable 1.5

Aiming to fill knowledge gaps identified in Enable 1.0, CEPI is coordinating the continuation of the study (under Enable 1.5), focusing on Lassa fever at five sites in Liberia, Nigeria (three sites), and Sierra Leone. Focusing on Lassa fever hotspots, the enrolment of eligible participants was swift across the three sites in Nigeria, and has also now concluded in Liberia and Sierra Leone. Some of the contacted households and individuals had been identified during Enable 1.0, while Enable 1.5 recruitment also extended to under-2s. The study will assess the incidence of symptomatic reverse transcription (RT)-polymerase chain reaction (PCR)-confirmed Lassa fever disease, including co-infection with malaria (also endemic in the region). A minimum of 5,000 participants were recruited, targeting 1,000 individuals of all ages per site, with the follow-up lasting for 12 months. Baseline data collection will gather key variables and blood specimens from all participants, with baseline SNHL prevalence assessed at three study sites. Active follow-up of all participants will involve symptom assessments every 2 weeks and a blood draw every 3 months for serological (antibody) testing. Suspected Lassa fever cases will undergo thorough evaluations, including clinical assessments and laboratory testing including RT-PCR and malaria blood smear microscopy. 

Summary

Through Enable, CEPI underscores the significance of collaborative, integrative, and sustainable efforts in future Lassa research, including the execution of vaccine trials. Building on previous experience and knowledge, Enable 1.5 is now underway to continue to shed light on the epidemiology of Lassa fever in West Africa. Country ownership and lasting community engagement are paramount for the global endeavor to eliminate the threat of Lassa fever.

Sensorineural hearing loss assessment

Infection with the Lassa virus may result in sensorineural hearing loss (SNHL), which can affect survivors for a lifetime. Understanding the baseline level of SNHL in communities where CEPI is studying Lassa fever is key, as well as ascertaining the incidence of new SNHL cases due to new Lassa virus infections. As part of Enable 1.5, CEPI has provided KUDUwave audiometers with laptops, and newly trained staff are testing participants' hearing.

Resources and Publications

From the pain of Ebola to the passion to fight Lassa - an interview with Dr Donald Grant, Sierra Leone Ministry of Health 

A deadly viral illness is exploding in West Africa. Researchers are scrambling to figure out why  Science | Vol 383, Issue 6685 

Events

Incidence of Lassa fever disease and Lassa Virus infection in five West African countries: a prospective, multi-site, cohort study presentation at the American Society of Tropical Medicine and Hygiene Conference by Professor Danny Asogun | New Orleans on 16 November 2024

The ENABLE Lassa research programme: addressing key epidemiology gaps for Lassa fever vaccine development - a symposium at the World Congress of Epidemiology (25 September 2024, Cape Town) Programme | World Congress of Epidemiology 2024 (wce2024.org)

Official Launch of Enable 1.5 in Nigeria in early October 2024. Evidence generated by the Enable Programme will be critical for the upcoming Lassa fever phase III vaccine trials: