Lassa Epidemiological Programme: Overview

Lassa fever (LF), a zoonotic acute viral haemorrhagic disease caused by Lassa virus, has persisted as an endemic threat in Western Africa since its discovery in 1969. Annually, 10%-16% of people admitted to hospitals have LF (CDC 2022), underscoring its significance as a regional public health concern. Current primary treatments for patients involve early supportive care (e.g. fluids & pain relief) and the administration of the anti-viral drug Ribavirin. However, as with other viral haemorrhagic fevers and in view of the global response to Ebola outbreaks in the past decade, the need persists for a more tailored preventive intervention against Lassa 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 LF vaccine trials and delivery strategies, in 2019 CEPI launched a prospective multi-site cohort study and research capacity strengthening effort named the “Enable Lassa Research Programme.”

Study participants were followed up over time to estimate the incidence of Lassa infection and disease. For 24 months, >23,000 participants were followed across five West African countries (Benin, Guinea, Liberia, Nigeria, and Sierra Leone. The overall participation rate was high, with only 5% refusing, primarily due to reluctance in giving blood. The overall Lassa fever baseline seroprevalence, a measure how many people have antibodies against LF at a given time, was 30%, ranging from 2% in Benin to 48% in Liberia. During the study 39 cases of symptomatic LF were observed, resulting in an overall disease incidence rate of 1/1000 person-years, which means that on average one new case of Lassa fever disease is expected to occur for every 1,000 people over the course of one year. The incidence rates varied by countries with the highest observed in Nigeria and Liberia.

The Enable programme partners are now concluding study activities and analyses are being finalised for publication in 2024. Notable successes of the programme include the successful recruitment and follow up of more than 23,000 subjects across West Africa, collection of extensive data to inform future work, going beyond Lassa infection and disease incidence, establishment of valuable regional partnerships, and 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 burden of disease in infants remains ill-defined and the frequently observed co-infections with malaria and Lassa fever should be further elucidated. Furthermore, as there is increasing evidence of mild or subclinical LF cases with different disease expression, this suggests that some non-febrile LF disease cases may have been missed. 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.

CEPI celebrates the achievements of Enable in advancing our knowledge and awareness of a disease of high consequence, but whose impact has nevertheless remained poorly understood for decades. Recognising the work still ahead, CEPI is now exploring ways to address the remaining knowledge gaps to inform the design of upcoming pivotal clinical trials of Lassa vaccine candidates. Future studies might involve more frequent sampling and enhanced serological and malaria testing, as well as a broadened case definition to include non-febrile cases and infants under two years of age, though with careful considerations of the ethics of enrolling infants. Furthermore, qualitative approaches should be employed to investigate vaccine and healthcare hesitancy, emphasising collaboration with in-country research institutions.

Regardless of the path chosen for Lassa research going forward, CEPI underscores the significance of collaborative, integrative, and sustainable efforts in future Lassa research. Country ownership and lasting community engagement are paramount for the global endeavor to eliminate the threat of Lassa fever and other devastating illnesses.

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

Essential documents

Enable Lassa Research Programme Mid-term Workshop Report | 22-24 October 2022, Abuja, Nigeria. To discuss the interim results of the Enable study and share experiences and lessons learned, a mid-term Workshop of the Enable Lassa Research Programme was conducted. The workshop was co-organized by CEPI together with Programme Headquarters partners and hosted by the National Centre for Disease Control in Nigeria.

Lassa fever generic protocol: Prospective multisite cohort study to estimate incidence of infection and disease due to Lassa fever virus in West African countries.

Workshop reports 2018/9:

   a) Workshop report: Preparing for Lassa vaccine clinical trials with targeted epidemiology studies | 8th and 9th November 2018, Accra, Ghana. Our first workshop, which involved potential partners in West Africa as well as international experts and stakeholders, aimed to identify Lassa data needs and study objectives as well as discussion opportunities for collaboration. These discussions provided the basis for the development of a harmonized core protocol.

   b) Meeting brief: Lassa International Conference (LIC) | 15 – 19 Jan 2019, Abuja, Nigeria. The LIC, hosted by the Nigerian Centre for Disease Control, was an opportunity to reflect on advances in research since the discovery of Lassa and to describe gaps and priorities for future research. CEPI also held a side-meeting with the Lassa epidemiology program PIs to progress protocol development and obtain key feedback.

   C) Workshop Report: Launching Lassa fever epidemiology studies across West Africa | 8th and 9th of October 2019, Accra, Ghana. This workshop was the final meeting of the Lassa epidemiology programme implementing partners ahead of the  core protocol finalisation. The workshop discussion focused on finalising key technical details, reviewing study launch plans, and sharing best practices and experiences.