Research in Nature Medicine in August 2024 presents the importance of a safe and effective Lassa vaccine deployed across 15 countries of continental West Africa. The authors find that vaccination against Lassa fever could save nearly 3,300 lives over 10 years and avert up to $128 million in societal costs. Alongside estimating the health-economic burden of Lassa fever in West Africa, the study models the emergence of ‘Lassa-X’, a hypothetical pandemic Lassa virus variant, and projects the effects of achieving 100 Days Mission vaccination goals.
Lassa fever
Lassa fever, a viral haemorrhagic disease that is endemic to West Africa, is caused by Lassa mammarenavirus (LASV). Although infections are common but “widely undetected”, it is believed that most human LASV infections are caused by zoonotic transmission from the Natal multimammate mouse (Mastomys natalensis). It can also spread through human-to-human contact, largely in healthcare settings with “inadequate infection prevention and control practices”.
Most LASV infections are asymptomatic or cause mild febrile illness, but Lassa fever has a “large negative impact” on population health and economies. Among patients who present to hospital, the case-fatality ratio is around 15%. Long-term sequalae, including bilateral sensorineural hearing loss, are common in survivors. Costs per hospitalisation are “high” and often (at least partly) paid out of pocket by patients. There are no licensed vaccines against Lassa fever, but several candidates are in development. Lassa fever is considered a threat by WHO because it has epidemic potential and an absence of effective countermeasures.
The study
The authors estimated the current health-economic burden of Lassa fever in West Africa and project the possible effects of different reactive and preventive vaccination campaigns. They also project the potential effects of vaccination in line with the 100 Days Mission in response to a hypothetical future variant of LASV with pandemic potential. Their epidemiological model project the human Lassa fever burden over 10 years in 15 countries: Benin, Burkina Faso, Côte d’Ivoire, The Gambia, Ghana, Guinea, Guinea-Bissau, Liberia, Mali, Mauritania, Niger, Nigeria, Senegal, Sierra Leone, and Togo. These countries had 183 level 1 administrative units, known in the study as “districts”.
“Due to large gaps in Lassa fever surveillance and limited case reporting throughout much of its endemic range, we favoured a bottom-up modelling approach, synthesising best available ecological, epidemiological, clinical, and economic data to project the cumulative health and economic burden of disease.”
The model comprised six main components:
- A previously published geospatial risk map was used to predict the risk of spillover at the level of 0.05° x 0.05° spatial pixels throughout West Africa.
- Modelled spillover risk estimates were used as inputs in a generalised linear model (GLM) to predict human LASV seroprevalence.
- Modelled human LASV seroprevalence estimates were used as inputs in a serocatalytic model including country-level population projections to predict spillover infection incidence.
- Spillover infections were aggregated at district level and a stochastic branching process model was used to simulate onward human-to-human LASV transmission.
- A computational algorithm was applied retrospectively to spillover infections and ensuing transmission chains to simulate a range of reactive and preventive vaccination campaigns and to project the number of infections averted by vaccination.
- Modelled estimates of LASV infection and infections averted through vaccination strategies were used as inputs in a probabilistic decision-analytic model used to project the health burden of Lassa fever and associated economic costs and the health and economic burden averted due to vaccination over 10 years.
Vaccination
Vaccination was introduced in a series of six scenarios that reflected “realistic assumptions” about vaccine stockpile, administration, and efficacy. Every scenario included reactive vaccination, in which outbreaks trigger the local deployment of a limited vaccine stockpile in affected districts. The authors considered two main mechanisms of vaccine efficacy:
- Protection against infection prevents individuals from acquiring LASV infection from either M. natalensis or other humans
- Protection against disease prevents vaccinated individuals who become infected from progressing to disease, thus averting outpatient consultation, hospitalisation, chronic sequalae, and death
In the simulations, the researchers’ projections feature a vaccine that is 70% of 90% effective only against disease or 70% or 90% effective against both infection and disease.
Lassa-X
The paper also presents modelling of the emergence of “Lassa-X”, assumed to emerge in humans after a single spillover event. Prior LASV immunity was assumed to offer no protection against Lassa-X. Lassa-X was conceptualised with “Ebola-like transmission characteristics” and a 10-fold increase in hospitalisation risk relative to Lassa fever. Vaccination against Lassa-X was also considered; the “most ambitious” vaccination scenario achieved the 100 Days Mission of administration 100 days after initial detection of the first hospitalised case.
Findings
The researchers estimate that 2.1-3.4 million human LASV infections occur each year in West Africa, resulting in 15,000-35,000 hospitalisations and 1,300-8,300 deaths. Lassa fever was estimated to cause 2.0 million disability-adjusted life years (DALYs), $1.6 billion in societal costs, and $15.3 billion in lost value of statistical life (VSL) over 10 years.
The modelling suggests that administering Lassa vaccines preventively to districts classed as endemic in Nigeria, Guinea, Liberia, and Sierra Leone would avert a “substantial share of the burden of disease in those areas”. In the most expansive rollout scenario, in which a vaccine reaches around 80% of individuals in endemic districts and 5% of individuals elsewhere over 3 years, a vaccine that is 70% effective against disease is projected to avert 164,000 DALYs, $128 million in societal costs, and $1.3 billion in VSL lost over 10 years. For the same scenario, a vaccine that is 90% effective against both infection and disease could avert 240,000 DALYs, $188 million in societal costs, and $1.9 billion in VSL lost.
Vaccination campaigns in the other countries in the analysis had “modest” effects due to a reflection of a “constrained global vaccine stockpile”, meaning limited allocation to non-endemic districts.
“It is important to put Lassa fever’s projected health-economic burden and impacts of vaccination in context, in particular given limited economic resources available for investment in infectious disease prevention in West Africa and, hence, opportunity costs to investing in Lassa vaccination in lieu of other interventions.”
Real-world cost-effectiveness of a Lassa vaccine would depend on dosage, price, and clinical efficacy as well as the alternative interventions that are available. For example, novel small-molecule antivirals and monoclonal antibodies may be “promising alternatives” for prevention of severe disease. However, investment in Lassa vaccination has the “major potential benefit” of “increased readiness” for the rapid development and deployment of vaccines against future variants with pandemic potential.
Conclusions and comments
The authors conclude that vaccination campaigns that target “known Lassa fever hotspots” will help to reduce the large health-economic burden. However, it will be important to expand vaccination beyond WHO-classified endemic districts. Improved surveillance is also “greatly needed”, particularly to inform vaccination campaigns. Finally, in the hypothetical event of a novel, highly pathogenic pandemic variant “emerging and devastating the region”, the study suggests that the 100 Days Mission vaccination targets could have “critical impact”.
“The probability of such a variant evolving is exceedingly difficult to predict, but investment in Lassa vaccination now could nonetheless have great additional health-economic value if facilitating a more rapid vaccine response in the event of a pandemic Lassa-related virus emerging.”
CEPI’s CEO Dr Richard Hatchett warned that Lassa fever, a “serious public health problem in West Africa”, is already likely to spread to other regions as “climate and environmental change increase epidemic risk”.
“This study demonstrates the urgent need for a vaccine to protect people from this debilitating and sometimes deadly disease which we believe affects many more than those who are reported, due to limited access to diagnostics and healthcare.”
Lassa fever remains a priority for CEPI, and Dr Hatchett is “proud” that CEPI is a world leading Lassa vaccine R&D funder. Dr Virgil Lokossou, Head of Division, Preparedness and Response at the West African Health Organisation, reflected on the “burden” and “significant socioeconomic consequences” highlighted in the paper, revealing the “urgent need to accelerate vaccine research and development”.
“The West African Health Organisation remains committed to working with our Member States, CEPI, and all stakeholders to ensure that we fast-track the development of a vaccine and other tools we need to control the spread of Lassa fever and protect our communities. Time is now up for concrete actions.”
Dr David Smith, Senior Researcher at Oxford Population Health’s Health Economics Research Centre, joint first author, called for investment in Lassa vaccination.
“One major potential benefit of present investment in Lassa vaccination development is increased readiness to rapidly develop and deploy vaccines against future Lassa variants with pandemic potential.”
Dr Joanne Turner, research associate at the University of Liverpool, joint first author, shared that the analysis included vaccination campaigns designed to reflect “realistic assumptions”.
“Consequently, the impacts of our simulated Lassa vaccination campaigns were modest in countries other than Nigeria, Guinea, Liberia, and Sierra Leone. Yet the data underlying our model suggest that there is likely already a significant burden of Lassa fever outside these countries.”
Professor of Infectious Disease Epidemiology at the University of Oxford Big Data Institute, Déidre Hollingsworth, emphasised the importance of a vaccine to key populations.
“Lassa fever predominantly affects low-income populations in rural areas and is likely to be underreported due to poor health access in these areas.”
We will hear more about a Lassa fever vaccine candidate and the “challenges” of a field efficacy study in West Africa from IAVI’s Dr Marion Gruber at the Congress in Barcelona this October. Get your tickets to join us there, and don’t forget to subscribe for weekly vaccine updates.
