Conference Material > Slide Presentation
Rapoud D, Cramer E, Al Asmar M, Sagara F, Ndiaye B, et al.
MSF Scientific Day International 2024. 16 May 2024; DOI:10.57740/2acXDPpuix
Conference Material > Video
Malou N
MSF Scientific Day International 2024. 16 May 2024; DOI:10.57740/FYVqmt4gsw
Conference Material > Abstract
Camacho A
Epicentre Scientific Day Paris 2023. 8 June 2023
BACKGROUND
Lassa fever (LF), a haemorrhagic illness caused by the Lassa fever virus (LASV), is endemic in West Africa causing an estimated 300 000 to 500 000 cases and 5 000 fatalities every year. Due to its pandemic potential, LF has been placed on the WHO's list of priority pathogens in order to speed up the development of a safe and effective vaccine. However, the design of successful vaccine trials depends on the true prevalence and incidence rates of LF, which are unknown as infections are often asymptomatic and clinical presentations are varied. The aim of the Enable Lassa research programme is to estimate the incidences of LASV infection and LF disease in five West African countries.
METHODS
We conducted a prospective cohort study in Benin, Guinea, Liberia, Nigeria (three sites), and Sierra Leone from 2020 to 2023, with 24 months of follow-up. Each site assessed the incidence of LASV infection, LF disease, or both. When both incidences are assessed the LASV cohort (n = 1 000 per site) was drawn from the LF cohort (n = 5 000 per site). During recruitment participants completed questionnaires on household composition, socioeconomic status, demographic characteristics, and LF history, and blood samples were collected to determine IgG LASV serostatus. LF disease cohort participants were contacted biweekly to identify acute febrile cases, from whom blood samples were drawn to test for active LASV infection using RT-PCR. LASV infection cohort participants were asked for a blood sample every six months to assess LASV IgG serostatus.
RESULTS
Interim results were obtained in October 2022 using partial data. We focus here on the Nigeria-Edo cohort with a follow-up period of 22 months and 3 serological time-points available (T0, T6, T12). We found a baseline seroprevalence of 43% (95% CI: 42% - 45%), an incidence rate of LASV infection of 13% (10% - 16%) and an incidence rate of LF disease of 0.2% (0.1% - 0.3%). These results suggest that LASV infection is common, but LF disease is rare in hotspot communities. Furthermore, our results suggest that pre-exposure to LASV may temporarily reduce the risk of LF disease. Finally, we found evidence that children may be at greater risk of LF disease than adults due to lower pre-exposure.
CONCLUSION
This is the first epidemiological study to measure the incidence of LF disease and LASV infection in West Africa. The estimates will serve as a basis for the design of future vaccine efficacy trials. The interim results, although limited due to partial data, already suggest that a large sample of several tens of thousands of participants will be required and that children should be included, provided that the candidate vaccine is safe and immunogenic in this group.
KEY MESSAGE
Incidence of Lassa fever is needed to inform vaccine trials. Preliminary results show frequent infections but rare disease, suggesting the need for large vaccine trials.
This abstract is not to be quoted for publication.
Lassa fever (LF), a haemorrhagic illness caused by the Lassa fever virus (LASV), is endemic in West Africa causing an estimated 300 000 to 500 000 cases and 5 000 fatalities every year. Due to its pandemic potential, LF has been placed on the WHO's list of priority pathogens in order to speed up the development of a safe and effective vaccine. However, the design of successful vaccine trials depends on the true prevalence and incidence rates of LF, which are unknown as infections are often asymptomatic and clinical presentations are varied. The aim of the Enable Lassa research programme is to estimate the incidences of LASV infection and LF disease in five West African countries.
METHODS
We conducted a prospective cohort study in Benin, Guinea, Liberia, Nigeria (three sites), and Sierra Leone from 2020 to 2023, with 24 months of follow-up. Each site assessed the incidence of LASV infection, LF disease, or both. When both incidences are assessed the LASV cohort (n = 1 000 per site) was drawn from the LF cohort (n = 5 000 per site). During recruitment participants completed questionnaires on household composition, socioeconomic status, demographic characteristics, and LF history, and blood samples were collected to determine IgG LASV serostatus. LF disease cohort participants were contacted biweekly to identify acute febrile cases, from whom blood samples were drawn to test for active LASV infection using RT-PCR. LASV infection cohort participants were asked for a blood sample every six months to assess LASV IgG serostatus.
RESULTS
Interim results were obtained in October 2022 using partial data. We focus here on the Nigeria-Edo cohort with a follow-up period of 22 months and 3 serological time-points available (T0, T6, T12). We found a baseline seroprevalence of 43% (95% CI: 42% - 45%), an incidence rate of LASV infection of 13% (10% - 16%) and an incidence rate of LF disease of 0.2% (0.1% - 0.3%). These results suggest that LASV infection is common, but LF disease is rare in hotspot communities. Furthermore, our results suggest that pre-exposure to LASV may temporarily reduce the risk of LF disease. Finally, we found evidence that children may be at greater risk of LF disease than adults due to lower pre-exposure.
CONCLUSION
This is the first epidemiological study to measure the incidence of LF disease and LASV infection in West Africa. The estimates will serve as a basis for the design of future vaccine efficacy trials. The interim results, although limited due to partial data, already suggest that a large sample of several tens of thousands of participants will be required and that children should be included, provided that the candidate vaccine is safe and immunogenic in this group.
KEY MESSAGE
Incidence of Lassa fever is needed to inform vaccine trials. Preliminary results show frequent infections but rare disease, suggesting the need for large vaccine trials.
This abstract is not to be quoted for publication.
Conference Material > Video
Camacho A
Epicentre Scientific Day Paris 2023. 8 June 2023
English
Français
Journal Article > ProtocolFull Text
PLOS One. 30 March 2023; Volume 18 (Issue 3); e0283643.; DOI:10.1371/journal.pone.0283643
Penfold S, Adegnika AA, Asogun D, Ayodeji O, Azuogu BN, et al.
PLOS One. 30 March 2023; Volume 18 (Issue 3); e0283643.; DOI:10.1371/journal.pone.0283643
BACKGROUND
Lassa fever (LF), a haemorrhagic illness caused by the Lassa fever virus (LASV), is endemic in West Africa and causes 5000 fatalities every year. The true prevalence and incidence rates of LF are unknown as infections are often asymptomatic, clinical presentations are varied, and surveillance systems are not robust. The aim of the Enable Lassa research programme is to estimate the incidences of LASV infection and LF disease in five West African countries. The core protocol described here harmonises key study components, such as eligibility criteria, case definitions, outcome measures, and laboratory tests, which will maximise the comparability of data for between-country analyses.
METHOD
We are conducting a prospective cohort study in Benin, Guinea, Liberia, Nigeria (three sites), and Sierra Leone from 2020 to 2023, with 24 months of follow-up. Each site will assess the incidence of LASV infection, LF disease, or both. When both incidences are assessed the LASV cohort (n min = 1000 per site) will be drawn from the LF cohort (n min = 5000 per site). During recruitment participants will complete questionnaires on household composition, socioeconomic status, demographic characteristics, and LF history, and blood samples will be collected to determine IgG LASV serostatus. LF disease cohort participants will be contacted biweekly to identify acute febrile cases, from whom blood samples will be drawn to test for active LASV infection using RT-PCR. Symptom and treatment data will be abstracted from medical records of LF cases. LF survivors will be followed up after four months to assess sequelae, specifically sensorineural hearing loss. LASV infection cohort participants will be asked for a blood sample every six months to assess LASV serostatus (IgG and IgM).
DISCUSSION
Data on LASV infection and LF disease incidence in West Africa from this research programme will determine the feasibility of future Phase IIb or III clinical trials for LF vaccine candidates.
Lassa fever (LF), a haemorrhagic illness caused by the Lassa fever virus (LASV), is endemic in West Africa and causes 5000 fatalities every year. The true prevalence and incidence rates of LF are unknown as infections are often asymptomatic, clinical presentations are varied, and surveillance systems are not robust. The aim of the Enable Lassa research programme is to estimate the incidences of LASV infection and LF disease in five West African countries. The core protocol described here harmonises key study components, such as eligibility criteria, case definitions, outcome measures, and laboratory tests, which will maximise the comparability of data for between-country analyses.
METHOD
We are conducting a prospective cohort study in Benin, Guinea, Liberia, Nigeria (three sites), and Sierra Leone from 2020 to 2023, with 24 months of follow-up. Each site will assess the incidence of LASV infection, LF disease, or both. When both incidences are assessed the LASV cohort (n min = 1000 per site) will be drawn from the LF cohort (n min = 5000 per site). During recruitment participants will complete questionnaires on household composition, socioeconomic status, demographic characteristics, and LF history, and blood samples will be collected to determine IgG LASV serostatus. LF disease cohort participants will be contacted biweekly to identify acute febrile cases, from whom blood samples will be drawn to test for active LASV infection using RT-PCR. Symptom and treatment data will be abstracted from medical records of LF cases. LF survivors will be followed up after four months to assess sequelae, specifically sensorineural hearing loss. LASV infection cohort participants will be asked for a blood sample every six months to assess LASV serostatus (IgG and IgM).
DISCUSSION
Data on LASV infection and LF disease incidence in West Africa from this research programme will determine the feasibility of future Phase IIb or III clinical trials for LF vaccine candidates.
Conference Material > Poster
Goodyer J, Pont T, Lah ED, Mayronne S, Carreras I
MSF Paediatric Days 2022. 30 November 2022; DOI:10.57740/1aam-y067
Conference Material > Poster
Goodyer J, Elbadawi H, Mayronne S, Lynch E, Michel J, et al.
MSF Paediatric Days 2022. 30 November 2022; DOI:10.57740/2cfg-vx89
Journal Article > ResearchAbstract Only
Vaccine. 5 October 2022; Volume e-pub ahead of print; DOI:10.1016/j.vaccine.2022.09.037
Simon JK, Kennedy SB, Mahon BE, Dubey SA, Grant-Klein RJ, et al.
Vaccine. 5 October 2022; Volume e-pub ahead of print; DOI:10.1016/j.vaccine.2022.09.037
BACKGROUND
ERVEBO®, a live recombinant vesicular stomatitis virus (VSV) vaccine containing the Zaire ebolavirus glycoprotein (GP) in place of the VSV GP (rVSVΔG-ZEBOV-GP), was advanced through clinical development by Merck & Co., Inc., Rahway, NJ, USA in collaboration with multiple partners to prevent Ebola virus disease (EVD) and has been approved for human use in several countries.
METHODS
We evaluated data from three Phase 2/3 clinical trials conducted in Liberia (PREVAIL), Guinea (FLW), and Sierra Leone (STRIVE) during the 2013–2016 West African EVD outbreak to assess immune responses using validated assays. We performed a post hoc analysis of the association of vaccine response with sex, age (18–50 yrs & >50 yrs), and baseline (BL) GP-enzyme-linked immunosorbent assay (ELISA) titer (<200 & ≥200 EU/mL), including individual study (PREVAIL, FLW, or STRIVE) data and pooled data from all 3 studies. The endpoints were total IgG antibody response (EU/mL) measured by the GP-ELISA and neutralizing antibody response measured by the plaque reduction neutralization test (PRNT) to rVSVΔG-ZEBOV-GP at Days 28, 180, and 365 postvaccination.
RESULTS
In the overall pooled population, in all subgroups, and in each trial independently, GP-ELISA and PRNT geometric mean titers increased from BL, generally peaking at Day 28 and persisting through Day 365. Immune responses were greater in women and participants with BL GP-ELISA ≥ 200 EU/mL, but did not differ across age groups.
CONCLUSION
These data demonstrate that rVSVΔG-ZEBOV-GP elicits a robust and durable immune response through 12 months postvaccination in participants regardless of age, sex, or BL GP-ELISA titer. The higher immune responses observed in women and participants with pre-existing immunity are consistent with those described previously and for other vaccines.
Trials were registered as follows: PREVAIL: ClinicalTrials.gov NCT02344407; FLW: Pan African Clinical Trials Registry PACTR201503001057193; STRIVE: ClinicalTrials.gov NCT02378753. Protocols V920-009, 011, and 018.
ERVEBO®, a live recombinant vesicular stomatitis virus (VSV) vaccine containing the Zaire ebolavirus glycoprotein (GP) in place of the VSV GP (rVSVΔG-ZEBOV-GP), was advanced through clinical development by Merck & Co., Inc., Rahway, NJ, USA in collaboration with multiple partners to prevent Ebola virus disease (EVD) and has been approved for human use in several countries.
METHODS
We evaluated data from three Phase 2/3 clinical trials conducted in Liberia (PREVAIL), Guinea (FLW), and Sierra Leone (STRIVE) during the 2013–2016 West African EVD outbreak to assess immune responses using validated assays. We performed a post hoc analysis of the association of vaccine response with sex, age (18–50 yrs & >50 yrs), and baseline (BL) GP-enzyme-linked immunosorbent assay (ELISA) titer (<200 & ≥200 EU/mL), including individual study (PREVAIL, FLW, or STRIVE) data and pooled data from all 3 studies. The endpoints were total IgG antibody response (EU/mL) measured by the GP-ELISA and neutralizing antibody response measured by the plaque reduction neutralization test (PRNT) to rVSVΔG-ZEBOV-GP at Days 28, 180, and 365 postvaccination.
RESULTS
In the overall pooled population, in all subgroups, and in each trial independently, GP-ELISA and PRNT geometric mean titers increased from BL, generally peaking at Day 28 and persisting through Day 365. Immune responses were greater in women and participants with BL GP-ELISA ≥ 200 EU/mL, but did not differ across age groups.
CONCLUSION
These data demonstrate that rVSVΔG-ZEBOV-GP elicits a robust and durable immune response through 12 months postvaccination in participants regardless of age, sex, or BL GP-ELISA titer. The higher immune responses observed in women and participants with pre-existing immunity are consistent with those described previously and for other vaccines.
Trials were registered as follows: PREVAIL: ClinicalTrials.gov NCT02344407; FLW: Pan African Clinical Trials Registry PACTR201503001057193; STRIVE: ClinicalTrials.gov NCT02378753. Protocols V920-009, 011, and 018.
Journal Article > Short ReportFull Text
Morbidity and Mortality Weekly Report. 8 May 2015
Christie A, Davies-Wayne GJ, Cordier-Lassalle T, Blackley DJ, Laney AS, et al.
Morbidity and Mortality Weekly Report. 8 May 2015
Journal Article > LetterFull Text
N Engl J Med. 18 June 2015; Volume 372 (Issue 25); DOI:10.1056/NEJMc1503275
Akerlund E, Prescott JB, Tampellini L
N Engl J Med. 18 June 2015; Volume 372 (Issue 25); DOI:10.1056/NEJMc1503275