Journal Article > ProtocolFull Text
PLOS One. 2023 March 30; 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. 2023 March 30; 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.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2021 March 8; Volume 15 (Issue 3); e0009169.; DOI:10.1371/journal.pntd.0009169
Chika Igwenyi N, Harrison RE, Psarra C, Gil Cuesta J, Gulamhusein M, et al.
PLoS Negl Trop Dis. 2021 March 8; Volume 15 (Issue 3); e0009169.; DOI:10.1371/journal.pntd.0009169
Lassa fever (LF) is an acute viral haemorrhagic illness with various non-specific clinical manifestations. Neurological symptoms are rare at the early stage of the disease, but may be seen in late stages, in severely ill patients.The aim of this study was to describe the epidemiological evolution, socio-demographic profiles, clinical characteristics, and outcomes of patients seen during two Lassa fever outbreaks in Ebonyi State, between December 2017 and December 2018. Routinely collected clinical data from all patients admitted to the Virology Centre of the hospital during the period were analysed retrospectively. Out of a total of 83 cases, 70(84.3%) were RT-PCR confirmed while 13 (15.7%) were probable cases. Sixty-nine (83.1%) patients were seen in outbreak 1 of whom 53.6% were urban residents, while 19%, 15%, and 10% were farmers, students and health workers respectively. There were 14 (16.8%) patients, seen in second outbreak with 92.9% rural residents. There were differences in clinical symptoms, signs and laboratory findings between the two outbreaks. The case fatality rates were 29.9% in outbreak 1 and 85.7% for outbreak 2. Neurological features and abnormal laboratory test results were associated with higher mortality rate, seen in outbreak 2. This study revealed significant differences between the two outbreaks. Of particular concern was the higher case fatality during the outbreak 2 which may be from a more virulent strain of the Lassa virus. This has important public health implications and further molecular studies are needed to better define its characteristics.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2022 January 6; Volume 16 (Issue 1); E0010089.; DOI:10.1371/journal.pntd.0010089
Olayinka A, Bourner J, Akpede GO, Okoeguale J, Abejegah C, et al.
PLoS Negl Trop Dis. 2022 January 6; Volume 16 (Issue 1); E0010089.; DOI:10.1371/journal.pntd.0010089
BACKGROUND
Only one recommendation currently exists for the treatment of Lassa fever (LF), which is ribavirin administered in conjunction with supportive care. This recommendation is primarily based on evidence generated from a single clinical trial that was conducted more than 30 years ago-the methodology and results of which have recently come under scrutiny. The requirement for novel therapeutics and reassessment of ribavirin is therefore urgent. However, a significant amount of work now needs to be undertaken to ensure that future trials for LF can be conducted consistently and reliably to facilitate the efficient generation of evidence.
METHODOLOGY
We convened a consultation group to establish the position of clinicians and researchers on the core components of future trials. A Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV) were developed through the process of a multi-stakeholder consultation that took place using a modified-Delphi methodology.
RESULTS
A consensus position was achieved for each aspect of the framework, which accounts for the inclusion of pregnant women and children in future LF clinical trials. The framework consists of 8 core criteria, as well as additional considerations for trial protocols.
CONCLUSIONS
This project represents the first step towards delineating the clinical development pathway for new Lassa fever therapeutics, following a period of 40 years without advancement. Future planned projects will bolster the work initiated here to continue the advancement of LF clinical research through a regionally-centred, collaborative methodology, with the aim of delineating a clear pathway through which LF clinical trials can progress efficiently and ensure sustainable investments are made in research capacity at a regional level.
Only one recommendation currently exists for the treatment of Lassa fever (LF), which is ribavirin administered in conjunction with supportive care. This recommendation is primarily based on evidence generated from a single clinical trial that was conducted more than 30 years ago-the methodology and results of which have recently come under scrutiny. The requirement for novel therapeutics and reassessment of ribavirin is therefore urgent. However, a significant amount of work now needs to be undertaken to ensure that future trials for LF can be conducted consistently and reliably to facilitate the efficient generation of evidence.
METHODOLOGY
We convened a consultation group to establish the position of clinicians and researchers on the core components of future trials. A Core Eligibility Criteria (CEC), Core Case Definition (CCD), Core Outcome Set (COS) and Core Data Variables (CDV) were developed through the process of a multi-stakeholder consultation that took place using a modified-Delphi methodology.
RESULTS
A consensus position was achieved for each aspect of the framework, which accounts for the inclusion of pregnant women and children in future LF clinical trials. The framework consists of 8 core criteria, as well as additional considerations for trial protocols.
CONCLUSIONS
This project represents the first step towards delineating the clinical development pathway for new Lassa fever therapeutics, following a period of 40 years without advancement. Future planned projects will bolster the work initiated here to continue the advancement of LF clinical research through a regionally-centred, collaborative methodology, with the aim of delineating a clear pathway through which LF clinical trials can progress efficiently and ensure sustainable investments are made in research capacity at a regional level.
Conference Material > Poster
Elsinga J, Sunyoto T, Di Stefano L, Giorgetti PF, Kyi HA, et al.
MSF Scientific Day International 2024. 2024 May 16; DOI:10.57740/63l6oZ
Conference Material > Abstract
Camacho A
Epicentre Scientific Day Paris 2023. 2023 June 8
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. 2023 June 8
English
Français
Journal Article > ResearchAbstract Only
Int J Infect Dis. 2020 December 1; Volume 101 (Issue Supplement 1); 495.; DOI:10.1016/j.ijid.2020.09.1290
Chika Igwenyi N, Harrison RE, Unigwe US, Psarra C, Onwe Ogah E, et al.
Int J Infect Dis. 2020 December 1; Volume 101 (Issue Supplement 1); 495.; DOI:10.1016/j.ijid.2020.09.1290
BACKGROUND
Lassa fever (LF) is an acute viral haemorrhagic illness with various clinical manifestations. Neurological symptoms are not commonly present at the early stage of the disease; however, early manifestation of central nervous system features depicts poor prognostication. In Ebonyi state, an unusual pattern was observed between two outbreaks with patients presenting early neurological symptoms and a high mortality rate in the second outbreak. The study described the epidemiological evolution, socio-demographic profiles, clinical characteristics and patients’ outcomes.
METHODS AND MATERIALS
A retrospective analytic analysis of routinely collected clinical data was conducted of all confirmed and probable LF patients admitted to the Virology Centre of the AEFUTHA in Ebonyi State, December 2017 to January 2019.
RESULTS In a total of 83 cases, 70 were RT-PCR confirmed and 13 probable cases. In outbreak 1, 69 were seen with 53.6% being urban residents, 19% farmers, 15% students, and 10% health workers. Fourteen cases were seen in outbreak 2 with 92.9% rural residents, 58.3% being farmers and 49.9% students. There were differences in clinical and laboratory signs and symptoms between the two outbreaks with neurological symptoms present 43% of the time in outbreak 1 and 93% in outbreak 2 (p = 0.001), with a shorter time of onset for these symptoms in outbreak 2. The mortality rate was 85.7% in outbreak 2 versus 29.9% in outbreak 1 (p < 0.001). Patients with neurological symptoms, who were more common in outbreak 2 had a RR of dying of 8.5 compared to those without.
CONCLUSION
This study revealed a different form of LF that is of great concern due to its high mortality rate. Further studies are needed to better define its characteristics.
Lassa fever (LF) is an acute viral haemorrhagic illness with various clinical manifestations. Neurological symptoms are not commonly present at the early stage of the disease; however, early manifestation of central nervous system features depicts poor prognostication. In Ebonyi state, an unusual pattern was observed between two outbreaks with patients presenting early neurological symptoms and a high mortality rate in the second outbreak. The study described the epidemiological evolution, socio-demographic profiles, clinical characteristics and patients’ outcomes.
METHODS AND MATERIALS
A retrospective analytic analysis of routinely collected clinical data was conducted of all confirmed and probable LF patients admitted to the Virology Centre of the AEFUTHA in Ebonyi State, December 2017 to January 2019.
RESULTS In a total of 83 cases, 70 were RT-PCR confirmed and 13 probable cases. In outbreak 1, 69 were seen with 53.6% being urban residents, 19% farmers, 15% students, and 10% health workers. Fourteen cases were seen in outbreak 2 with 92.9% rural residents, 58.3% being farmers and 49.9% students. There were differences in clinical and laboratory signs and symptoms between the two outbreaks with neurological symptoms present 43% of the time in outbreak 1 and 93% in outbreak 2 (p = 0.001), with a shorter time of onset for these symptoms in outbreak 2. The mortality rate was 85.7% in outbreak 2 versus 29.9% in outbreak 1 (p < 0.001). Patients with neurological symptoms, who were more common in outbreak 2 had a RR of dying of 8.5 compared to those without.
CONCLUSION
This study revealed a different form of LF that is of great concern due to its high mortality rate. Further studies are needed to better define its characteristics.
Journal Article > Case Report/SeriesFull Text
Int J Infect Dis. 2019 December 1; Volume 89; 84-86.; DOI:10.1016/j.ijid.2019.08.023
Agboeze J, Nwali MI, Nwakpakpa E, Ogah OE, Onoh R, et al.
Int J Infect Dis. 2019 December 1; Volume 89; 84-86.; DOI:10.1016/j.ijid.2019.08.023
BACKGROUND
The signs and symptoms of Lassa fever are initially indistinguishable from other febrile illnesses common in the tropics and complications of pregnancy. Surviving Lassa fever during pregnancy is rare. Only few cases have been documented. The antiviral drug of choice is ribavirin.
CASE DESCRIPTION
A 25-year-old multigravida farmer with fever who was initially thought to have malaria in pregnancy at 29 weeks gestation. Further changes in her clinical state and laboratory tests led to a confirmation of Lassa fever. The liver enzymes were markedly deranged and the packed cell volume was 27%. She commenced on ribavirin and subsequently was delivered of a live male neonate who was RT PCR negative for Lassa fever virus. Her clinical state improved, repeat RT PCR on day 15 was negative and she made full recovery.
DISCUSSION
The case reported had similar clinical features of fever and abdominal pain and resulted in the initial diagnoses of Malaria in pregnancy. When she failed to respond to antimalarial and antibiotics treatments, a strong suspicion of viral hemorrhagic fever was made. At this time the patient was in advanced stage of the disease with bleeding from vagina and puncture sites. On the third day of admission she was delivered of a live male neonate who remained negative after 2 consecutive RT PCR tests for Lassa fever virus. Lassa fever carries a high risk of death to the fetus throughout pregnancy and to the mother in the third trimester. Mothers with Lassa fever improved rapidly after evacuation of the uterus by spontaneous abortion, or normal delivery. She was clinically stable following delivery. Her laboratory investigations were essentially normal. Throughout her management transmission based precautions were observed. None of the six close contacts developed symptoms after been followed up for 21 days.
CONCLUSION
This report adds to the body of literature that individuals can survive Lassa fever during pregnancy with good maternal and fetal outcome.
The signs and symptoms of Lassa fever are initially indistinguishable from other febrile illnesses common in the tropics and complications of pregnancy. Surviving Lassa fever during pregnancy is rare. Only few cases have been documented. The antiviral drug of choice is ribavirin.
CASE DESCRIPTION
A 25-year-old multigravida farmer with fever who was initially thought to have malaria in pregnancy at 29 weeks gestation. Further changes in her clinical state and laboratory tests led to a confirmation of Lassa fever. The liver enzymes were markedly deranged and the packed cell volume was 27%. She commenced on ribavirin and subsequently was delivered of a live male neonate who was RT PCR negative for Lassa fever virus. Her clinical state improved, repeat RT PCR on day 15 was negative and she made full recovery.
DISCUSSION
The case reported had similar clinical features of fever and abdominal pain and resulted in the initial diagnoses of Malaria in pregnancy. When she failed to respond to antimalarial and antibiotics treatments, a strong suspicion of viral hemorrhagic fever was made. At this time the patient was in advanced stage of the disease with bleeding from vagina and puncture sites. On the third day of admission she was delivered of a live male neonate who remained negative after 2 consecutive RT PCR tests for Lassa fever virus. Lassa fever carries a high risk of death to the fetus throughout pregnancy and to the mother in the third trimester. Mothers with Lassa fever improved rapidly after evacuation of the uterus by spontaneous abortion, or normal delivery. She was clinically stable following delivery. Her laboratory investigations were essentially normal. Throughout her management transmission based precautions were observed. None of the six close contacts developed symptoms after been followed up for 21 days.
CONCLUSION
This report adds to the body of literature that individuals can survive Lassa fever during pregnancy with good maternal and fetal outcome.
Journal Article > ResearchFull Text
Lancet Infect Dis. 2024 September 1; Volume 24 (Issue 9); 1037-1044.; DOI:10.1016/S1473-3099(24)00184-1
Elsinga J, Sunyoto T, di Stefano L, Giorgetti PF, Kyi HA, et al.
Lancet Infect Dis. 2024 September 1; Volume 24 (Issue 9); 1037-1044.; DOI:10.1016/S1473-3099(24)00184-1
BACKGROUND
Lassa fever is a viral haemorrhagic fever with few options for diagnosis and treatment; it is also under-researched with knowledge gaps on its epidemiology. A point-of-care bedside test diagnosing Lassa fever, adhering to REASSURED criteria, is not currently available but is urgently needed in west African regions with high Lassa fever burden. We aimed to assess the validity and feasibility of a rapid diagnostic test (RDT) to confirm Lassa fever in people in Nigeria.
METHODS
We estimated the diagnostic performance of the ReLASV Pan-Lassa RDT (Zalgen Labs, Frederick, MD, USA) as a research-use-only test, compared to RT-PCR as a reference standard, in 217 participants at a federal tertiary hospital in Abakaliki, Nigeria. We recruited participants between Feb 17, 2022, and April 17, 2023. The RDT was performed using capillary blood at the patient bedside and using plasma at the laboratory. The performance of the test, based on REASSURED criteria, was assessed for user friendliness, rapidity and robustness, sensitivity, and specificity.
FINDINGS
Participants were aged between 0 and 85 years, with a median age of 33·0 years (IQR 22·0-44·3), and 24 participants were younger than 18 years. 107 (50%) participants were women and 109 (50%) were men; one participant had missing sex data. Although the specificity of the Pan-Lassa RDT was high (>90%), sensitivity at bedside using capillary blood was estimated as 4% (95% CI 1-14) at 15 min and 10% (3-22) at 25 min, far below the target of 90%. The laboratory-based RDT using plasma showed better sensitivity (46% [32-61] at 15 min and 50% [36-64] at 25 min) but did not reach the target sensitivity. Among the 52 PCR-positive participants with Lassa fever, positive RDT results were associated with lower cycle threshold values (glycoprotein precursor [GPC] gene mean 30·3 [SD 4·3], Large [L] gene mean 32·3 [3·7] vs GPC gene mean 24·5 [3·9], L gene mean 28·0 [3·6]). Personnel conducting the bedside test procedure reported being hindered by the inconvenient use of full personal protective equipment and long waiting procedures before a result could be read.
INTERPRETATION
The Pan-Lassa RDT is not currently recommended as a diagnostic or screening tool for suspected Lassa fever cases. Marked improvement in sensitivity and user friendliness is needed for the RDT to be adopted clinically. There remains an urgent need for better Lassa fever diagnostics to promote safety of in-hospital care and better disease outcomes in low-resource settings.
Lassa fever is a viral haemorrhagic fever with few options for diagnosis and treatment; it is also under-researched with knowledge gaps on its epidemiology. A point-of-care bedside test diagnosing Lassa fever, adhering to REASSURED criteria, is not currently available but is urgently needed in west African regions with high Lassa fever burden. We aimed to assess the validity and feasibility of a rapid diagnostic test (RDT) to confirm Lassa fever in people in Nigeria.
METHODS
We estimated the diagnostic performance of the ReLASV Pan-Lassa RDT (Zalgen Labs, Frederick, MD, USA) as a research-use-only test, compared to RT-PCR as a reference standard, in 217 participants at a federal tertiary hospital in Abakaliki, Nigeria. We recruited participants between Feb 17, 2022, and April 17, 2023. The RDT was performed using capillary blood at the patient bedside and using plasma at the laboratory. The performance of the test, based on REASSURED criteria, was assessed for user friendliness, rapidity and robustness, sensitivity, and specificity.
FINDINGS
Participants were aged between 0 and 85 years, with a median age of 33·0 years (IQR 22·0-44·3), and 24 participants were younger than 18 years. 107 (50%) participants were women and 109 (50%) were men; one participant had missing sex data. Although the specificity of the Pan-Lassa RDT was high (>90%), sensitivity at bedside using capillary blood was estimated as 4% (95% CI 1-14) at 15 min and 10% (3-22) at 25 min, far below the target of 90%. The laboratory-based RDT using plasma showed better sensitivity (46% [32-61] at 15 min and 50% [36-64] at 25 min) but did not reach the target sensitivity. Among the 52 PCR-positive participants with Lassa fever, positive RDT results were associated with lower cycle threshold values (glycoprotein precursor [GPC] gene mean 30·3 [SD 4·3], Large [L] gene mean 32·3 [3·7] vs GPC gene mean 24·5 [3·9], L gene mean 28·0 [3·6]). Personnel conducting the bedside test procedure reported being hindered by the inconvenient use of full personal protective equipment and long waiting procedures before a result could be read.
INTERPRETATION
The Pan-Lassa RDT is not currently recommended as a diagnostic or screening tool for suspected Lassa fever cases. Marked improvement in sensitivity and user friendliness is needed for the RDT to be adopted clinically. There remains an urgent need for better Lassa fever diagnostics to promote safety of in-hospital care and better disease outcomes in low-resource settings.