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. 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.
Journal Article > ResearchFull Text
BMJ Glob Health. 2020 April 14; Volume 5 (Issue 4); e002141.; DOI:10.1136/bmjgh-2019-002141.
Farley ES, Oyemakinde MJ, Schuurmans J, Ariti C, Saleh F, et al.
BMJ Glob Health. 2020 April 14; Volume 5 (Issue 4); e002141.; DOI:10.1136/bmjgh-2019-002141.
BACKGROUND
Noma, a rapidly progressing infection of the oral cavity, mainly affects children. The true burden is unknown. This study reports estimated noma prevalence in children in northwest Nigeria.
METHODS
Oral screening was performed on all ≤15 year olds, with caretaker consent, in selected households during this cross-sectional survey. Noma stages were classified using WHO criteria and caretakers answered survey questions. The prevalence of noma was estimated stratified by age group (0–5 and 6–15 years). Factors associated with noma were estimated using logistic regression.
RESULTS
A total of 177 clusters, 3499 households and 7122 children were included. In this sample, 4239 (59.8%) were 0–5 years and 3692 (52.1%) were female. Simple gingivitis was identified in 3.1% (n=181; 95% CI 2.6 to 3.8), acute necrotising gingivitis in 0.1% (n=10; CI 0.1 to 0.3) and oedema in 0.05% (n=3; CI 0.02 to 0.2). No cases of late-stage noma were detected. Multivariable analysis in the group aged 0–5 years showed having a well as the drinking water source (adjusted odds ratio (aOR) 2.1; CI 1.2 to 3.6) and being aged 3–5 years (aOR 3.9; CI 2.1 to 7.8) was associated with being a noma case. In 6–15 year olds, being male (aOR 1.5; CI 1.0 to 2.2) was associated with being a noma case and preparing pap once or more per week (aOR 0.4; CI 0.2 to 0.8) was associated with not having noma. We estimated that 129120 (CI 105294 to 1 52 947) individuals <15 years of age would have any stage of noma at the time of the survey within the two states. Most of these cases (93%; n=120 082) would be children with simple gingivitis.
CONCLUSIONS
Our study identified a high prevalence of children at risk of developing advanced noma. This disease is important but neglected and therefore merits inclusion in the WHO neglected tropical diseases list.
Noma, a rapidly progressing infection of the oral cavity, mainly affects children. The true burden is unknown. This study reports estimated noma prevalence in children in northwest Nigeria.
METHODS
Oral screening was performed on all ≤15 year olds, with caretaker consent, in selected households during this cross-sectional survey. Noma stages were classified using WHO criteria and caretakers answered survey questions. The prevalence of noma was estimated stratified by age group (0–5 and 6–15 years). Factors associated with noma were estimated using logistic regression.
RESULTS
A total of 177 clusters, 3499 households and 7122 children were included. In this sample, 4239 (59.8%) were 0–5 years and 3692 (52.1%) were female. Simple gingivitis was identified in 3.1% (n=181; 95% CI 2.6 to 3.8), acute necrotising gingivitis in 0.1% (n=10; CI 0.1 to 0.3) and oedema in 0.05% (n=3; CI 0.02 to 0.2). No cases of late-stage noma were detected. Multivariable analysis in the group aged 0–5 years showed having a well as the drinking water source (adjusted odds ratio (aOR) 2.1; CI 1.2 to 3.6) and being aged 3–5 years (aOR 3.9; CI 2.1 to 7.8) was associated with being a noma case. In 6–15 year olds, being male (aOR 1.5; CI 1.0 to 2.2) was associated with being a noma case and preparing pap once or more per week (aOR 0.4; CI 0.2 to 0.8) was associated with not having noma. We estimated that 129120 (CI 105294 to 1 52 947) individuals <15 years of age would have any stage of noma at the time of the survey within the two states. Most of these cases (93%; n=120 082) would be children with simple gingivitis.
CONCLUSIONS
Our study identified a high prevalence of children at risk of developing advanced noma. This disease is important but neglected and therefore merits inclusion in the WHO neglected tropical diseases list.
Journal Article > CommentaryFull Text
PLoS Negl Trop Dis. 2021 June 17; Volume 15 (Issue 6); e0009437.; DOI:10.1371/journal.pntd.0009437
Farley ES, Ariti C, Amirtharajah M, Kamu C, Oluyide B, et al.
PLoS Negl Trop Dis. 2021 June 17; Volume 15 (Issue 6); e0009437.; DOI:10.1371/journal.pntd.0009437
Journal Article > ResearchFull Text
PLOS Med. 2007 January 1; Volume 4 (Issue 1); DOI:10.1371/journal.pmed.0040016
Grais RF, Dubray C, Gerstl S, Guthmann JP, Djibo A, et al.
PLOS Med. 2007 January 1; Volume 4 (Issue 1); DOI:10.1371/journal.pmed.0040016
BACKGROUND: Despite the comprehensive World Health Organization (WHO)/United Nations Children's Fund (UNICEF) measles mortality-reduction strategy and the Measles Initiative, a partnership of international organizations supporting measles mortality reduction in Africa, certain high-burden countries continue to face recurrent epidemics. To our knowledge, few recent studies have documented measles mortality in sub-Saharan Africa. The objective of our study was to investigate measles mortality in three recent epidemics in Niamey (Niger), N'Djamena (Chad), and Adamawa State (Nigeria). METHODS AND FINDINGS: We conducted three exhaustive household retrospective mortality surveys in one neighbourhood of each of the three affected areas: Boukoki, Niamey, Niger (April 2004, n = 26,795); Moursal, N'Djamena, Chad (June 2005, n = 21,812); and Dong District, Adamawa State, Nigeria (April 2005, n = 16,249), where n is the total surveyed population in each of the respective areas. Study populations included all persons resident for at least 2 wk prior to the study, a duration encompassing the measles incubation period. Heads of households provided information on measles cases, clinical outcomes up to 30 d after rash onset, and health-seeking behaviour during the epidemic. Measles cases and deaths were ascertained using standard WHO surveillance-case definitions. Our main outcome measures were measles attack rates (ARs) and case fatality ratios (CFRs) by age group, and descriptions of measles complications and health-seeking behaviour. Measles ARs were the highest in children under 5 y old (under 5 y): 17.1% in Boukoki, 17.2% in Moursal, and 24.3% in Dong District. CFRs in under 5-y-olds were 4.6%, 4.0%, and 10.8% in Boukoki, Moursal, and Dong District, respectively. In all sites, more than half of measles cases in children aged under 5 y experienced acute respiratory infection and/or diarrhoea in the 30 d following rash onset. Of measles cases, it was reported that 85.7% (979/1,142) of patients visited a health-care facility within 30 d after rash onset in Boukoki, 73.5% (519/706) in Moursal, and 52.8% (603/1,142) in Dong District. CONCLUSIONS: Children in these countries still face unacceptably high mortality from a completely preventable disease. While the successes of measles mortality-reduction strategies and progress observed in measles control in other countries of the region are laudable and evident, they should not overshadow the need for intensive efforts in countries that have just begun implementation of the WHO/UNICEF comprehensive strategy.
Journal Article > ResearchFull Text
Sci Rep. 2022 May 10; Volume 12 (Issue 1); 7616.; DOI:10.1038/s41598-022-11797-2
Oguzie JU, Nwangwu UC, Oluniyi PE, Olumade TJ, George UE, et al.
Sci Rep. 2022 May 10; Volume 12 (Issue 1); 7616.; DOI:10.1038/s41598-022-11797-2
Mosquito vectors are a tremendous public health threat. One in six diseases worldwide is vector-borne transmitted mainly by mosquitoes. In the last couple of years, there have been active Yellow fever virus (YFV) outbreaks in many settings in Nigeria, and nationwide, entomological surveillance has been a significant effort geared towards understanding these outbreaks. In this study, we used a metagenomic sequencing approach to characterize viruses present in vector samples collected during various outbreaks of Yellow fever (YF) in Nigeria between 2017 and 2020. Mosquito samples were grouped into pools of 1 to 50 mosquitoes, each based on species, sex and location. Twenty-five pools of Aedes spp and one pool of Anopheles spp collected from nine states were sequenced and metagenomic analysis was carried out. We identified a wide diversity of viruses belonging to various families in this sample set. Seven different viruses detected included: Fako virus, Phasi Charoen-like virus, Verdadero virus, Chaq like-virus, Aedes aegypti totivirus, cell fusing agent virus and Tesano Aedes virus. Although there are no reports of these viruses being pathogenic, they are an understudied group in the same families and closely related to known pathogenic arboviruses. Our study highlights the power of next generation sequencing in identifying Insect specific viruses (ISVs), and provide insight into mosquito vectors virome in Nigeria.