Journal Article > ResearchSubscription Only
Lancet Infect Dis. 8 January 2025; Volume S1473-3099 (Issue 24); 00719-9.; DOI:10.1016/S1473-3099(24)00719-9
Coldiron ME, Soumana I, Baudin E, Langendorf C, Mamiafo Tchoula C, et al.
Lancet Infect Dis. 8 January 2025; Volume S1473-3099 (Issue 24); 00719-9.; DOI:10.1016/S1473-3099(24)00719-9
BACKGROUND
In settings with low pneumococcal conjugate vaccine (PCV) coverage, multi-age cohort mass campaigns could increase population immunity, and fractional dosing could increase affordability. We aimed to evaluate the effect of mass campaigns on nasopharyngeal pneumococcal carriage of Pneumosil (PCV10) in children aged 1-9 years in Niger.
METHODS
In this three-arm, open-label, cluster-randomised trial, 63 clusters of one to four villages in Niger were randomly assigned (3:3:1) using block randomisation to receive campaigns consisting of a single full dose of a 10-valent PCV (Pneumosil), a single one-fifth dose of Pneumosil, or no campaign. Independently sampled carriage surveys were done among 2268 households 6 months before and after vaccination, collecting nasopharyngeal swabs from healthy children for culture and serotyping; those with contraindication to nasopharyngeal swabbing were excluded. The primary outcome was nasopharyngeal carriage of vaccine-serotype pneumococcus. We tested whether vaccine-type carriage was reduced in full-dose versus control clusters; and whether fractional doses were non-inferior to full-doses (lower bound 95% CI more than -7·5%), using generalised estimating equations to analyse cluster summaries at baseline and follow-up, controlling for covariates to estimate risk differences and their 95% CIs. The study is registered with ClinicalTrials.gov (NCT05175014) and the Pan-African Clinical Trials Registry (PACTR20211257448484).
FINDINGS
Surveys were done between Dec 22, 2021, and March 18, 2022, and between Dec 12, 2022, and March 9, 2023. The vaccination campaign ran from June 15 to Aug 2, 2022. Participants' characteristics were consistent across surveys and groups. Pre-vaccination, vaccine-type carriage was 15·6% (149 of 955 participants) in the full-dose group, 17·9% (170 of 948) in the fractional-dose group, and 18·8% (60 of 320) in the control group. Post-vaccination, vaccine-type carriage was 4·6% (44 of 967) in the full-dose group, 8·0% (77 of 962) in the fractional-dose group, and 16·5% (53 of 321) in the control group. The primary analysis showed a risk difference of -16·2% (95% CI -28·6 to -3·0) between the full-dose group and control group (p=0·002 for superiority), and -3·8% (-6·1 to -1·6) between the full-dose group and fractional-dose group, meeting the non-inferiority criteria. No adverse events were judged to be related to vaccination.
INTERPRETATION
Multi-age cohort campaigns had a marked effect on vaccine-type carriage and fractional-dose campaigns met non-inferiority criteria. Such campaigns should be considered in low-coverage settings, including humanitarian emergencies, to accelerate population protection.
Conference Material > Poster
Mamaty AA, Atti S, Sani KA, Tonamou G, Ciglenecki I, et al.
MSF Scientific Day International 2024. 16 May 2024; DOI:10.57740/QLiHOZ
Journal Article > ResearchAbstract Only
J. Infect.. 25 June 2023; Volume S0163-4453 (Issue 23); 00336-5.; DOI:10.1016/j.jinf.2023.06.015
Jacquier H, Assao B, Chau F, Guindo O, Condamine B, et al.
J. Infect.. 25 June 2023; Volume S0163-4453 (Issue 23); 00336-5.; DOI:10.1016/j.jinf.2023.06.015
OBJECTIVE
Whole genome sequencing (WGS) of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. coli faecal isolates in rural Southern Niger.
METHODS
Stools of 383 healthy participants were collected among which 92.4% were ESBL-Enterobacterales carriers. A subset of 90 ESBL-E. coli containing stools (109 ESBL-E. coli isolates) were further analysed by WGS, using short- and long-reads.
RESULTS
Most isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. The blaCTX-M-15 gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne, blaCTX-M-15 was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis of blaCTX-M-15 in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome.
CONCLUSIONS
Massive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration of blaCTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.
Whole genome sequencing (WGS) of extended-spectrum ß-lactamase-producing Escherichia coli (ESBL-E. coli) in developing countries is lacking. Here we describe the population structure and molecular characteristics of ESBL-E. coli faecal isolates in rural Southern Niger.
METHODS
Stools of 383 healthy participants were collected among which 92.4% were ESBL-Enterobacterales carriers. A subset of 90 ESBL-E. coli containing stools (109 ESBL-E. coli isolates) were further analysed by WGS, using short- and long-reads.
RESULTS
Most isolates belonged to the commensalism-adapted phylogroup A (83.5%), with high clonal diversity. The blaCTX-M-15 gene was the major ESBL determinant (98.1%), chromosome-integrated in approximately 50% of cases, in multiple integration sites. When plasmid-borne, blaCTX-M-15 was found in IncF (57.4%) and IncY plasmids (26.2%). Closely related plasmids were found in different genetic backgrounds. Genomic environment analysis of blaCTX-M-15 in closely related strains argued for mobilisation between plasmids or from plasmid to chromosome.
CONCLUSIONS
Massive prevalence of community faecal carriage of CTX-M-15-producing E. coli was observed in a rural region of Niger due to the spread of highly diverse A phylogroup commensalism-adapted clones, with frequent chromosomal integration of blaCTX-M-15. Plasmid spread was also observed. These data suggest a risk of sustainable implementation of ESBL in community faecal carriage.
Conference Material > Abstract
Idrissa AA, Atti S, Wasaulua RK, Kazadi S, Guindo O, et al.
MSF Scientific Day International 2023. 7 June 2023; DOI:10.57740/wg9g-dq47
INTRODUCTION
MSF supported Niger’s Ministry of Health (MoH) in responding to a serogroup C meningococcal meningitis epidemic in Magaria and Dungass Districts in 2022. WHO’s global roadmap for defeating meningitis by 2030 emphasises appropriate care for meningitis sequelae, but this is not yet part of standard epidemic response. Meningitis sequelae in the African meningitis belt are poorly described, hampering access to rehabilitation services. To better orient future care for sequelae, we performed a follow-up survey of survivors 9 months after the 2022 epidemic.
METHODS
WHO case definitions were used during the epidemic. Patient-level line-lists detailing village of origin were obtained from authorities, and results of polymerase chain reaction testing on cerebrospinal fluid were integrated. Guided by village leaders, study nurses attempted to visit cases at home to assess for sequelae. Nurses administered questionnaires asking about history including seizures and subjective vision and hearing loss; and carried out physical examinations assessing anosmia, weakness, and paralysis. Data were collected tablets using REDCap software. Prevalence of sequelae among survivors was calculated.
ETHICS
This study was approved by the MSF Ethics Review Board and by the National Ethics Committee for Health Research of Niger.
RESULTS
1001 suspected cases and 50 deaths (case fatality rate, CFR, 5.0%) originating in 230 villages were recorded on the line-lists. 469 cases (47%) had lumbar puncture, and 220 (47%) had a causative agent identified, including 192 cases of Neisseria meningitidis serogroup C (NmC) and 22 Streptococcus pneumoniae. After excluding 82 cases living in villages difficult to access, we attempted to trace 919 cases, of whom 570 (62%) were found and consented to interview. Among these cases, 49 had died (CFR 8.6%). Among the cases visited, 151 had confirmed NmC and 10 S. pneumoniae. Among the 521 surviving cases evaluated, 62 (12%) had sequelae; the most common were hearing loss (29), paralysis (16), epilepsy (9), and developmental regression (6). Among the 138 surviving confirmed cases of NmC, 25 (18%) had one or more sequelae.
CONCLUSION
We documented a higher CFR than reported during the epidemic, and a high burden of sequelae among survivors, particularly among those with confirmed NmC infection. To our knowledge, this is the second time that meningitis sequelae have been documented in Niger; these findings help identify priorities for integrating meningitis after-care into epidemic responses. MSF and the MoH should work to ensure linkages to long-term care and support for meningitis survivors and their caregivers. We were unable to find all cases, so the true prevalence of sequelae among survivors may differ. This follow-up survey used simple methods adapted for in-home evaluation, and formal audiometry may have led to detection of more subtle hearing loss.
CONFLICTS OF INTEREST
None declared
MSF supported Niger’s Ministry of Health (MoH) in responding to a serogroup C meningococcal meningitis epidemic in Magaria and Dungass Districts in 2022. WHO’s global roadmap for defeating meningitis by 2030 emphasises appropriate care for meningitis sequelae, but this is not yet part of standard epidemic response. Meningitis sequelae in the African meningitis belt are poorly described, hampering access to rehabilitation services. To better orient future care for sequelae, we performed a follow-up survey of survivors 9 months after the 2022 epidemic.
METHODS
WHO case definitions were used during the epidemic. Patient-level line-lists detailing village of origin were obtained from authorities, and results of polymerase chain reaction testing on cerebrospinal fluid were integrated. Guided by village leaders, study nurses attempted to visit cases at home to assess for sequelae. Nurses administered questionnaires asking about history including seizures and subjective vision and hearing loss; and carried out physical examinations assessing anosmia, weakness, and paralysis. Data were collected tablets using REDCap software. Prevalence of sequelae among survivors was calculated.
ETHICS
This study was approved by the MSF Ethics Review Board and by the National Ethics Committee for Health Research of Niger.
RESULTS
1001 suspected cases and 50 deaths (case fatality rate, CFR, 5.0%) originating in 230 villages were recorded on the line-lists. 469 cases (47%) had lumbar puncture, and 220 (47%) had a causative agent identified, including 192 cases of Neisseria meningitidis serogroup C (NmC) and 22 Streptococcus pneumoniae. After excluding 82 cases living in villages difficult to access, we attempted to trace 919 cases, of whom 570 (62%) were found and consented to interview. Among these cases, 49 had died (CFR 8.6%). Among the cases visited, 151 had confirmed NmC and 10 S. pneumoniae. Among the 521 surviving cases evaluated, 62 (12%) had sequelae; the most common were hearing loss (29), paralysis (16), epilepsy (9), and developmental regression (6). Among the 138 surviving confirmed cases of NmC, 25 (18%) had one or more sequelae.
CONCLUSION
We documented a higher CFR than reported during the epidemic, and a high burden of sequelae among survivors, particularly among those with confirmed NmC infection. To our knowledge, this is the second time that meningitis sequelae have been documented in Niger; these findings help identify priorities for integrating meningitis after-care into epidemic responses. MSF and the MoH should work to ensure linkages to long-term care and support for meningitis survivors and their caregivers. We were unable to find all cases, so the true prevalence of sequelae among survivors may differ. This follow-up survey used simple methods adapted for in-home evaluation, and formal audiometry may have led to detection of more subtle hearing loss.
CONFLICTS OF INTEREST
None declared
Conference Material > Slide Presentation
Idrissa AA, Atti S, Wasaulua RK, Kazadi S, Guindo O, et al.
MSF Scientific Day International 2023. 7 June 2023; DOI:10.57740/0c2k-z823
Conference Material > Video
Coldiron ME
MSF Scientific Day International 2023. 7 June 2023; DOI:10.57740/1bf1-9f33
Journal Article > ResearchFull Text
Lancet Global Health. 1 February 2023; Volume 11 (Issue 2); e296-e300.; DOI:10.1016/S2214-109X(22)00479-X
Abouyannis M, Esmail H, Hamaluba M, Ngama M, Mwangudzah H, et al.
Lancet Global Health. 1 February 2023; Volume 11 (Issue 2); e296-e300.; DOI:10.1016/S2214-109X(22)00479-X
Snakebite clinical trials have often used heterogeneous outcome measures and there is an urgent need for standardisation. A globally representative group of key stakeholders came together to reach consensus on a globally relevant set of core outcome measurements. Outcome domains and outcome measurement instruments were identified through searching the literature and a systematic review of snakebite clinical trials. Outcome domains were shortlisted by use of a questionnaire and consensus was reached among stakeholders and the patient group through facilitated discussions and voting. Five universal core outcome measures should be included in all future snakebite clinical trials-mortality, WHO disability assessment scale, patient-specific functional scale, acute allergic reaction by Brown criteria, and serum sickness by formal criteria. Additional syndrome-specific core outcome measures should be used depending on the biting species. This core outcome measurement set provides global standardisation, supports the priorities of patients and clinicians, enables meta-analysis, and is appropriate for use in low-income and middle-income settings.
Journal Article > ResearchFull Text
Med Trop Sante Int
MTSI
MTSI bulletin
MTSI magazine
MTSI-Revue
Médecine tropicale et santé internationale. Bulletin
Médecine tropicale et santé internationale. Magazine
MTSI, la revue de la Société francophone de médecine tropicale et santé internationale. 1 February 2023; Volume 3 (Issue 3); DOI:10.48327/mtsi.v3i3.2023.421
Abouyannis M, Esmail H, Hamaluba M, Ngama M, Mwangudzah H, et al.
Med Trop Sante Int
MTSI
MTSI bulletin
MTSI magazine
MTSI-Revue
Médecine tropicale et santé internationale. Bulletin
Médecine tropicale et santé internationale. Magazine
MTSI, la revue de la Société francophone de médecine tropicale et santé internationale. 1 February 2023; Volume 3 (Issue 3); DOI:10.48327/mtsi.v3i3.2023.421
English
Français
CONTEXTE
Les essais cliniques sur les morsures de serpent ont souvent utilisé des critères de décision hétérogènes qui demandent à être standardisés.
MÉTHODE
Un groupe d'acteurs clés mondialement représentatifs s'est réuni pour parvenir à un consensus sur un jeu universel de critères de décision de base. Les domaines d'intérêt et les instruments d'évaluation des critères de décision ont été identifiés à partir d'une recherche documentaire et d'un examen systématique des essais cliniques concernant les envenimations par morsure de serpent. Les domaines d'intérêt ont été présélectionnés à l'aide d'un questionnaire et un consensus a été obtenu entre le groupe d'acteurs et un groupe représentatif de patients à la suite de discussions orientées et d'un vote.
RÉSULTATS
Cinq critères de décision de base universels devraient être inclus dans tous les futurs essais cliniques sur les morsures de serpent : la mortalité, l'échelle d'évaluation du handicap de l'OMS, l'échelle fonctionnelle propre à chaque patient, la réaction allergique immédiate selon les critères de Brown et la maladie sérique en fonction de critères formels. D'autres critères de décision spécifiques aux différents syndromes observés lors des envenimations par morsure de serpent doivent être utilisés en fonction de l'espèce responsable de la morsure.
CONCLUSION
Ce jeu universel de critères de décision de base permet une standardisation mondiale, répond aux priorités des patients et des cliniciens, favorise des méta-analyses et est compatible avec une utilisation dans les pays à revenu faible ou intermédiaire.
Les essais cliniques sur les morsures de serpent ont souvent utilisé des critères de décision hétérogènes qui demandent à être standardisés.
MÉTHODE
Un groupe d'acteurs clés mondialement représentatifs s'est réuni pour parvenir à un consensus sur un jeu universel de critères de décision de base. Les domaines d'intérêt et les instruments d'évaluation des critères de décision ont été identifiés à partir d'une recherche documentaire et d'un examen systématique des essais cliniques concernant les envenimations par morsure de serpent. Les domaines d'intérêt ont été présélectionnés à l'aide d'un questionnaire et un consensus a été obtenu entre le groupe d'acteurs et un groupe représentatif de patients à la suite de discussions orientées et d'un vote.
RÉSULTATS
Cinq critères de décision de base universels devraient être inclus dans tous les futurs essais cliniques sur les morsures de serpent : la mortalité, l'échelle d'évaluation du handicap de l'OMS, l'échelle fonctionnelle propre à chaque patient, la réaction allergique immédiate selon les critères de Brown et la maladie sérique en fonction de critères formels. D'autres critères de décision spécifiques aux différents syndromes observés lors des envenimations par morsure de serpent doivent être utilisés en fonction de l'espèce responsable de la morsure.
CONCLUSION
Ce jeu universel de critères de décision de base permet une standardisation mondiale, répond aux priorités des patients et des cliniciens, favorise des méta-analyses et est compatible avec une utilisation dans les pays à revenu faible ou intermédiaire.
Journal Article > CommentaryFull Text
Toxicon: X. 21 December 2022; Volume 17; 100146.; DOI:10.1016/j.toxcx.2022.100146
Potet J, Singh SN, Ritmeijer KKD, Sisay K, Alcoba G, et al.
Toxicon: X. 21 December 2022; Volume 17; 100146.; DOI:10.1016/j.toxcx.2022.100146
The medical humanitarian organization Médecins Sans Frontières (MSF) provides medical care in more than 70 countries and admits more than 7000 cases of snakebite in its facilities each year.
We describe our activities against snakebite in three African countries: Central African Republic, South Sudan and Ethiopia, in which different models of care have been developed. A standard protocol using two different antivenoms depending on the patient's syndrome has been introduced, and a simple blood coagulation test is performed to detect venom-induced coagulopathy. Other services, including surgery for necrotizing wounds, are offered in the facilities where MSF admits a large number of snakebite patients. All services, including provision of antivenom, are offered free-of-charge in MSF-supported facilities. Community-based activities focusing on preventive measures and prompt transport to hospital have been developed in a few MSF projects.
The provision of quality care and treatment, including effective antivenoms, without out-of-pocket payments by the patients, probably explains why MSF has admitted an increasing number of snakebite victims over the last years. This model requires significant resources and monitoring, including regular training of healthcare workers on treatment protocols and a considerable budget for antivenom procurement.
We describe our activities against snakebite in three African countries: Central African Republic, South Sudan and Ethiopia, in which different models of care have been developed. A standard protocol using two different antivenoms depending on the patient's syndrome has been introduced, and a simple blood coagulation test is performed to detect venom-induced coagulopathy. Other services, including surgery for necrotizing wounds, are offered in the facilities where MSF admits a large number of snakebite patients. All services, including provision of antivenom, are offered free-of-charge in MSF-supported facilities. Community-based activities focusing on preventive measures and prompt transport to hospital have been developed in a few MSF projects.
The provision of quality care and treatment, including effective antivenoms, without out-of-pocket payments by the patients, probably explains why MSF has admitted an increasing number of snakebite victims over the last years. This model requires significant resources and monitoring, including regular training of healthcare workers on treatment protocols and a considerable budget for antivenom procurement.
Journal Article > ResearchFull Text
Malar J. 9 September 2022; Volume 21 (Issue 1); 261.; DOI:10.1186/s12936-022-04280-w
Lynch E, Jensen TO, Assao B, Chihana ML, Turuho T, et al.
Malar J. 9 September 2022; Volume 21 (Issue 1); 261.; DOI:10.1186/s12936-022-04280-w
BACKGROUND
Rapid diagnostic tests (RDT) for malaria are the primary tool for malaria diagnosis in sub-Saharan Africa but the utility of the most commonly used histidine-rich protein 2 (HRP2) antigen-based tests is limited in high transmission settings due to the long duration of positivity after successful malaria treatment. HRP2 tests are also threatened by the emergence of Plasmodium that do not carry pfhrp2 or pfhrp 3 genes. Plasmodium lactate dehydrogenase (pLDH)-based tests are promising alternatives, but less available. This study assessed the performances of HRP2 and pLDH(pan) tests under field conditions.
METHODS
The study performed a prospective facility-based diagnostic evaluation of two malaria RDTs in Aweil, South Sudan, during the high transmission season. Capillary blood by fingerprick was collected from 800 children under 15 years of age with fever and no signs of severity. SD Bioline HRP2 and CareStart pLDH(pan) RDTs were performed in parallel, thick and thin smears for microscopy were examined, and dried blood was used for PCR testing.
RESULTS
Using microscopy as the gold standard, the sensitivity of both tests was estimated at > 99%, but the specificity of each was lower: 55.0% for the pLDH test and 61.7% for the HRP2 test. When using PCR as the gold standard, the sensitivity of both tests was lower than the values assessed using microscopy (97.0% for pLDH and 96.5% for HRP2), but the specificity increased (65.1% for pLDH and 72.9% for HRP2). Performance was similar across different production lots, sex, and age. Specificity of both the pLDH and HRP2 tests was significantly lower in children who reported taking a therapeutic course of anti-malarials in the 2 months prior to enrollment. The prevalence of pfhrp2/3 deletions in the study population was 0.6%.
CONCLUSIONS
The low specificity of the pLDH RDT in this setting confirms previous results and suggests a problem with this specific test. The prevalence of pfhrp2/3 deletions in the study area warrants continued monitoring and underscores the relevance of assessing deletion prevalence nationally. Improved malaria RDTs for high-transmission environments are needed.
Rapid diagnostic tests (RDT) for malaria are the primary tool for malaria diagnosis in sub-Saharan Africa but the utility of the most commonly used histidine-rich protein 2 (HRP2) antigen-based tests is limited in high transmission settings due to the long duration of positivity after successful malaria treatment. HRP2 tests are also threatened by the emergence of Plasmodium that do not carry pfhrp2 or pfhrp 3 genes. Plasmodium lactate dehydrogenase (pLDH)-based tests are promising alternatives, but less available. This study assessed the performances of HRP2 and pLDH(pan) tests under field conditions.
METHODS
The study performed a prospective facility-based diagnostic evaluation of two malaria RDTs in Aweil, South Sudan, during the high transmission season. Capillary blood by fingerprick was collected from 800 children under 15 years of age with fever and no signs of severity. SD Bioline HRP2 and CareStart pLDH(pan) RDTs were performed in parallel, thick and thin smears for microscopy were examined, and dried blood was used for PCR testing.
RESULTS
Using microscopy as the gold standard, the sensitivity of both tests was estimated at > 99%, but the specificity of each was lower: 55.0% for the pLDH test and 61.7% for the HRP2 test. When using PCR as the gold standard, the sensitivity of both tests was lower than the values assessed using microscopy (97.0% for pLDH and 96.5% for HRP2), but the specificity increased (65.1% for pLDH and 72.9% for HRP2). Performance was similar across different production lots, sex, and age. Specificity of both the pLDH and HRP2 tests was significantly lower in children who reported taking a therapeutic course of anti-malarials in the 2 months prior to enrollment. The prevalence of pfhrp2/3 deletions in the study population was 0.6%.
CONCLUSIONS
The low specificity of the pLDH RDT in this setting confirms previous results and suggests a problem with this specific test. The prevalence of pfhrp2/3 deletions in the study area warrants continued monitoring and underscores the relevance of assessing deletion prevalence nationally. Improved malaria RDTs for high-transmission environments are needed.