Toward Health System Recovery in the Aftermath of Ebola Outbreak in Guinea: New Approaches for Improved Knowledge of Target Populations at the Community Level.

BACKGROUND: Before the COVID-19 pandemic, Guinea has been the epicenter of the huge West Africa Ebola outbreak (2014-2016), that impact heavily the health system. Demographic information is one of the most basic data sources for health systems and services delivery, and yet can be very difficult to obtain with any accuracy. The objectives were to contribute among other to: (i) a determination of the catchment area (health coverage area and responsibility) of the Kirikilan health facility (PCM); (ii) geocoded mapping to find out exactly where these populations per sector of Kirikilan neighborhood lives; (iii) an approach for regular and systematic annual demographic follow up of target populations. METHODS: The study was a 3-year community-based survey with annual follow up of the population within the quartier of Kirikilan in Dubreka Prefecture in Guinea. It was an exhaustive enumeration of the population, sector by sector of the quartier, then there was no sampling size neither estimation. RESULTS: In October 2017 as a baseline of the study, the enumeration showed the total population was 8824 persons, 936 compounds, 1435 households, and the breakdown by sub quartier (sector) has been performed. It's showed the interest of the mapping of the target populations with geo-referenced localization. The annual follow up by demographic enumerus showed a dramatic increase of the size of the population, including strong migration of the evicted population due to urbanization purpose in some districts of Conakry, the capital. CONCLUSION: The study showed the importance of the enumeration and follow up of the target populations, but also of the setting up community data based to improve the district health information system (DHIS 2) in Guinea. The approach has a best practice could be an importunity to improve data sharing, mapping, health quality access, and affordability for a sustainable health toward universal health coverage.

Plasma Proteomic Analysis Distinguishes Severity Outcomes of Human Ebola Virus Disease.

Ebola virus (EBV) disease (EVD) is a highly virulent systemic disease characterized by an aggressive systemic inflammatory response and impaired vascular and coagulation systems, often leading to uncontrolled hemorrhaging and death. In this study, the proteomes of 38 sequential plasma samples from 12 confirmed EVD patients were analyzed. Of these 12 cases, 9 patients received treatment with interferon beta 1a (IFN-ß-1a), 8 survived EVD, and 4 died; 2 of these 4 fatalities had received IFN-ß-1a. Our analytical strategy combined three platforms targeting different plasma subproteomes: a liquid chromatography-mass spectrometry (LC-MS)-based analysis of the classical plasma proteome, a protocol that combines the depletion of abundant plasma proteins and LC-MS to detect less abundant plasma proteins, and an antibody-based cytokine/chemokine multiplex assay. These complementary platforms provided comprehensive data on 1,000 host and viral proteins. Examination of the early plasma proteomes revealed protein signatures that differentiated between fatalities and survivors. Moreover, IFN-ß-1a treatment was associated with a distinct protein signature. Next, we examined those proteins whose abundances reflected viral load measurements and the disease course: resolution or progression. Our data identified a prognostic 4-protein biomarker panel (histone H1-5, moesin, kininogen 1, and ribosomal protein L35 [RPL35]) that predicted EVD outcomes more accurately than the onset viral load. IMPORTANCE As evidenced by the 2013-2016 outbreak in West Africa, Ebola virus (EBV) disease (EVD) poses a major global health threat. In this study, we characterized the plasma proteomes of 12 individuals infected with EBV, using two different LC-MS-based proteomics platforms and an antibody-based multiplexed cytokine/chemokine assay. Clear differences were observed in the host proteome between individuals who survived and those who died, at both early and late stages of the disease. From our analysis, we derived a 4-protein prognostic biomarker panel that may help direct care. Given the ease of implementation, a panel of these 4 proteins or subsets thereof has the potential to be widely applied in an emergency setting in resource-limited regions.

Human Diversity of Killer Cell Immunoglobulin-Like Receptors and Human Leukocyte Antigen Class I Alleles and Ebola Virus Disease Outcomes.

We investigated the genetic profiles of killer cell immunoglobulin-like receptors (KIRs) in Ebola virus-infected patients. We studied the relationship between KIR-human leukocyte antigen (HLA) combinations and the clinical outcomes of patients with Ebola virus disease (EVD). We genotyped KIRs and HLA class I alleles using DNA from uninfected controls, EVD survivors, and persons who died of EVD. The activating 2DS4-003 and inhibitory 2DL5 genes were significantly more common among persons who died of EVD; 2DL2 was more common among survivors. We used logistic regression analysis and Bayesian modeling to identify 2DL2, 2DL5, 2DS4-003, HLA-B-Bw4-Thr, and HLA-B-Bw4-Ile as probably having a significant relationship with disease outcome. Our findings highlight the importance of innate immune response against Ebola virus and show the association between KIRs and the clinical outcome of EVD.

Longitudinal antibody and T cell responses in Ebola virus disease survivors and contacts: an observational cohort study.

BACKGROUND: The 2013-16 Ebola virus disease epidemic in west Africa caused international alarm due to its rapid and extensive spread resulting in a significant death toll and social unrest within the affected region. The large number of cases provided an opportunity to study the long-term kinetics of Zaire ebolavirus-specific immune response of survivors in addition to known contacts of those infected with the virus. METHODS: In this observational cohort study, we worked with leaders of Ebola virus disease survivor associations in two regions of Guinea, Guéckédou and Coyah, to recruit survivors of Ebola virus disease, contacts from households of individuals known to have had Ebola virus disease, and individuals who were not knowingly associated with infected individuals or had not had Ebola virus disease symptoms to serve as negative controls. We did Zaire ebolavirus glycoprotein-specific T cell analysis on peripheral blood mononuclear cells (PBMCs) on location in Guinea and transported plasma and PBMCs back to Europe for antibody quantification by ELISA, functional neutralising antibody analysis using live Zaire ebolavirus, and T cell phenotype studies. We report on the longitudinal cellular and humoral response among Ebola virus disease survivors and highlight potentially paucisymptomatic infection. FINDINGS: We recruited 117 survivors of Ebola virus disease, 66 contacts, and 23 negative controls. The mean neutralising antibody titre among the Ebola virus disease survivors 3-14 months after infection was 1/174 (95% CI 1/136-1/223). Individual results varied greatly from 1/10 to more than 1/1000 but were on average ten times greater than that induced after 1 month by single dose Ebola virus vaccines. Following reactivation with glycoprotein peptide, the mean T cell responses among 116 Ebola virus disease survivors as measured by ELISpot was 305 spot-forming units (95% CI 257-353). The dominant CD8+ polyfunctional T cell phenotype, as measured among 53 Ebola virus disease survivors, was interferon γ+, tumour necrosis factor+, interleukin-2-, and the mean response was 0·046% of total CD8+ T cells (95% CI 0·021-0·071). Additionally, both neutralising antibody and T cell responses were detected in six (9%) of 66 Ebola virus disease contacts. We also noted that four (3%) of 117 individuals with Ebola virus disease infections did not have circulating Ebola virus-specific antibodies 3 months after infection. INTERPRETATION: The continuous high titre of neutralising antibodies and increased T cell response might support the concept of long-term protective immunity in survivors. The existence of antibody and T cell responses in contacts of individuals with Ebola virus disease adds further evidence to the existence of sub-clinical Ebola virus infection. FUNDING: US Food & Drug Administration, Horizon 2020 EU EVIDENT, Wellcome, UK Department for International Development. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Néoplasies intraépithéliales du col utérin chez la congolaise à Kinshasa : intérêt des biomarqueurs immunohistochimiques

Contexte et objectif.Bien que le cancer du col utérin soit le deuxième cancer plus fréquent chez la femme en Afrique, le recours aux biomarqueurs immunohistochimiques reste exceptionnel en Afrique subsaharienne. La présente étude avait pour objectif de montrer l'apport des biomarqueurs p16 et Ki-67 dans le diagnostic des néoplasies intra-épithéliales du col utérin. Méthodes. C'était une étude rétrospective réalisée dans cinq laboratoires d'Anatomie Pathologique de Kinshasa. Des lames biopsiques ont été relues et reclassées par au moins deux pathologistes indépendants aux Cliniques Universitaires de Kinshasa en suivant la nomenclature de Bethesda/OMS. L'immunomarquage (p16 et Ki-67) a été réalisé avec un contrôle qualité externe en Europe. Résultats. 70 cas ont été inclus. Les 24 cas des néoplasies intra-épithéliales de haut grade (CIN2, CIN3 et CIS) étaient marquées positivement par p16 et Ki-67 alors que celles de bas grade étaient marquées positivement pour 41 cas de CIN1 et négativement pour 5 cas (3 de CIN1 et 2 de CP). Certaines lésions ont été requalifiées. L'immunomarquage était significativement associé au grade des néoplasies pour la p16 (p=0,001) et pour le Ki-67 (p=0,004). Conclusion. P16 et Ki-67 sont des biomarqueurs spécifiques et efficaces pour un diagnostic optimal des néoplasies intra-épithéliales du col utérin

Fréquence des néphropathies congénitales au Centre hospitalier universitaire de Donka à Conakry

Contexte et objectif. L'ampleur réelle des néphropathies congénitales est peu connue en Afrique et notamment en Guinée. L'objectif de cette étude était de déterminer la fréquence des néphropathies congénitales rencontrées. Méthodes. Cette étude documentaire de type descriptif sur la néphropathie congénitale, a été conduite entre les 1er janvier 2007 et 30 juin 2012, dans les services de pédiatrie et de chirurgie pédiatrique de Donka. Les paramètres d'intêret englobaient les données épidémiologiques, cliniques et paracliniques. Résultats. Parmi les 34.448 dossiers colligés, 26 présentaient une néphropathie congénitale. Il s'agissait des néphroblastomes (n=17), des syndromes de jonction pyélo-urétérale (n=6), d'une hydronéphrose sur rein multikystique gauche (n=1), d'un rein multikystique en ptose (n=1) et d'une ectopie rénale (n=1). Le sexe masculin était prépondérant (21/26) avec un sexe ratio de 4,2/1. Les enfants de 29 jours à 2 ans étaient les plus touchés. Conclusion. Les néphropathies congénitales sont paraissent moins fréquentes dans cette institution hospitalière, à cause du manque d'un plateau technique diagnostique optimal. Le diagnostic précoce des néphropathies congénitales devrait être fait dans la période prénatale ce qui permettrait une meilleure prise en charge des enfants affectés