Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in adults in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial.

BACKGROUND: The 2014 Zaire Ebola virus disease epidemic accelerated vaccine development for the virus. We aimed to assess the safety, reactogenicity, and immunogenicity of one dose of monovalent, recombinant, chimpanzee adenovirus type-3 vectored Zaire Ebola glycoprotein vaccine (ChAd3-EBO-Z) in adults. METHODS: This phase 2, randomised, observer-blind, controlled trial was done in study centres in Cameroon, Mali, Nigeria, and Senegal. Healthy adults (≥18 years) were randomly assigned with a web-based system (1:1; minimisation procedure accounting for age, gender, centre) to receive ChAd3-EBO-Z (day 0), or saline placebo (day 0) and ChAd3-EBO-Z (month 6). The study was observer-blind until planned interim day 30 analysis, single-blind until month 6, and open-label after month 6 vaccination. Primary outcomes assessed in the total vaccinated cohort, which comprised all participants with at least one study dose administration documented, were serious adverse events (up to study end, month 12); and for a subcohort were solicited local or general adverse events (7 days post-vaccination), unsolicited adverse events (30 days post-vaccination), haematological or biochemical abnormalities, and clinical symptoms of thrombocytopenia (day 0-6). Secondary endpoints (subcohort; per-protocol cohort) evaluated anti-glycoprotein Ebola virus antibody titres (ELISA) pre-vaccination and 30 days post-vaccination. This study is registered with ClinicalTrials.gov, NCT02485301. FINDINGS: Between July 22, 2015, and Dec 10, 2015, 3030 adults were randomly assigned; 3013 were included in the total vaccinated cohort (1509 [50·1%] in the ChAd3-EBO-Z group and 1504 [49·9%] in the placebo/ChAd3-EBO-Z group), 17 were excluded because no vaccine was administered. The most common solicited injection site symptom was pain (356 [48%] of 748 in the ChAd3-EBO-Z group vs 57 [8%] of 751 in the placebo/ChAd3-EBO-Z group); the most common solicited general adverse event was headache (345 [46%] in the ChAd3-EBO-Z group vs 136 [18%] in the placebo/ChAd3-EBO-Z group). Unsolicited adverse events were reported by 123 (16%) of 749 in the ChAd3-EBO-Z group and 119 (16%) of 751 in the placebo/ChAd3-EBO-Z group. Serious adverse events were reported for 11 (1%) of 1509 adults in the ChAd3-EBO-Z group, and 18 (1%) of 1504 in the placebo/ChAd3-EBO-Z group; none were considered vaccination-related. No clinically meaningful thrombocytopenia was reported. At day 30, anti-glycoprotein Ebola virus antibody geometric mean concentration was 900 (95% CI 824-983) in the ChAd3-EBO-Z group. There were no treatment-related deaths. INTERPRETATION: ChAd3-EBO-Z was immunogenic and well tolerated in adults. Our findings provide a strong basis for future development steps, which should concentrate on multivalent approaches (including Sudan and Marburg strains). Additionally, prime-boost approaches should be a focus with a ChAd3-based vaccine for priming and boosted by a modified vaccinia Ankara-based vaccine. FUNDING: EU's Horizon 2020 research and innovation programme and GlaxoSmithKline Biologicals SA.

Safety, reactogenicity, and immunogenicity of a chimpanzee adenovirus vectored Ebola vaccine in children in Africa: a randomised, observer-blind, placebo-controlled, phase 2 trial.

BACKGROUND: During the large 2013-16 Ebola virus outbreak caused by the Zaire Ebola virus, about 20% of cases were reported in children. This study is the first, to our knowledge, to evaluate an Ebola vaccine in children younger than 6 years. We aimed to evaluate the safety, reactogenicity, and immunogenicity of a monovalent, recombinant, chimpanzee adenovirus type-3 vectored Zaire Ebola glycoprotein vaccine (ChAd3-EBO-Z) in a paediatric population. METHODS: This phase 2, randomised, observer-blind, controlled trial was done in a vaccine centre in Mali and a university hospital centre in Senegal. Healthy children were randomly assigned through a web-based system (1:1; stratified by age group, gender, and centre) to receive ChAd3-EBO-Z (day 0) and meningococcal serogroups A,C,W-135,Y tetanus toxoid conjugate vaccine (MenACWY-TT; month 6), or MenACWY-TT (day 0) and ChAd3-EBO-Z (month 6). The study was observer-blind from study start until interim day 30 analysis and became single-blind as of interim analysis. Primary outcomes assessed were serious adverse events (up to study end, month 12), solicited local or general adverse events (7 days post-vaccination), unsolicited adverse events (30 days post-vaccination), haematological or biochemical abnormalities, and clinical symptoms of thrombocytopenia (day 0-6). As secondary endpoints, we evaluated anti-glycoprotein Zaire Ebola virus antibody titres (ELISA) pre-vaccination and 30 days post-vaccination. This study is registered with ClinicalTrials.gov, NCT02548078. FINDINGS: From Nov 11, 2015, to May 9, 2016, of 776 children screened for eligibility, 600 were randomly assigned (200 [33%] in each age strata: 1-5, 6-12, 13-17 years), 300 (50%) to the ChAd3-EBO-Z/MenACWY-TT group and 300 (50%) to the MenACWY-TT/ChAd3-EBO-Z group; all were included in the total vaccinated cohort. Post-day 0 vaccination, the most common solicited injection site symptom was pain (127 [42%] of 300 in the ChAd3-EBO-Z/MenACWY-TT group vs 60 [20%] of 300 in the MenACWY-TT/ChAd3-EBO-Z group); the most common solicited general adverse event was fever (95 [32%] of 300 in the ChAd3-EBO-Z/MenACWY-TT group vs 28 [9%] of 300 in the MenACWY-TT/ChAd3-EBO-Z group). Unsolicited adverse events post-day 0 vaccination were reported by 41 (14%) of 300 participants in the ChAd3-EBO-Z/MenACWY-TT group and 24 (8%) of 300 MenACWY-TT/ChAd3-EBO-Z recipients. Serious adverse events were reported for two (1%) of 300 children in each group; none were considered vaccination related. No clinical symptoms of thrombocytopenia were reported. At day 30, anti-glycoprotein Ebola virus antibody geometric mean concentrations (GMC) in the ChAd3-EBO-Z/MenACWY-TT group were 1564 (95% CI 1340-1826) for those aged 13-17 years, 1395 (1175-1655) for 6-12 years, and 2406 (1942-2979) for 1-5 years. Anti-glycoprotein Ebola virus IgG antibody responses persisted up to 12 months post-vaccination, with a GMC of 716 (95% CI 619-828) for those aged 13-17 years, 752 (645-876) for 6-12 years, and 1424 (1119-1814) for 1-5 years. INTERPRETATION: ChAd3-EBO-Z was immunogenic and well tolerated in children aged 1-17 years. This study provides the first ChAd3-EBO-Z data in a paediatric population. Further development should focus on multivalent approaches including Sudan and Marburg strains, and heterologous prime-boost strategies, for instance using modified vaccinia Ankara-based vaccine to boost the immune response. FUNDING: EU's Horizon 2020 research and innovation programme and GlaxoSmithKline Biologicals SA.

[Smoking in People Living with HIV (PLHA) and followed up in the Outpatient Department of the Hospital Fann of Dakar]. / Le tabagisme chez les patients vivant avec le VIH (PvVIH) suivis au Centre de Traitement Ambulatoire de l'Hôpital Fann de Dakar.

INTRODUCTION: PLHA who smoke have twice the never-smoker mortality rate and have an increased risk of developing non-AIDS diseases. The prevalence of tobacco smoking is higher among PLHA than in the general population. The purpose of this study was to assess the prevalence of smoking among PLHA, to describe the clinical and spirometric features of smokers and ex-smokers and to assess their knowledge and attitudes toward smoking. METHODS: We conducted a cross-sectional, descriptive and analytical study among PLHA followed up in the Outpatient Department of the National University Hospital Center of Fann from 15 July to 15 December 2015. RESULTS: Three hundred (300) PLHA were included in the study. Sex ratio was 0.8. Out of the study population, 15% were smokers and 23.7% were ex-smokers. The average age of patients was 44.38±9.55 years. The quasi-totality of the smokers (91.1%) had already started smoking before the detection of the serological status and 35.6% of them had increased tobacco use after. Respiratory symptoms among smokers were dominated by respiratory distress (64.4%). Smokers who underwent spirometry had obstructive ventilatory impairment not improved by beta-2-mimetic agents (67%) and restrictive disease (28.1%). Out of ex-smokers, 40.8% reported that their serological status was the reason for smoking cessation. CONCLUSION: People may begin or increase smoking after knowledge of serological status. In PLHA, smoking causes cardiovascular and respiratory diseases as well as complications.

[Intestinal tuberculosis revealed by acute bowel obstruction during paradoxical reaction to antituberculosis treatment in an immunocompetent patient: about a case and literature review]. / Tuberculose intestinale révélée par une occlusion intestinale aigüe au cours d'une réaction paradoxale au traitement anti-tuberculeux chez un patient immunocompétent: à propos d'un cas et revue de la littérature.

Abdominal tuberculosis accounts for 3 to 5% of all visceral diseases. Despite the demonstrated effectiveness of anti-tuberculosis treatments, some cases of exacerbation of the initial clinical presentation have been described during the initiation of treatment. However, these reactions also known as "paradoxical" have been rarely reported in immunocompetent patients and much less in the case of bowel obstruction. We report a case of intestinal tuberculosis revealed by acute bowel obstruction during paradoxical reaction to anti-tuberculosis treatment. The study included a 26-year old immunocompetent patient with occlusive syndrome after a month of treatment for pleuropulmonary tuberculosis. Abdominal computed tomography (CT) showed small bowel obstruction. Laparotomy objectified intraperitoneal mass with multiple adhesions. Anatomo-pathological examination of the surgical specimen showed intestinal tuberculosis. Patient's outcome was favorable after the continuation of initial antituberculosis treatment.

Use and Acceptability of HIV Self-Testing Among First-Time Testers at Risk for HIV in Senegal.

HIV Self-Testing (HIVST) aims to increase HIV testing coverage and can facilitate reaching the UNAIDS 90-90-90 targets. In Senegal, key populations bear a disproportionate burden of HIV and report limited uptake of HIV testing given pervasive stigma and criminalization. In these contexts, HIVST may represent a complementary approach to reach populations reporting barriers to engagement with existing and routine HIV testing services. In this study, 1839 HIVST kits were distributed in Senegal, with 1149 individuals participating in a pre-test questionnaire and 817 participating in a post-test questionnaire. Overall, 46.9% (536/1144) were first-time testers and 26.2% (300/1144) had tested within the last year; 94.3% (768/814) reported using the HIVST, and 2.9% (19/651) reported a reactive result which was associated with first-time testers (p = 0.024). HIVST represents an approach that reached first-time testers and those who had not tested recently. Implementation indicators suggest the importance of leveraging existing community structures and programs for distribution.

Prevalence, predictors, and management of advanced HIV disease among individuals initiating ART in Senegal, West Africa.

BACKGROUND: The WHO guidelines for the management of advanced HIV disease recommend a package of care consisting of rapid initiation of antiretroviral therapy (ART), enhanced screening and diagnosis of tuberculosis (TB) and cryptococcal meningitis, co-trimoxazole prophylaxis, isoniazid preventive therapy (IPT), fluconazole pre-emptive therapy, and adherence support. The goals of this study were to determine the prevalence of advanced HIV disease among individuals initiating ART in Senegal, to identify predictors of advanced disease, and to evaluate adherence to the WHO guidelines. METHODS: This study was conducted among HIV-positive individuals initiating ART in Dakar and Ziguinchor, Senegal. Clinical evaluations, laboratory analyses, questionnaires and chart review were conducted. Logistic regression was used to identify predictors of advanced disease. RESULTS: A total of 198 subjects were enrolled; 70% were female. The majority of subjects (71%) had advanced HIV disease, defined by the WHO as a CD4 count < 200 cells/mm3 or clinical stage 3 or 4. The median CD4 count was 185 cells/mm3. The strongest predictors of advanced disease were age ≥ 35 (OR 5.80, 95%CI 2.35-14.30) and having sought care from a traditional healer (OR 3.86, 95%CI 1.17-12.78). Approximately one third of subjects initiated ART within 7 days of diagnosis. Co-trimoxazole prophylaxis was provided to 65% of subjects with CD4 counts ≤350 cells/mm3 or stage 3 or 4 disease. TB symptom screening was available for 166 subjects; 54% reported TB symptoms. Among those with TB symptoms, 39% underwent diagnostic evaluation. Among those eligible for IPT, one subject received isoniazid. No subjects underwent CrAg screening or received fluconazole to prevent cryptococcal meningitis. CONCLUSIONS: This is the first study to report an association between seeking care from a traditional healer and presentation with WHO defined advanced disease in sub-Saharan Africa. Given the widespread use of traditional healers in sub-Saharan Africa, future studies to further explore this finding are indicated. Although the majority of individuals in this study presented with advanced disease and warranted management according to WHO guidelines, there were numerous missed opportunities to prevent HIV-associated morbidity and mortality. Programmatic evaluation is needed to identify barriers to implementation of the WHO guidelines and enhanced funding for operational research is indicated.

HIV screening in men and women in Senegal: coverage and associated factors; analysis of the 2017 demographic and health survey.

BACKGROUND: Despite the adoption of the provider-initiated HIV testing strategy, the rate of HIV testing is still very low in sub-Saharan Africa. The aim of this study was to assess the factors associated with HIV testing among sexually active women and men in Senegal. Knowledge of HIV status is the gateway to antiretroviral treatment. METHODS: A secondary analysis of the 2017 Senegal Demographic and Health Survey (DHS) was performed, using data on sexually active women aged 15-49 and men aged 15-59. The outcome variable was the proportion of women and men who reported ever being tested for HIV in the last 12 months before the survey. Descriptive, bivariate, and multivariable logistic regression analyses were performed to identify the socio-demographic, HIV-knowledge, media exposure, and behavioral factors associated with HIV testing in Senegal. RESULTS: The study found that 61.1% (95%CI: 59.2-62.9) of women and 26.2% (95%CI: 24.2-28.3) of men were tested for HIV at the last 12 months. In multivariate analysis, among men the factors independently associated with being tested for HIV were: age groups 20-24 to 40-44 and age group 50-54; a higher level of education; being in the richest household wealth quintile; being married; knowing about the efficacy of HAART during pregnancy; having 2 or more lifetime sex partners and owning a mobile phone. Among women factors independently associated with HIV testing were: being in any age groups versus 15-19; a higher level of education; being in the richest household wealth quintile; being married; knowing about the efficacy of HAART during pregnancy; having any STI in last 12 months; fearing stigma; owning a mobile phone; and having any number of ANC visits, versus none. CONCLUSION: Although HIV remains a public health threat, HIV testing's prevalence is still low in Senegal, making it difficult to interrupt the transmission chain within the community and to reach the UNAIDS goal for 2020 of "90-90-90". Innovative community-based strategies are needed to address barriers and improve access to HIV testing in Senegal, particularly for men and for the youngest and poorest populations.

[TB/HIV co-infection associated with Kaposi's sarcoma under opioid substitution treatment using methadone: about a case]. / Co-infection tuberculose/VIH et Maladie de kaposi sous traitement de substitution par la méthadone: à propos d'un cas.

Late diagnosis of HIV infection can be fatal because it favors the appearance of opportunistic infections whose management requires the use of several molecules which can cause drug interactions. We report the case of a 45-year old female patient under heroin substitution treatment, using methadone and with HIV1 under antiretroviral treatment. This patient had nonspecific pulmonary appearance associated with dry nagging cough and progressive dyspnea evolving in a feverish context. Moreover, clinical examination showed left lower limb lymphedema with painless angiomatous nodules evolving over three years associated with plaques, angiomatous nodules occurred more recently at the level of the anterior face of the thorax. Sputum GeneXpert test allowed isolation of Mycobacterium tuberculosis. The diagnosis of pulmonary tuberculosis associated with Kaposi's sarcoma and immunosuppression caused by HIV was retained.

Feasibility, safety and effectiveness of combining home based malaria management and seasonal malaria chemoprevention in children less than 10 years in Senegal: a cluster-randomised trial.

BACKGROUND: Home-based management of malaria (HMM) may improve access to diagnostic testing and treatment with artemisinin combination therapy (ACT). In the Sahel region, seasonal malaria chemoprevention (SMC) is now recommended for the prevention of malaria in children. It is likely that combinations of antimalarial interventions can reduce the malaria burden. This study assessed the feasibility, effectiveness and safety of combining SMC and HMM delivered by community health workers (CHWs). METHODS: A cluster-randomised trial was carried out during two transmission seasons in eight villages located in the south-eastern part of Senegal. Intervention communities received HMM+SMC while control communities received HMM. Primary end point was the incidence of malaria attacks during the follow up period. Secondary end points included: malaria diagnostic accuracy; access to ACT treatment; SMC coverage; safety and drug tolerability. RESULTS: The adjusted rate ratio for incidence of malaria attacks in intervention and control communities was 0.15, indicating a protective effect of HMM+SMC of 85% (95% CI: 39.9-96.3%, p=0.01). Access to ACT treatment was 96.4% while SMC coverage represented 97.3% (95% CI: 91.3-100%) in 2010, and 88.8% (95% CI: 84.2-93.6%) in 2011. No serious adverse events were recorded. CONCLUSION: It seems feasible and safe to combine SMC with HMM intervention, while achieving high coverage and effectiveness of both SMC and HMM. TRIAL REGISTRATION: (www.pactr.org) PACTR201305000551876.

Cryptococcal meningitis in Senegal: epidemiology, laboratory findings, therapeutic and outcome of cases diagnosed from 2004 to 2011.

BACKGROUND: Cryptococcal meningitis is one of the most important opportunistic infection and a major contributor to early mortality. In sub-Saharan Africa, particularly in Senegal, prevalence of cryptococcal meningitis remains high. This study aimed to describe the epidemiology, laboratory profile, therapeutic and outcome of cases diagnosed in Dakar. METHODS: We analyzed the cryptococcosis cases diagnosed at the department of parasitology-mycology in Fann Teaching Hospital in Dakar from 2004 to 2011. The diagnosis was confirmed by culture on Sabouraud's dextrose agar and/or by India ink preparation and/or by cryptococcal antigen detection. The diagnosis methods were assessed by using culture as reference. RESULTS: A total of 106 cases of cryptococcal meningitis were diagnosed. The prevalence of cryptococcal meningitis was 7.8 %. The mean age of the patients was 40.17 ± 9.89 years. There were slightly more male (53.8 %) than female (46.2 %) patients; 89.6 % were found to be infected with HIV, and the median CD4+ count was 27/mm(3). Approximately 79.5 % of the patients had <100 CD4+ lymphocytes/mm(3). India ink staining presented sensitivity at 94.11 % and specificity at 100 %. Sensitivity and specificity of cryptococcal antigen detection in cerebrospinal fluid were, respectively, 96.96 and 15.78 %. The most frequently used antifungal drug was fluconazole (86.7 %), and the mortality rate was 62.2 % (66 deaths). CONCLUSION: Early diagnosis is essential to control cryptococcosis, and countries should prioritize widespread and reliable access to rapid diagnostic cryptococcus antigen assays. But it is important to make available conventional methods (India ink and culture) in the maximum of laboratory in regional health facilities.

Acceptability by community health workers in Senegal of combining community case management of malaria and seasonal malaria chemoprevention.

BACKGROUND: Community case management of malaria (CCMm) and seasonal malaria chemoprevention (SMC) are anti-malarial interventions that can lead to substantial reduction in malaria burden acting in synergy. However, little is known about the social acceptability of these interventions. A study was undertaken to assess whether combining the interventions would be an acceptable approach to malaria control for community health workers (CHWs). METHODS: Sixty-one interviews and six focus group discussions were conducted nested in a cluster-randomized trial assessing the impact of combining CCMm and SMC in a rural area of Senegal. Participants consisted of: (i) members of village associations, (ii) members of families who had access to the interventions as well as members of families who did not access the interventions, (iii) CHWs, and (iv) community leaders, e g, religious guides and village chiefs. RESULTS: The interventions were acceptable to the local population and perceived as good strategy to make health care services available to community members and thus, to reduce the delays in access to anti-malarial treatment as well as expenses related to patients' transfer to the health post. The use of malaria rapid diagnostic test (RDT) contributed to improving CHWs diagnostic capacity as well as malaria treatment practices. Study participants notified RDT and drugs stock-out as the major risk for sustainability of the intervention at community level. CONCLUSION: Combining CCMm and SMC is a well accepted, community-based approach that can contribute to control malaria in areas where malaria transmission is seasonal.