Case fatality risk among individuals vaccinated with rVSVΔG-ZEBOV-GP: a retrospective cohort analysis of patients with confirmed Ebola virus disease in the Democratic Republic of the Congo.

BACKGROUND: The rVSVΔG-ZEBOV-GP vaccine constitutes a valuable tool to control Ebola virus disease outbreaks. This retrospective cohort study aimed to assess the protective effect of the vaccine against death among patients with confirmed Ebola virus disease. METHODS: In this retrospective cohort analysis of patients with confirmed Ebola virus disease admitted to Ebola health facilities in the Democratic Republic of the Congo between July 27, 2018, and April 27, 2020, we performed univariate and multivariate analyses to assess case fatality risk and cycle threshold for nucleoprotein according to vaccination status, Ebola virus disease-specific treatments (eg, mAb114 and REGN-EB3), and other risk factors. FINDINGS: We analysed all 2279 patients with confirmed Ebola virus disease. Of these 2279 patients, 1300 (57%) were female and 979 (43%) were male. Vaccination significantly lowered case fatality risk (vaccinated: 25% [106/423] vs not vaccinated: 56% [570/1015]; p<0·0001). In adjusted analyses, vaccination significantly lowered the risk of death compared with no vaccination, with protection increasing as time elapsed from vaccination to symptom onset (vaccinated ≤2 days before onset: 27% [27/99], adjusted relative risk 0·56 [95% CI 0·36-0·82, p=0·0046]; 3-9 days before onset: 20% [28/139], 0·44 [0·29-0·65, p=0·0001]; ≥10 days before onset: 18% [12/68], 0·40 [0·21-0·69; p=0·0022]; vaccination date unknown: 33% [39/117], 0·69 [0·48-0·96; p=0·0341]; and vaccination status unknown: 52% [441/841], 0·80 [0·70-0·91, p=0·0011]). Longer time from symptom onset to admission significantly increased risk of death (49% [1117/2279], 1·03 [1·02-1·05; p<0·0001]). Cycle threshold values for nucleoprotein were significantly higher-indicating lower viraemia-among patients who were vaccinated compared with those who were not vaccinated; the highest difference was observed among those vaccinated 21 days or longer before symptom onset (median 30·0 cycles [IQR 24·6-33·7]) compared with patients who were not vaccinated (21·4 cycles [18·4-25·9], p<0·0001). INTERPRETATION: To our knowledge, this is the first observational study describing the protective effect of rVSVΔG-ZEBOV-GP vaccination against death among patients with confirmed Ebola virus disease admitted to an Ebola health facility. Vaccination was protective against death for all patients, even when adjusted for Ebola virus disease-specific treatment, age group, and time from symptom onset to admission. FUNDING: Médecins Sans Frontières. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Correction: What gaps remain in the HIV cascade of care? Results of a population-based survey in Nsanje District, Malawi.

[This corrects the article DOI: 10.1371/journal.pone.0248410.].

Differential symptomology of possible and confirmed Ebola virus disease infection in the Democratic Republic of the Congo: a retrospective cohort study.

BACKGROUND: In its earliest phases, Ebola virus disease's rapid-onset, high fever, and gastrointestinal symptoms are largely indistinguishable from other infectious illnesses. We aimed to characterise the clinical indicators associated with Ebola virus disease to improve outbreak response. METHODS: In this retrospective analysis, we assessed routinely collected data from individuals with possible Ebola virus disease attending 30 Ebola health facilities in two provinces of the Democratic Republic of the Congo between Aug 1, 2018, and Aug 28, 2019. We used logistic regression analysis to model the probability of Ebola infection across 34 clinical variables and four types of possible Ebola virus disease exposures: contact with an individual known to have Ebola virus disease, attendance at any funeral, health facility consultation, or consultation with an informal health practitioner. FINDINGS: Data for 24 666 individuals were included. If a patient presented to care in the early symptomatic phase (ie, days 0-2), Ebola virus disease positivity was most associated with previous exposure to an individual with Ebola virus disease (odds ratio [OR] 11·9, 95% CI 9·1-15·8), funeral attendance (2·1, 1·6-2·7), or health facility consultations (2·1, 1·6-2·8), rather than clinical parameters. If presentation occurred on day 3 or later (after symptom onset), bleeding at an injection site (OR 33·9, 95% CI 12·7-101·3), bleeding gums (7·5, 3·7-15·4), conjunctivitis (2·4, 1·7-3·4), asthenia (1·9, 1·5-2·3), sore throat (1·8, 1·3-2·4), dysphagia (1·8, 1·4-2·3), and diarrhoea (1·6, 1·3-1·9) were additional strong predictors of Ebola virus disease. Some Ebola virus disease-specific signs were less prevalent among vaccinated individuals who were positive for Ebola virus disease when compared with the unvaccinated, such as dysphagia (-47%, p=0·0024), haematemesis (-90%, p=0·0131), and bleeding gums (-100%, p=0·0035). INTERPRETATION: Establishing the exact time an individual first had symptoms is essential to assessing their infection risk. An individual's exposure history remains of paramount importance, especially in the early phase. Ebola virus disease vaccination reduces symptom severity and should also be considered when assessing the likelihood of infection. These findings about symptomatology should be translated into practice during triage and should inform testing and quarantine procedures. FUNDING: Médecins Sans Frontières and its research affiliate Epicentre.

What gaps remain in the HIV cascade of care? Results of a population-based survey in Nsanje District, Malawi.

INTRODUCTION: The Malawi Ministry of Health (MoH) has been in collaboration with Médecins sans Frontières (MSF) to increase access to quality HIV care through decentralization of antiretroviral therapy (ART) diagnosis and treatment from hospital to clinics in Nsanje District since 2011. A population-based household survey was implemented to provide information on HIV prevalence and cascade of care to inform and prioritize community-based HIV interventions in the district. METHODS: A cross-sectional survey was conducted between September 2016 and January 2017. Using two-stage cluster sampling, eligible adult individuals aged ≥15 years living in the selected households were asked to participate. Participants were interviewed and tested for HIV at home. Those tested HIV-positive had their HIV-RNA viral load (VL) measured, regardless of their ART status. All participants tested HIV-positive at the time of the survey were advised to report their HIV test result to the health facility of their choice that MSF was supported in the district. HIV-RNA VL results were made available in this health facility. RESULTS: Among 5,315 eligible individuals, 91.1% were included in the survey and accepted an HIV test. The overall prevalence was 12.1% (95% Confidence Interval (CI): 11.2-13.0) and was higher in women than in men: 14.0% versus 9.5%, P<0.001. Overall HIV-positive status awareness was 80.0% (95%CI: 76.4-83.1) and was associated with sex (P<0.05). Linkage to care was 78.0% (95%CI: 74.3-81.2) and participants in care 76.2% (95%CI: 72.4-79.5). ART coverage among participants aware of their HIV-positive status was 95.3% (95%CI: 92.9-96.9) and was not associated with sex (P = 0.55). Viral load suppression among participants on ART was 89.9% (95%CI: 86.6-92.4) and was not statistically different by sex (p = 0.40). CONCLUSIONS: Despite encouraging results in HIV testing coverage, cascade of care, and UNAIDS targets in Nsanje District, some gap remains in the first 90, specifically among men and young adults. Enhanced community engagement and new strategies of testing, such as index testing, could be implemented to identify those who are still undiagnosed, particularly men and young adults.

Successes and gaps in the HIV cascade of care of a high HIV prevalence setting in Zimbabwe: a population-based survey.

INTRODUCTION: Gutu, a rural district in Zimbabwe, has been implementing comprehensive HIV care with the support of Médecins Sans Frontières (MSF) since 2011, decentralizing testing and treatment services to all rural healthcare facilities. We evaluated HIV prevalence, incidence and the cascade of care, in Gutu District five years after MSF began its activities. METHODS: A cross-sectional study was implemented between September and December 2016. Using multistage cluster sampling, individuals aged ≥15 years living in the selected households were eligible. Individuals who agreed to participate were interviewed and tested for HIV at home. All participants who tested HIV-positive had their HIV-RNA viral load (VL) measured, regardless of their antiretroviral therapy (ART) status, and those not on ART with HIV-RNA VL ≥ 1000 copies/mL had Limiting-Antigen-Avidity EIA Assay for cross-sectional estimation of population-level HIV incidence. RESULTS: Among 5439 eligible adults ≥15 years old, 89.0% of adults were included in the study and accepted an HIV test. The overall prevalence was 13.6% (95%: Confidence Interval (CI): 12.6 to 14.5). Overall HIV-positive status awareness was 87.4% (95% CI: 84.7 to 89.8), linkage to care 85.5% (95% CI: 82.5 to 88.0) and participants in care 83.8% (95% CI: 80.7 to 86.4). ART coverage among HIV-positive participants was 83.0% (95% CI: 80.0 to 85.7). Overall, 71.6% (95% CI 68.0 to 75.0) of HIV-infected participants had a HIV-RNA VL < 1000 copies/mL. Women achieved higher outcomes than men in the five stages of the cascade of care. Viral Load Suppression (VLS) among participants on ART was 83.2% (95% CI: 79.7 to 86.2) and was not statistically different between women and men (p = 0.98). The overall HIV incidence was estimated at 0.35% (95% CI 0.00 to 0.70) equivalent to 35 new cases/10,000 person-years. CONCLUSIONS: Our study provides population-level evidence that achievement of HIV cascade of care coverage overall and among women is feasible in a context with broad access to services and implementation of a decentralized model of care. However, the VLS was relatively low even among participants on ART. Quality care remains the most critical gap in the cascade of care to further reduce mortality and HIV transmission.

Field evaluation of GeneXpert® (Cepheid) HCV performance for RNA quantification in a genotype 1 and 6 predominant patient population in Cambodia.

GeneXpert® (Cepheid) is the only WHO prequalified platform for hepatitis C virus (HCV) nucleic acid amplification testing that is suitable for point-of-care use in resource-limited contexts. However, its application is constrained by the lack of evidence on genotype 6 (GT6) HCV. We evaluated its field performance among a patient population in Cambodia predominantly infected with GT6. Between August and September 2017, we tested plasma samples obtained from consenting patients at Médecins Sans Frontières' HCV clinic at Preah Kossamak Hospital for HCV viral load (VL) using GeneXpert® and compared its results to those obtained using COBAS® AmpliPrep/Cobas® TaqMan® HCV Quantitative Test, v2.0 (Roche) at the Institut Pasteur du Cambodge. Among 769 patients, 77% of the seropositive patients (n = 454/590) had detectable and quantifiable VL using Roche and 43% (n = 195/454) were GT6. The sensitivity and specificity of GeneXpert® against Roche were 100% (95% CI 99.2, 100.0) and 98.5% (95% CI 94.8, 99.8). The mean VL difference was -0.01 (95% CI -0.05, 0.02) log10  IU/mL for 454 samples quantifiable on Roche and -0.07 (95% CI -0.12, -0.02) log10  IU/mL for GT6 (n = 195). The limit of agreement (LOA) was -0.76 to 0.73 log10  IU/mL for all GTs and -0.76 to 0.62 log10 IU/mL for GT6. Twenty-nine GeneXpert® results were outside the LOA. Frequency of error and the median turnaround time (TAT) for GeneXpert® were 1% and 0 days (4 days using Roche). We demonstrated that the GeneXpert® HCV assay has good sensitivity, specificity, quantitative agreement, and TAT in a real-world, resource-limited clinical setting among GT6 HCV patients.

Syrian refugees in Greece: experience with violence, mental health status, and access to information during the journey and while in Greece.

BACKGROUND: Since 2015, Europe has been facing an unprecedented arrival of refugees and migrants: more than one million people entered via land and sea routes. During their travels, refugees and migrants often face harsh conditions, forced detention, and violence in transit countries. However, there is a lack of epidemiological quantitative evidence on their experiences and the mental health problems they face during their displacement. We aimed to document the types of violence experienced by migrants and refugees during their journey and while settled in Greece, and to measure the prevalence of anxiety disorders and access to legal information and procedures. METHODS: We conducted a cross-sectional population-based quantitative survey combined with an explanatory qualitative study in eight sites (representing the range of settlements) in Greece during winter 2016/17. The survey consisted of a structured questionnaire on experience of violence and an interviewer-administered anxiety disorder screening tool (Refugee Health Screener). RESULTS: In total, 1293 refugees were included, of whom 728 were Syrians (41.3% females) of median age 18 years (interquartile range 7-30). Depending on the site, between 31% and 77.5% reported having experienced at least one violent event in Syria, 24.8-57.5% during the journey to Greece, and 5-8% in their Greek settlement. Over 75% (up to 92%) of respondents ≥15 years screened positive for anxiety disorder, which warranted referral for mental health evaluation, which was only accepted by 69-82% of participants. Access to legal information and assistance about asylum procedures were considered poor to non-existent for the majority, and the uncertainty of their status exacerbated their anxiety. CONCLUSIONS: This survey, conducted during a mass refugee crisis in a European Community country, provides important data on experiences in different refugee settings and reports the high levels of violence experienced by Syrian refugees during their journeys, the high prevalence of anxiety disorders, and the shortcomings of the international protective response.

Rapid Fractionation and Isolation of Whole Blood Components in Samples Obtained from a Community-based Setting.

Collection and processing of whole blood samples in a non-clinical setting offers a unique opportunity to evaluate community-dwelling individuals both with and without preexisting conditions. Rapid processing of these samples is essential to avoid degradation of key cellular components. Included here are methods for simultaneous peripheral blood mononuclear cell (PBMC), DNA, RNA and serum isolation from a single blood draw performed in the homes of consenting participants across a metropolitan area, with processing initiated within 2 hr of collection. We have used these techniques to process over 1,600 blood specimens yielding consistent, high quality material, which has subsequently been used in successful DNA methylation, genotyping, gene expression and flow cytometry analyses. Some of the methods employed are standard; however, when combined in the described manner, they enable efficient processing of samples from participants of population- and/or community-based studies who would not normally be evaluated in a clinical setting. Therefore, this protocol has the potential to obtain samples (and subsequently data) that are more representative of the general population.

Pooled HIV-1 viral load testing using dried blood spots to reduce the cost of monitoring antiretroviral treatment in a resource-limited setting.

Rollout of routine HIV-1 viral load monitoring is hampered by high costs and logistical difficulties associated with sample collection and transport. New strategies are needed to overcome these constraints. Dried blood spots from finger pricks have been shown to be more practical than the use of plasma specimens, and pooling strategies using plasma specimens have been demonstrated to be an efficient method to reduce costs. This study found that combination of finger-prick dried blood spots and a pooling strategy is a feasible and efficient option to reduce costs, while maintaining accuracy in the context of a district hospital in Malawi.

Facemasks, hand hygiene, and influenza among young adults: a randomized intervention trial.

UNLABELLED: Limited vaccine availability and the potential for resistance to antiviral medications have led to calls for establishing the efficacy of non-pharmaceutical measures for mitigating pandemic influenza. Our objective was to examine if the use of face masks and hand hygiene reduced rates of influenza-like illness (ILI) and laboratory-confirmed influenza in the natural setting. A cluster-randomized intervention trial was designed involving 1,178 young adults living in 37 residence houses in 5 university residence halls during the 2007-2008 influenza season. Participants were assigned to face mask and hand hygiene, face mask only, or control group during the study. Discrete-time survival models using generalized estimating equations to estimate intervention effects on ILI and confirmed influenza A/B infection over a 6-week study period were examined. A significant reduction in the rate of ILI was observed in weeks 3 through 6 of the study, with a maximum reduction of 75% during the final study week (rate ratio [RR] = 0.25, [95% CI, 0.07 to 0.87]). Both intervention groups compared to the control showed cumulative reductions in rates of influenza over the study period, although results did not reach statistical significance. Generalizability limited to similar settings and age groups. Face masks and hand hygiene combined may reduce the rate of ILI and confirmed influenza in community settings. These non-pharmaceutical measures should be recommended in crowded settings at the start of an influenza pandemic. TRIAL REGISTRATION: [corrected] Clinicaltrials.gov NCT00490633.

Research findings from nonpharmaceutical intervention studies for pandemic influenza and current gaps in the research.

In June 2006, the Centers for Disease Control and Prevention released a request for applications to identify, improve, and evaluate the effectiveness of nonpharmaceutical interventions (NPIs)-strategies other than vaccines and antiviral medications-to mitigate the spread of pandemic influenza within communities and across international borders (RFA-CI06-010). These studies have provided major contributions to seasonal and pandemic influenza knowledge. Nonetheless, key concerns were identified related to the acceptability and protective efficacy of NPIs. Large-scale intervention studies conducted over multiple influenza epidemics, as well as smaller studies in controlled laboratory settings, are needed to address the gaps in the research on transmission and mitigation of influenza in the community setting. The current novel influenza A (H1N1) pandemic underscores the importance of influenza research.

Mask use, hand hygiene, and seasonal influenza-like illness among young adults: a randomized intervention trial.

BACKGROUND: During the influenza A(H1N1) pandemic, antiviral prescribing was limited, vaccines were not available early, and the effectiveness of nonpharmaceutical interventions (NPIs) was uncertain. Our study examined whether use of face masks and hand hygiene reduced the incidence of influenza-like illness (ILI). METHODS: A randomized intervention trial involving 1437 young adults living in university residence halls during the 2006-2007 influenza season was designed. Residence halls were randomly assigned to 1 of 3 groups-face mask use, face masks with hand hygiene, or control- for 6 weeks. Generalized models estimated rate ratios for clinically diagnosed or survey-reported ILI weekly and cumulatively. RESULTS: We observed significant reductions in ILI during weeks 4-6 in the mask and hand hygiene group, compared with the control group, ranging from 35% (confidence interval [CI], 9%-53%) to 51% (CI, 13%-73%), after adjusting for vaccination and other covariates. Face mask use alone showed a similar reduction in ILI compared with the control group, but adjusted estimates were not statistically significant. Neither face mask use and hand hygiene nor face mask use alone was associated with a significant reduction in the rate of ILI cumulatively. CONCLUSIONS: These findings suggest that face masks and hand hygiene may reduce respiratory illnesses in shared living settings and mitigate the impact of the influenza A(H1N1) pandemic. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00490633.

Effect of hand hygiene on infectious disease risk in the community setting: a meta-analysis.

To quantify the effect of hand-hygiene interventions on rates of gastrointestinal and respiratory illnesses and to identify interventions that provide the greatest efficacy, we searched 4 electronic databases for hand-hygiene trials published from January 1960 through May 2007 and conducted meta-analyses to generate pooled rate ratios across interventions (N=30 studies). Improvements in hand hygiene resulted in reductions in gastrointestinal illness of 31% (95% confidence intervals [CI]=19%, 42%) and reductions in respiratory illness of 21% (95% CI=5%, 34%). The most beneficial intervention was hand-hygiene education with use of nonantibacterial soap. Use of antibacterial soap showed little added benefit compared with use of nonantibacterial soap. Hand hygiene is clearly effective against gastrointestinal and, to a lesser extent, respiratory infections. Studies examining hygiene practices during respiratory illness and interventions targeting aerosol transmission are needed.