The recombinant vesicular stomatitis virus–Zaire Ebola virus (rVSV-ZEBOV) vaccine is the only vaccine recommended for use to respond to Zaire ebolavirus outbreaks by SAGE. A single ring vaccination trial found the efficacy to be 100%; however, no estimates of real-world effectiveness have yet been published.
METHODS
We conducted a retrospective test-negative case-control analysis to estimate effectiveness of rVSV-ZEBOV vaccination against Ebola virus disease (EVD) during the 2018 - 2020 epidemic in the Democratic Republic of the Congo (DRC), using data on suspected cases collected at Ebola treatment centres. Missing data were imputed using multivariate imputation. Among those who reported contact with an Ebola case before symptom onset, each EVD-positive case was matched to one EVD-negative control by sex, age, health zone and month of symptom onset. Effectiveness was then estimated from the odds ratio of being vaccinated vs. unvaccinated among cases and controls, after adjusting for the matching factors.
RESULTS
The primary study population contained 309 cases and controls each, on average, of which between 11 and 23 cases (3.6– 7.4%) and between 48 and 80 controls (16 – 26%) were recorded as vaccinated at least ten days before symptom onset. We found rVSV-ZEBOV vaccination at least ten days before symptom onset was 84% effective against developing EVD (95% credible interval [70%, 92%]). There was no apparent difference in effectiveness by sex, age, or due to a change in vaccination protocol.
CONCLUSION
This study is the first to estimate real-world effectiveness of rVSV-ZEBOV vaccination EVD during the second largest EVD outbreak ever recorded. Our findings confirm that rVSV-ZEBOV vaccination is highly protective against developing EVD and support its reactive, targeted use in at-risk people during future outbreaks.
BACKGROUND
Mobility of people living with HIV (PWH) among urban population in Goma and the fisherfolk community in western Uganda can serve as a barrier to retention in care. To address this challenge, MSF supported MoH in deployment of WHO recommended Differentiated Services Delivery Models (DSDM), especially Community ART groups (CAG) where clients form groups and rotate drug pick-up. In these studies, we aimed to explore retention-in-care, viral load coverage and suppression among PWH enrolled in DSDM and describe acceptability and satisfaction of these models in Goma, DRC and Kasese, Uganda.
METHODS
In both contexts, we carried out a retrospective cohort analysis complemented by a cross-sectional survey in Goma and a qualitative survey in Kasese. For the cohort analysis, we examined the characteristics of PWH enrolled in DSDM. Utilizing Kaplan-Meier survival analysis, we estimated retention in care and calculated viral coverage and suppression rates at 12 months post-model initiation. In Goma, we administered a satisfaction questionnaire to a subset of the active cohort, while in Kasese, we conducted interviews and facilitated focus group discussions to document the acceptability and relevance of DSDM.
RESULTS
In total, 1950 PWH in Goma and 1773 PWH in Kasese were included in the cohort analyses. After one year of model initiation, more than 90% of PWH enrolled in MSF-supported DSDM were retained in care (94.1% among PWH in Goma and 97.6% in Kasese). Of PWH who retained in care at 1-year, proportion of virally suppressed PWH was high in both contexts (96.4% in Goma and 97.0% in Goma). PWH and healthcare providers expressed positive sentiments towards DSMD, acknowledging their utility in enhancing convenience and reducing transport expenses for ART access. Moreover, they noted benefits such as decreased waiting times, alleviation of overcrowding and workload at healthcare facilities, as well as the role of DSDM in mitigating stigma and fostering responsibility sharing among group members.
CONCLUSION
Although great progress has been made in the fight against the HIV epidemic in recent years, a one-size-fits-all approach to caring for people living with HIV is no longer appropriate. The findings from these evaluations underscore the effectiveness of tailored, differentiated services, which maintain high retention rates in care, even within mobile communities, while also garnering strong acceptability. It is imperative to consider integrating DSDM into routine programming for chronic illnesses. By adapting clinical care to suit the lifestyles of PWH, such models can offer enhanced support to patients, ultimately improving health outcomes.
BACKGROUND
Fighting erupted on 15 April 2023 in Sudan between the army and the paramilitary Rapid Support Forces. By September 2023, more than 420,000 people had fled to Chad. To describe the health status of the displaced populations in camps in eastern Chad, several surveys were realised. We describe retrospective crude and under five mortality rates, reported causes of death and frequency and type of violence events experienced by displaced populations in three camps in eastern Chad.
METHODS
Cross-sectional surveys were carried out in August and September 2023 in Toumtouma, Ourang and Arkoum camps. Each survey included retrospective mortality and frequency and type of violent events experienced. All surveys considered a pre-crisis and crisis phase.
RESULTS
In all sites, the crude mortality rate (CMR) was significantly higher in the crisis phase than in the pre-crisis phase. The CMR was particularly elevated in Ourang camp (CMR: 2.25 deaths/10,000 people/day [95% CI: 1.77 - 2.74] in the crisis phase versus CMR: 0.11 deaths/10,000 people/day [95% CI: 0.02 - 0.20] in the pre-crisis phase). Violence was the leading self-reported cause of death in all sites. Among households in Ourang, more than 90 percent originating from El Geneina, more than 1 in 10 of all men aged 30 and over died of violent causes. In Toumtouma, Ourang and Arkoum camps, the overall frequency of violence among households was 3.3%, 11.7% and 4.4% respectively, with beatings and shooting most frequently cited.
CONCLUSIONS
In the three camps investigated, excess mortality was observed among households during the crisis phase, with excess mortality primarily linked to violence among men. The population in Ourang camp, largely from El Geneina, appears to have been particularly affected by the violence, with CMR 20 times higher than in the pre-crisis period and mortality rates exceeding the standard emergency threshold (1 death/10,000 people/day).
KEY MESSAGE
Several cross-sectional surveys were carried out among displaced populations arriving in Chad. We provide epidemiological evidence of the high rates of mortality and violence since the start of the conflict in Sudan.
Outbreak alert systems can offset the severity of measles epidemics by minimising response delays. Existing systems, however, are often too sensitive to be practical when identifying areas for reactive interventions. To redress this challenge, we present a simple alternative system that combines a weekly and triweekly suspected case threshold. First evaluated in the DRC in 2022, here we extend the evaluation of this system to the context of Niger.
METHODS
A large number of threshold combinations were evaluated against indicators of cases captured by intervention and false alert risk. Combinations were evaluated against admin 2 level surveillance data from the DRC and Niger from 2015-2024. Performance was then compared to standard recommendations from the WHO and MSF.
RESULTS
The two example countries have distinct epidemic profiles, with the DRC exhibiting mas epidemics and Niger showing strong annual seasonality. In both settings, the proposed alternative alert system outperformed the existing WHO and MSF recommendation. The WHO recommendation, which is triggered by four suspected cases occuring within one month in a given locale (here, admin level 2), performs similarly to the proposed alternative when selecting the most sensitive of threshold combinations. The MSF recommendation, which is triggered by a raw increase in number of cases for three consecutive weeks, performed markedly worse, capturing 50% or less of cases. This poor performance is predominantly attributable to the high volatility of weekly measles surveillance data.
CONCLUSION
This analysis presents a simple evidence based alert system to improve measles outbreak response. It has been assessed in two countries, Niger and the DRC, and found to outperform standard recommendations. At present the system is available for use in both countries via their respective surveillance dashboards. Ongoing work is being conducted to evaluate the system in settings with additional epidemic profiles, including areas with low burden and areas with poor surveillance.
endTB is a Phase 3, randomized, controlled, non-inferiority trial, comparing five 9-month experimental regimens consisting of 4-5 drugs (including bedaquiline, delamanid, clofazimine, linezolid, fluoroquinolones, and pyrazinamide) to the standard of care for rifampicin-resistant, fluoroquinolone-susceptible tuberculosis. Three experimental regimens (endTB1, endTB2, endTB3) were non-inferior to the control in the primary analysis. This analysis explores the efficacy results of the endTB clinical trial in key subgroups (HIV positive, low BMI, diabetes, severe disease) to help clinicians to make the choice between these three regimens for patients with a more difficult to treat form of disease.
METHODS
For each subgroup, proportion of favourable outcome at Week 73 was calculated in each arm. Risk differences and 95% confidence intervals were estimated in the modified intention-to-treat population (mITT), which included all randomized participants who took at least one dose of study treatment and had a positive pre-randomization tuberculosis culture. Results in each arm were plotted on forest plots.
RESULTS
In HIV-infected patients, efficacy results are consistent with the overall results in endTB1 and endTB2 while in endTB3 the effect of trt favours the control arm. No differences from the overall population were observed in any of the 3 arms in patients with a more severe disease, while treatment effect in patients with low BMI, favours the control arm in all 3 arms. Treatment effect in patients with diabetes, favours the experimental arm in all 3 arms.
CONCLUSION
All 3 arms could reasonably be used in patients with severe disease or diabetes. endTB1 and endTB2 appeared to be particularly efficacious in HIV positive patients. Longer or regimens with more drugs may achieve better results in patients with low BMI. Additional research is needed to confirm these findings.
In September 2023, the South Sudan Ministry of Health declared an outbreak of hepatitis E virus in Fangak County, Jonglei State. From April to November 2023, MSF identified 169 hepatitis E cases, among them 45% pregnant women. Cases reported at the hospital were severe and the case fatality ratio (CFR) was high with 18 deaths, 53% were women of reproductive age and 42% were pregnant women. In response, MSF together with the Ministry of Health conducted the 2nd ever reactive vaccination campaign with the Hecolin vaccine. The 1st to target exclusively women of reproductive age.
METHODS
This is a descriptive, cross-sectional cluster survey with a two-stage cluster sampling design. The two strata selected were the Old Fangak and Mareang/Toch Payams.
To complement the vaccination coverage estimates, understand perception of the vaccine, and the acceptance of the strategy to vaccinate only women of reproductive age, qualitative methods were utilized following the second round of vaccination.
RESULTS
High coverage was observed of at least one dose of hepatitis E vaccine, according to recall or card, among vaccine eligible women: 94% [95% CI 92-95] in Old Fangak and Mareang /Toch Payams. Coverage of two doses was lower, with estimated coverage of 77% [95% CI 74-80%] according to recall or card. Vaccination coverage was similar in both strata, even in hard-to-reach areas.
While community members reported high acceptance of vaccine, many were critical of the vaccine strategy targeting women aged 16 to 45. This was perceived to conflict with the observed cases of Hepatitis E among the population and physical reproductive age, exclude other vulnerable groups, and not consider community priorities or decision-making structures.
CONCLUSION
The vaccination campaign reached high coverage despite challenging field conditions, and low acceptance of the strategy.
BACKGROUND
Hepatitis E was first identified in the 1990s, but major epidemics date back to the 1950s. There is no specific treatment, and it can be fatal especially for pregnant women, causing spontaneous abortion and stillbirths. In 2011, the first vaccine was made available, and in 2015, the WHO recommended its use during epidemics, including for pregnant women. However, several major epidemics occurred without vaccine use. The first mass reactive vaccination took place in 2022 at the Bentiu camp in South Sudan, alongside operational research.
METHODS
We assessed vaccination feasibility and acceptance through coverage surveys and conducted focus group discussions on acceptance. We monitored adverse events following immunization (AEFI) for pharmacovigilance. To assess safety in pregnancy, we monitored the pregnancy outcomes of all women identified as pregnant during the vaccination campaign through a census. Despite the significant efficacy shown in a phase 3 clinical trial after three doses, we aimed to evaluate the vaccine's efficacy in South Sudan during an epidemic after administering two doses through a case-control study.
RESULTS
Coverage of at least one dose of the Hecolin vaccine after three rounds was estimated at 86% (95% CI: 84-88), with no cases of severe AEFI. Focus groups revealed strong concern about hepatitis E and high confidence and demand for the vaccine. An emulated target trial showed a relative risk of foetal loss between vaccinated and unvaccinated pregnant women at 1.1 (95% CI: 0.7-1.8). Vaccine effectiveness after two doses was estimated at 88.3% (95% CI: 53.8-97.6) using a test-negative design.
CONCLUSION
We found high vaccine coverage, good acceptance, and demand from the population. There was no evidence of increased risk of foetal loss among vaccinated pregnant women. Despite the small number of cases, the reduced dose regimen appeared effective in reducing disease risk in this highly exposed population.
KEY MESSAGE
Studies from the first mass reactive vaccination against hepatitis E demonstrated high coverage and acceptance, no safety issues among pregnant women, and good effectiveness after two doses.
In Carnot, Central African Republic, MSF collaborates with the Ministry of Health at the District Hospital (DH), providing comprehensive care for chronic diseases, including integrated HIV services. Since 2016, HIV differentiated treatment models (DTMs) have been introduced, including multi-monthly dispensing of antiretroviral therapy, Community ART Groups (CAGs), and decentralized care. A multi-methods study was conducted to describe and understand the continuum of care of patients in the cohort, including retention indicators, treatment adherence, perceptions of DTMs and reasons for late presentation to care.
METHODS
Programmatic data of the HIV cohort in Carnot between 2011 and 2022 was analysed retrospectively. A cross-sectional survey was conducted on a random sample of active patients who underwent a clinical examination, CD4, viral load (VL) and ARV resistance tests to estimate the proportion of virological failures and resistance profiles. Lastly, semi-structured interviews were conducted with key informants, health care workers, active patients, and patients late for their appointments (<6months).
RESULTS
In 2023, the cohort included 4,745 patients on treatment, with 35.5% (N=1,684) lost-to-follow-up. The probability of retention in care decreased over time and adherence to care (% of late appointment to the health centre) was lower than 80%. Among the 341 patients surveyed, 96% of them were on a treatment based on dolutegravir (DTG), and 12% (N=40, 95%CI 8-16) had virological failure. Among those, nearly one third (29.6%) presented drug resistances to the class of molecules currently used and 2.4% presented resistance to DTG, indicating that lack of adherence was likely the cause of virological failure. DTMs were not optimally implemented, and perceptions were mixed. Reasons for late presentations to appointments included access and service-related barriers, stigmatisation and socio-economic vulnerability, however, patients facing these barriers were often excluded from accessing DTM.
CONCLUSION
Despite DTMs, patients’ retention in care remains low. Strategies for better implementation and equitable access for patients are urgently needed.