Effectiveness of rVSV-ZEBOV vaccination during the 2018-20 Ebola virus disease epidemic in the Democratic Republic of the Congo: a retrospective test-negative study.

BACKGROUND: The recombinant vesicular stomatitis virus-Zaire Ebola virus (rVSV-ZEBOV) vaccine is the only WHO prequalified vaccine recommended for use to respond to outbreaks of Ebola virus (species Zaire ebolavirus) by WHO's Strategic Advisory Group of Experts on Immunization. Despite the vaccine's widespread use during several outbreaks, no real-world effectiveness estimates are currently available in the literature. METHODS: We conducted a retrospective test-negative analysis to estimate effectiveness of rVSV-ZEBOV vaccination against Ebola virus disease during the 2018-20 epidemic in the Democratic Republic of the Congo, using data on suspected Ebola virus disease cases collected from Ebola treatment centres. Those eligible for inclusion had an available Ebola virus RT-PCR result, available key data, were eligible for vaccination during the outbreak, and had symptom onset aligning with the period in which a ring-vaccination protocol was in use. After imputing missing data, each individual confirmed by RT-PCR to be Ebola virus disease-positive (defined as a case) was matched to one individual negative for Ebola virus disease (control) by sex, age, health zone, and month of symptom onset. Effectiveness was estimated from the odds ratio of being vaccinated (≥10 days before symptom onset) versus being unvaccinated among cases and controls, after adjusting for the matching factors. The imputation, matching and effectiveness estimation, was repeated 500 times. FINDINGS: 1273 (4·8%) of 26 438 eligible individuals were positive for Ebola virus disease (cases) and 25 165 (95·2%) were negative (controls). 40 (3·1%) cases and 1271 (5·1%) controls were reported as being vaccinated at least 10 days before symptom onset. After selecting individuals who reported exposure to an individual with Ebola virus disease within the 21 days before symptom onset and matching, the analysis datasets comprised a median of 309 cases and 309 controls. 10 days or more after vaccination, the effectiveness of rVSV-ZEBOV against Ebola virus disease was estimated to be 84% (95% credible interval 70-92). INTERPRETATION: This analysis is the first to provide estimates of the real-world effectiveness of the rVSV-ZEBOV vaccine against Ebola virus disease, amid the widespread use of the vaccine during a large Ebola virus disease outbreak. Our findings confirm that rVSV-ZEBOV is highly protective against Ebola virus disease and support its use during outbreaks, even in challenging contexts such as in the eastern Democratic Republic of the Congo. FUNDING: Médecins Sans Frontières. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Effect of large-scale mass drug administration for malaria on mortality and morbidity in Angumu health zone, Ituri, Democratic Republic of Congo.

BACKGROUND: Angumu health zone in Ituri, Democratic Republic of Congo, is a highly malaria-endemic area with an overburdened health system and hosting internally displaced persons (IDP). The World Health Organization recommends mass drug administration (MDA) for malaria in complex emergencies. Therefore, three MDA rounds were implemented by Ministry of Public Health and Médecins sans Frontières from September 2020 to January 2021 in four health areas selected for epidemiological (high malaria incidence) and logistic reasons. Reported mortality and morbidity were compared in locations where MDA has been performed and locations where it has not. METHODS: A non-randomized controlled population-based retrospective mortality survey was conducted in March 2021. Two-stage cluster sampling was used in villages; all IDP sites were surveyed with systematic random sampling. The main (mortality rates) and secondary (morbidity) outcomes were estimated and compared between locations where MDA had been conducted and where it had not, using mixed Poisson and binomial regression models respectively. RESULTS: Data was collected for 2554 households and 15470 individuals, of whom 721 died in the 18-month recall period. The under-five mortality rate (U5MR) decreased in the locations where MDA had been implemented from 2.32 [1.48-3.16] "before" the MDA to 1.10 [0.5-1.71] deaths/10,000 children under 5 years/day "after", whereas it remained stable from 2.74 [2.08-3.40] to 2.67 [1.84-3.50] deaths/10,000 children/day in the same time periods in locations where MDA had not been implemented. The U5MR and malaria-specific mortality was significantly higher in non-MDA locations after MDA was implemented (aRR = 2.17 [1.36-3.49] and 2.60 [1.56-4.33], respectively, for all-cause and malaria-specific mortality among children < 5 years). Morbidity (all age and < 5 years, all cause or malaria-specific) appeared lower in MDA locations 2.5 months after last round: reported malaria-specific morbidity was 14.7% [11-18] and 25.0% [19-31] in villages and IDP sites where MDA had been implemented, while it was 30.4% [27-33] and 49.3% [45-54] in villages and IDP sites with no MDA. CONCLUSIONS: Despite traditional limitations associated with non-randomized controlled retrospective surveys, the documented sharp decrease of under-5 mortality and morbidity shows that MDA has the potential to become an important malaria-control tool in emergency settings. Based on these results, new MDA rounds, along with indoor residual spraying campaigns, have been planned in the health zone in 2022. A set of surveys will be conducted before, during and after these rounds to confirm the effect observed in 2021 and assess its duration.

Prevalence of malaria in an area receiving seasonal malaria chemoprevention in Niger.

BACKGROUND: Malaria transmission is highly seasonal in Niger. Despite the introduction of seasonal malaria chemoprevention (SMC) in the Magaria District, malaria incidence remains high, and the epidemiology of malaria in the community is not well-understood. METHODS: Four cross-sectional, household-based malaria prevalence surveys were performed in the Magaria District of Niger between October 2016 and February 2018. Two occurred during the peak malaria season and two during the low malaria season. Individuals in each of three age strata (3-59 months, 5-9 years, and 10 years and above) were sampled in randomly-selected households. Capillary blood was collected by fingerprick, thick and thin blood films were examined. Microscopy was performed at Epicentre, Maradi, Niger, with external quality control. The target sample size was 396 households during the high-season surveys and 266 households during the low-season surveys. RESULTS: Prevalence of parasitaemia was highest in children aged 5-9 years during all four surveys, ranging between 53.6% (95%CI 48.8-63.6) in February 2018 and 73.2% (66.2-79.2) in September 2017. Prevalence of parasitaemia among children aged 3-59 months ranged between 39.6% (33.2-46.4) in February 2018 and 51.9% (45.1-58.6) in October 2016. Parasite density was highest in children aged 3-59 months during all four surveys, and was higher in high season surveys than in low season surveys among all participants. The prevalence of gametocytaemia in children aged 3-59 months ranged between 9.9% (6.5-14.8) in February 2018 and 19.3% (14.6-25.2) in October 2016. The prevalence of gametocytaemia in children aged 5-9 years ranged between 6.3% (3.5-11.1) in February 2018 and 18.5% (12.7-26.1) in October 2016. CONCLUSIONS: Asymptomatic malaria infection is highly prevalent in this area, even during the season with low incidence of clinical malaria. The high prevalence of parasitaemia in children aged 5-9 years warrants considering their inclusion in SMC programmes in this context.

The impact of control strategies and behavioural changes on the elimination of Ebola from Lofa County, Liberia.

The Ebola epidemic in West Africa was stopped by an enormous concerted effort of local communities and national and international organizations. It is not clear, however, how much the public health response and behavioural changes in affected communities, respectively, contributed to ending the outbreak. Here, we analyse the epidemic in Lofa County, Liberia, lasting from March to November 2014, by reporting a comprehensive time line of events and estimating the time-varying transmission intensity using a mathematical model of Ebola transmission. Model fits to the epidemic show an alternation of peaks and troughs in transmission, consistent with highly heterogeneous spread. This is combined with an overall decline in the reproduction number of Ebola transmission from early August, coinciding with an expansion of the local Ebola treatment centre. We estimate that healthcare seeking approximately doubled over the course of the outbreak, and that isolation of those seeking healthcare reduced their reproduction number by 62% (mean estimate, 95% credible interval (CI) 59-66). Both expansion of bed availability and improved healthcare seeking contributed to ending the epidemic, highlighting the importance of community engagement alongside clinical intervention.This article is part of the themed issue 'The 2013-2016 West African Ebola epidemic: data, decision-making and disease control'.

Community-Based Surveillance to Monitor Mortality in a Malaria-Endemic and Ebola-Epidemic Setting in Rural Guinea.

Multiple community-based approaches can aid in quantifying mortality in the absence of reliable health facility data. Community-based sentinel site surveillance that was used to document mortality and the systems utility for outbreak detection was evaluated. We retrospectively analyzed data from 46 sentinel sites in three sous-préfectures with a reinforced malaria control program and one sous-préfecture without (Koundou) in Guinea. Deaths were recorded by key informants and classified as due to malaria or another cause. Malaria deaths were those reported as due to malaria or fever in the 3 days before death with no other known cause. Suspect Ebola virus disease (sEVD) deaths were those due to select symptoms in the EVD case definition. Deaths were aggregated by sous-préfecture and analyzed by a 6-month period. A total of 43,000 individuals were monitored by the surveillance system; 1,242 deaths were reported from July 2011-June 2014, of which 55.2% (N = 686) were reported as due to malaria. Malaria-attributable proportional mortality decreased by 26.5% (95% confidence interval [CI] = 13.9-33.1, P < 0.001) in the program area and by 6.6% (95% CI = -17.3-30.5, P = 0.589) in Koundou. Sixty-eight deaths were classified as sEVD and increased by 6.1% (95% CI = 1.3-10.8, P = 0.021). Seventeen sEVD deaths were reported from November 2013 to March 2014 including the first two laboratory-confirmed EVD deaths. Community surveillance can capture information on mortality in areas where data collection is weak, but determining causes of death remains challenging. It can also be useful for outbreak detection if timeliness of data collection and reporting facilitate real-time data analysis.

Encouraging impact following 2.5 years of reinforced malaria control interventions in a hyperendemic region of the Republic of Guinea.

BACKGROUND: Malaria is one of the principal causes of morbidity and mortality in the Republic of Guinea, particularly in the highly endemic regions. To assist in malaria control efforts, a multi-component malaria control intervention was implemented in the hyperendemic region of Guéckédou Prefecture. The coverage of the intervention and its impact on malaria parasite prevalence were assessed. METHODS: Five cross-sectional surveys using cluster-based sampling and stratified by area were conducted from 2011 to 2013 in three sous-préfectures of Guéckédou Préfecture that received the intervention: Guéckédou City, Tékoulo and Guendembou in addition to one comparison sous-préfecture that did not receive the intervention, Koundou. Surveys were repeated every 6 months, corresponding with the dry and rainy seasons. Rapid diagnostic tests (RDT) were used to diagnose malaria infection. In each selected household, bed net use and ownership were assessed. RESULTS: A total of 35,123 individuals participated in the surveys. Malaria parasite prevalence declined in all intervention sous-préfectures from 2011 to 2013 (56.4-45.9 % in Guéckédou City, 64.9-54.1 % in Tékoulo and 69.4-56.9 % in Guendembou) while increasing in the comparison sous-préfecture (64.5-69 %). It was consistently higher in children 5-14 years of age followed by those 1-59 months and ≥15 years. Indicators of intervention coverage, the proportion of households reporting ownership of at least one bed net and the proportion of survey participants with fever who received treatment from a health facility or community health worker also increased significantly in the intervention areas. CONCLUSIONS: Implementation of the multi-component malaria control intervention significantly reduced the prevalence of malaria in the sous-préfectures of intervention while also increasing the coverage of bed nets. However, malaria prevalence remains unacceptably high and disproportionately affects children <15 years of age. In such situations additional vector control interventions and age specific interventions should be considered.

Ebola Virus Disease Complications as Experienced by Survivors in Sierra Leone.

BACKGROUND: Thousands of people have survived Ebola virus disease (EVD) during the ongoing outbreak. However, data about the frequency and risk factors of long-term post-EVD complications remain scarce. We describe the clinical characteristics of EVD survivors followed in a survivor clinic in Freetown, Sierra Leone. METHODS: A survivor clinic opened within an Ebola treatment center compound in Freetown, Sierra Leone. At each visit, clinical and psychological assessments were conducted and free treatment was offered. Survivors were referred to a partner's hospitals if their condition could not be managed in the clinic. We used routinely collected data from the clinic to describe long-term complications of EVD and their risk factors. RESULTS: A total of 1001 medical consultations for 166 patients were performed between 3 February and 21 June 2015. The most frequent complaints and diagnoses were arthralgia (n = 129 [77.7%]), fatigue (n = 116 [69.8%]), abdominal pain (n = 90 [54.2%]), headache (n = 87 [52.4%]), anemia (n = 83 [50%]), skin disorders (n = 81 [48.8%]), back pain (n = 54 [32.5%]), and alopecia (n = 53 [31.9%]). Ocular complications were diagnosed in 94 survivors (56.7%); uveitis was the most common (n = 57 [34%]). Survivors were 10 times more likely to develop uveitis post-EVD if they presented with red/injected eyes during the acute phase of their illness. CONCLUSIONS: Post-EVD complications among our patients were similar to those described previously and were detected early following the acute phase of disease. Follow-up of survivors should begin immediately after discharge to address sequelae as they arise and reduce the potential for development of long-term disabilities such as blindness.

Effect of Artesunate-Amodiaquine on Mortality Related to Ebola Virus Disease.

BACKGROUND: Malaria treatment is recommended for patients with suspected Ebola virus disease (EVD) in West Africa, whether systeomatically or based on confirmed malaria diagnosis. At the Ebola treatment center in Foya, Lofa County, Liberia, the supply of artemether-lumefantrine, a first-line antimalarial combination drug, ran out for a 12-day period in August 2014. During this time, patients received the combination drug artesunate-amodiaquine; amodiaquine is a compound with anti-Ebola virus activity in vitro. No other obvious change in the care of patients occurred during this period. METHODS: We fit unadjusted and adjusted regression models to standardized patient-level data to estimate the risk ratio for death among patients with confirmed EVD who were prescribed artesunate-amodiaquine (artesunate-amodiaquine group), as compared with those who were prescribed artemether-lumefantrine (artemether-lumefantrine group) and those who were not prescribed any antimalarial drug (no-antimalarial group). RESULTS: Between June 5 and October 24, 2014, a total of 382 patients with confirmed EVD were admitted to the Ebola treatment center in Foya. At admission, 194 patients were prescribed artemether-lumefantrine and 71 were prescribed artesunate-amodiaquine. The characteristics of the patients in the artesunate-amodiaquine group were similar to those in the artemether-lumefantrine group and those in the no-antimalarial group. A total of 125 of the 194 patients in the artemether-lumefantrine group (64.4%) died, as compared with 36 of the 71 patients in the artesunate-amodiaquine group (50.7%). In adjusted analyses, the artesunate-amodiaquine group had a 31% lower risk of death than the artemether-lumefantrine group (risk ratio, 0.69; 95% confidence interval, 0.54 to 0.89), with a stronger effect observed among patients without malaria. CONCLUSIONS: Patients who were prescribed artesunate-amodiaquine had a lower risk of death from EVD than did patients who were prescribed artemether-lumefantrine. However, our analyses cannot exclude the possibility that artemether-lumefantrine is associated with an increased risk of death or that the use of artesunate-amodiaquine was associated with unmeasured patient characteristics that directly altered the risk of death.

Evidence for a decrease in transmission of Ebola virus--Lofa County, Liberia, June 8-November 1, 2014.

Lofa County has one of the highest cumulative incidences of Ebola virus disease (Ebola) in Liberia. Recent situation reports from the Liberian Ministry of Health and Social Welfare (MoHSW) have indicated a decrease in new cases of Ebola in Lofa County. In October 2014, the Liberian MoHSW requested the assistance of CDC to further characterize recent trends in Ebola in Lofa County. Data collected during June 8-November 1, 2014 from three sources were analyzed: 1) aggregate data for newly reported cases, 2) case-based data for persons admitted to the dedicated Ebola treatment unit (ETU) for the county, and 3) test results for community decedents evaluated for Ebola. Trends from all three sources suggest that transmission of Ebola virus decreased as early as August 17, 2014, following rapid scale-up of response activities in Lofa County after a resurgence of Ebola in early June 2014. The comprehensive response strategy developed with participation from the local population in Lofa County might serve as a model to implement in other affected areas to accelerate control of Ebola.

Clinical manifestations and case management of Ebola haemorrhagic fever caused by a newly identified virus strain, Bundibugyo, Uganda, 2007-2008.

A confirmed Ebola haemorrhagic fever (EHF) outbreak in Bundibugyo, Uganda, November 2007-February 2008, was caused by a putative new species (Bundibugyo ebolavirus). It included 93 putative cases, 56 laboratory-confirmed cases, and 37 deaths (CFR = 25%). Study objectives are to describe clinical manifestations and case management for 26 hospitalised laboratory-confirmed EHF patients. Clinical findings are congruous with previously reported EHF infections. The most frequently experienced symptoms were non-bloody diarrhoea (81%), severe headache (81%), and asthenia (77%). Seven patients reported or were observed with haemorrhagic symptoms, six of whom died. Ebola care remains difficult due to the resource-poor setting of outbreaks and the infection-control procedures required. However, quality data collection is essential to evaluate case definitions and therapeutic interventions, and needs improvement in future epidemics. Organizations usually involved in EHF case management have a particular responsibility in this respect.