BACKRGOUND
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.
BACKGROUND
Traditionally in the Democratic Republic of the Congo (DRC), centralised Ebola treatment centres (ETCs) have been set exclusively for Ebola virus disease (EVD) case management during outbreaks. During the 2020 EVD outbreak in DRC’s Equateur Province, existing health centres were equipped as decentralised treatment centres (DTC) to improve access for patients with suspected EVD. Between ETCs and DTCs, we compared the time from symptom onset to admission and diagnosis among patients with suspected EVD.
METHODS
This was a cohort study based on analysis of a line-list containing demographic and clinical information of patients with suspected EVD admitted to any EVD health facility during the outbreak.
RESULTS
Of 2359 patients with suspected EVD, 363 (15%) were first admitted to a DTC. Of 1996 EVD-suspected patients initially admitted to an ETC, 72 (4%) were confirmed as EVD-positive. Of 363 EVD-suspected patients initially admitted to a DTC, 6 (2%) were confirmed and managed as EVD-positive in the DTC. Among all EVD-suspected patients, the median (interquartile range) duration between symptom onset and admission was 2 (1-4) days in a DTC compared to 4 (2-7) days in an ETC (p<0.001). Similarly, time from symptom onset to admission was significantly shorter among EVD-suspected patients ultimately diagnosed as EVD-negative.
CONCLUSIONS
Since <5% of the EVD-suspected patients admitted were eventually diagnosed with EVD, there is a need for better screening to optimise resource utilization and outbreak control. Only one in seven EVD-suspected patients were admitted to a DTC first, as the DTCs were piloted in a limited and phased manner. However, there is a case to be made for considering decentralized care especially in remote and hard-to-reach areas in places like the DRC to facilitate early access to care, contain viral shedding by patients with EVD and ensure no disrupted provision of non-EVD services.
During a measles epidemic, the Ministry of Public Health (MOH) of the Democratic Republic of the Congo conducted supplementary immunization activities (2016-SIA) from August 28-September 3, 2016 throughout Maniema Province. From October 29-November 4, 2016, Médecins Sans Frontières and the MOH conducted a reactive measles vaccination campaign (2016-RVC) targeting children six months to 14 years old in seven health areas with heavy ongoing transmission despite inclusion in the 2016-SIA, and a post-vaccination survey. We report the measles vaccine coverage (VC) and effectiveness (VE) of the 2016-SIA and VC of the 2016-RVC.
METHODS:
A cross-sectional VC cluster survey stratified by semi-urban/rural health area and age was conducted. A retrospective cohort analysis of measles reported by the parent/guardian allowed calculation of the cumulative measles incidence according to vaccination status after the 2016-SIA for an estimation of crude and adjusted VE.
RESULTS:
In November 2016, 1145 children (6-59 months old) in the semi-urban and 1158 in the rural areas were surveyed. Post-2016-SIA VC (documentation/declaration) was 81.6% (95%CI: 76.5-85.7) in the semi-urban and 91.0% (95%CI: 84.9-94.7) in the rural areas. The reported measles incidence in October among children less than 5 years old was 5.0% for 2016-SIA-vaccinated and 11.2% for 2016-SIA-non-vaccinated in the semi-urban area, and 0.7% for 2016-SIA-vaccinated and 4.0% for 2016-SIA-non-vaccinated in the rural area. Post-2016-SIA VE (adjusted for age, sex) was 53.9% (95%CI: 2.9-78.8) in the semi-urban and 78.7% (95%CI: 0-97.1) in the rural areas. Post 2016-RVC VC (documentation/declaration) was 99.1% (95%CI: 98.2-99.6) in the semi-urban and 98.8% (95%CI: 96.5-99.6) in the rural areas.
CONCLUSIONS:
Although our VE estimates could be underestimated due to misclassification of measles status, the VC and VE point estimates of the 2016-SIA in the semi-urban area appear suboptimal, and in combination, could not limit the epidemic. Further research is needed on vaccination strategies adapted to urban contexts.
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.
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.
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.