Journal Article > ResearchFull Text
PLOS One. 2023 May 18; Volume 18 (Issue 5); e0278251.; DOI:10.1371/journal.pone.0278251
Otshudiema JO, Folefack GLT, Nsio JM, Kakema CH, Minikulu L, et al.
PLOS One. 2023 May 18; Volume 18 (Issue 5); e0278251.; DOI:10.1371/journal.pone.0278251
A community-based coronavirus disease (COVID-19) active case-finding strategy using an antigen-detecting rapid diagnostic test (Ag-RDT) was implemented in the Democratic Republic of Congo (DRC) to enhance COVID-19 case detection. With this pilot community-based active case finding and response program that was designed as a clinical, prospective testing performance, and implementation study, we aimed to identify insights to improve community diagnosis and rapid response to COVID-19. This pilot study was modeled on the DRC’s National COVID-19 Response Plan and the COVID-19 Ag-RDT screening algorithm defined by the World Health Organization (WHO), with case findings implemented in 259 health areas, 39 health zones, and 9 provinces. In each health area, a 7-member interdisciplinary field team tested the close contacts (ring strategy) and applied preventive and control measures to each confirmed case. The COVID-19 testing capacity increased from 0.3 tests per 10,000 inhabitants per week in the first wave to 0.4, 1.6, and 2.2 in the second, third, and fourth waves, respectively. From January to November 2021, this capacity increase contributed to an average of 10.5% of COVID-19 tests in the DRC, with 7,110 positive Ag-RDT results for 40,226 suspected cases and close contacts who were tested (53.6% female, median age: 37 years [interquartile range: 26.0–50.0)]. Overall, 79.7% (n = 32,071) of the participants were symptomatic and 7.6% (n = 3,073) had comorbidities. The Ag-RDT sensitivity and specificity were 55.5% and 99.0%, respectively, based on reverse transcription polymerase chain reaction analysis, and there was substantial agreement between the tests (k = 0.63). Despite its limited sensitivity, the Ag-RDT has improved COVID-19 testing capacity, enabling earlier detection, isolation, and treatment of COVID-19 cases. Our findings support the community testing of suspected cases and asymptomatic close contacts of confirmed cases to reduce disease spread and virus transmission.
Journal Article > ResearchFull Text
PLoS Negl Trop Dis. 2018 December 7
Ingelbeen B, Weregemere NA, Noel H, Tshapenda G, Mossoko M, et al.
PLoS Negl Trop Dis. 2018 December 7
Background
Between December 2015 and July 2016, a yellow fever (YF) outbreak affected urban areas
of Angola and the Democratic Republic of the Congo (DRC). We described the outbreak in
DRC and assessed the accuracy of the YF case definition, to facilitate early diagnosis of
cases in future urban outbreaks.
Methodology/Principal findings
In DRC, suspected YF infection was defined as jaundice within 2 weeks after acute fever
onset and was confirmed by either IgM serology or PCR for YF viral RNA. We used case
investigation and hospital admission forms. Comparing clinical signs between confirmed
and discarded suspected YF cases, we calculated the predictive values of each sign for confirmed YF and the diagnostic accuracy of several suspected YF case definitions. Fifty seven
of 78 (73%) confirmed cases had travelled from Angola: 88% (50/57) men; median age 31
years (IQR 25–37). 15 (19%) confirmed cases were infected locally in urban settings in
DRC. Median time from symptom onset to healthcare consultation was 7 days (IQR 6–9), to
appearance of jaundice 8 days (IQR 7–11), to sample collection 9 days (IQR 7–14), and to
hospitalization 17 days (IQR 11–26). A case definition including fever or jaundice, combined
with myalgia or a negative malaria test, yielded an improved sensitivity (100%) and specificity (57%).
Conclusions/Significance
As jaundice appeared late, the majority of cases were diagnosed too late for supportive care
and prompt vector control. In areas with known local YF transmission, a suspected case definition without jaundice as essential criterion could facilitate earlier YF diagnosis, care and control.
Between December 2015 and July 2016, a yellow fever (YF) outbreak affected urban areas
of Angola and the Democratic Republic of the Congo (DRC). We described the outbreak in
DRC and assessed the accuracy of the YF case definition, to facilitate early diagnosis of
cases in future urban outbreaks.
Methodology/Principal findings
In DRC, suspected YF infection was defined as jaundice within 2 weeks after acute fever
onset and was confirmed by either IgM serology or PCR for YF viral RNA. We used case
investigation and hospital admission forms. Comparing clinical signs between confirmed
and discarded suspected YF cases, we calculated the predictive values of each sign for confirmed YF and the diagnostic accuracy of several suspected YF case definitions. Fifty seven
of 78 (73%) confirmed cases had travelled from Angola: 88% (50/57) men; median age 31
years (IQR 25–37). 15 (19%) confirmed cases were infected locally in urban settings in
DRC. Median time from symptom onset to healthcare consultation was 7 days (IQR 6–9), to
appearance of jaundice 8 days (IQR 7–11), to sample collection 9 days (IQR 7–14), and to
hospitalization 17 days (IQR 11–26). A case definition including fever or jaundice, combined
with myalgia or a negative malaria test, yielded an improved sensitivity (100%) and specificity (57%).
Conclusions/Significance
As jaundice appeared late, the majority of cases were diagnosed too late for supportive care
and prompt vector control. In areas with known local YF transmission, a suspected case definition without jaundice as essential criterion could facilitate earlier YF diagnosis, care and control.
Journal Article > ResearchFull Text
BMJ Glob Health. 2021 August 1; Volume 6 (Issue 8); e006736.
Carter SE, Ahuka-Mundeke S, Pfaffmann Zambruni J, Navarro-Colorado C, van Kleef E, et al.
BMJ Glob Health. 2021 August 1; Volume 6 (Issue 8); e006736.
The emerging field of outbreak analytics calls attention to the need for data from multiple sources to inform evidence-based decision making in managing infectious diseases outbreaks. To date, these approaches have not systematically integrated evidence from social and behavioural sciences. During the 2018-2020 Ebola outbreak in Eastern Democratic Republic of the Congo, an innovative solution to systematic and timely generation of integrated and actionable social science evidence emerged in the form of the Cellulle d'Analyse en Sciences Sociales (Social Sciences Analytics Cell) (CASS), a social science analytical cell. CASS worked closely with data scientists and epidemiologists operating under the Epidemiological Cell to produce integrated outbreak analytics (IOA), where quantitative epidemiological analyses were complemented by behavioural field studies and social science analyses to help better explain and understand drivers and barriers to outbreak dynamics. The primary activity of the CASS was to conduct operational social science analyses that were useful to decision makers. This included ensuring that research questions were relevant, driven by epidemiological data from the field, that research could be conducted rapidly (ie, often within days), that findings were regularly and systematically presented to partners and that recommendations were co-developed with response actors. The implementation of the recommendations based on CASS analytics was also monitored over time, to measure their impact on response operations. This practice paper presents the CASS logic model, developed through a field-based externally led consultation, and documents key factors contributing to the usefulness and adaption of CASS and IOA to guide replication for future outbreaks.
Journal Article > ResearchFull Text
Lancet Infect Dis. 2024 February 1; Volume 24 (Issue 6); 602-610.; DOI:10.1016/S1473-3099(23)00819-8
Coulborn RM, Bastard M, Peyraud N, Gignoux EM, Luquero FJ, et al.
Lancet Infect Dis. 2024 February 1; Volume 24 (Issue 6); 602-610.; DOI:10.1016/S1473-3099(23)00819-8
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.
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.
Journal Article > CommentaryFull Text
J Infect Dis. 2023 August 19; online ahead of print; jiad354.; DOI:10.1093/infdis/jiad354
Sprecher A, Cross RW, Marzi A, Martins KA, Wolfe D, et al.
J Infect Dis. 2023 August 19; online ahead of print; jiad354.; DOI:10.1093/infdis/jiad354
Although there are now approved treatments and vaccines for Ebola virus disease (EVD), the case fatality of EVD remains unacceptably high even when treated with the newly approved therapeutics; furthermore, these countermeasures are not expected to be effective against disease caused by other filoviruses. A meeting of subject matter experts from public health, research, and countermeasure development agencies and manufacturers was held during the 10th International Filovirus Symposium to discuss strategies to address these gaps, including how newer countermeasures could be advanced for field readiness. Several investigational therapeutics, vaccine candidates, and combination strategies were presented. In all, a common theme emerged: the greatest challenge to completing development was the implementation of well-designed clinical trials of safety and efficacy during filovirus disease outbreaks. These outbreaks are usually of short duration, providing but a brief opportunity for trials to be launched, and have too few cases to allow for full enrollment during a single outbreak, so clinical trials will necessarily need to span multiple outbreaks which may occur in a number of at-risk countries. Preparing for this will require agreed-upon common protocols for trials intended to bridge multiple outbreaks across all at-risk countries. A multi-national research consortium including, and led by, at-risk countries would be an ideal mechanism to negotiate agreement on protocol design and coordinate preparation. Discussion participants recommended a follow-up meeting be held in Africa with national public health and research agencies from at-risk countries to establish such a consortium.
Journal Article > ResearchAbstract Only
Lancet Infect Dis. 2022 November 9; Online ahead of print; S1473-3099(22)00584-9.; DOI:10.1016/S1473-3099(22)00584-9
Nsio JM, Ardiet DL, Coulborn RM, Grellety E, Albela M, et al.
Lancet Infect Dis. 2022 November 9; Online ahead of print; S1473-3099(22)00584-9.; DOI:10.1016/S1473-3099(22)00584-9
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.
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.
Journal Article > ResearchFull Text
Lancet Infect Dis. 2023 January 1; Volume 23 (Issue 1); 91-102.; DOI:10.1016/S1473-3099(22)00584-9
Nsio JM, Ardiet DL, Coulborn RM, Grellety E, Albela M, et al.
Lancet Infect Dis. 2023 January 1; Volume 23 (Issue 1); 91-102.; DOI:10.1016/S1473-3099(22)00584-9
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.
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.