Multi-Pathogen Innovative (5 in 1) Vaccine for Viral Haemorrhagic Fevers will Save More Lives.

Mankind has developed strategies to mitigate calamitous pandemics, by using vaccines. Eradication of some diseases was successful through usage of vaccines. Lassa, Yellow, Crimean-Congo, Marburg and Ebola viruses need special attention. Lassa fever, that now has a candidate vaccine, was discovered in 1969 when two missionary nurses died in Nigeria, while Yellow fever has a vaccine from its 17D attenuated strain. Crimean-Congo haemorrhagic fever is a widespread tick-borne viral disease, and the nucleoprotein and glycoproteins are identified for inclusion in a vaccine. Marburg virus is highly pathogenic with mortality rate of 90%. Ebola virus outbreak in West Africa in 2013-2016 necessitated an early introduction of a vaccine. The classical vaccine platforms are commonly used for human vaccines, and next-generation platforms, are being developed. Development of a novel multivalent vaccine against viral haemorrhagic fevers will eliminate the difficulties of single vaccines and may lead to the eradication of these diseases.

L'Humanité a développé des strategies pour atténuer les pandémiescalamiteuses, en utilisant des vaccins. L'éradication de certaines maladies a été réussie grâce à l'utilisation de vaccins. Les virus de Lassa, de la fièvre jaune, de la fièvre de Crimée-Congo, de Marburg et d'Ebola méritent une attention particulière. La fièvre de Lassa, qui dispose aujourd'hui d'un candidat vaccin, a été découverte en 1969 lors du décès de deux infirmières missionnaires au Nigeria, tandis que la fièvre jaune dispose d'un vaccin à partir de sa souche atténuée 17D. La fièvre hémorragique de Crimée-Congo est une maladie virale répandue, transmise par les tiques, et la nucléoprotéine et les glycoprotéines sont identifiées pour être incluses dans un vaccin. Le virus de Marburg est hautement pathogène avec un taux de mortalité de 90 %. L'épidémie de virus Ebola en Afrique de l'Ouest en 2013- 2016 a nécessité l'introduction rapide d'un vaccin. Les plateformes vaccinales classiques sont couramment utilisées pour les vaccins humains, et des plateformes de nouvelle sont en cours de développement. Le développement d'un nouveau vaccin multivalent contre les fièvres hémorragiques virales éliminera les difficultés des vaccins uniques et pourrait conduire à l'éradication de ces maladies. Mots clés: Innovant ; Multi-pathogène ; Développement de vaccins; Fièvres hémorragiques virales.

The East African Community (EAC) mobile laboratory networks in Kenya, Burundi, Tanzania, Rwanda, Uganda, and South Sudan-from project implementation to outbreak response against Dengue, Ebola, COVID-19, and epidemic-prone diseases.

BACKGROUND: East Africa is home to 170 million people and prone to frequent outbreaks of viral haemorrhagic fevers and various bacterial diseases. A major challenge is that epidemics mostly happen in remote areas, where infrastructure for Biosecurity Level (BSL) 3/4 laboratory capacity is not available. As samples have to be transported from the outbreak area to the National Public Health Laboratories (NPHL) in the capitals or even flown to international reference centres, diagnosis is significantly delayed and epidemics emerge. MAIN TEXT: The East African Community (EAC), an intergovernmental body of Burundi, Rwanda, Tanzania, Kenya, Uganda, and South Sudan, received 10 million € funding from the German Development Bank (KfW) to establish BSL3/4 capacity in the region. Between 2017 and 2020, the EAC in collaboration with the Bernhard-Nocht-Institute for Tropical Medicine (Germany) and the Partner Countries' Ministries of Health and their respective NPHLs, established a regional network of nine mobile BSL3/4 laboratories. These rapidly deployable laboratories allowed the region to reduce sample turn-around-time (from days to an average of 8h) at the centre of the outbreak and rapidly respond to epidemics. In the present article, the approach for implementing such a regional project is outlined and five major aspects (including recommendations) are described: (i) the overall project coordination activities through the EAC Secretariat and the Partner States, (ii) procurement of equipment, (iii) the established laboratory setup and diagnostic panels, (iv) regional training activities and capacity building of various stakeholders and (v) completed and ongoing field missions. The latter includes an EAC/WHO field simulation exercise that was conducted on the border between Tanzania and Kenya in June 2019, the support in molecular diagnosis during the Tanzanian Dengue outbreak in 2019, the participation in the Ugandan National Ebola response activities in Kisoro district along the Uganda/DRC border in Oct/Nov 2019 and the deployments of the laboratories to assist in SARS-CoV-2 diagnostics throughout the region since early 2020. CONCLUSIONS: The established EAC mobile laboratory network allows accurate and timely diagnosis of BSL3/4 pathogens in all East African countries, important for individual patient management and to effectively contain the spread of epidemic-prone diseases.

Association between treatment with oral third-generation cephalosporin antibiotics and mortality outcomes in Ebola virus disease: a multinational retrospective cohort study.

OBJECTIVE: To evaluate the association between oral third-generation cephalosporin antibiotic treatment and mortality in Ebola virus disease (EVD). METHODS: This retrospective cohort studied EVD-infected patients admitted to five Ebola Treatment Units in Sierra Leone and Liberia during 2014-15. Empiric treatment with cefixime 400 mg once daily for five days was the clinical protocol; however, due to resource variability, only a subset of patients received treatment. Data on sociodemographics, clinical characteristics, malaria status and Ebola viral loads were collected. The primary outcome was mortality compared between cases treated with cefixime within 48 h of admission to those not treated within 48 h. Propensity scores were derived using clinical covariates. Mortality between treated and untreated cases was compared using propensity-matched conditional logistic regression and bootstrapped log-linear regression analyses to calculate an odds ratio (OR) and relative risk (RR), respectively, with associated 95% confidence intervals (CI). RESULTS: Of 424 cases analysed, 360 (84.9%) met the cefixime treatment definition. The mean age was 30.5 years and 40.3% were male. Median cefixime treatment duration was 4 days (IQR: 3, 5). Among cefixime-treated patients, mortality was 54.7% (95% CI: 49.6-59.8%) vs. 73.4% (95% CI: 61.5-82.7%) in untreated patients. In conditional logistic regression, mortality likelihood was significantly lower among cases receiving cefixime (OR = 0.48, 95% CI: 0.32-0.71; P = 0.01). In the bootstrap analysis, a non-significant risk reduction was found with cefixime treatment (RR = 0.82, 95% CI: 0.64-1.16, P = 0.11). CONCLUSION: Early oral cefixime may be associated with reduced mortality in EVD and warrants further investigation.

OBJECTIF: Evaluer l'association entre le traitement antibiotique oral avec des céphalosporine de troisième génération et la mortalité dans la maladie au virus Ebola (MVE). MÉTHODES: Cette étude de cohorte rétrospective a été menée chez des patients infectés par la maladie au virus Ebola admis dans cinq unités de traitement Ebola en Sierra Leone et au Libéria en 2014-2015. Le traitement empirique avec Cefixime 400 mg une fois par jour pendant cinq jours était le protocole clinique. Cependant, en raison de la variabilité des ressources, seul un sous-ensemble de patients a reçu un traitement. Des données sur la sociodémographie, les caractéristiques cliniques, le statut du paludisme et les charges virales d'Ebola ont été collectées. Le critère principal était la mortalité comparée entre les cas traités au céfixime dans les 48 heures suivant l'admission et ceux non traités dans les 48 heures. Les scores de propension ont été dérivés à l'aide de covariables cliniques. La mortalité entre les cas traités et non traités a été comparée à l'aide d'analyses de régression logistique conditionnelle et de régression log-linéaire bootstrapées pour calculer respectivement un rapport de cotes (OR) et un risque relatif (RR), avec des intervalles de confiance (IC) à 95% associés. RÉSULTATS: Sur 424 cas analysés, 360 (84,9%) répondaient à la définition du traitement au céfixime. L'âge moyen était de 30,5 ans et 40,3% étaient des hommes. La durée médiane du traitement par le céfixime était de 4 jours (IQR: 3, 5). Parmi les patients traités au Cefixime, la mortalité était de 54,7% (IC95%: 49,6 à 59,8%) vs 73,4% (IC95%: 61,5 à 82,7%) chez les patients non traités. Dans la régression logistique conditionnelle, la probabilité de mortalité était significativement plus faible parmi les cas recevant du céfixime (OR = 0,48 ; IC95%: 0,32 à 0,71; P = 0,01). Dans l'analyse bootstrap, une réduction du risque non significative a été trouvée avec le traitement au céfixime (RR = 0,82, IC95%: 0,64 à 1,16 ; P = 0,11). CONCLUSION: Le céfixime par voie orale rapide peut être associé à une mortalité réduite dans la MVE et mérite une investigation plus approfondie.

Knowledge, attitudes and practices towards viral haemorrhagic fevers amongst healthcare workers in urban and rural public healthcare facilities in the N'zérékoré prefecture, Guinea: a cross-sectional study.

BACKGROUND: The 2013-2016 Ebola epidemic in West Africa began in Guinea's Forest region, a region now considered to be at high risk for future epidemics of viral haemorrhagic fevers (VHF). Good knowledge, attitudes and practices towards VHF amongst healthcare workers in such regions are a central pillar of infection prevention and control (IPC). To inform future training in IPC, this study assesses the knowledge, attitudes and practices (KAP) towards VHF amongst healthcare workers in public healthcare facilities in the most populated prefecture in Forest Guinea, and compares results from urban and rural areas. METHODS: In June and July 2019, we interviewed 102 healthcare workers in the main urban and rural public healthcare facilities in the N'zérékoré prefecture in Forest Guinea. We used an interviewer-administered questionnaire adapted from validated KAP surveys. RESULTS: The great majority of respondents demonstrated good knowledge and favourable attitudes towards VHF. However, respondents reported some gaps in preventive practices such as VHF suspect case detection. They also reported a shortage of protective medical equipment used in everyday clinical work in both urban and rural healthcare facilities and a lack of training in IPC, especially in rural healthcare facilities. However, whether or not healthcare workers had been trained in IPC did not seem to influence their level of KAP towards VHF. CONCLUSIONS: Three years after the end of the Ebola epidemic, our findings suggest that public healthcare facilities in the N'zérékoré prefecture in Forest Guinea still lack essential protective equipment and some practical training in VHF suspect case detection. To minimize the risk of future VHF epidemics and improve management of outbreaks of infectious diseases in the region, current efforts to strengthen the public healthcare system in Guinea should encompass questions of supply and IPC training.

Identifying hotspots of viral haemorrhagic fevers in the Eastern Mediterranean Region: perspectives for the Emerging and Dangerous Pathogens Laboratory Network.

BACKGROUND: The emergence and re-emergence of viral haemorrhagic fevers (VHFs) is a growing concern worldwide. They are associated with major epidemics with an estimated 51-101 million cases each year, of which around 67 000 are fatal. In 2007, 13 countries in the Eastern Mediterranean Region reported VHF cases. AIMS: The main purpose of the study was to review the epidemiological situation in the Region vis-à-vis VHFs to obtain baseline epidemiological information for the establishment of the Emerging Dangerous Pathogen Laboratory Network (EDPLN). METHODS: A literature search was performed using PubMed, ProMED-Mail and GIDEON databases. Reported data included disease burden (reported cases and deaths), human prevalence (general population, high-risk groups), vectors and reservoirs. A scoring method was employed to divide countries into 4 groups (very highly, highly, medium and low affected countries). RESULTS: Very highly affected countries were Afghanistan, Egypt, Islamic Republic of Iran, Saudi Arabia and Sudan. Highly affected countries were Djibouti, Morocco, Oman, Pakistan, Tunisia and Yemen. Medium affected countries were Iraq, Somalia and United Arab Emirates. Low affected countries were Bahrain, Jordan, Lebanon, Libya, Palestine, Qatar and Syrian Arab Republic. CONCLUSIONS: This study contributes in prioritizing countries to be part of EDPLN and in addressing specific needs related to outbreak investigations, surveillance and research.

How feasible or useful are timeliness metrics as a tool to optimise One Health outbreak responses?

INTRODUCTION: As timeliness metrics gain traction to assess and optimise outbreak detection and response performance, implementation and scale-up require insight into the perspectives of stakeholders adopting these tools. This study sought to characterise the feasibility and utility of tracking One Health outbreak milestones across relevant human, animal, plant, and environmental sectors to systematically quantify timeliness metrics in Uganda, a country prone to outbreaks of WHO priority diseases. METHODS: A database of outbreak events occurring in Uganda between 2018 and 2022 was compiled. Outbreak reports meeting our inclusion criteria were reviewed to quantify the frequency of milestone reporting. Key informant interviews were conducted with expert stakeholders to explore the feasibility and utility of tracking metrics using a framework analysis. Quantitative and qualitative data were collected and analysed concurrently. RESULTS: Of the 282 public health emergencies occurring between 2018 and 2022, 129 events met our inclusion criteria, and complete data were available for 82 outbreaks. For our qualitative portion, 10 informants were interviewed from 7 institutions, representing the human, animal and environmental sectors. Informants agreed most One Health milestones are feasible to track, which was supported by the frequency of milestone reporting; however, there was a demonstrated need for increased reporting of after-action reviews, as well as outbreak start and end dates. Predictive alerts signalling potential outbreaks and preventive responses to alerts are seen as challenging to routinely capture, reflecting the lack of public health action for these domains. CONCLUSION: Despite consensus among stakeholders that timeliness metrics are a beneficial tool to assess outbreak performance, not all One Health metrics are being tracked consistently, thereby missing opportunities to optimise epidemic intelligence, preparedness and prevention. The feasibility of tracking these metrics depends on the integration of reporting channels, enhanced documentation of milestones and development of guidance for early adopters, recognising country-specific on-the-ground realities and challenges to national scaling efforts.

Widening geographic range of Rift Valley fever disease clusters associated with climate change in East Africa.

BACKGROUND: Recent epidemiology of Rift Valley fever (RVF) disease in Africa suggests growing frequency and expanding geographic range of small disease clusters in regions that previously had not reported the disease. We investigated factors associated with the phenomenon by characterising recent RVF disease events in East Africa. METHODS: Data on 100 disease events (2008-2022) from Kenya, Uganda and Tanzania were obtained from public databases and institutions, and modelled against possible geoecological risk factors of occurrence including altitude, soil type, rainfall/precipitation, temperature, normalised difference vegetation index (NDVI), livestock production system, land-use change and long-term climatic variations. Decadal climatic variations between 1980 and 2022 were evaluated for association with the changing disease pattern. RESULTS: Of 100 events, 91% were small RVF clusters with a median of one human (IQR, 1-3) and three livestock cases (IQR, 2-7). These clusters exhibited minimal human mortality (IQR, 0-1), and occurred primarily in highlands (67%), with 35% reported in areas that had never reported RVF disease. Multivariate regression analysis of geoecological variables showed a positive correlation between occurrence and increasing temperature and rainfall. A 1°C increase in temperature and a 1-unit increase in NDVI, one months prior were associated with increased RVF incidence rate ratios of 1.20 (95% CI 1.1, 1.2) and 1.93 (95% CI 1.01, 3.71), respectively. Long-term climatic trends showed a significant decadal increase in annual mean temperature (0.12-0.3°C/decade, p<0.05), associated with decreasing rainfall in arid and semi-arid lowlands but increasing rainfall trends in highlands (p<0.05). These hotter and wetter highlands showed increasing frequency of RVF clusters, accounting for 76% and 43% in Uganda and Kenya, respectively. CONCLUSION: These findings demonstrate the changing epidemiology of RVF disease. The widening geographic range of disease is associated with climatic variations, with the likely impact of wider dispersal of virus to new areas of endemicity and future epidemics.

The state of mental health among Ebola virus disease survivors through a cross-sectional study in Sierra Leone.

BACKGROUND: The West African Ebola virus disease (EVD) epidemic resulted in >28 000 disease cases and >11 000 fatalities. The unprecedented number of survivors from this epidemic has raised questions about the long-term mental health impacts of EVD survivorship and the capacity to meet these needs. OBJECTIVES: Assess the frequency and factors associated with mental health consequences of EVD survivorship in Sierra Leone. METHODS: A cross-sectional study of 595 EVD survivors and 403 close contacts (n=998) from Sierra Leone assessed via in-person survey between November 2021 and March 2022. The assessment included validated mental health screening tools (Patient Health Questionnaire-9, PTSD Checklist-5, Alcohol Use Disorders Identification Test, Drug Abuse Screening Test-20) to indicate the presence/absence of disorder. The frequency of each disorder and factors associated with each disorder were assessed. FINDINGS: EVD-associated post-traumatic stress disorder (PTSD) was reported by 45.7% (n=257) of EVD survivors. Moreover, 3.9% (n=22) and 12.0% (n=67) of EVD survivors reported major depression (MD) and substance use, respectively; all mental health outcomes were higher than baseline rates in the region (PTSD: 6%-16%, MD: 1.1%, substance use: 2.2%). PTSD among EVD survivors was associated with acute EVD duration of ≥21 days (adjusted OR, AOR 2.24, 95% CI 1.16 to 4.43), 35-44 years of age (AOR 3.31, 95% CI 1.33 to 8.24; AOR 2.99, 95% CI 1.09 to 8.24) and residential mobility (AOR 4.16, 95% CI 2.35 to 7.35). CONCLUSIONS: Concerningly, the levels of mental health disorders among EVD survivors in Sierra Leone remained elevated 6-8 years after recovery. CLINICAL IMPLICATIONS: Results can be used to inform policy efforts and target resources to address mental health in EVD survivors.

A community-based contact isolation strategy to reduce the spread of Ebola virus disease: an analysis of the 2018-2020 outbreak in the Democratic Republic of the Congo.

INTRODUCTION: Despite tremendous progress in the development of diagnostics, vaccines and therapeutics for Ebola virus disease (EVD), challenges remain in the implementation of holistic strategies to rapidly curtail outbreaks. We investigated the effectiveness of a community-based contact isolation strategy to limit the spread of the disease in the Democratic Republic of Congo (DRC). METHODS: We did a quasi-experimental comparison study. Eligible participants were EVD contacts registered from 12 June 2019 to 18 May 2020 in Beni and Mabalako Health Zones. Intervention group participants were isolated to specific community sites for the duration of their follow-up. Comparison group participants underwent contact tracing without isolation. The primary outcome was measured as the reproduction number (R) in the two groups. Secondary outcomes were the delay from symptom onset to isolation and case management, case fatality rate (CFR) and vaccination uptake. RESULTS: 27 324 EVD contacts were included in the study; 585 in the intervention group and 26 739 in the comparison group. The intervention group generated 32 confirmed cases (5.5%) in the first generation, while the comparison group generated 87 (0.3%). However, the 32 confirmed cases arising from the intervention contacts did not generate any additional transmission (R=0.00), whereas the 87 confirmed cases arising from the comparison group generated 99 secondary cases (R=1.14). The average delay between symptom onset and case isolation was shorter (1.3 vs 4.8 days; p<0.0001), CFR lower (12.5% vs 48.4%; p=0.0001) and postexposure vaccination uptake higher (86.0% vs 56.8%; p<0.0001) in the intervention group compared with the comparison group. A significant difference was also found between intervention and comparison groups in survival rate at the discharge of hospitalised confirmed patients (87.9% vs 47.7%, respectively; p=0.0004). CONCLUSION: The community-based contact isolation strategy used in DRC shows promise as a potentially effective approach for the rapid cessation of EVD transmission, highlighting the importance of rapidly implemented, community-oriented and trust-building control strategies.

A narrative review of high-level isolation unit operational and infrastructure features.

High-level isolation units (HLIUs) are specially designed facilities for care and management of patients with suspected or confirmed high-consequence infectious diseases (HCIDs), equipped with unique infrastructure and operational features. While individual HLIUs have published on their experiences caring for patients with HCIDs and two previous HLIU consensus efforts have outlined key components of HLIUs, we aimed to summarise the existing literature that describes best practices, challenges and core features of these specialised facilities. A narrative review of the literature was conducted using keywords associated with HLIUs and HCIDs. A total of 100 articles were used throughout the manuscript from the literature search or from alternate methods like reference checks or snowballing. Articles were sorted into categories (eg, physical infrastructure, laboratory, internal transport); for each category, a synthesis of the relevant literature was conducted to describe best practices, experiences and operational features. The review and summary of HLIU experiences, best practices, challenges and components can serve as a resource for units continuing to improve readiness, or for hospitals in early stages of developing their HLIU teams and planning or constructing their units. The COVID-19 pandemic, a global outbreak of mpox, sporadic cases of viral haemorrhagic fevers in Europe and the USA, and recent outbreaks of Lassa fever, Sudan Ebolavirus, and Marburg emphasise the need for an extensive summary of HLIU practices to inform readiness and response.

Evaluation of Ebola virus disease surveillance system capability to promptly detect a new outbreak in Liberia.

INTRODUCTION: Liberia was heavily affected by the 2014-2016 Ebola virus disease (EVD) outbreak. With substantial investments in interventions to combat future outbreaks, it is hoped that Liberia is well prepared for a new incursion. We assessed the performance of the current EVD surveillance system in Liberia, focusing on its ability to promptly detect a new EVD outbreak. METHODS: We integrated WHO and US Centers for Disease Control and Prevention guidelines for public health surveillance system evaluation and used standardised indicators to measure system performance. We conducted 23 key informant interviews, 150 health facility assessment surveys and a standardised patient (SP) study (19 visits) from January 2020 to January 2021. Data were summarised and a gap analysis conducted. RESULTS: We found basic competencies of case detection and reporting necessary for a functional surveillance system were in place. At the higher (national, county and district) levels, we found performance gaps in 2 of 6 indicators relating to surveillance system structure, 3 of 14 indicators related to core functions, 1 of 5 quality indicators and 2 of 8 indicators related to support functions. The health facility assessment found performance gaps in 9 of 10 indicators related to core functions, 5 of 6 indicators related to support functions and 3 of 7 indicators related to quality. The SP simulations revealed large gaps between expected and actual practice in managing a patient warranting investigation for EVD. Major challenges affecting the system's operations across all levels included limited access to resources to support surveillance activities, persistent stock out of sample collection materials and attrition of trained staff. CONCLUSION: The EVD surveillance system in Liberia may fail to promptly detect a new EVD outbreak. Specific improvements are required, and regular evaluations recommended. SP studies could be crucial in evaluating surveillance systems for rarely occurring diseases that are important to detect early.

The diagnostic accuracy of rapid diagnostic tests for Ebola virus disease: a systematic review.

BACKGROUND: Ebola virus disease (EVD) is a dangerous condition that can cause an epidemic. Several rapid diagnostic tests (RDTs) have been developed to diagnose EVD. These RDTs promise to be quicker and easier to use than the current reference standard diagnostic test, PCR. OBJECTIVES: To assess the diagnostic accuracy of RDTs for EVD. METHODS: A systematic review of diagnostic accuracy studies. DATA SOURCES: The following bibliographic databases were searched from inception to present: MEDLINE (Ovid), Embase, Global Health, Cochrane Central Register of Controlled Trials, WHO Global Index Medicus database, Web of Science, PROSPERO register of Systematic Reviews, and Clinical Trials.Gov. STUDY ELIGIBILITY CRITERIA: Diagnostic accuracy studies. PARTICIPANTS: Patients presenting to the Ebola treatment units with symptoms of EVD. INTERVENTIONS: RDTs; reference standard, RT-PCR. ASSESSMENT OF RISK OF BIAS: Quality Assessment of Diagnostic Accuracy Studies-2 tool. METHODS OF DATA SYNTHESIS: Summary estimates of diagnostic accuracy study were produced for each device type. Subgroup analyses were performed for RDT type and specimen material. A sensitivity analysis was performed to assess the effect of trial design and bias. RESULTS: We included 15 diagnostic accuracy studies. The summary estimate of sensitivity for lateral flow assays was 86.1% (95% CI, 86-86.2%), with specificity of 97% (95% CI, 96.1-97.9%). The summary estimate for rapid PCR devices was sensitivity of 96.2% (95% CI, 95.3-97.9%), with a specificity of 96.8% (95% CI, 95.3-97.9%). Pre-specified subgroup analyses demonstrated that RDTs were effective on a range of specimen material. Overall, the risk of bias throughout the included studies was low, but it was high in patient selection and uncertain in the flow and timing domains. CONCLUSIONS: RDTs possess both high sensitivity and specificity compared with RT-PCR among symptomatic patients presenting to the Ebola treatment units. Our findings support the use of RDTs as a 'rule in' test to expedite treatment and vaccination.

Viral haemorrhagic fevers and malaria co-infections among febrile patients seeking health care in Tanzania.

BACKGROUND: In recent years there have been reports of viral haemorrhagic fever (VHF) epidemics in sub-Saharan Africa where malaria is endemic. VHF and malaria have overlapping clinical presentations making differential diagnosis a challenge. The objective of this study was to determine the prevalence of selected zoonotic VHFs and malaria co-infections among febrile patients seeking health care in Tanzania. METHODS: This facility-based cross-sectional study was carried out between June and November 2018 in Buhigwe, Kalambo, Kyela, Kilindi, Kinondoni, Kondoa, Mvomero, and Ukerewe districts in Tanzania. The study involved febrile patients seeking health care from primary healthcare facilities. Blood samples were collected and tested for infections due to malaria, Crimean-Congo haemorrhagic fever (CCHF), Ebola virus disease (EVD), Marburg virus disease (MVD), Rift Valley fever (RVF) and yellow fever (YF). Malaria infections were tested using rapid diagnostics tests while exposure to VHFs was determined by screening for immunoglobulin M antibodies using commercial enzyme-linked immunosorbent assays. The Chi-square test was used to compare the proportions. RESULTS: A total of 308 participants (mean age = 35 ± 19 years) were involved in the study. Of these, 54 (17.5%) had malaria infection and 15 (4.8%) were positive for IgM antibodies against VHFs (RVF = 8; CCHF = 2; EBV = 3; MBV = 1; YF = 1). Six (1.9%) individuals had both VHF (RVF = 2; CCHF = 1; EVD = 2; MVD = 1) and malaria infections. The highest co-infection prevalence (0.6%) was observed among individuals aged 46‒60 years (P < 0.05). District was significantly associated with co-infection (P < 0.05) with the highest prevalence recorded in Buhigwe (1.2%) followed by Kinondoni (0.9%) districts. Headache (100%) and muscle, bone, back and joint pains (83.3%) were the most significant complaints among those infected with both VHFs and malaria (P = 0.001). CONCLUSIONS: Co-infections of VHF and malaria are prevalent in Tanzania and affect more the older than the younger population. Since the overlapping symptoms in co-infected individuals may challenge accurate diagnosis, adequate laboratory diagnosis should be emphasized in the management of febrile illnesses.

The response is like a big ship': community feedback as a case study of evidence uptake and use in the 2018-2020 Ebola epidemic in the Democratic Republic of the Congo.

INTRODUCTION: The 2018-2020 Ebola outbreak in the Democratic Republic of the Congo (DRC) took place in the highly complex protracted crisis regions of North Kivu and Ituri. The Red Cross developed a community feedback (CF) data collection process through the work of hundreds of Red Cross personnel, who gathered unprompted feedback in order to inform the response coordination mechanism and decision-making. AIM: To understand how a new CF system was used to make operational and strategic decisions by Ebola response leadership. METHODS: Qualitative data collection in November 2019 in Goma and Beni (DRC), including document review, observation of meetings and CF activities, key informant interviews and focus group discussions. FINDINGS: The credibility and use of different evidence types was affected by the experiential and academic backgrounds of the consumers of that evidence. Ebola response decision-makers were often medics or epidemiologists who tended to view quantitative evidence as having more rigour than qualitative evidence. The process of taking in and using evidence in the Ebola response was affected by decision-makers' bandwidth to parse large volumes of data coming from a range of different sources. The operationalisation of those data into decisions was hampered by the size of the response and an associated reduction in agility to new evidence. CONCLUSION: CF data collection has both instrumental and intrinsic value for outbreak response and should be normalised as a critical data stream; however, a failure to act on those data can further frustrate communities.

Sudan virus disease outbreak in Uganda: urgent research gaps.

The Sudan ebolavirus (SUDV) outbreak highlights our ongoing vulnerability to re-emerging high-consequence infectious diseases. Although the Minister of health in Uganda has initiated public health measures in collaboration with neighbouring countries and with support of the WHO, cases have continued to spread to several regions including the capital. The ongoing transmission, uncertain case numbers and no licensed vaccine or therapeutics available are a cause for concern. We searched four databases for SUDV research using the search terms "SUDV", "Sudan Virus" and "Ebola Sudan". Our analysis identified only 20 SUDV research studies. Most were implemented in the USA and only one in Uganda. Nine studies were on therapeutics, eight on vaccines, one on diagnostics, one in one health and one in social science. Our data highlight a lack of SUDV research and an urgent need for investment to identify an effective vaccine, and optimal supportive care and therapeutic strategies for all at risk groups as a key research priority. Research investments should be prioritised into vaccines and treatment strategies that will be accessible to high-risk populations in affected regions during the outbreak, to protect populations, improve individual outcomes and facilitate outbreak control.

Implementing a DHIS2 Ebola virus disease module during the 2021 Guinea Ebola outbreak.

In 2017, the national agency for health security (L'Agence Nationale de Sécurité Sanitaire-ANSS) in Guinea implemented the District Health Information Software (DHIS2) as the Ministry of Health national surveillance system to capture and report aggregate disease data. During 2019, the ANSS started using DHIS2 Tracker to collect case-based (individual-level) data for epidemic-prone diseases. In 2020, the capability was expanded, and it was used during the COVID-19 pandemic to capture data relevant to the COVID-19 response. When an Ebola virus disease (EVD) outbreak was announced in February 2021, the Tracker module was updated, and enhanced functionalities were developed to meet the needs for the emerging epidemic. This novel EVD module has components to capture information on cases, contacts, alerts, laboratory and vaccinations and provides a centralised site for all EVD outbreak data. It has since been expanded for use with future viral haemorrhagic fever outbreaks.

Scoping future outbreaks: a scoping review on the outbreak prediction of the WHO Blueprint list of priority diseases.

BACKGROUND: The WHO's Research and Development Blueprint priority list designates emerging diseases with the potential to generate public health emergencies for which insufficient preventive solutions exist. The list aims to reduce the time to the availability of resources that can avert public health crises. The current SARS-CoV-2 pandemic illustrates that an effective method of mitigating such crises is the pre-emptive prediction of outbreaks. This scoping review thus aimed to map and identify the evidence available to predict future outbreaks of the Blueprint diseases. METHODS: We conducted a scoping review of PubMed, Embase and Web of Science related to the evidence predicting future outbreaks of Ebola and Marburg virus, Zika virus, Lassa fever, Nipah and Henipaviral disease, Rift Valley fever, Crimean-Congo haemorrhagic fever, Severe acute respiratory syndrome, Middle East respiratory syndrome and Disease X. Prediction methods, outbreak features predicted and implementation of predictions were evaluated. We conducted a narrative and quantitative evidence synthesis to highlight prediction methods that could be further investigated for the prevention of Blueprint diseases and COVID-19 outbreaks. RESULTS: Out of 3959 articles identified, we included 58 articles based on inclusion criteria. 5 major prediction methods emerged; the most frequent being spatio-temporal risk maps predicting outbreak risk periods and locations through vector and climate data. Stochastic models were predominant. Rift Valley fever was the most predicted disease. Diseases with complex sociocultural factors such as Ebola were often predicted through multifactorial risk-based estimations. 10% of models were implemented by health authorities. No article predicted Disease X outbreaks. CONCLUSIONS: Spatiotemporal models for diseases with strong climatic and vectorial components, as in River Valley fever prediction, may currently best reduce the time to the availability of resources. A wide literature gap exists in the prediction of zoonoses with complex sociocultural and ecological dynamics such as Ebola, COVID-19 and especially Disease X.

Evaluation of infection prevention and control practices in Lassa fever treatment centers in north-central Nigeria during an ongoing Lassa fever outbreak.

BACKGROUND: Outbreaks of Lassa fever (LF) in Nigeria have become more frequent, with increasing more healthcare worker infections. Prevention of infection is dependent on strict compliance to infection prevention and control (IPC) practices in treatment centres where patients are managed. OBJECTIVE: To evaluate IPC practices during an ongoing LF outbreak in the two major tertiary hospitals serving as the referral LF treatment centres in the north-central region of Nigeria. METHODS: This cross-sectional survey was carried out by the IPC subteam of the National Rapid Response Team of the Nigeria Centre for Disease Control (NCDC) deployed to Plateau State, north-central Nigeria during the 2019 LF outbreak. Information on IPC in these facilities was collected using the NCDC viral haemorrhagic fevers (VHFs) isolation and treatment facility IPC survey tool. RESULTS: Both treatment centres had national VHF IPC isolation guidelines and few health workers had received IPC training. In both centres, there were no clearly demarcated entry points for staff going into clinical areas after putting on personal protective equipment, and there were also no standard operating procedures in place for reporting occupational exposure of staff to infected blood or body fluids in both centres. DISCUSSION: The LF treatment centers located in Plateau State during the 2019 LF outbreak were not fully implementing the national VHF IPC guidelines. Periodic assessments of IPC are recommended for proper management of cases and effective control of LF in the State.

The impact of the COVID-19 pandemic on hospital utilisation in Sierra Leone.

INTRODUCTION: The COVID-19 pandemic has adversely affected health systems in many countries, but little is known about effects on health systems in sub-Saharan Africa. This study examines the effects of COVID-19 on hospital utilisation in a sub-Saharan country, Sierra Leone. METHODS: Mixed-methods study using longitudinal nationwide hospital data (admissions, operations, deliveries and referrals) and qualitative interviews with healthcare workers and patients. Hospital data were compared across quarters (Q) in 2020, with day 1 of Q2 representing the start of the pandemic in Sierra Leone. Admissions are reported in total and disaggregated by sex, service (surgical, medical, maternity and paediatric) and hospital type (government or private non-profit). Referrals in 2020 were compared with 2019 to assess whether any changes were the result of seasonality. Comparisons were performed using Student's t-test. Qualitative data were analysed using thematic analysis. RESULTS: From Q1 to Q2, weekly mean hospital admissions decreased by 14.7% (p=0.005). Larger decreases were seen in male 18.8% than female 12.5% admissions. The largest decreases were in surgical admissions, a 49.8% decrease (p<0.001) and medical admissions, a 28.7% decrease (p=0.002). Paediatric and maternity admissions did not significantly change. Total operations decreased by 13.9% (p<0.001), while caesarean sections and facility-based deliveries showed significant increases: 12.7% (p=0.014) and 7.5% (p=0.03), respectively. In Q3, total admissions remained 13.2% lower (p<0.001) than Q1. Mean weekly referrals were lower in Q2 and Q3 of 2020 compared with 2019, suggesting findings were unlikely to be seasonal. Qualitative analysis identified both supply-side factors, prioritisation of essential services, introduction of COVID-19 services and pausing elective care, and demand-side factors, fear of nosocomial infection and financial hardship. CONCLUSION: The study demonstrated a decrease in hospital utilisation during COVID-19, the decrease is less than reported in other countries during COVID-19 and less than reported during the Ebola epidemic.

How to improve outbreak response: a case study of integrated outbreak analytics from Ebola in Eastern Democratic Republic of the Congo.

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.