Rapid diagnostic test: a critical need for outbreak preparedness and response for high priority pathogens.

Rapid diagnostic tests (RDTs) are critical for preparedness and response against an outbreak or pandemic and have been highlighted in the 100 Days Mission, a global initiative that aims to prepare the world for the next epidemic/pandemic by driving the development of diagnostics, vaccines and therapeutics within 100 days of recognition of a novel Disease X threat.RDTs play a pivotal role in early case identification, surveillance and case management, and are critical for initiating deployment of vaccine and monoclonal antibodies. Currently available RDTs, however, have limited clinical sensitivity and specificity and inadequate validation. The development, validation and implementation of RDTs require adequate and sustained financing from both public and private sources. While the World Health Assembly recently passed a resolution on diagnostic capacity strengthening that urges individual Member States to commit resources towards this, the resolution is not binding and implementation will likely be impeded by limited financial resources and other competing priorities, particularly in low-income countries. Meanwhile, the diagnostic industry has not sufficiently invested in RDT development for high priority pathogens.Currently, vaccine development projects are getting the largest funding support among medical countermeasures. Yet vaccines are insufficient tools in isolation, and pandemic preparedness will be incomplete without parallel investment in diagnostics and therapeutics.The Pandemic Fund, a global financing mechanism recently established for strengthening pandemic prevention, preparedness and response, may be a future avenue for supporting diagnostic development.In this paper, we discuss why RDTs are critical for preparedness and response. We also discuss RDT investment challenges and reflect on the way forward.

The promise, problems, and pitfalls of including pregnant women in clinical trials of Lassa fever vaccine: a qualitative assessment of sub-Sahara Africa investigators' perception.

Introduction: Lassa fever runs a uniquely severe course in pregnancy. There are plans for Lassa fever vaccine clinical trials in endemic West African countries. We assessed the perception of West African investigators to include pregnant women in these studies. Methods: interviews were conducted with eight sub-Saharan African investigators. These investigators, listed as speakers at the 9th European and developing countries clinical trials partnership (EDCTP) congress and had clinical research experience in sub-Saharan Africa, were purposefully included as study participants. Six are from West Africa. The information was analyzed thematically. Results: we interviewed eight (six in-person and two on the phone) out of fifteen earmarked investigators. Respondents had limited experience with pregnant women in clinical trials, but desired a paradigm shift. They identified pregnant women's willingness, a robust community engagement strategy, and adequate safety data as enablers, while lack of safety data, persistent fears about potential harm to pregnant women and offspring, and inappropriate community engagement activities as potential barriers. Conclusion: the inclusion of pregnant women in Lassa fever vaccine clinical trials should be a priority of vaccine developers. Investigators are willing to conduct these studies provided adequate measures to ensure safety is in place.

Community engagement in research in sub-Saharan Africa: approaches, barriers, facilitators, ethical considerations and the role of gender - a systematic review protocol.

INTRODUCTION: Meaningful community engagement (CE) is increasingly being considered the major determinant of successful research, innovation and intervention uptake. Community leaders, policy makers and funders have expressed the need to engage communities in research. CE in research empowers the host community to participate in addressing its own health needs and health disparities while ensuring that researchers understand community priorities. Thus, appropriate CE opens a unique way to promote coproduction, coimplementation and coevaluation, which may strengthen both the sense of inclusion, ownership and the effectiveness of the research life-cycle. The aim of this review is to synthesise available evidence on how to engage communities in research in a gender-sensitive, ethical, culture-appropriate and sustainable way in sub-Saharan Africa (SSA). This protocol has been developed following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols and follows the guidance provided by the Cochrane Handbook for Systematic Reviews. METHODS AND ANALYSIS: A combination of key text words and medical subject headings such as 'Community Engagement' or 'Community Involvement' will be used to search 009 databases for all literature published between 1 January 2000 and 31 July 2021. Citations retrieved from database searches will be exported into EndNote X9 to remove duplicate citations and imported into Rayyan QCRI for screening. Two independent reviewers will conduct the screening and data extraction process. Disagreements between review authors will be resolved through discussions, consensus a third reviewer serving as a tiebreaker. The risk of bias will be assessed using the 10-item Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research. The three-staged process described by Thomas and Harden will be used for the thematic and narrative synthesis of findings. ETHICS AND DISSEMINATION: This is a systematic review which uses already collected data thus ethical approval not required. Findings will be published in an open access peer-reviewed journal and presented in relevant conferences and workshops. PROSPERO REGISTRATION NUMBER: This protocol has been submitted for registration in PROSPERO and has been published under registration number CRD42021282503 .

Critical success factors for conducting human challenge trials for vaccine development in low- and middle-income countries.

BACKGROUND: Owing to the globalization of vaccine clinical trials, as well as advances in technologies, improved research accountability, and robust regulatory and ethical scrutiny, the choice to perform human challenge trials has become evident, and one of the most significant applications of human challenge trials is the assessment of vaccine efficacy. While human challenge trials have largely been conducted in high-income countries, the concept is relatively new in many low- and middle-income countries. Thus, the aim of this study was to identify the critical success factors for conducting human challenge trials for vaccine development in low- and middle-income countries. METHODOLOGY: Using a two-step methodology, we first carried out a systematic literature review that was centered on identifying low- and middle-income countries that are either establishing a framework for, have conducted, or are conducting human challenge trials for vaccine development; secondly, we conducted a descriptive cross-sectional survey using a standardized semi-structured online questionnaire administered to eligible stakeholders, to identify the critical success factors for conducting human challenge trials for vaccine development in low- and middle-income countries. Seventeen low- and middle-income countries were identified and included in the survey. RESULTS: The most cited critical success factors for conducting human challenge trials for vaccine development in low- and middle-income countries were Informed Consent, Risk Compensation and/or Reimbursement, Participant Safety and/or Public Protection, Community Engagement, Infrastructural Capacity, and Ethical and Regulatory Frameworks. CONCLUSION: From an empirical perspective, this study provides a list of critical success factors that form the basic structure to guide the design and implementation of further human challenge trials in low- and middle-income countries. Further studies are needed to establish a standardized conceptual framework to aid in the review, approval and overall conduct of human challenge trials in low- and middle-income countries.

Paving the way for human vaccination against Rift Valley fever virus: A systematic literature review of RVFV epidemiology from 1999 to 2021.

BACKGROUND: Rift Valley fever virus (RVFV) is a lethal threat to humans and livestock in many parts of Africa, the Arabian Peninsula, and the Indian Ocean. This systematic review's objective was to consolidate understanding of RVFV epidemiology during 1999-2021 and highlight knowledge gaps relevant to plans for human vaccine trials. METHODOLOGY/PRINCIPAL FINDINGS: The review is registered with PROSPERO (CRD42020221622). Reports of RVFV infection or exposure among humans, animals, and/or vectors in Africa, the Arabian Peninsula, and the Indian Ocean during the period January 1999 to June 2021 were eligible for inclusion. Online databases were searched for publications, and supplemental materials were recovered from official reports and research colleagues. Exposures were classified into five groups: 1) acute human RVF cases, 2) acute animal cases, 3) human RVFV sero-surveys, 4) animal sero-surveys, and 5) arthropod infections. Human risk factors, circulating RVFV lineages, and surveillance methods were also tabulated. In meta-analysis of risks, summary odds ratios were computed using random-effects modeling. 1104 unique human or animal RVFV transmission events were reported in 39 countries during 1999-2021. Outbreaks among humans or animals occurred at rates of 5.8/year and 12.4/year, respectively, with Mauritania, Madagascar, Kenya, South Africa, and Sudan having the most human outbreak years. Men had greater odds of RVFV infection than women, and animal contact, butchering, milking, and handling aborted material were significantly associated with greater odds of exposure. Animal infection risk was linked to location, proximity to water, and exposure to other herds or wildlife. RVFV was detected in a variety of mosquito vectors during interepidemic periods, confirming ongoing transmission. CONCLUSIONS/SIGNIFICANCE: With broad variability in surveillance, case finding, survey design, and RVFV case confirmation, combined with uncertainty about populations-at-risk, there were inconsistent results from location to location. However, it was evident that RVFV transmission is expanding its range and frequency. Gaps assessment indicated the need to harmonize human and animal surveillance and improve diagnostics and genotyping. Given the frequency of RVFV outbreaks, human vaccination has strong potential to mitigate the impact of this now widely endemic disease.

Community engagement in research in sub-Saharan Africa: current practices, barriers, facilitators, ethical considerations and the role of gender - a systematic review.

Introduction: meaningful community engagement is increasingly being considered the major determinant of successful research, innovation and intervention uptake. Even though there is available literature recommending community engagement in health research, there are still knowledge gaps in how communities might be best engaged in Sub-Saharan Africa. We, therefore, synthesized the existing literature on the current practices, barriers and facilitators, ethical considerations, and gender mainstreaming in the engagement of communities in research in sub-Saharan Africa. Methods: this synthesis was developed following the Preferred Reporting Items for Systematic review and Meta-Analysis (PRISMA). A combination of keywords and medical subject headings was used to search MEDLINE, EMBASE, Global Health Library through OVID SP, the Cochrane Library, PsychINFO, CINAHL, WHO Afro Library, WHO Global Index Medicus and the National Institute for Health Research, for all literature published between 1 January 2000 to 31 July 2021. Results: thirty articles met our inclusion criteria. The key reported facilitators of effective community engagement in research included appropriate community entry and engagement of stakeholders. Barriers to effective community engagement in research included the availability of prohibitive cultural, historical and religious practices; geographical/spatial limitations, difficulties in planning and executing community engagement activities and communication barriers. Awareness creation and sensitization on the research through drama, social media, documentaries, and community durbars are some of the existing practices adopted in engaging communities in research. Gender mainstreaming was not considered appropriately in the engagement of communities in research, as only a few studies made provisions for gender considerations, and most of the time, interchanging gender for sex. Respect for autonomy, privacy and informed consent were the main ethical issues reported. Conclusion: gender mainstreaming and ethical standards were reported as important, but not explored in depth. Gender as a social construct needs to be carefully integrated in the entire research cycle. Clear ethical concerns within a research project have to be co-discussed by the research team, community members and potential research participants.

Mapping time use in clinical trials for vaccines against emerging infectious diseases.

BACKGROUND: Vaccines are potent tools to prevent outbreaks of emerging infectious diseases from becoming epidemics and need to be developed at an accelerated pace to have any impact on the course of an ongoing epidemic. The aim of this study was to describe time use in the execution of vaccine trials, to identify steps that could be accelerated to improve preparedness and planning for future emerging infectious diseases vaccine trials. METHODS: We used a mixed-methods approach to map time use and process steps that could be accelerated during vaccine trials. Trials for vaccines against infectious diseases registered in three global trial databases reported in the period 2011-2017 were eligible to join the survey. We invited sponsors to contribute data through a predefined structured questionnaire for clinical trial process metrics. Data were stratified by trial phase, disease type (i.e. emerging infectious diseases or not emerging infectious diseases), sponsor type, and continent. Qualitative interviews were conducted with purposively selected sponsors, and thematic analysis of the interview transcripts was performed. RESULTS: Based on data from 155 vaccine trials including 29,071 subjects, 52% were phase I, 23% phase II, and 25% phase III. We found that the regulatory approval, subject enrollment, study execution, and study close-out accounted for most of the cycle time of the vaccine trial process. Cycle times for the regulatory and ethical approvals, contract agreement, site initiation, and study execution were shorter in trials conducted during outbreaks. Qualitative interviews indicated that early engagement of the regulatory and independent ethical committee authorities in planning the vaccine trials was critical for saving time in trial approval. Furthermore, adapting the trial implementation to the reality of the study sites and active involvement of the local investigators during the planning of the trial and protocol writing were stated to be of paramount importance to successful completion of trials at an accelerated pace. CONCLUSION: The regulatory approval, subject recruitment, study execution, and close-out cycle times accounted for most of the vaccine trial time use and are activities that could be accelerated during a vaccine trial planning and implementation. We encourage tracking of key cycle time metrics and facilitating sharing of knowledge across industry and academia, as this may serve to reduce the time from index case detection to access of a vaccine during emerging infectious diseases epidemics.

Seroepidemiology of respiratory syncytial virus infection in rural and semi-rural areas of the Littoral region of Cameroon.

BACKGROUND: The respiratory syncytial virus (RSV) has been established as a leading cause of acute lower respiratory illness (ALRI) in infants and children. In 2015, the global disease burden (GBD) study estimated that the overall RSV-ALRI mortality could be as high as 118,200, with most death occurring in low- and middle-incomes countries (LMIC). This study aimed to assess the burden of RSV infection among children less than 2 years with acute respiratory infections (ARI) in the Littoral region of Cameroon. METHODS: We carried out a cross-sectional study in seven health centres in the Littoral region of Cameroon. Venous blood was collected using serum separation tubes from eligible children who visited these health centres with acute respiratory infections. ELISA (Enzyme-linked immunosorbent assay) testing was used to assess the seroprevalence of anti-IgM RSV for the total population and by selected demographic and health parameters and potential risk factors. RESULTS: The overall RSV-associated ARI seroprevalence was 33% (95%CI:23.6-42.3; 33/100 children). The only demographic factor significantly associated with RSV acquisition was age of 6 months and below (odds ratio: 7.54 (2.62, 23.36); p = 0.000). Children who were clinically diagnosed to be concomitantly infected with malaria had a lower risk of RSV infection (odds ratio: 0.38 (0.14, 0.95; P = 0.03). CONCLUSIONS: The RSV burden is high among children less than 2 years with ARI in the Littoral region of Cameroon. There is a need for an effective public health RSV surveillance system with standard laboratory techniques and equipment to better understand the RSV disease age-specific incidence, seasonality, risk factors and RSV burden among patients in communities in Cameroon.

Correction to: Developing vaccines against epidemic-prone emerging infectious diseases.

In the original publication of this article, the author name Richard Hatchett was incorrectly published.

Developing vaccines against epidemic-prone emerging infectious diseases.

Today's world is characterized by increasing population density, human mobility, urbanization, and climate and ecological change. This global dynamic has various effects, including the increased appearance of emerging infectious diseases (EIDs), which pose a growing threat to global health security.Outbreaks of EIDs, like the 2013-2016 Ebola outbreak in West Africa or the current Ebola outbreak in Democratic Republic of the Congo (DRC), have not only put populations in low- and middle-income countries (LMIC) at risk in terms of morbidity and mortality, but they also have had a significant impact on economic growth in affected regions and beyond.The Coalition for Epidemic Preparedness Innovation (CEPI) is an innovative global partnership between public, private, philanthropic, and civil society organizations that was launched as the result of a consensus that a coordinated, international, and intergovernmental plan was needed to develop and deploy new vaccines to prevent future epidemics.CEPI is focusing on supporting candidate vaccines against the World Health Organization (WHO) Blueprint priority pathogens MERS-CoV, Nipah virus, Lassa fever virus, and Rift Valley fever virus, as well as Chikungunya virus, which is on the WHO watch list. The current vaccine portfolio contains a wide variety of technologies, ranging across recombinant viral vectors, nucleic acids, and recombinant proteins. To support and accelerate vaccine development, CEPI will also support science projects related to the development of biological standards and assays, animal models, epidemiological studies, and diagnostics, as well as build capacities for future clinical trials in risk-prone contexts.

Relationship between multiple drug resistance and biofilm formation in Staphylococcus aureus isolated from medical and non-medical personnel in Yaounde, Cameroon.

INTRODUCTION: Monitoring the prevalence of nasal carriage of multiple drug resistance (MDR) Staphylococcus aureus (SA) strains in hospital personnel is essential. These strains when transmitted from hospital personnel to patients with already weakened immune states or in-built medical devices, may limit the latter's treatment options. This study aimed at assessing the potential exposure of patients to these MDR SA in a resource-limited hospital setting by assessing the prevalence and relationship between antimicrobial susceptibility and biofilm forming capacity of SA isolates from hospital personnel. METHODS: A total of 59 bacteria isolates phenotypically identified as Staphylococcus aureus obtained from medical (39) and non-medical personnel (20) in Yaounde were used in the study. Multiple drug resistance defined as resistance to four or more of twelve locally used antibiotics were determined by Kirby Bauer disc diffusion technique whereas quantification of biofilm production was by the microtitre plate method. RESULTS: Among the 59 SA isolates, the prevalence of MDR was 50.9%. Among medical personnel 48.7% had MDR as against 55.9% for non-medical personnel (p-value=0.648). The overall percentage of weak biofilm producers was 35.6%. Although the prevalence of weak biofilm formers was higher in isolates from non-medical personnel (40%) than medical personnel (33.3%) the difference was not statistically significant (p-value= 0.246). Slightly less than half (42.9%) of the weak biofilm producers were MDR. CONCLUSION: Considering the high rates of MDR and that slightly less than half of biofilm formers were MDR, these trends need to be monitored regularly among hospital personnel in Yaounde.

Antibiotics susceptibility profile of staphylococcus aureus isolated from the anterior nares of hospital personnel in Yaounde, Cameroon

Purpose: Hospital personnel are often colonized with resistant strains of Staphylococcus aureus (SA). These strains could be transmitted to patients; complicating treatment options particularly in resource-limited areas where antimicrobial susceptibility assessment is not systematic. In view of guiding empiric treatment in such patients; we assessed antimicrobial susceptibility profile of SA isolated from the anterior nares of hospital personnel of three health institutions in Yaounde; Cameroon in a cross sectional study. We also assessed risk factors associated with the presence of Methicillin Resistant Staphylococcus aureus (MRSA). Methods: The antibiotic susceptibility profile of fifty eight SA strains isolated from hospital personnel to sixteen commonly used antibiotics was assessed using the Kirby Bauer disk diffusion method. Methicillin resistant strains were determined by the Oxacillin Minimum Inhibitory concentration technique.Results: All the isolates were resistant to penicillin; ampicillin; and amikacin. No resistance was recorded for netilmicin; vancomycin; and low for gentamicin; rifampin and cephalotin. Eight (13.8) of the isolates were found to be MRSA. We found 85of MRSA to be resistant to more than six of the tested antibiotics. No association was found between demographic variables or personal habits and nasal colonization with methicillin-resistant strains.Conclusion: A relatively high proportion of SA isolates in this study were resistant to commonly used antibiotics. This calls for regular monitoring of susceptibility patterns