Randomized Trial of Vaccines for Zaire Ebola Virus Disease.

BACKGROUND: Questions remain concerning the rapidity of immune responses and the durability and safety of vaccines used to prevent Zaire Ebola virus disease. METHODS: We conducted two randomized, placebo-controlled trials - one involving adults and one involving children - to evaluate the safety and immune responses of three vaccine regimens against Zaire Ebola virus disease: Ad26.ZEBOV followed by MVA-BN-Filo 56 days later (the Ad26-MVA group), rVSVΔG-ZEBOV-GP followed by placebo 56 days later (the rVSV group), and rVSVΔG-ZEBOV-GP followed by rVSVΔG-ZEBOV-GP 56 days later (the rVSV-booster group). The primary end point was antibody response at 12 months, defined as having both a 12-month antibody concentration of at least 200 enzyme-linked immunosorbent assay units (EU) per milliliter and an increase from baseline in the antibody concentration by at least a factor of 4. RESULTS: A total of 1400 adults and 1401 children underwent randomization. Among both adults and children, the incidence of injection-site reactions and symptoms (e.g., feverishness and headache) was higher in the week after receipt of the primary and second or booster vaccinations than after receipt of placebo but not at later time points. These events were largely low-grade. At month 12, a total of 41% of adults (titer, 401 EU per milliliter) and 78% of children (titer, 828 EU per milliliter) had a response in the Ad26-MVA group; 76% (titer, 992 EU per milliliter) and 87% (titer, 1415 EU per milliliter), respectively, had a response in the rVSV group; 81% (titer, 1037 EU per milliliter) and 93% (titer, 1745 EU per milliliter), respectively, had a response in the rVSV-booster group; and 3% (titer, 93 EU per milliliter) and 4% (titer, 67 EU per milliliter), respectively, had a response in the placebo group (P<0.001 for all comparisons of vaccine with placebo). In both adults and children, antibody responses with vaccine differed from those with placebo beginning on day 14. CONCLUSIONS: No safety concerns were identified in this trial. With all three vaccine regimens, immune responses were seen from day 14 through month 12. (Funded by the National Institutes of Health and others; PREVAC ClinicalTrials.gov number, NCT02876328; EudraCT numbers, 2017-001798-18 and 2017-001798-18/3rd; and Pan African Clinical Trials Registry number, PACTR201712002760250.).

Mapping male circumcision for HIV prevention efforts in sub-Saharan Africa.

BACKGROUND: HIV remains the largest cause of disease burden among men and women of reproductive age in sub-Saharan Africa. Voluntary medical male circumcision (VMMC) reduces the risk of female-to-male transmission of HIV by 50-60%. The World Health Organization (WHO) and Joint United Nations Programme on HIV/AIDS (UNAIDS) identified 14 priority countries for VMMC campaigns and set a coverage goal of 80% for men ages 15-49. From 2008 to 2017, over 18 million VMMCs were reported in priority countries. Nonetheless, relatively little is known about local variation in male circumcision (MC) prevalence. METHODS: We analyzed geo-located MC prevalence data from 109 household surveys using a Bayesian geostatistical modeling framework to estimate adult MC prevalence and the number of circumcised and uncircumcised men aged 15-49 in 38 countries in sub-Saharan Africa at a 5 × 5-km resolution and among first administrative level (typically provinces or states) and second administrative level (typically districts or counties) units. RESULTS: We found striking within-country and between-country variation in MC prevalence; most (12 of 14) priority countries had more than a twofold difference between their first administrative level units with the highest and lowest estimated prevalence in 2017. Although estimated national MC prevalence increased in all priority countries with the onset of VMMC campaigns, seven priority countries contained both subnational areas where estimated MC prevalence increased and areas where estimated MC prevalence decreased after the initiation of VMMC campaigns. In 2017, only three priority countries (Ethiopia, Kenya, and Tanzania) were likely to have reached the MC coverage target of 80% at the national level, and no priority country was likely to have reached this goal in all subnational areas. CONCLUSIONS: Despite MC prevalence increases in all priority countries since the onset of VMMC campaigns in 2008, MC prevalence remains below the 80% coverage target in most subnational areas and is highly variable. These mapped results provide an actionable tool for understanding local needs and informing VMMC interventions for maximum impact in the continued effort towards ending the HIV epidemic in sub-Saharan Africa.

The remaining unknowns: a mixed methods study of the current and global health research priorities for COVID-19.

INTRODUCTION: In March 2020, the WHO released a Global Research Roadmap in an effort to coordinate and accelerate the global research response to combat COVID-19 based on deliberations of 400 experts across the world. Three months on, the disease and our understanding have both evolved significantly. As we now tackle a pandemic in very different contexts and with increased knowledge, we sought to build on the work of the WHO to gain a more current and global perspective on these initial priorities. METHODS: We undertook a mixed methods study seeking the views of the global research community to (1) assess which of the early WHO roadmap priorities are still most pressing; (2) understand whether they are still valid in different settings, regions or countries; and (3) identify any new emerging priorities. RESULTS: Thematic analysis of the significant body of combined data shows the WHO roadmap is globally relevant; however, new important priorities have emerged, in particular, pertinent to low and lower middle-income countries (less resourced countries), where health systems are under significant competing pressures. We also found a shift from prioritising vaccine and therapeutic development towards a focus on assessing the effectiveness, risks, benefits and trust in the variety of public health interventions and measures. Our findings also provide insight into temporal nature of these research priorities, highlighting the urgency of research that can only be undertaken within the period of virus transmission, as well as other important research questions but which can be answered outside the transmission period. Both types of studies are key to help combat this pandemic but also importantly to ensure we are better prepared for the future. CONCLUSION: We hope these findings will help guide decision-making across the broad research system including the multilateral partners, research funders, public health practitioners, clinicians and civil society.

Immunization: vital progress, unfinished agenda.

Vaccination against infectious diseases has changed the future of the human species, saving millions of lives every year, both children and adults, and providing major benefits to society as a whole. Here we show, however, that national and sub-national coverage of vaccination varies greatly and major unmet needs persist. Although scientific progress opens exciting perspectives in terms of new vaccines, the pathway from discovery to sustainable implementation can be long and difficult, from the financing, development and licensing to programme implementation and public acceptance. Immunization is one of the best investments in health and should remain a priority for research, industry, public health and society.

Emergent threats: lessons learnt from Ebola.

Recent disease outbreaks have demonstrated the severe health, economic and political crises that epidemics can trigger. The rate of emergence of infectious diseases is accelerating and, with deepening globalisation, pathogens are increasingly mobile. Yet the 2014-2015 West African Ebola epidemic exposed major gaps in the world's capacity to prevent and respond to epidemics. In the midst of the world's second largest ever recorded Ebola outbreak in the Democratic Republic of the Congo, we reflect on six of the many lessons learnt from the epidemic in West Africa, focusing on progress made and the challenges ahead in preparing for future threats. While Ebola and other emerging epidemics will remain a challenge in the years to come, by working in partnership with affected communities and across sectors, and by investing in robust health systems, it is within our power to be better prepared when they strike.

Mapping HIV prevalence in sub-Saharan Africa between 2000 and 2017.

HIV/AIDS is a leading cause of disease burden in sub-Saharan Africa. Existing evidence has demonstrated that there is substantial local variation in the prevalence of HIV; however, subnational variation has not been investigated at a high spatial resolution across the continent. Here we explore within-country variation at a 5 × 5-km resolution in sub-Saharan Africa by estimating the prevalence of HIV among adults (aged 15-49 years) and the corresponding number of people living with HIV from 2000 to 2017. Our analysis reveals substantial within-country variation in the prevalence of HIV throughout sub-Saharan Africa and local differences in both the direction and rate of change in HIV prevalence between 2000 and 2017, highlighting the degree to which important local differences are masked when examining trends at the country level. These fine-scale estimates of HIV prevalence across space and time provide an important tool for precisely targeting the interventions that are necessary to bringing HIV infections under control in sub-Saharan Africa.

Importance of diagnostics in epidemic and pandemic preparedness.

Diagnostics are fundamental for successful outbreak containment. In this supplement, 'Diagnostic preparedness for WHO Blueprint pathogens', we describe specific diagnostic challenges presented by selected priority pathogens most likely to cause future epidemics. Some challenges to diagnostic preparedness are common to all outbreak situations, as highlighted by recent outbreaks of Ebola, Zika and yellow fever. In this article, we review these overarching challenges and explore potential solutions. Challenges include fragmented and unreliable funding pathways, limited access to specimens and reagents, inadequate diagnostic testing capacity at both national and community levels of healthcare and lack of incentives for companies to develop and manufacture diagnostics for priority pathogens during non-outbreak periods. Addressing these challenges in an efficient and effective way will require multiple stakeholders-public and private-coordinated in implementing a holistic approach to diagnostics preparedness. All require strengthening of healthcare system diagnostic capacity (including surveillance and education of healthcare workers), establishment of sustainable financing and market strategies and integration of diagnostics with existing mechanisms. Identifying overlaps in diagnostic development needs across different priority pathogens would allow more timely and cost-effective use of resources than a pathogen by pathogen approach; target product profiles for diagnostics should be refined accordingly. We recommend the establishment of a global forum to bring together representatives from all key stakeholders required for the response to develop a coordinated implementation plan. In addition, we should explore if and how existing mechanisms to address challenges to the vaccines sector, such as Coalition for Epidemic Preparedness Innovations and Gavi, could be expanded to cover diagnostics.

From 1976 to 2018: reflections on early investigations into the Ebola virus.

In the late 1970s, early investigations into the Ebola virus informed the world's understanding of what was then an unknown disease. One such study, published by Bowen and colleagues in 1978, laid the foundations for future research into its prevention and treatment. However, nearly four decades later, scientific progress had not translated into action on the ground with no approved drugs, no vaccines, and no diagnostic tests available when the 2014-15 outbreak began in West Africa. Encouragingly, it appears that we have learned important lessons from the 2014-2015 outbreak, with a swift and rigorous response to the most recent outbreaks in Équateur Province, Democratic Republic of Congo, including the deployment of a vaccine. Ebola will certainly remain a challenge in the years to come and we as the global health community must ensure that innovative research translates into policy and action on the ground, with the full participation of affected communities.