Abstract Background Artemisinin-based combination therapy (ACT) is currently recommended for treatment of uncomplicated malaria. However, the emergence and spread of partial artemisinin resistance threatens their effectiveness for malaria treatment in sub-Saharan Africa where the burden of malaria is highest. Early detection and reporting of validated molecular markers (pfk13 mutations) in Plasmodium falciparum is useful for tracking the emergence and spread of partial artemisinin resistance to inform containment efforts. Methods Genomic surveillance was conducted at 50 surveillance sites across four regions of Uganda in Karamoja, Lango, Acholi and West Nile from June 2021 to August 2023. Symptomatic malaria suspected patients were recruited and screened for presence of parasites. In addition, dried blood spots (DBS) were collected for parasite genomic analysis with PCR and sequencing. Out of 563 available dried blood spots (DBS), a random subset of 240 P. falciparum mono-infections, confirmed by a multiplex PCR were selected and used for detecting the pfk13 mutations by Sanger sequencing using Big Dye Terminator method. Regional variations in the proportions of pfk13 mutations were assessed using the chi square or Fisher’s exact tests while Kruskal–Wallis test was used to compare absolute parasite DNA levels between wild type and mutant parasites. Results Overall, 238/240 samples (99.2%) contained sufficient DNA and were successfully sequenced. Three mutations were identified within the sequenced samples; pfk13 C469Y in 32/238 (13.5%) samples, pfk13 A675V in 14/238 (5.9%) and pfk13 S522C in (1/238 (0.42%) samples across the four surveyed regions. The prevalence of pfk13 C469Y mutation was significantly higher in Karamoja region (23.3%) compared to other regions, P = 0.007. The majority of parasite isolates circulating in West Nile are of wild type (98.3), P = 0.002. Relative parasite DNA quantity did not differ in samples carrying the wild type, C469Y and A675V alleles (Kruskal–Wallis test, P = 0.6373). Conclusion Detection of validated molecular markers of artemisinin partial resistance in multiple geographical locations in this setting provides additional evidence of emerging threat of artemisinin partial resistance in Uganda. In view of these findings, periodic genomic surveillance is recommended to detect and monitor levels of pfk13 mutations in other regions in parallel with TES to assess potential implication on delayed parasite clearance and associated treatment failure in this setting. Future studies should consider identification of potential drivers of artemisinin partial resistance in the different malaria transmission settings in Uganda.

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.).

The coronavirus disease 2019 (COVID-19) pandemic is undoubtedly the greatest challenge in peacetime facing the world for more than 100 years No country is untouched with more than 100 million confirmed cases and over 2 million deaths as of January 28, 2021 (1), and the actual number of infections is probably closer to one billion as few countries had sufficient testing capacity to identify all cases, particularly throughout early 2020 The effectiveness of national responses to the pandemic has been very unequal Whereas some countries, particularly in East and Southeast Asia and Oceania, have been able to bring the epidemic provisionally under control though with continuing outbreaks, much of the rest of the world is still struggling with expanding epidemics and an escalating death toll In addition to the physical and mental health impact and disruptions to health services, it is likely that the social and economic devastation will be with us for years to come The sobering reality is that we are only at the end of the beginning, not the beginning of the end While dealing with the acute stage of the pandemic, we need to start planning for the long-term and shift our thinking to societies living with COVID-19, even if we should benefit from the protection of vaccines The future trajectory of the pandemic will vary by country and depend on a combination of at least five factors: societal and public health responses, vaccine coverage, the duration of natural and vaccine-induced immunity, seasonality, and future mutations of the virus (2–3)

This Viewpoint discusses the prospect that COVID-19 could become a recurrent seasonal disease like influenza and proposes strategies to mitigate the consequences for communities and health systems, including changes in surveillance, medical and public health response, and socioeconomic programs.

This Medical News article is a roundup of insights from recent livestream interviews with leading experts.

The COVID-19 pandemic has been met by unequal responses in different countries1Brauner JM Mindermann S Sharma M et al.Inferring the effectiveness of government interventions against COVID-19.Science. 2020; (published online Dec 15.)https://doi.org/10.1126/science.abd9338Crossref PubMed Scopus (576) Google Scholar, 2Allen K Buklijas T Chen A et al.Tracking global evidence-to-policy pathways in the coronavirus crisis: a preliminary report. International Network for Government Science Advice, Auckland2020https://www.ingsa.org/wp-content/uploads/2020/09/INGSA-Evidence-to-Policy-Tracker_Report-1_FINAL_17Sept.pdfDate accessed: February 15, 2021Google Scholar and led to unequal impacts, with populations in Europe, the USA, and Latin America disproportionately impacted.3Roser M Ritchie H Ortiz-Ospina E Hasell J Coronavirus pandemic (COVID-19).https://ourworldindata.org/coronavirusDate: 2020Date accessed: February 14, 2021Google Scholar Science has uncovered much about SARS-CoV-2 and made extraordinary and unprecedented progress on the development of COVID-19 vaccines, but there is still great uncertainty as the pandemic continues to evolve. COVID-19 vaccines are being rolled out in many countries, but this does not mean the crisis is close to being resolved. We are simply moving to a new phase of the pandemic. What emerges next will partly depend on the ongoing evolution of SARS-CoV-2, on the behaviour of citizens, on governments' decisions about how to respond to the pandemic, on progress in vaccine development and treatments and also in a broader range of disciplines in the sciences and humanities that focus both on bringing this pandemic to an end and learning how to reduce the impacts of future zoonoses, and on the extent to which the international community can stand together in its efforts to control COVID-19. Vaccines alone, unless they achieve high population coverage, offer long-lasting protection, and are effective in preventing both SARS-CoV-2 transmission and COVID-19, will not end the pandemic or allow the world to return to "business as usual". Until high levels of global vaccine-mediated protection are achieved across the world, it could be catastrophic if measures such as mask wearing, physical distancing, and hand hygiene are relaxed prematurely.4Haug N Geyrhofer L Londei A et al.Ranking the effectiveness of worldwide COVID-19 government interventions.Nat Human Behav. 2020; 4: 1303-1312Crossref PubMed Scopus (887) Google Scholar Countries, communities, and individuals must be prepared to cope in the longer-term with both the demands and the consequences of living with such essential containment and prevention measures. Many factors will determine the overall outcome of the pandemic. A nationalistic rather than global approach to vaccine delivery is not only morally wrong but will also delay any return to a level of "normality" (including relaxed border controls) because no country can be safe until all countries are safe. SARS-CoV-2 could continue to mutate in ways that both accelerate virus transmission and reduce vaccine effectiveness.5Fontanet A Autran B Lina B Kieny MP Abdool Karim SS Sridhar D SARS-CoV-2 variants and ending the COVID-19 pandemic.Lancet. 2021; (published online Feb 11.)https://doi.org/10.1016/S0140-6736(21)00370-6Summary Full Text Full Text PDF PubMed Scopus (390) Google Scholar, 6Chand M Hopkins S Dabrera G et al.Investigation of novel SARS-CoV-2 variant: variant of concern 202012/01. Public Health England, London2020Google Scholar, 7Tegally H Wilkinson E Giovanetti M et al.Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa.MedRxiv. 2020; (published online Dec 22.) (preprint)https://doi.org/10.1101/2020.12.21.20248640Google Scholar Vaccine hesitancy, misinformation, and disinformation could compromise the global COVID-19 response.8de Figueiredo A Simas C Karafillakis E Paterson P Larson HJ Mapping global trends in vaccine confidence and investigating barriers to vaccine uptake: a large-scale retrospective temporal modelling study.Lancet. 2020; 396: 898-908Summary Full Text Full Text PDF PubMed Scopus (618) Google Scholar Naive assumptions about herd immunity, given the appearance of new and challenging SARS-CoV-2 variants,5Fontanet A Autran B Lina B Kieny MP Abdool Karim SS Sridhar D SARS-CoV-2 variants and ending the COVID-19 pandemic.Lancet. 2021; (published online Feb 11.)https://doi.org/10.1016/S0140-6736(21)00370-6Summary Full Text Full Text PDF PubMed Scopus (390) Google Scholar, 9Sridhar D Gurdasani D Herd immunity by infection is not an option.Science. 2021; 371: 230-231Crossref PubMed Scopus (42) Google Scholar could seriously risk repeated outbreaks and recurrences. SARS-CoV-2 can probably never be globally eradicated, because of its presence in many animals (including cats and dogs)10Mahdy MAA Younis W Ewaida Z An overview of SARS-CoV-2 and animal infection.Front Vet Sci. 2020; 7596391Crossref PubMed Scopus (93) Google Scholar and because of incomplete vaccine coverage and variable degrees of immunological protection.11Jain S Batra H Yadav P Chand S COVID-19 vaccines currently under preclinical and clinical studies, and associated antiviral immune response.Vaccines. 2020; 8: 649Crossref Scopus (43) Google Scholar Hence, ongoing strategies to deal with the endemic presence of SARS-CoV-2 in populations over the long term will be needed. Furthermore, we do not yet know if, and when, revaccination with current or new COVID-19 vaccines will be required since the duration of immunological protection and the efficacy against emergent SARS-CoV-2 variants remain unknown. With such uncertainties, we should not assume that recent scientific progress on COVID-19 diagnostics, vaccines, and treatments will end the pandemic. The world is likely to have many more years of COVID-19 decision making ahead—there is no quick solution available at present. The decisions of global agencies and governments, as well as the behaviours of citizens in every society, will greatly affect the journey ahead. There are many possible outcomes. At one extreme is the most optimistic scenario, in which new-generation COVID-19 vaccines are effective against all SARS-CoV-2 variants (including those that may yet emerge) and viral control is pursued effectively in every country in a coordinated effort to achieve global control. Even with international cooperation and adequate funding, this scenario would inevitably take a long time to achieve. The COVAX initiative is just an initial step towards addressing vaccine equity and global coordination for vaccine access, especially for lower income countries.12Commissioners of the Lancet COVID-19 CommissionTask Force Chairs and members of the Lancet COVID-19 CommissionCommission Secretariat and Staff of the Lancet COVID-19 CommissionPriorities for the COVID-19 pandemic at the start of 2021: statement of the Lancet COVID-19 Commission.Lancet. 2021; (published online Feb 12.)https://doi.org/10.1016/S0140-6736(21)00388-3Google Scholar At the other extreme is a pessimistic scenario, in which SARS-CoV-2 variants emerge repeatedly with the ability to escape vaccine immunity, so that only high-income countries can respond by rapidly manufacturing adapted vaccines for multiple rounds of population reimmunisation in pursuit of national control while the rest of the world struggles with repeated waves and vaccines that are not sufficiently effective against newly circulating viral variants. In such a scenario, even in high-income countries, there would probably be repeated outbreaks and the path to "normality" in society and business would be much longer. And there are many other intermediate or alternate scenarios. Countries that have kept SARS-CoV-2 in check and countries where there are high levels of viral transmission will in time all probably reach a similar destination, even though their paths to arrive there will be quite different, because no countries can remain permanently isolated from the rest of the world. Unfortunately, countries working in isolation from each other and from global agencies will prolong the pandemic. A nationalistic rather than a global approach to COVID-19 vaccine availability, distribution, and delivery will make a pessimistic outcome much more likely. Additionally, unless countries work together to scale up prevention efforts, the risk of other pandemics, or other transboundary disasters with similar consequences, including those fuelled by climate change, will remain a constant threat. The International Science Council (ISC), as the independent, global voice for science in the broadest sense, believes it is crucial that the range of COVID-19 scenarios over the mid-term and long-term is explored to assist our understanding of the options that will make better outcomes more likely. Decisions to be made in the coming months need to be informed not only by short-term priorities, but also by awareness of how those decisions are likely to affect the ultimate destination. Providing such analyses to policy makers and citizens should assist informed decision making. In developing its COVID-19 Scenarios Project, the ISC has consulted with WHO and the UN Office for Disaster Risk Reduction. The ISC has established in February, 2021, a multidisciplinary Oversight Panel made up of globally representative world experts in relevant disciplines to work with a technical team to produce the scenario map. The Oversight Panel will report within 6–8 months to the global community on the possible COVID-19 scenarios that lie ahead over the next 3–5 years, and on the choices that could be made by governments, agencies, and citizens to provide a pathway to an optimistic outcome for the world. The authors are members of the Interim COVID-19 Working Group of the ISC. DS is convener of the interim working group. PG is President-Elect of the ISC. GB is a member of the ISC Governing Board. HH is Chief Executive Officer of the ISC. SSAK is Co-chair of the South African Ministerial Advisory Committee on COVID-19. PP has received grants from the Bill & Melinda Gates Foundation and personal fees as special adviser from the European Commission and as Chair of the Board from the HMG SCOR Board, unrelated to the current project. CW is a member of the working group on pandemics and crisis of the Group of Chief Science Advisors to the European Commission and the European Group on Ethics in Science and New Technologies and has received grants from the German Federal Ministry of Research and Education, the German Federal Ministry for Family and Seniors, the Bertelsmann Foundation, the German Federal Ministry for Health, the German Federal Ministry of Justice and for Consumer Protection, personal fees from Agaplesion gAG as a member of supervisory board, and personal fees from several companies and organisations all unrelated to this Comment. We thank Felicia Low for her help in preparing this Comment.

Good health and nutrition during childhood and adolescence are crucial to human development yet are currently areas of significant underinvestment by the health sector. This symposium brought together multisectoral perspectives on addressing this challenge.

a Phase I trial of an experimental comprising a recombinant Ebola virus glycoprotein nanoparticle as measured by both immunoglobulin G and neutralizing antibody responses. The antibody 2 (days of adjuvanted vaccine, at day 35 and persisting through 1 of the some waning. Nevertheless, based on a pseudovirion neutralization assay, comparatively higher levels of neutralizing elicited from the nanoparticle vaccine of the

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.

Abstract 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.