Engaging the public in decisions about emergency vaccine deployment strategies: Lessons from scenario-based discussions in Sierra Leone.

ABSTRACTThe COVID-19 pandemic has amplified discussions on emergency vaccine deployment strategies, with current perspectives often neglecting extensive community involvement in ethical, logistical and political aspects. Existing social science literature predominantly delves into factors influencing trust, overlooking the untapped potential for community engagement.Our study examines community preparedness in Sierra Leone's Kambia District, exploring diverse viewpoints on vaccine deployment strategies, emphasising Ebola and COVID-19 vaccinations. Utilising extensive ethnographic research from the Ebola vaccine trials (EBOVAC Salone) conducted in Kambia District from 2015 to 2021, including participant observation and tailored focus group discussions, we investigated various deployment scenarios with community leaders and citizens.Our findings underscore the multifaceted contributions of social science research with communities in shaping emergency vaccination strategies. These contributions span logistical insights, aligning campaigns with local livelihoods and social structures, and grounded ethical concerns assessing social justice outcomes across epidemic scenarios. This study emphasises the imperative of integrating discussions on vaccine confidence and deployment. It highlights communities' proficiency in epidemiological reasoning and their ability to bring this in conversation with salient socio-cultural, economic and religious dimensions. We therefore promote the cultivation of public dialogue, collaborative creation of impactful vaccination initiatives alongside relevant communities in recognition of their invaluable perspectives .

Comparing one dose of HPV vaccine in girls aged 9-14 years in Tanzania (DoRIS) with one dose in young women aged 15-20 years in Kenya (KEN SHE): an immunobridging analysis of randomised controlled trials.

BACKGROUND: The first randomised controlled trial of single-dose human papillomavirus (HPV) vaccine efficacy, the Kenya single-dose HPV-vaccine efficacy (KEN SHE) trial, showed greater than 97% efficacy against persistent HPV16 and HPV18 infection at 36 months among women in Kenya. We compared antibody responses after one dose of HPV vaccine in the Dose Reduction Immunobridging and Safety Study (DoRIS), the first randomised trial of the single- dose regimen in girls aged 9-14 years, the target age range for vaccination, with those after one dose of the same vaccine in KEN SHE. METHODS: In the DoRIS trial, 930 girls aged 9-14 years in Tanzania were randomly assigned to one, two, or three doses of the 2-valent vaccine (Cervarix) or the 9-valent vaccine (Gardasil-9). The proportion seroconverting and geometric mean concentrations (GMCs) at month 24 after one dose were compared with those in women aged 15-20 years who were randomly assigned to one dose of the same vaccines at the same timepoint in KEN SHE. Batched samples were tested together by virus-like particle ELISA for HPV16 and HPV18 IgG antibodies. Non-inferiority of GMC ratios (DoRIS trial:KEN SHE) was predefined as a lower bound of the 95% CI less than 0·50. FINDINGS: Month 24 HPV16 and HPV18 antibody GMCs in DoRIS were similar or higher than those in KEN SHE. 2-valent GMC ratios were 0·90 (95% CI 0·72-1·14) for HPV16 and 1·02 (0·78-1·33) for HPV18. 9-valent GMC ratios were 1·44 (95% CI 1·14-1·82) and 1·47 (1·13-1·90), respectively. Non-inferiority of antibody GMCs and seropositivity was met for HPV16 and HPV18 for both vaccines. INTERPRETATION: HPV16 and HPV18 immune responses in young girls 24 months after a single dose of 2-valent or 9-valent HPV vaccine were comparable to those in young women who were randomly assigned to a single dose of the same vaccines and in whom efficacy had been shown. A single dose of HPV vaccine, when given to girls in the target age range for vaccination, induces immune responses that could be effective against persistent HPV16 and HPV18 infection at least two years after vaccination. FUNDING: The UK Department of Health and Social Care, the Foreign, Commonwealth, & Development Office, the Global Challenges Research Fund, the UK Medical Research Council and Wellcome Trust Joint Global Health Trials scheme, the Bill and Melinda Gates Foundation, the US National Cancer Institute; the US National Institutes of Health, and the Francis and Dorothea Reed Endowed Chair in Infectious Diseases. TRANSLATION: For the KiSwahili translation of the abstract see Supplementary Materials section.

Long-Term Clinical Safety of the Ad26.ZEBOV and MVA-BN-Filo Ebola Vaccines: A Prospective, Multi-Country, Observational Study.

In this prospective, observational study (ClinicalTrials.gov Identifier: NCT02661464), long-term safety information was collected from participants previously exposed to the Ebola vaccines Ad26.ZEBOV and/or MVA-BN-Filo while enrolled in phase 1, 2, or 3 clinical studies. The study was conducted at 15 sites in seven countries (Burkina Faso, France, Kenya, Tanzania, Uganda, the United Kingdom, and the United States). Adult participants and offspring from vaccinated female participants who became pregnant (estimated conception ≤28 days after vaccination with MVA-BN-Filo or ≤3 months after vaccination with Ad26.ZEBOV) were enrolled. Adults were followed for 60 months after their first vaccination, and children born to female participants were followed for 60 months after birth. In the full analysis set (n = 614 adults; median age [range]: 32.0 [18-65] years), 49 (8.0%) had ≥1 serious adverse event (SAE); the incidence rate of any SAE was 27.4 per 1000 person-years (95% confidence interval: 21.0, 35.2). The unrelated SAEs of malaria were reported in the two infants in the full analysis set, aged 11 and 18 months; both episodes were resolved. No deaths or life-threatening SAEs occurred during the study. Overall, no major safety issues were identified; one related SAE was reported. These findings support the long-term clinical safety of the Ad26.ZEBOV and MVA-BN-Filo vaccines.

A dataset of small-mammal detections in West Africa and their associated micro-organisms.

Rodents, a globally distributed and ecologically important mammalian order, serve as hosts for various zoonotic pathogens. However, sampling of rodents and their pathogens suffers from taxonomic and spatial biases. This affects consolidated databases, such as IUCN and GBIF, limiting inference regarding the spillover hazard of zoonotic pathogens into human populations. Here, we synthesised data from 127 rodent trapping studies conducted in 14 West African countries between 1964 and 2022. We combined occurrence data with pathogen screening results to produce a dataset containing detection/non-detection data for 65,628 individual small mammals identified to the species level from at least 1,611 trapping sites. We also included 32 microorganisms, identified to the species or genus levels, that are known or potential pathogens. The dataset is formatted to Darwin Core Standard with associated metadata. This dataset can mitigate spatial and taxonomic biases of current databases, improving understanding of rodent-associated zoonotic pathogen spillover across West Africa.

Safety and immunogenicity of an Ad26.ZEBOV booster vaccine in Human Immunodeficiency Virus positive (HIV+) adults previously vaccinated with the Ad26.ZEBOV, MVA-BN-Filo vaccine regimen against Ebola: A single-arm, open-label Phase II clinical trial in Kenya and Uganda.

BACKGROUND: People living with HIV constitute an important part of the population in regions at risk of Ebola virus disease outbreaks. The two-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen induces strong immune responses in HIV-positive (HIV+) adults but the durability of this response is unknown. It is also unclear whether this regimen can establish immune memory to enable an anamnestic response upon re-exposure to antigen. METHODS: This paper describes an open-label, phase 2 trial, conducted in Kenya and Uganda, of Ad26.ZEBOV booster vaccination in HIV+ participants who had previously received the Ad26.ZEBOV, MVA-BN-Filo primary regimen. HIV+ adults with well-controlled infection and on highly active antiretroviral therapy were enrolled, vaccinated with booster, and followed for 28 days. The primary objectives were to assess Ad26.ZEBOV booster safety and antibody responses against the Ebola virus glycoprotein using the Filovirus Animal Non-Clinical Group ELISA. RESULTS: The Ad26.ZEBOV booster was well-tolerated in HIV+ adults with mostly mild to moderate symptoms. No major safety concerns or serious adverse events were reported. Four and a half years after the primary regimen, 24/26 (92 %) participants were still classified as responders, with a pre-booster antibody geometric mean concentration (GMC) of 726 ELISA units (EU)/mL (95 %CI 447-1179). Seven days after the booster, the GMC increased 54-fold to 38,965 EU/mL (95 %CI 23532-64522). Twenty-one days after the booster, the GMC increased 176-fold to 127,959 EU/mL (95 %CI 93872-174422). The responder rate at both post-booster time points was 100 %. CONCLUSIONS: The Ad26.ZEBOV booster is safe and highly immunogenic in HIV+ adults with well-controlled infection. The Ad26.ZEBOV, MVA-BN-Filo regimen can generate long-term immune memory persisting for at least 4·5 years, resulting in a robust anamnestic response. TRIAL REGISTRATION: Pan African Clinical Trial Registry (PACTR202102747294430). CLINICALTRIALS: gov (NCT05064956).

Immunogenicity and vaccine shedding after 1 or 2 doses of rVZVΔG-ZEBOV-GP Ebola vaccine (ERVEBO®): Results from a phase 2, randomized, placebo-controlled trial in children and adults.

BACKGROUND: The rVSVΔG-ZEBOV-GP vaccine (ERVEBO®) is a single-dose, live-attenuated, recombinant vesicular stomatitis virus vaccine indicated for the prevention of Ebola virus disease (EVD) caused by Zaire ebolavirus in individuals 12 months of age and older. METHODS: The Partnership for Research on Ebola VACcination (PREVAC) is a multicenter, phase 2, randomized, double-blind, placebo-controlled trial of 3 vaccine strategies in healthy children (ages 1-17) and adults, with projected 5 years of follow-up (NCT02876328). Using validated assays (GP-ELISA and PRNT), we measured antibody responses after 1-dose rVSVΔG-ZEBOV-GP, 2-dose rVSVΔG-ZEBOV-GP (given on Day 0 and Day 56), or placebo. Further, we quantified vaccine virus shedding in a subset of children's saliva using RT-PCR. RESULTS: 819 children and 783 adults were randomized to receive rVSVΔG-ZEBOV-GP (1 or 2 doses) or placebo. A single dose of rVSVΔG-ZEBOV-GP increased antibody responses by Day 28 that were sustained through Month 12. A second dose of rVSVΔG-ZEBOV-GP given on Day 56 transiently boosted antibody concentrations. In vaccinated children, GP-ELISA titers were superior to placebo and non-inferior to vaccinated adults. Vaccine virus shedding was observed in 31.7% of children, peaking by Day 7, with no shedding observed after Day 28 post-dose 1 or any time post-dose 2. CONCLUSIONS: A single dose of rVSVΔG-ZEBOV-GP induced robust antibody responses in children that was non-inferior to the responses induced in vaccinated adults. Vaccine virus shedding in children was time-limited and only observed after the first dose. Overall, these data support the use of rVSVΔG-ZEBOV-GP for the prevention of EVD in at-risk children.

Safety and immunogenicity of the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen in infants: a phase 2, randomised, double-blind, active-controlled trial in Guinea and Sierra Leone.

BACKGROUND: This study assessed the safety and immunogenicity of the Ad26.ZEBOV and MVA-BN-Filo Ebola virus (EBOV) vaccine regimen in infants aged 4-11 months in Guinea and Sierra Leone. METHODS: In this phase 2, randomised, double-blind, active-controlled trial, we randomly assigned healthy infants (1:1 in a sentinel cohort, 5:2 for the remaining infants via an interactive web response system) to receive Ad26.ZEBOV followed by MVA-BN-Filo (Ebola vaccine group) or two doses of meningococcal quadrivalent conjugate vaccine (control group) administered 56 days apart. Infants were recruited at two sites in west Africa: Conakry, Guinea, and Kambia, Sierra Leone. All infants received the meningococcal vaccine 8 months after being randomly assigned. The primary objective was safety. The secondary objective was immunogenicity, measured as EBOV glycoprotein-binding antibody concentration 21 days post-dose 2, using the Filovirus Animal Non-Clinical Group ELISA. This study is registered with ClinicalTrials.gov (NCT03929757) and the Pan African Clinical Trials Registry (PACTR201905827924069). FINDINGS: From Aug 20 to Nov 29, 2019, 142 infants were screened and 108 were randomly assigned (Ebola vaccine n=75; control n=33). The most common solicited local adverse event was injection-site pain (Ebola vaccine 15 [20%] of 75; control four [12%] of 33). The most common solicited systemic adverse events with the Ebola vaccine were irritability (26 [35%] of 75), decreased appetite (18 [24%] of 75), pyrexia (16 [21%] of 75), and decreased activity (15 [20%] of 75). In the control group, ten (30%) of 33 had irritability, seven (21%) of 33 had decreased appetite, three (9%) of 33 had pyrexia, and five (15%) of 33 had decreased activity. The frequency of unsolicited adverse events was 83% (62 of 75 infants) in the Ebola vaccine group and 85% (28 of 33 infants) in the control group. No serious adverse events were vaccine-related. In the Ebola vaccine group, EBOV glycoprotein-binding antibody geometric mean concentrations (GMCs) at 21 days post-dose 2 were 27 700 ELISA units (EU)/mL (95% CI 20 477-37 470) in infants aged 4-8 months and 20 481 EU/mL (15 325-27 372) in infants aged 9-11 months. The responder rate was 100% (74 of 74 responded). In the control group, GMCs for both age groups were less than the lower limit of quantification and the responder rate was 3% (one of 33 responded). INTERPRETATION: Ad26.ZEBOV and MVA-BN-Filo was well tolerated and induced strong humoral responses in infants younger than 1 year. There were no safety concerns related to vaccination. FUNDING: Janssen Vaccines & Prevention and Innovative Medicines Initiative 2 Joint Undertaking. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

Continuity and Rupture in Crisis: from Ebola to COVID-19 in Sierra Leone and the eastern Democratic Republic of the Congo.

This article examines the experience of healthcare professionals working in primary healthcare provision during the first wave of the COVID-19 pandemic in North Kivu, the Democratic Republic of the Congo, and in Kambia District, Sierra Leone. Drawing on ethnographic observation, interviews and focus groups, we explore everyday narratives of 'crisis' in these two regions which had recently seen Ebola epidemics. In describing the impact of COVID-19 on their life, work, and relationships with patients, healthcare workers made sense of the pandemic in relation to broader experiences of structural economic and political crisis, as well as differing experiences of recent Ebola epidemics. There were contradictory experiences of rupture and continuity: whilst COVID-19 disrupted routine health provision and exacerbated tensions with patients, the pandemic was also described as continuity, interacting with broader structural problems and longer-term experiences of 'crisis'. In effect, healthcare workers experienced the COVID-19 pandemic at the crossroads between the exceptional and the everyday, where states of exception brought by emergency measures shed new light on long-standing tensions and structural crisis.

An update on one-dose HPV vaccine studies, immunobridging and humoral immune responses - A meeting report.

The 12th HPV Prevention and Control meeting was held on June 2-3, 2022, in Antwerp, Belgium. This technical meeting focused on several topics. This report summarises the discussions and lessons learned on two topics: an update on one-dose HPV vaccination studies and humoral immune responses upon HPV vaccination. Long-term follow-up studies from Costa Rica (eleven years) and India (ten years) report stable levels of antibodies after a single HPV vaccination. High vaccine effectiveness against incident persistent HPV 16/18 infection was seen in India (95.4%, 85.0-99.9) ten years postvaccination and in Kenya (97.5%, 81.7-99.7) eighteen months postvaccination, an important observation in a setting with a higher HPV prevalence. The potential impact of HPV vaccination using a one-dose schedule in India was modelled and showed that implementation of one-dose schedule can contribute towards achieving WHO Cervical Cancer elimination goals. These data support the WHO SAGE recommendations for adopting a one-dose schedule for females aged 9-20 years. Immunobridging studies were discussed during the meeting. General agreement was reached that when thoughtfully applied, they can support and accelerate the expanded use of HPV vaccine with new vaccine schedules, age cohorts, or vaccine formulations. Internationally standardised measurements of HPV immune responses important for the progress of HPV vaccinology field. Humoral immune responses upon HPV vaccination plateau at 24 months regardless of number of doses, therefore, data should be analysed after at least 24 months of follow-up to bridge studies accurately.

The Effect of Previous Exposure to Malaria Infection and Clinical Malaria Episodes on the Immune Response to the Two-Dose Ad26.ZEBOV, MVA-BN-Filo Ebola Vaccine Regimen.

We assessed whether the immunogenicity of the two-dose Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen with a 56-day interval between doses was affected by exposure to malaria before dose 1 vaccination and by clinical episodes of malaria in the period immediately after dose 1 and after dose 2 vaccinations. Previous malaria exposure in participants in an Ebola vaccine trial in Sierra Leone (ClinicalTrials.gov: NCT02509494) was classified as low, intermediate, and high according to their antibody responses to a panel of Plasmodium falciparum antigens detected using a Luminex MAGPIX platform. Clinical malaria episodes after vaccinations were recorded as part of the trial safety monitoring. Binding antibody responses against the Ebola virus (EBOV) glycoprotein (GP) were measured 57 days post dose 1 and 21 days post dose 2 by ELISA and summarized as Geometric Mean Concentrations (GMCs). Geometric Mean Ratios (GMRs) were used to compare groups with different levels of exposure to malaria. Overall, 587 participants, comprising 188 (32%) adults (aged ≥ 18 years) and 399 (68%) children (aged 1-3, 4-11, and 12-17 years), were included in the analysis. There was no evidence that the anti-EBOV-GP antibody GMCs post dose 1 and post dose 2 differed between categories of previous malaria exposure. There was weak evidence that the GMC at 57 days post dose 1 was lower in participants who had had at least one episode of clinical malaria post dose 1 compared to participants with no diagnosed clinical malaria in the same period (GMR = 0.82, 95% CI: 0.69-0.98, p-value = 0.02). However, GMC post dose 2 was not reduced in participants who experienced clinical malaria post-dose 1 and/or post-dose 2 vaccinations. In conclusion, the Ad26.ZEBOV, MVA-BN-Filo Ebola vaccine regimen is immunogenic in individuals with previous exposure to malaria and in those who experience clinical malaria after vaccination. This vaccine regimen is suitable for prophylaxis against Ebola virus disease in malaria-endemic regions.

Immune response of a two-dose heterologous Ebola vaccine regimen: summary of three African clinical trials using a single validated Filovirus Animal Nonclinical Group enzyme-linked immunosorbent assay in a single accredited laboratory.

BACKGROUND: This analysis evaluated the immune response to the two-dose, heterologous Ad26.ZEBOV, MVA-BN-Filo Ebola virus vaccine regimen, administered 56-days apart, from multiple African sites based on results from one analytic laboratory. METHODS: Immunogenicity across three trials (EBL2002, EBL2004/PREVAC, EBL3001) conducted in East and West Africa is summarised. Vaccine-induced Ebola glycoprotein-binding antibody concentrations were analysed by Q2 Solutions laboratory at baseline, 21 days (EBL2002 and EBL3001) or 28 days (EBL2004) post-dose 2 (regimen completion), and 12 months post-dose 1 using the validated Filovirus Animal Nonclinical Group Ebola glycoprotein enzyme-linked immunosorbent assay (ELISA). Responders were defined as those with a >2.5-fold increase from baseline or the lower limit of quantification (LLOQ) if 

Protection, health seeking, or a laissez-passer: Participants' decision-making in an EVD vaccine trial in the eastern Democratic Republic of the Congo.

During the 10th Ebola virus disease (EVD) epidemic in the eastern Democratic Republic of the Congo (DRC) (2018-2020), two experimental EVD vaccines were deployed in North Kivu. This province has been at the centre of conflict in the region for the last 25 years. Amidst ambivalence towards protracted foreign intervention and controversy about introducing two experimental vaccines, the existing literature has focused on mistrust and 'resistance' towards the Ebola response and vaccines. In this article, we examine why people in the eastern DRC did decide to volunteer for a trial of a second EVD vaccine in North Kivu, despite the controversy. Drawing on ethnographic observation, interviews, and focus groups with trial participants conducted between September 2020 and April 2021, we analyse three motivations for participating: protection, health seeking, and expectations surrounding travel requirements. We make three points. First, participation in vaccine trials may be understood locally to have advantages which have not been considered by the trial, because they go beyond medical considerations and are specific to a particular social setting. Second, despite much of the literature focusing on a causal relationship between rumours and 'vaccine hesitancy', some rumours may in fact encourage participation. Third, material objects associated with trial participation - such as participant vaccine cards - can hold social and political meaning beyond the confines of the vaccine clinic, and influence decisions surrounding participation. Empirical investigation of how medical interventions become entangled in political economies is essential to understanding the perceived functions of participation, and thus the reasons why people volunteer in clinical trials. Participants' narratives about their decision-making provide an insight into how international bioethical debates interact with, but may also stand apart from, the situated social and economic realities driving decision-making around clinical trials on the ground. This highlights the need for ethical approaches that foreground the political, social, and economic context.

Prevalence of immunoglobulin G and M to SARS-CoV-2 and other human coronaviruses in The Democratic Republic of Congo, Sierra Leone, and Uganda: A longitudinal study.

OBJECTIVES: We assessed the prevalence of immunoglobulin G (IgG) and IgM against four endemic human coronaviruses and two SARS-CoV-2 antigens among vaccinated and unvaccinated staff at health care centers in Uganda, Sierra Leone, and the Democratic Republic of Congo. METHODS: The government health facility staff who had patient contact in Goma (Democratic Republic of Congo), Kambia District (Sierra Leone), and Masaka District (Uganda) were enrolled. Questionnaires and blood samples were collected at three time points over 4 months. Blood samples were analyzed with the Luminex MAGPIXⓇ. RESULTS: Among unvaccinated participants, the prevalence of IgG/IgM antibodies against SARS-CoV-2 receptor-binding domain or nucleocapsid protein at enrollment was 70% in Goma (138 of 196), 89% in Kambia (112 of 126), and 89% in Masaka (190 of 213). The IgG responses against endemic human coronaviruses at baseline were not associated with SARS-CoV-2 sero-acquisition during follow-up. Among the vaccinated participants, those who had evidence of SARS-CoV-2 IgG/IgM at baseline tended to have higher IgG responses to vaccination than those who were SARS-CoV-2 seronegative at baseline, controlling for the time of sample collection since vaccination. CONCLUSION: The high levels of natural immunity and hybrid immunity should be incorporated into both vaccination policies and prediction models of the impact of subsequent waves of infection in these settings.

Rodent trapping studies as an overlooked information source for understanding endemic and novel zoonotic spillover.

Rodents, a diverse, globally distributed and ecologically important order of mammals are nevertheless important reservoirs of known and novel zoonotic pathogens. Ongoing anthropogenic land use change is altering these species' abundance and distribution, which among zoonotic host species may increase the risk of zoonoses spillover events. A better understanding of the current distribution of rodent species is required to guide attempts to mitigate against potentially increased zoonotic disease hazard and risk. However, available species distribution and host-pathogen association datasets (e.g. IUCN, GBIF, CLOVER) are often taxonomically and spatially biased. Here, we synthesise data from West Africa from 127 rodent trapping studies, published between 1964-2022, as an additional source of information to characterise the range and presence of rodent species and identify the subgroup of species that are potential or known pathogen hosts. We identify that these rodent trapping studies, although biased towards human dominated landscapes across West Africa, can usefully complement current rodent species distribution datasets and we calculate the discrepancies between these datasets. For five regionally important zoonotic pathogens (Arenaviridae spp., Borrelia spp., Lassa mammarenavirus, Leptospira spp. and Toxoplasma gondii), we identify host-pathogen associations that have not been previously reported in host-association datasets. Finally, for these five pathogen groups, we find that the proportion of a rodent hosts range that have been sampled remains small with geographic clustering. A priority should be to sample rodent hosts across a greater geographic range to better characterise current and future risk of zoonotic spillover events. In the interim, studies of spatial pathogen risk informed by rodent distributions must incorporate a measure of the current sampling biases. The current synthesis of contextually rich rodent trapping data enriches available information from IUCN, GBIF and CLOVER which can support a more complete understanding of the hazard of zoonotic spillover events.

Associations between age of menarche, early sexual debut and high-risk sexual behaviour among urban Tanzanian schoolgirls: A cross-sectional study.

OBJECTIVES: This cross-sectional survey aimed to explore associations between age of menarche, early sexual debut and high-risk sexual behaviour among urban Tanzanian schoolgirls. METHODS: Secondary schoolgirls aged 17-18 years from Mwanza, Tanzania, participated in structured face-to-face questionnaire-based interviews, conducted by nurses and clinicians. Age of menarche was evaluated in categories of 11-12, 13-14, 15-16 or ≥17 years. Primary outcome measures were self-reported early sexual debut (first vaginal sex at <16 years) and high-risk sexual behaviour, including non-use of condoms, having sex for gifts/money, having older sexual partners and/or other risky behaviours. RESULTS: Of 401 girls enrolled, 174 (43.4%) reported prior vaginal sex. Prevalence of early sexual debut was 14.2% but pressured/forced sex and risky sexual behaviours were common. Adjusted for potential confounding, younger age at menarche was associated with early sexual debut (adjusted odds ratio for linear trend: 1.88 per category, 95% confidence interval: 1.21-2.92, p = 0.005). This association remained after excluding girls with first sex at <8 years or experiencing pressure or force at first sex. Further, adjusted for potential confounding (including ever experiencing forced sex), early sexual debut was associated with high-risk sexual behaviour (adjusted odds ratio: 2.85, 95% confidence interval: 1.38-5.88, p = 0.004). CONCLUSIONS: Among urban Tanzanian school girls, younger age of menarche was associated with early sexual debut, and early sexual debut was associated with high-risk sexual behaviour. Researchers and public health professionals developing and delivering interventions aimed at preventing adverse sexual health outcomes should consider the impact of these early biological and sexual exposures.

Heterosexual Oral and Anal Sex: Perceptions, Terminologies, and Attitudes of Younger and Older Adults in Ibadan, Nigeria.

Although heterosexual oral and anal sexual behaviors have been reported in sub-Saharan Africa, little is known about how they are understood and perceived, particularly, in West Africa. We undertook a qualitative exploration of local terminologies and sexual scripts associated with heterosexual oral and anal sex in preparation for a quantitative survey. We held focus group discussions (18) and interviews (44) with younger and middle-aged men and women from the general population and female sex workers (FSWs) in selected communities in Ibadan. Most participants had heard of oral and anal sex. Younger adults aged 18-25 years, particularly male participants and FSWs, appeared more informed than older adults in the general population. Sexually explicit movies were the most cited source of information. Oral and anal sexual behaviors were considered sensitive, with different local names, meanings, and interpretations. Participants advised against the use of slang terms in research. We identified six different scripts employed by participants in discussing oral and anal sex practices: protecting sexual relationship, financial reward, an alternative to vaginal sex, pleasure, male dominance and control, and risk, stigma, and disgust.

Costs of delivering human papillomavirus vaccination using a one- or two-dose strategy in Tanzania.

OBJECTIVE: As part of the Dose Reduction Immunobridging and Safety Study of Two HPV Vaccines in Tanzanian Girls (DoRIS; NCT02834637), the current study is one of the first to evaluate the financial and economic costs of the national rollout of an HPV vaccination program in school-aged girls in sub-Saharan Africa and the potential costs associated with a single dose HPV vaccine program, given recent evidence suggesting that a single dose may be as efficacious as a two-dose regimen. METHODS: The World Health Organization's (WHO) Cervical Cancer Prevention and Control Costing (C4P) micro-costing tool was used to estimate the total financial and economic costs of the national vaccination program from the perspective of the Tanzanian government. Cost data were collected in 2019 via surveys, workshops, and interviews with local stakeholders for vaccines and injection supplies, microplanning, training, sensitization, service delivery, supervision, and cold chain. The cost per two-dose and one-dose fully immunized girl (FIG) was calculated. RESULTS: The total financial and economic costs were US$10,117,455 and US$45,683,204, respectively, at a financial cost of $5.17 per two-dose FIG, and an economic cost of $23.34 per FIG. Vaccine and vaccine-related costs comprised the largest proportion of costs, followed by service delivery. In a one-dose scenario, the cost per FIG reduced to $2.51 (financial) and $12.18 (economic), with the largest reductions in vaccine and injection supply costs, and service delivery. CONCLUSIONS: The overall cost of Tanzania's HPV vaccination program was lower per vaccinee than costs estimated from previous demonstration projects in the region, especially in a single-dose scenario. Given the WHO Strategic Advisory Group of Experts on Immunization's recent recommendation to update dosing schedules to either one or two doses of the HPV vaccine, these data provide important baseline data for Tanzania and may serve as a guide for improving coverage going forward. The findings may also aid in the prioritization of funding for countries that have not yet added HPV vaccines to their routine immunizations.

Safety and immunogenicity of an Ad26.ZEBOV booster dose in children previously vaccinated with the two-dose heterologous Ad26.ZEBOV and MVA-BN-Filo Ebola vaccine regimen: an open-label, non-randomised, phase 2 trial.

BACKGROUND: Children account for a substantial proportion of cases and deaths during Ebola virus disease outbreaks. We aimed to evaluate the safety and immunogenicity of a booster dose of the Ad26.ZEBOV vaccine in children who had been vaccinated with a two-dose regimen comprising Ad26.ZEBOV as dose one and MVA-BN-Filo as dose two. METHODS: We conducted an open-label, non-randomised, phase 2 trial at one clinic in Kambia Town, Sierra Leone. Healthy children, excluding pregnant or breastfeeding girls, who had received the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen in a previous study, and were aged 1-11 years at the time of their first vaccine dose, received an intramuscular injection of Ad26.ZEBOV (5 × 1010 viral particles) and were followed up for 28 days. Primary outcomes were safety (measured by adverse events) and immunogenicity (measured by Ebola virus glycoprotein-specific IgG binding antibody geometric mean concentration) of the booster vaccine dose. Safety was assessed in all participants who received the booster vaccination; immunogenicity was assessed in all participants who received the booster vaccination, had at least one evaluable sample after the booster, and had no major protocol deviations that could have influenced the immune response. This trial is registered with ClinicalTrials.gov, NCT04711356. FINDINGS: Between July 8 and Aug 18, 2021, 58 children were assessed for eligibility and 50 (27 aged 4-7 years and 23 aged 9-15 years) were enrolled and received an Ad26.ZEBOV booster vaccination, more than 3 years after receiving dose one of the Ad26.ZEBOV and MVA-BN-Filo vaccine regimen. The booster was well tolerated. The most common solicited local adverse event during the 7 days after vaccination was injection site pain, reported in 18 (36%, 95% CI 23-51) of 50 participants. The most common solicited systemic adverse event during the 7 days after vaccination was headache, reported in 11 (22%, 12-36) of 50 participants. Malaria was the most common unsolicited adverse event during the 28 days after vaccination, reported in 25 (50%, 36-64) of 50 participants. No serious adverse events were observed during the study period. 7 days after vaccination, the Ebola virus glycoprotein-specific IgG binding antibody geometric mean concentration was 28 561 ELISA units per mL (95% CI 20 255-40 272), which was 44 times higher than the geometric mean concentration before the booster dose. 21 days after vaccination, the geometric mean concentration reached 64 690 ELISA units per mL (95% CI 48 356-86 541), which was 101 times higher than the geometric mean concentration before the booster dose. INTERPRETATION: A booster dose of Ad26.ZEBOV in children who had received the two-dose Ad26.ZEBOV and MVA-BN-Filo vaccine regimen more than 3 years earlier was well tolerated and induced a rapid and robust increase in binding antibodies against Ebola virus. These findings could inform Ebola vaccination strategies in paediatric populations. FUNDING: Innovative Medicines Initiative 2 Joint Undertaking. TRANSLATION: For the French translation of the abstract see Supplementary Materials section.

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.).

COVID-19 Vaccine Acceptability Among Healthcare Facility Workers in Sierra Leone, the Democratic Republic of Congo and Uganda: A Multi-Centre Cross-Sectional Survey.

Objectives: This cross-sectional survey explored COVID-19 vaccine acceptability among public healthcare facility workers in Kambia (Sierra Leone), Goma (Democratic Republic of Congo) and Masaka (Uganda). Methods: Questionnaire-based interviews conducted between April-October 2021 explored participants' knowledge and perceptions of, and attitudes towards, the COVID-19 pandemic and COVID-19 vaccines, as well as COVID-19 vaccine acceptability (defined as uptake of ≥1 dose or intent to get vaccinated). Results: Whilst most (n = 444; 81.8%) of the 543 participants had one or more concerns about COVID-19 vaccines, 487 (89.7%) nonetheless perceived that they were important for pandemic control. Most participants from Kambia or Masaka either were vaccinated (n = 137/355; 38.6%) or intended to get vaccinated (n = 211/355; 59.4%) against COVID-19. In Goma, all 188 participants were unvaccinated; only 81 (43.1%) participants intended to get vaccinated, and this was associated with positive perceptions about COVID-19 vaccines. In Goma, the most common reasons for not wanting a COVID-19 vaccine were concerns that the vaccines were new (n = 75/107; 70.1%) and fear of side effects (n = 74/107; 69.2%). Conclusion: Reported COVID-19 vaccine acceptability was high among healthcare facility workers in Kambia and Masaka. The lower vaccine acceptability in Goma may highlight the importance of social mobilisation and accurate, accessible information that addresses specific concerns.