'It's about time': policymakers' and health practitioners' perspectives on implementing fertility care in the Gambian health system.

BACKGROUND: Infertility is a major health issue worldwide, yet very few examples of interventions addressing infertility in the Global South have been documented to date. In The Gambia, West Africa, infertility is recognised as a burden and the health authorities have included it in several health policies and the new National Reproductive Health Strategy however, a detailed operationalisation plan for fertility care has not yet been established. Here, we aim to understand and document the factors that influence the implementation of fertility care in The Gambia. METHODS: We conducted 46 semi-structured interviews with policymakers, implementers, and health practitioners in both the public and private sectors from July to November 2021. The interviews were transcribed, anonymised and analysed with NVivo Pro version 1.6.1. The analysis was initially inductive, with themes arising from the coding categorised according to the WHO health systems building blocks framework. RESULTS: This study identified several barriers to a successful implementation of fertility care in The Gambia, including (i) a lack of routinely collected infertility data; (ii) an absence of financial protection mechanisms for patients, and/or a specific budget for infertility; (iii) limited cooperation between the public and private sectors in the provision of fertility care; and (iv) gaps in fertility care training among health practitioners. Conversely, enablers included: (i) strong national infertility leadership; and (ii) the integration of infertility care within public reproductive health services. CONCLUSION: The Gambian health system is not yet in the position to support a comprehensive fertility care package in its public health facilities. Several aspects of the implementation of fertility care must be considered in operationalising the health strategy including the systematic collection of infertility data, fertility awareness, and the provision of specialised fertility care training. Furthermore, a stronger partnership between the public and private sectors must be developed. Given the increasing availability of assisted reproductive technologies in the sub-Saharan Africa region, and the tendency to locate these technologies in the private sector, further research is needed to understand and identify the processes underlying the implementation of fertility care and to foster better integration with the existing health system.

Capacity assessment and spatial analysis of cervical cancer services in The Gambia.

BACKGROUND: Cervical cancer is the most common cancer and the leading cause of cancer-related death in Gambian women. The Gambian Ministry of Health is striving to improve access to screening, diagnostic, and treatment services for cervical cancer, but comprehensive data on currently available services is limited making it challenging to appropriately prioritize the ideal next steps for expanding care. This study aims to describe the current services available for the prevention, screening, and treatment of cervical cancer in The Gambia and provide suggestions for expanding geographic access to care. METHODS: A survey aimed at assessing the availability of key cervical cancer-related services was developed and then administered in person by research assistants to all secondary and tertiary health facilities (HFs) in The Gambia. ArcGIS Pro Software and 2020 LandScan population density raster were used to visualize and quantify geographic access to care. Survey results were compared with published targets outlined by the Gambian Ministry of Health in the "Strategic Plan for the Prevention and Control of Cervical Cancer in The Gambia: 2016-2020." RESULTS: One hundred and two HFs were surveyed including 12 hospitals, 3 major health centers, 56 minor health centers, and 31 medical centers/clinics. Seventy-eight of these HFs provided some form of cervical cancer-related service. HPV vaccination was available in all health regions. Two-thirds of the population lived within 10 km of a HF that offered screening for cervical cancer and half lived within 10 km of a HF that offered treatment for precancerous lesions. Ten HFs offered hysterectomy, but nine were located in the same region. Two HFs offered limited chemotherapy. Radiotherapy was not available. If all major health centers and hospitals started offering visual inspection with acetic acid and cryotherapy, 86.1% of the population would live within 25 km of a HF with both services. CONCLUSIONS: Geographic access to cervical cancer screening, and precancer treatment is relatively widespread across The Gambia, but targeted expansion in line with the country's "Strategic Plan" would improve access for central and eastern Gambia. The availability of treatment services for invasive cancer is limited, and establishing radiotherapy in the country should continue to be prioritized.

Evaluating the hypertension care cascade in middle-aged and older adults in The Gambia: findings from a nationwide survey.

Background: Hypertension is a major public health problem in sub-Saharan Africa with poor treatment coverage and high case-fatality rates. This requires assessment of healthcare performance to identify areas where intervention is most needed. To identify areas where health resources should be most efficiently targeted, we assessed the hypertension care cascade i.e., loss and retention across the various stages of care, in Gambian adults aged 35 years and above. Methods: This study was embedded within the nationally representative 2019 Gambia National Eye Health Survey of adults ≥35 years. We constructed a hypertension care cascade with four categories: prevalence of hypertension (defined as systolic blood pressure ≥140 mmHg and/or diastolic blood pressure ≥90 mmHg, and/or current use of medication prescribed for hypertension); those aware of their diagnosis; those treated; and those with a controlled blood pressure (defined as blood pressure <140/90 mmHg). Analyses were age- and sex-standardised to the population structure of The Gambia. Logistic regression was used to assess the socio-demographic factors associated with prevalence, awareness, treatment and control of hypertension. Findings: Of 9171 participants with data for blood pressure, the prevalence of hypertension was 47.0%. Among people with hypertension, the prevalence of awareness was 54.7%, the prevalence of hypertension treatment was 32.5%, and prevalence of control was 10.0% with little difference between urban and rural residence. The cascade of care performance was better in women. However, there was no difference in achieving blood pressure control between men and women who were receiving treatment. Female sex, older age and higher body mass index were associated with higher hypertension awareness whilst having an occupation compared to being unemployed was associated with higher odds of being treated. Patients in the underweight category had higher odds of achieving blood pressure control. Interpretation: There is a high prevalence of hypertension and low performance of the health care system that impact on the hypertension care cascade among middle-aged and older adults in The Gambia. Addressing the full cascade will be paramount especially in reducing the mounting prevalence and improving diagnosis of patients with hypertension, where the greatest dividends will be gained. Funding: The Queen Elizabeth Diamond Jubilee Trust, Wellcome Trust.

Concealed pregnancy as an act of care? A qualitative analysis of motivations for concealing and non-disclosure of early pregnancy in The Gambia.

BACKGROUND: A barrier to achieving first trimester antenatal care (ANC) attendance in many countries has been the widespread cultural practice of not discussing pregnancies in the early stages. Motivations for concealing pregnancy bear further study, as the interventions necessary to encourage early ANC attendance may be more complicated than targeting infrastructural barriers to ANC attendance such as transportation, time, and cost. METHODS: Five focus groups with a total of 30 married, pregnant women were conducted to assess the feasibility of conducting a randomised controlled trial to evaluate the effectiveness of early initiation of physical activity and/or yoghurt consumption in reducing Gestational Diabetes Mellitus in pregnant women in The Gambia. Focus group transcripts were coded through a thematic analysis approach, assessing themes as they arose in relation to failure to attend early ANC. RESULTS: Two reasons for the concealment of pregnancies in the first trimester or ahead of a pregnancy's obvious visibility to others were given by focus group participants. These were 'pregnancy outside of marriage' and 'evil spirits and miscarriage.' Concealment on both grounds was motivated through specific worries and fears. In the case of a pregnancy outside of marriage, this was worry over social stigma and shame. Evil spirits were widely considered to be a cause of early miscarriage, and as such, women may choose to conceal their pregnancies in the early stages as a form of protection. CONCLUSION: Women's lived experiences of evil spirits have been under-explored in qualitative health research as they relate specifically to women's access to early antenatal care. Better understanding of how such sprits are experienced and why some women perceive themselves as vulnerable to related spiritual attacks may help healthcare workers or community health workers to identify in a timely manner the women most likely to fear such situations and spirits and subsequently conceal their pregnancies.

Acute Kidney Injury Among Children Likely Associated with Diethylene Glycol-Contaminated Medications - The Gambia, June-September 2022.

On July 26, 2022, a pediatric nephrologist alerted The Gambia's Ministry of Health (MoH) to a cluster of cases of acute kidney injury (AKI) among young children at the country's sole teaching hospital, and on August 23, 2022, MoH requested assistance from CDC. CDC epidemiologists arrived in The Gambia, a West African country, on September 16 to assist MoH in characterizing the illness, describing the epidemiology, and identifying potential causal factors and their sources. Investigators reviewed medical records and interviewed caregivers to characterize patients' symptoms and identify exposures. The preliminary investigation suggested that various contaminated syrup-based children's medications contributed to the AKI outbreak. During the investigation, MoH recalled implicated medications from a single international manufacturer. Continued efforts to strengthen pharmaceutical quality control and event-based public health surveillance are needed to help prevent future medication-related outbreaks.

Persistence of the immune response after two doses of ChAdOx1 nCov-19 (AZD1222): 1 year of follow-up of two randomized controlled trials.

The trajectory of immune responses following the primary dose series determines the decline in vaccine effectiveness over time. Here we report on maintenance of immune responses during the year following a two-dose schedule of ChAdOx1 nCoV-19/AZD1222, in the absence of infection, and also explore the decay of antibody after infection. Total spike-specific IgG antibody titres were lower with two low doses of ChAdOx1 nCoV-19 vaccines (two low doses) (P = 0.0006) than with 2 standard doses (the approved dose) or low dose followed by standard dose vaccines regimens. Longer intervals between first and second doses resulted in higher antibody titres (P < 0.0001); however, there was no evidence that the trajectory of antibody decay differed by interval or by vaccine dose, and the decay of IgG antibody titres followed a similar trajectory after a third dose of ChAdOx1 nCoV-19. Trends in post-infection samples were similar with an initial rapid decay in responses but good persistence of measurable responses thereafter. Extrapolation of antibody data, following two doses of ChAdOx1 nCov-19, demonstrates a slow rate of antibody decay with modelling, suggesting that antibody titres are well maintained for at least 2 years. These data suggest a persistent immune response after two doses of ChAdOx1 nCov-19 which will likely have a positive impact against serious disease and hospitalization.

Genomic epidemiology of SARS-CoV-2 infections in The Gambia: an analysis of routinely collected surveillance data between March, 2020, and January, 2022.

BACKGROUND: COVID-19, caused by SARS-CoV-2, is one of the deadliest pandemics of the past 100 years. Genomic sequencing has an important role in monitoring of the evolution of the virus, including the detection of new viral variants. We aimed to describe the genomic epidemiology of SARS-CoV-2 infections in The Gambia. METHODS: Nasopharyngeal or oropharyngeal swabs collected from people with suspected cases of COVID-19 and international travellers were tested for SARS-CoV-2 with standard RT-PCR methods. SARS-CoV-2-positive samples were sequenced according to standard library preparation and sequencing protocols. Bioinformatic analysis was done using ARTIC pipelines and Pangolin was used to assign lineages. To construct phylogenetic trees, sequences were first stratified into different COVID-19 waves (waves 1-4) and aligned. Clustering analysis was done and phylogenetic trees constructed. FINDINGS: Between March, 2020, and January, 2022, 11 911 confirmed cases of COVID-19 were recorded in The Gambia, and 1638 SARS-CoV-2 genomes were sequenced. Cases were broadly distributed into four waves, with more cases during the waves that coincided with the rainy season (July-October). Each wave occurred after the introduction of new viral variants or lineages, or both, generally those already established in Europe or in other African countries. Local transmission was higher during the first and third waves (ie, those that corresponded with the rainy season), in which the B.1.416 lineage and delta (AY.34.1) were dominant, respectively. The second wave was driven by the alpha and eta variants and the B.1.1.420 lineage. The fourth wave was driven by the omicron variant and was predominantly associated with the BA.1.1 lineage. INTERPRETATION: More cases of SARS-CoV-2 infection were recorded in The Gambia during peaks of the pandemic that coincided with the rainy season, in line with transmission patterns for other respiratory viruses. The introduction of new lineages or variants preceded epidemic waves, highlighting the importance of implementing well structured genomic surveillance at a national level to detect and monitor emerging and circulating variants. FUNDING: Medical Research Unit The Gambia at London School of Hygiene & Tropical Medicine, UK Research and Innovation, WHO.

Availability of services for the diagnosis and treatment of infertility in The Gambia`s public and private health facilities: a cross-sectional survey.

BACKGROUND: Infertility is a long-standing reproductive health issue, which affects both men and women worldwide and it is especially problematic in the Global South. In sub-Saharan Africa, understanding the current availability of diagnostic and treatment services for infertility is important because this could guide health systems to improve access to fertility care for all. Yet, few studies have explicitly started from a health system perspective to grasp the availability and integration of infertility services in sub-Saharan Africa. This quantitative study, the first in The Gambia, West Africa, examines the availability of infertility services in public and private facilities as part of a wider endeavour to improve fertility care policy and practice in the country. METHODS: A cross-sectional survey using Qualtrics was administered to 38 health facilities. The survey was carried out between March and August 2021 and involved closed-ended questions. Data analysis consisted of descriptive statistics and t-tests performed using SPSS version 26. RESULTS: A total of 25 facilities (66%) offered infertility services, of which 13 (52%) were public and 12 (47%) private. Although the availability of screening tests was similar between health institutions, most diagnostic and treatment services were available only in the private sector. Treatment services included: (i) ovarian stimulation (n = 16, 42%); (ii) reversal of tubal ligation and/or blockage (tuboplasty) (n = 4, 11%); and (iii) intrauterine insemination (n = 3, 8%). Assisted reproductive technologies such as IVF and ICSI were not available in public or private sectors. The Gambian health management information system lacked a dedicated space to capture data on infertility. Reported barriers to integration of infertility services in existing reproductive health services included a lack of specialised training, an absence of national guidance on infertility management, and a shortage of appropriate equipment, supplies, and medication. CONCLUSIONS: The availability of infertility services in The Gambia follows a trajectory that is similar to other SSA countries in which services are mostly obtainable through the private sector. Yet, access to private care is expensive and geographically restricted, which exacerbates inequalities in accessing fertility care for all. Improving the provision of infertility services in the public sector requires systematically capturing data on infertility and investing in the provision of a full-range fertility care package.

Facility and Community Results-Based Financing to Improve Maternal and Child Nutrition and Health in The Gambia.

In 2013, the Government of The Gambia implemented a novel results-based financing (RBF) intervention designed to improve maternal and child nutrition and health through a combination of community, facility and individual incentives. In a mixed-methods study, we used a randomized 2 × 2 study design to measure these interventions' impact on the uptake of priority maternal health services, hygiene and sanitation. Conditional cash transfers to individuals were bundled with facility results-based payments. Community groups received incentive payments conditional on completion of locally-designed health projects. Randomization occurred separately at health facility and community levels. Our model pools baseline, midline and endline exposure data to identify evidence of the interventions' impact in isolation or combination. Multivariable linear regression models were estimated. A qualitative study was embedded, with data thematically analyzed. We analyzed 5,927 household surveys: 1,939 baseline, 1,951 midline, and 2,037 endline. On average, community group interventions increased skilled deliveries by 11 percentage points, while the facility interventions package increased them by seven percentage points. No impact was found, either in the community group or facility intervention package arms on early ANC. The community group intervention led to 49, 43 and 48 percentage point increases in handwashing stations, soaps at station and water at station, respectively. No impact was found on improved sanitation facilities. The qualitative data help understand factors underlying these changes. No interaction was found between the community and facility interventions. Where demand-side barriers predominate and community governance structures exist, community group RBF interventions may be more effective than facility designs.

Durability of ChAdOx1 nCoV-19 vaccination in people living with HIV.

Duration of protection from SARS-CoV-2 infection in people living with HIV (PWH) following vaccination is unclear. In a substudy of the phase II/III the COV002 trial (NCT04400838), 54 HIV+ male participants on antiretroviral therapy (undetectable viral loads, CD4+ T cells > 350 cells/µL) received 2 doses of ChAdOx1 nCoV-19 (AZD1222) 4-6 weeks apart and were followed for 6 months. Responses to vaccination were determined by serology (IgG ELISA and Meso Scale Discovery [MSD]), neutralization, ACE-2 inhibition, IFN-γ ELISpot, activation-induced marker (AIM) assay and T cell proliferation. We show that, 6 months after vaccination, the majority of measurable immune responses were greater than prevaccination baseline but with evidence of a decline in both humoral and cell-mediated immunity. There was, however, no significant difference compared with a cohort of HIV-uninfected individuals vaccinated with the same regimen. Responses to the variants of concern were detectable, although they were lower than WT. Preexisting cross-reactive T cell responses to SARS-CoV-2 spike were associated with greater postvaccine immunity and correlated with prior exposure to beta coronaviruses. These data support the ongoing policy to vaccinate PWH against SARS-CoV-2, and they underpin the need for long-term monitoring of responses after vaccination.

Obstetric outcome of female genital mutilation in the Gambia - an observational study.

Background: A 2010 survey in The Gambia among women of reproductive age put the prevalence rate of FGM/C at 76.3%. FGM/C was banned in 2015, but there is no real effort at enforcement of the ban. This study aimed to provide national data on obstetric outcomes to support advocacy and health education. A multicentre observational study to assess the obstetric and neonatal outcomes of parturient women with and without FGM/C was carried out across 4 healthcare facilities in The Gambia. The primary outcome was postpartum haemorrhage (>500ml) and secondary outcomes were caesarean section, perineal tears (including episiotomy), neonatal resuscitation and perinatal death. Of the 1,569 participants recruited into the study, 23% had no FGM/C while 77% had FGM/C of varying severity. The risk of postpartum haemorrhage was doubled for women with type I FGM/C, tripled in type II FGM/C and increased by 5-fold for those with type III and IV FGM/C. Caesarean section and perineal tears were also increased. FGM/C was associated with increased risk for neonatal resuscitation and perinatal death. FGM/C is associated with poor obstetric and neonatal outcomes in the Gambia with degree of risk correlating with the severity of FGM/C.

Safety and immunogenicity of ChAdOx1 MERS vaccine candidate in healthy Middle Eastern adults (MERS002): an open-label, non-randomised, dose-escalation, phase 1b trial.

BACKGROUND: ChAdOx1-vectored vaccine candidates against several pathogens have been developed and tested in clinical trials and ChAdOx1 nCoV-19 has now been licensed for emergency use for COVID-19. We assessed the safety and immunogenicity of the ChAdOx1 MERS vaccine in a phase 1b trial in healthy Middle Eastern adults. METHOD: MERS002 is an open-label, non-randomised, dose-escalation, phase 1b trial. Healthy Middle Eastern adults aged 18-50 years were included in the study. ChAdOx1 MERS was administered as a single intramuscular injection into the deltoid muscle of the non-dominant arm at three different dose groups: 5·0 × 109 viral particles in a low-dose group, 2·5 × 1010 viral particles in an intermediate-dose group, and 5·0 × 1010 viral particles in a high-dose group. The primary objective was to assess the safety and tolerability of ChAdOx1 MERS, measured by the occurrence of solicited and unsolicited adverse events after vaccination for up to 28 days and occurrence of serious adverse events up to 6 months. The study is registered with ClinicalTrials.gov, NCT04170829. FINDINGS: Between Dec 17, 2019, and June 1, 2020, 24 participants were enrolled (six to the low-dose, nine to the intermediate-dose, and nine to the high-dose group) and received a dose; 23 were available for follow-up at 6 months. The one dose of ChAdOx1 MERS vaccine was well tolerated with no serious adverse event reported during the 6 months of follow-up. Most adverse events were mild (67, 74%) and moderate (17, 19%). Six (7%) severe adverse events were reported by two participants in the intermediate-dose group (two feverish, two headache, one joint pain, and one muscle pain). Pain at the injection site was the most common local and overall adverse event, reported by 15 (63%) of the 24 participants. The most common systemic adverse event was headache, reported by 14 (58%), followed by muscle pain reported by 13 (54%). The vaccine induced both antibody and T cell immune responses in all volunteers; antibodies peaked at day 28 and T cell responses peaked at day 14; and continued until the end of follow-up at 6 months. INTERPRETATION: The acceptable safety and immunogenicity data from this phase 1b trial of ChAdOx1 MERS vaccine candidate in Healthy Middle Eastern adults, combined with previous safety and immunogenicity data from a trial in the UK, support selecting the ChAdOx1 MERS vaccine for advancement into phase 2 clinical evaluation. FUNDING: UK Department of Health and Social Care, using UK Aid funding, managed by the UK National Institute for Health Research; and King Abdullah International Medical Research Center.

Reactogenicity and immunogenicity after a late second dose or a third dose of ChAdOx1 nCoV-19 in the UK: a substudy of two randomised controlled trials (COV001 and COV002).

BACKGROUND: COVID-19 vaccine supply shortages are causing concerns about compromised immunity in some countries as the interval between the first and second dose becomes longer. Conversely, countries with no supply constraints are considering administering a third dose. We assessed the persistence of immunogenicity after a single dose of ChAdOx1 nCoV-19 (AZD1222), immunity after an extended interval (44-45 weeks) between the first and second dose, and response to a third dose as a booster given 28-38 weeks after the second dose. METHODS: In this substudy, volunteers aged 18-55 years who were enrolled in the phase 1/2 (COV001) controlled trial in the UK and had received either a single dose or two doses of 5 × 1010 viral particles were invited back for vaccination. Here we report the reactogenicity and immunogenicity of a delayed second dose (44-45 weeks after first dose) or a third dose of the vaccine (28-38 weeks after second dose). Data from volunteers aged 18-55 years who were enrolled in either the phase 1/2 (COV001) or phase 2/3 (COV002), single-blinded, randomised controlled trials of ChAdOx1 nCoV-19 and who had previously received a single dose or two doses of 5 × 1010 viral particles are used for comparison purposes. COV001 is registered with ClinicalTrials.gov, NCT04324606, and ISRCTN, 15281137, and COV002 is registered with ClinicalTrials.gov, NCT04400838, and ISRCTN, 15281137, and both are continuing but not recruiting. FINDINGS: Between March 11 and 21, 2021, 90 participants were enrolled in the third-dose boost substudy, of whom 80 (89%) were assessable for reactogenicity, 75 (83%) were assessable for evaluation of antibodies, and 15 (17%) were assessable for T-cells responses. The two-dose cohort comprised 321 participants who had reactogenicity data (with prime-boost interval of 8-12 weeks: 267 [83%] of 321; 15-25 weeks: 24 [7%]; or 44-45 weeks: 30 [9%]) and 261 who had immunogenicity data (interval of 8-12 weeks: 115 [44%] of 261; 15-25 weeks: 116 [44%]; and 44-45 weeks: 30 [11%]). 480 participants from the single-dose cohort were assessable for immunogenicity up to 44-45 weeks after vaccination. Antibody titres after a single dose measured approximately 320 days after vaccination remained higher than the titres measured at baseline (geometric mean titre of 66·00 ELISA units [EUs; 95% CI 47·83-91·08] vs 1·75 EUs [1·60-1·93]). 32 participants received a late second dose of vaccine 44-45 weeks after the first dose, of whom 30 were included in immunogenicity and reactogenicity analyses. Antibody titres were higher 28 days after vaccination in those with a longer interval between first and second dose than for those with a short interval (median total IgG titre: 923 EUs [IQR 525-1764] with an 8-12 week interval; 1860 EUs [917-4934] with a 15-25 week interval; and 3738 EUs [1824-6625] with a 44-45 week interval). Among participants who received a third dose of vaccine, antibody titres (measured in 73 [81%] participants for whom samples were available) were significantly higher 28 days after a third dose (median total IgG titre: 3746 EUs [IQR 2047-6420]) than 28 days after a second dose (median 1792 EUs [IQR 899-4634]; Wilcoxon signed rank test p=0·0043). T-cell responses were also boosted after a third dose (median response increased from 200 spot forming units [SFUs] per million peripheral blood mononuclear cells [PBMCs; IQR 127-389] immediately before the third dose to 399 SFUs per milion PBMCs [314-662] by day 28 after the third dose; Wilcoxon signed rank test p=0·012). Reactogenicity after a late second dose or a third dose was lower than reactogenicity after a first dose. INTERPRETATION: An extended interval before the second dose of ChAdOx1 nCoV-19 leads to increased antibody titres. A third dose of ChAdOx1 nCoV-19 induces antibodies to a level that correlates with high efficacy after second dose and boosts T-cell responses. FUNDING: UK Research and Innovation, Engineering and Physical Sciences Research Council, National Institute for Health Research, Coalition for Epidemic Preparedness Innovations, National Institute for Health Research Oxford Biomedical Research Centre, Chinese Academy of Medical Sciences Innovation Fund for Medical Science, Thames Valley and South Midlands NIHR Clinical Research Network, AstraZeneca, and Wellcome.

A three-antigen Plasmodium falciparum DNA prime-Adenovirus boost malaria vaccine regimen is superior to a two-antigen regimen and protects against controlled human malaria infection in healthy malaria-naïve adults.

BACKGROUND: A DNA-prime/human adenovirus serotype 5 (HuAd5) boost vaccine encoding Plasmodium falciparum (Pf) circumsporozoite protein (PfCSP) and Pf apical membrane antigen-1 (PfAMA1), elicited protection in 4/15 (27%) of subjects against controlled human malaria infection (CHMI) that was statistically associated with CD8+ T cell responses. Subjects with high level pre-existing immunity to HuAd5 were not protected, suggesting an adverse effect on vaccine efficacy (VE). We replaced HuAd5 with chimpanzee adenovirus 63 (ChAd63), and repeated the study, assessing both the two-antigen (CSP, AMA1 = CA) vaccine, and a novel three-antigen (CSP, AMA1, ME-TRAP = CAT) vaccine that included a third pre-erythrocytic stage antigen [malaria multiple epitopes (ME) fused to the Pf thrombospondin-related adhesive protein (TRAP)] to potentially enhance protection. METHODOLOGY: This was an open label, randomized Phase 1 trial, assessing safety, tolerability, and VE against CHMI in healthy, malaria naïve adults. Forty subjects (20 each group) were to receive three monthly CA or CAT DNA priming immunizations, followed by corresponding ChAd63 boost four months later. Four weeks after the boost, immunized subjects and 12 infectivity controls underwent CHMI by mosquito bite using the Pf3D7 strain. VE was assessed by determining the differences in time to parasitemia as detected by thick blood smears up to 28-days post CHMI and utilizing the log rank test, and by calculating the risk ratio of each treatment group and subtracting from 1, with significance calculated by the Cochran-Mantel-Haenszel method. RESULTS: In both groups, systemic adverse events (AEs) were significantly higher after the ChAd63 boost than DNA immunizations. Eleven of 12 infectivity controls developed parasitemia (mean 11.7 days). In the CA group, 15 of 16 (93.8%) immunized subjects developed parasitemia (mean 12.0 days). In the CAT group, 11 of 16 (63.8%) immunized subjects developed parasitemia (mean 13.0 days), indicating significant protection by log rank test compared to infectivity controls (p = 0.0406) and the CA group (p = 0.0229). VE (1 minus the risk ratio) in the CAT group was 25% compared to -2% in the CA group. The CA and CAT vaccines induced robust humoral (ELISA antibodies against CSP, AMA1 and TRAP, and IFA responses against sporozoites and Pf3D7 blood stages), and cellular responses (IFN-γ FluoroSpot responses to CSP, AMA1 and TRAP) that were not associated with protection. CONCLUSIONS: This study demonstrated that the ChAd63 CAT vaccine exhibited significant protective efficacy, and confirmed protection was afforded by adding a third antigen (T) to a two-antigen (CA) formulation to achieve increased VE. Although the ChAd63-CAT vaccine was associated with increased frequencies of systemic AEs compared to the CA vaccine and, historically, compared to the HuAd5 vectored malaria vaccine encoding CSP and AMA1, they were transient and associated with increased vector dosing.

Geospatial analysis and impact of targeted development of breast cancer care in The Gambia: a cross-sectional study.

BACKGROUND: The Gambia has one of the lowest survival rates for breast cancer in Africa. Contributing factors are late presentation, delays within the healthcare system, and decreased availability of resources. We aimed to characterize the capacity and geographic location of healthcare facilities in the country and calculate the proportion of the population with access to breast cancer care. METHODS: A facility-based assessment tool was administered to secondary and tertiary healthcare facilities and private medical centers and clinics in The Gambia. GPS coordinates were obtained, and proximity of service availability and population analysis were performed. Distance thresholds of 10, 20, and 45 km were chosen to determine access to screening, pathologic diagnosis, and surgical management. An additional population analysis was performed to observe the potential impact of targeted development of resources for breast cancer care. RESULTS: All 102 secondary and tertiary healthcare facilities and private medical centers and clinics in The Gambia were included. Breast cancer screening is mainly performed through clinical breast examination and is available in 52 facilities. Seven facilities provide pathologic diagnosis and surgical management of breast cancer. The proportion of the Gambian population with access to screening, pathologic diagnosis, and surgical management is 72, 53, and 62%, respectively. A hypothetical targeted expansion of resources would increase the covered population to 95, 62, and 84%. CONCLUSIONS: Almost half of the Gambian population does not have access to pathologic diagnosis and surgical management of breast cancer within the distance threshold utilized in the study. Mapping and population analysis can identify areas for targeted development of resources to increase access to breast cancer care.

A single dose of ChAdOx1 Chik vaccine induces neutralizing antibodies against four chikungunya virus lineages in a phase 1 clinical trial.

Chikungunya virus (CHIKV) is a reemerging mosquito-borne virus that causes swift outbreaks. Major concerns are the persistent and disabling polyarthralgia in infected individuals. Here we present the results from a first-in-human trial of the candidate simian adenovirus vectored vaccine ChAdOx1 Chik, expressing the CHIKV full-length structural polyprotein (Capsid, E3, E2, 6k and E1). 24 adult healthy volunteers aged 18-50 years, were recruited in a dose escalation, open-label, nonrandomized and uncontrolled phase 1 trial (registry NCT03590392). Participants received a single intramuscular injection of ChAdOx1 Chik at one of the three preestablished dosages and were followed-up for 6 months. The primary objective was to assess safety and tolerability of ChAdOx1 Chik. The secondary objective was to assess the humoral and cellular immunogenicity. ChAdOx1 Chik was safe at all doses tested with no serious adverse reactions reported. The vast majority of solicited adverse events were mild or moderate, and self-limiting in nature. A single dose induced IgG and T-cell responses against the CHIKV structural antigens. Broadly neutralizing antibodies against the four CHIKV lineages were found in all participants and as early as 2 weeks after vaccination. In summary, ChAdOx1 Chik showed excellent safety, tolerability and 100% PRNT50 seroconversion after a single dose.

Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone progressive change, with variants conferring advantage rapidly becoming dominant lineages, e.g., B.1.617. With apparent increased transmissibility, variant B.1.617.2 has contributed to the current wave of infection ravaging the Indian subcontinent and has been designated a variant of concern in the United Kingdom. Here we study the ability of monoclonal antibodies and convalescent and vaccine sera to neutralize B.1.617.1 and B.1.617.2, complement this with structural analyses of Fab/receptor binding domain (RBD) complexes, and map the antigenic space of current variants. Neutralization of both viruses is reduced compared with ancestral Wuhan-related strains, but there is no evidence of widespread antibody escape as seen with B.1.351. However, B.1.351 and P.1 sera showed markedly more reduction in neutralization of B.1.617.2, suggesting that individuals infected previously by these variants may be more susceptible to reinfection by B.1.617.2. This observation provides important new insights for immunization policy with future variant vaccines in non-immune populations.

Intense and Mild First Epidemic Wave of Coronavirus Disease, The Gambia.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is evolving differently in Africa than in other regions. Africa has lower SARS-CoV-2 transmission rates and milder clinical manifestations. Detailed SARS-CoV-2 epidemiologic data are needed in Africa. We used publicly available data to calculate SARS-CoV-2 infections per 1,000 persons in The Gambia. We evaluated transmission rates among 1,366 employees of the Medical Research Council Unit The Gambia (MRCG), where systematic surveillance of symptomatic cases and contact tracing were implemented. By September 30, 2020, The Gambia had identified 3,579 SARS-CoV-2 cases, including 115 deaths; 67% of cases were identified in August. Among infections, MRCG staff accounted for 191 cases; all were asymptomatic or mild. The cumulative incidence rate among nonclinical MRCG staff was 124 infections/1,000 persons, which is >80-fold higher than estimates of diagnosed cases among the population. Systematic surveillance and seroepidemiologic surveys are needed to clarify the extent of SARS-CoV-2 transmission in Africa.