The future of public health doctoral education in Africa: transforming higher education institutions to enhance research and practice.

The African Union and the Africa Centers for Disease Control and Prevention issued a Call to Action in 2022 for Africa's New Public Health Order that underscored the need for increased capacity in the public health workforce. Additional domestic and global investments in public health workforce development are central to achieving the aspirations of Agenda 2063 of the African Union, which aims to build and accelerate the implementation of continental frameworks for equitable, people-centred growth and development. Recognising the crucial role of higher education and research, we assessed the capabilities of public health doctoral training in schools and programmes of public health in Africa across three conceptual components: instructional, institutional, and external. Six inter-related and actionable recommendations were derived to advance doctoral training, research, and practice capacity within and between universities. These can be achieved through equitable partnerships between universities, research centres, and national, regional, and global public health institutions.

Fidelity of implementation of national guidelines on malaria diagnosis for children under-five years in Rivers State, Nigeria.

BACKGROUND: Malaria is still a disease of global public health importance and children under-five years of age are the most vulnerable to the disease. Nigeria adopted the "test and treat" strategy in the national malaria guidelines as one of the ways to control malaria transmission. The level of adherence to the guidelines is an important indicator for the success or failure of the country's roadmap to malaria elimination by 2030. This study aimed to assess the fidelity of implementation of the national guidelines on malaria diagnosis for children under-five years and examine its associated moderating factors in health care facilities in Rivers State, Nigeria. METHODS: This was a descriptive, cross-sectional study conducted in Port Harcourt metropolis. Data were collected from 147 public, formal private and informal private health care facilities. The study used a questionnaire developed based on Carroll's Conceptual Framework for Implementation Fidelity. Frequency, mean and median scores for implementation fidelity and its associated factors were calculated. Associations between fidelity and the measured predictors were examined using Mann Whitney U test, Kruskal Wallis test, and multiple linear regression modelling using robust estimation of errors. Regression results are presented in adjusted coefficient (ß) and 95% confidence intervals. RESULTS: The median (IQR) score fidelity score for all participants was 65% (43.3, 85). Informal private facilities (proprietary patent medicine vendors) had the lowest fidelity scores (47%) compared to formal private (69%) and public health facilities (79%). Intervention complexity had a statistically significant inverse relationship to implementation fidelity (ß = - 1.89 [- 3.42, - 0.34]). Increase in participant responsiveness (ß = 8.57 [4.83, 12.32]) and the type of malaria test offered at the facility (e.g., RDT vs. no test, ß = 16.90 [6.78, 27.03]; microscopy vs. no test, ß = 21.88 [13.60, 30.16]) were positively associated with fidelity score. CONCLUSIONS: This study showed that core elements of the "test and treat" strategy, such as testing all suspected cases with approved diagnostic methods before treatment, are still not fully implemented by health facilities. There is a need for strategies to increase fidelity, especially in the informal private health sector, for malaria elimination programme outcomes to be achieved.

Bayesian spatio-temporal analysis of malaria prevalence in children between 2 and 10 years of age in Gabon.

BACKGROUND: Gabon still bears significant malaria burden despite numerous efforts. To reduce this burden, policy-makers need strategies to design effective interventions. Besides, malaria distribution is well known to be related to the meteorological conditions. In Gabon, there is limited knowledge of the spatio-temporal effect or the environmental factors on this distribution. This study aimed to investigate on the spatio-temporal effects and environmental factors on the distribution of malaria prevalence among children 2-10 years of age in Gabon. METHODS: The study used cross-sectional data from the Demographic Health Survey (DHS) carried out in 2000, 2005, 2010, and 2015. The malaria prevalence was obtained by considering the weighting scheme and using the space-time smoothing model. Spatial autocorrelation was inferred using the Moran's I index, and hotspots were identified with the local statistic Getis-Ord General Gi. For the effect of covariates on the prevalence, several spatial methods implemented in the Integrated Nested Laplace Approximation (INLA) approach using Stochastic Partial Differential Equations (SPDE) were compared. RESULTS: The study considered 336 clusters, with 153 (46%) in rural and 183 (54%) in urban areas. The prevalence was highest in the Estuaire province in 2000, reaching 46%. It decreased until 2010, exhibiting strong spatial correlation (P < 0.001), decreasing slowly with distance. Hotspots were identified in north-western and western Gabon. Using the Spatial Durbin Error Model (SDEM), the relationship between the prevalence and insecticide-treated bed nets (ITNs) coverage was decreasing after 20% of coverage. The prevalence in a cluster decreased significantly with the increase per percentage of ITNs coverage in the nearby clusters, and per degree Celsius of day land surface temperature in the same cluster. It slightly increased with the number of wet days and mean temperature per month in neighbouring clusters. CONCLUSIONS: In summary, this study showed evidence of strong spatial effect influencing malaria prevalence in household clusters. Increasing ITN coverage by 20% and prioritizing hotspots are essential policy recommendations. The effects of environmental factors should be considered, and collaboration with the national meteorological department (DGM) for early warning systems is needed.

Epidemiology and treatment outcomes of recurrent tuberculosis in Tanzania from 2018 to 2021 using the National TB dataset.

BACKGROUND: Patients with recurrent TB have an increased risk of higher mortality, lower success rate, and a relatively feeble likelihood of treatment completion than those with new-onset TB. This study aimed to assess the epidemiology of recurrent TB in Tanzania; specifically, we aim to determine the prevalence of TB recurrence and factors associated with unfavourable treatment outcomes among patients with recurrent TB in Tanzania from 2018 to 2021. METHODS: In this cross-sectional study, we utilized Tanzania's routinely collected national TB program data. The study involved a cohort of TB patients over a fixed treatment period registered in the TB and Leprosy case-based District Health Information System (DHIS2-ETL) database from 2018 to 2021 in Tanzania. We included patients' sociodemographic and clinical factors, facility characteristics, and TB treatment outcomes. We conducted bivariate analysis and multivariable multi-level mixed effects logistic regression of factors associated with TB recurrence and TB treatment outcomes to account for the correlations at the facility level. A purposeful selection method was used; the multivariable model included apriori selected variables (Age, Sex, and HIV status) and variables with a p-value <0.2 on bivariate analysis. The adjusted odds ratio and 95% confidence interval were recorded, and a p-value of less than 0.05 was considered statistically significant. FINDINGS: A total of 319,717 participants were included in the study; the majority were adults aged 25-49 (44.2%, n = 141,193) and above 50 years (31.6%, n = 101,039). About two-thirds were male (60.4%, n = 192,986), and more than one-fifth of participants (22.8%, n = 72,396) were HIV positive. Nearly two in every hundred TB patients had a recurrent TB episode (2.0%, n = 6,723). About 10% of patients with recurrent TB had unfavourable treatment outcomes (9.6%, n = 519). The odds of poor treatment outcomes were two-fold higher for participants receiving treatment at the central (aOR = 2.24; 95% CI 1.33-3.78) and coastal zones (aOR = 2.20; 95% CI 1.40-3.47) than the northern zone. HIV-positive participants had 62% extra odds of unfavourable treatment outcomes compared to their HIV-negative counterparts (aOR = 1.62; 95% CI 1.25-2.11). Bacteriological TB diagnosis (aOR = 1.39; 95% CI 1.02-1.90) was associated with a 39% additional risk of unfavourable treatment outcomes as compared to clinical TB diagnosis. Compared to community-based DOT, patients who received DOT at the facility had 1.39 times the odds of poor treatment outcomes (aOR = 1.39; 95%CI 1.04-1.85). CONCLUSION: TB recurrence in Tanzania accounts for 2% of all TB cases, and it is associated with poor treatment outcomes. Unfavourable treatment outcomes were recorded in 10% of patients with recurrent TB. Poor TB treatment outcome was associated with HIV-positive status, facility-based DOT, bacteriologically confirmed TB and receiving treatment at the hospital level, differing among regions. We recommend post-treatment follow-up for patients with recurrent TB, especially those coinfected with HIV. We also propose close follow-up for patients treated at the hospital facility level and strengthening primary health facilities in TB detection and management to facilitate early treatment initiation.

The South African breast cancer and HIV outcomes study: Profiling the cancer centres and cohort characteristics, diagnostic pathways, and treatment approaches.

The South African Breast Cancer and HIV Outcomes prospective cohort (SABCHO) study was established to investigate survival determinants among HIV-positive and HIV-negative SA women with breast cancer. This paper describes common and unique characteristics of the cancer centres and their participants, examining disparities in pathways to diagnosis, treatment resources and approaches adopted to mitigate resource constraints. The Johannesburg (Jhb), Soweto (Sow), and Durban (Dbn) sites treat mainly urban, relatively better educated and more socioeconomically advantaged patients whereas the Pietermaritzburg (Pmb) and Empangeni (Emp) sites treat predominantly rural, less educated and more impoverished communities The Sow, Jhb, and Emp sites had relatively younger patients (mean ages 54 ±14.5, 55±13.7 and 54±14.3 respectively), whereas patients at the Dbn and Pmb sites, with greater representation of Asian Indian women, were relatively older (mean age 57 ±13.9 and 58 ±14.6 respectively). HIV prevalence among the cohort was high, ranging from 15%-42%, (Cohort obesity (BMI ≥ 30 kg/m2) at 60%, self-reported hypertension (41%) and diabetes (13%). Direct referral of patients from primary care clinics to cancer centre occurred only at the Sow site which uniquely ran an open clinic and where early stage (I and II) proportions were highest at 48.5%. The other sites relied on indirect patient referral from regional hospitals where significant delays in diagnostics occurred and early-stage proportions were a low (15%- 37.3%). The Emp site referred patients for all treatments to the Dbn site located 200km away; the Sow site provided surgery and endocrine treatment services but referred patients to the Jhb site 30 Km away for chemo- and radiation therapy. The Jhb, Dbn and Pmb sites all provided complete oncology treatment services. All treatment centres followed international guidelines for their treatment approaches. Findings may inform policy interventions to address national and regional disparities in breast cancer care.

Measurement of and training for NCD guideline implementation in LMICs: a scoping review protocol.

INTRODUCTION: Globally, non-communicable diseases (NCDs) are the leading causes of morbidity and mortality with an estimated 41 million deaths (74% of all global deaths) annually. Despite the WHO's Global Action Plan for the Prevention and Control of NCDs since 2013, progress on implementation of the guidelines has been slow. Although research has shown success of some NCD prevention and treatment interventions, there is a dearth of research on NCD care delivery approaches, cost-effectiveness and larger implementation research, especially in low/middle-income countries (LMICs). The objective of this scoping review is to identify the existing variation in how, why and by whom implementation of NCD guidelines is measured as part of implementation research or non-research programme improvement. METHODS AND ANALYSIS: Using the methods established by Arksey and O'Malley, the search strategy was developed in consultation with a research librarian together with stakeholder feedback from content experts. We will apply the search to multiple electronic databases and grey literature sources. Two reviewers will independently screen title and abstract for inclusion followed by a full-text screening and all included records will be abstracted using a standardised tool that will be piloted with a sample of articles before application to all records. We will conduct a narrative synthesis of abstracted data and simple quantitative descriptive statistics. DISSEMINATION: The results will enable stakeholders in LMICs to leverage existing tools and resources for implementation and ongoing evaluation of NCD guidelines, to improve education and capacity building, and ultimately NCD care across the lifespan.

Association of alcohol use and multimorbidity among adults aged 40 years and above in rural South Africa.

We assessed the prevalence of reported alcohol use and its association with multimorbidity among adults aged 40 years and above in a rural, transitioning South African setting. Findings could potentially inform alcohol interventions integration in the prevention and treatment of chronic conditions. We analysed data from the first wave of The Health and Ageing in Africa-a longitudinal Study in an INDEPTH community (HAALSI) nested within the Agincourt Health and Demographic Surveillance Systems, conducted between November 2014 and November 2015 (n = 5059). We computed descriptive statistics and performed univariate analysis to determine factors independently associated with multimorbidity. Age, Body Mass Index, education, sex, and household wealth status and variables with a p-value < 0.20 in univariate analysis were included in multivariable Modified Poisson regression models. Any factors with a p-value of < 0.05 in the final models were considered statistically significant. The first wave of HAALSI was completed by 5059 participants aged 40 years and above and included 2714 (53.6%) females. The prevalence of reported ever alcohol use was 44.6% (n = 2253) and of these 51.9% (n = 1171) reported alcohol use in the last 30 days. The prevalence of HIV multimorbidity was 59.6% (3014/5059) and for multimorbidity without HIV 52.5% (2657/5059). Alcohol use was associated with HIV multimorbidity among all participants (RR: 1.05, 95% CI: 1.02-1.08), and separately for males (RR: 1.05, 95% CI: 1.00-1.10) and females (RR: 1.06, 95%CI: 1.02-1.11). Similarly, alcohol use was associated with multimorbidity without HIV among all participants (RR: 1.05, 95% CI: 1.02-1.09), and separately for males (RR: 1.06, 95% CI: 1.00-1.12) and females (RR: 1.06, 95% CI: 1.01-1.11). Reported alcohol use was common and associated with HIV multimorbidity and multimorbidity without HIV among older adults in rural northeast South Africa. There is a need to integrate Screening, Brief Interventions, and Referral for alcohol Treatment in the existing prevention and treatment of multimorbidity in South Africa.

Factors associated with the uptake of Intermittent Preventive Treatment (IPTp-SP) for malaria in pregnancy: Further analysis of the 2018 Nigeria Demographic and Health Survey.

Pregnancy-associated malaria is preventable and curable with intermittent preventive treatment with Sulfodoxine-Pyrimethamine (IPTp-SP). However, despite the effectiveness of IPTp-SP against malaria in pregnancy, the uptake among pregnant women in Nigeria remains very low. Thus, this study aimed to establish the factors associated with the uptake of at least one dose and optimal doses of IPTp-SP among pregnant women aged 15 to 49 years living in Nigeria in 2018. The study included 12,742 women aged 15 to 49 years with live births two years before or during the 2018 Nigeria Demographic Health Survey (NDHS) in the analysis. Descriptive analysis was carried out to determine the prevalence of IPTp-SP uptake. Multivariable logistic regression was used to establish the factors associated with receiving IPTp-SP during pregnancy, adjusting for possible confounding factors. Given the complex survey design, all analyses are adjusted for sampling weight, stratification, and clustering. The p-value of <0.05 was considered significant. In 2018, the prevalence of at least one dose of IPTp-SP was 63.6% (95% CI:62.0-65.1), and optimal doses of IPTp-SP were 16.8% (95% CI:15.8-17.8) during pregnancy. After the multivariable analysis, age group, region, frequency of ANC visits, belief in IPTp-SP effectiveness, and morbidity caused by malaria predicted the uptake of at least one IPTp-SP dose. Similar maternal characteristics, including household wealth index, spouse's educational level, and media exposure were significantly associated with taking optimal IPTp-SP doses. For instance, women in the wealthiest households whose husbands had secondary education predicted a four-fold increase in uptake of at least one IPTp-SP dose (aOR:4.17; 95% CI:1.11-8.85). The low prevalence and regional variations of IPTp-SP uptake in the study area imply that most pregnant women in Nigeria are at substantial risk of pregnancy-associated malaria. Therefore, stakeholders should explore context-specific strategies to improve the IPTp-SP coverage across the regions in Nigeria.

Drivers of disparities in stage at diagnosis among women with breast cancer: South African breast cancers and HIV outcomes cohort.

OBJECTIVE: In low- and middle-income countries (LMICs), advanced-stage diagnosis of breast cancer (BC) is common, and this contributes to poor survival. Understanding the determinants of the stage at diagnosis will aid in designing interventions to downstage disease and improve survival from BC in LMICs. METHODS: Within the South African Breast Cancers and HIV Outcomes (SABCHO) cohort, we examined factors affecting the stage at diagnosis of histologically confirmed invasive breast cancer at five tertiary hospitals in South Africa (SA). The stage was assessed clinically. To examine the associations of the modifiable health system, socio-economic/household and non-modifiable individual factors, hierarchical multivariable logistic regression with odds of late-stage at diagnosis (stage III-IV), was used. RESULTS: The majority (59%) of the included 3497 women were diagnosed with late-stage BC disease. The effect of health system-level factors on late-stage BC diagnosis was consistent and significant even when adjusted for both socio-economic- and individual-level factors. Women diagnosed in a tertiary hospital that predominantly serves a rural population were 3 times (OR = 2.89 (95% CI: 1.40-5.97) as likely to be associated with late-stage BC diagnosis when compared to those diagnosed at a hospital that predominantly serves an urban population. Taking more than 3 months from identifying the BC problem to the first health system entry (OR = 1.66 (95% CI: 1.38-2.00)), and having luminal B (OR = 1.49 (95% CI: 1.19-1.87)) or HER2-enriched (OR = 1.64 (95% CI: 1.16-2.32)) molecular subtype as compared to luminal A, were associated with a late-stage diagnosis. Whilst having a higher socio-economic level (a wealth index of 5) reduced the probability of late-stage BC at diagnosis, (OR = 0.64 (95% CI: 0.47-0.85)). CONCLUSION: Advanced-stage diagnosis of BC among women in SA who access health services through the public health system was associated with both modifiable health system-level factors and non-modifiable individual-level factors. These may be considered as elements in interventions to reduce the time to diagnosis of breast cancer in women.

Multimorbidity and overall survival among women with breast cancer: results from the South African Breast Cancer and HIV Outcomes Study.

BACKGROUND: Breast cancer survival in South Africa is low, but when diagnosed with breast cancer, many women in South Africa also have other chronic conditions. We investigated the impact of multimorbidity (≥ 2 other chronic conditions) on overall survival among women with breast cancer in South Africa. METHODS: Between 1 July 2015 and 31 December 2019, we enrolled women newly diagnosed with breast cancer at six public hospitals participating in the South African Breast Cancer and HIV Outcomes (SABCHO) Study. We examined seven chronic conditions (obesity, hypertension, diabetes, HIV, cerebrovascular diseases (CVD), asthma/chronic obstructive pulmonary disease, and tuberculosis), and we compared socio-demographic, clinical, and treatment factors between patients with and without each condition, and with and without multimorbidity. We investigated the association of multimorbidity with overall survival using multivariable Cox proportional hazard models. RESULTS: Of 3,261 women included in the analysis, 45% had multimorbidity; obesity (53%), hypertension (41%), HIV (22%), and diabetes (13%) were the most common individual conditions. Women with multimorbidity had poorer overall survival at 3 years than women without multimorbidity in both the full cohort (60.8% vs. 64.3%, p = 0.036) and stage groups: stages I-II, 80.7% vs. 86.3% (p = 0.005), and stage III, 53.0% vs. 59.4% (p = 0.024). In an adjusted model, women with diabetes (hazard ratio (HR) = 1.20, 95% confidence interval (CI) = 1.03-1.41), CVD (HR = 1.43, 95% CI = 1.17-1.76), HIV (HR = 1.21, 95% CI = 1.06-1.38), obesity + HIV (HR = 1.24 95% CI = 1.04-1.48), and multimorbidity (HR = 1.26, 95% CI = 1.13-1.40) had poorer overall survival than women without these conditions. CONCLUSIONS: Irrespective of the stage, multimorbidity at breast cancer diagnosis was an important prognostic factor for survival in our SABCHO cohort. The high prevalence of multimorbidity in our cohort calls for more comprehensive care to improve outcomes for South African women with breast cancer.

The impact of HIV on non-adherence for tamoxifen among women with breast cancer in South Africa.

PURPOSE: Women living with HIV (WLWH) and breast cancer (BC) have worse overall survival than HIV-negative women with BC, and poor adherence to prescribed tamoxifen is known to contribute to poor survival. We therefore investigated the association of HIV infection with adherence to adjuvant tamoxifen among women with localized hormone receptor (HR)-positive breast cancer in South Africa. METHODS: Among 4,097 women diagnosed with breast cancer at six hospitals in the prospective South African Breast Cancer and HIV Outcomes (SABCHO) cohort study between July 2015 and December 2020, we focused on black women with stages I-III HR-positive breast cancer who were prescribed 20 mg of adjuvant tamoxifen daily. We collected venous blood once from each participant during a routine clinic visit, and analyzed concentrations of tamoxifen and its metabolites using a triple quadruple mass spectrometer. We defined non-adherence as a tamoxifen level < 60 ng/mL after 3 months of daily tamoxifen use. We compared tamoxifen-related side effects, and concurrent medication use among women with and without HIV and developed multivariable logistic regression models of tamoxifen non-adherence. RESULTS: Among 369 subjects, 78 (21.1%) were WLWH and 291 (78.9%) were HIV-negative. After a median (interquartile range) time of 13.0 (6.2-25.2) months since tamoxifen initiation, the tamoxifen serum concentration ranged between 1.54 and 943.0 ng/mL and 208 (56.4%) women were non-adherent to tamoxifen. Women < 40 years of age were more likely to be non-adherent than women > 60 years (73.4% vs 52.6%, odds ratio (OR) = 2.49, 95% confidence interval (CI) = 1.26-4.94); likewise, WLWH (70.5% vs 52.6%, OR = 2.16, 95% CI = 1.26-3.70) than HIV-negative women. In an adjusted model WLWH had twice the odds of non-adherence to tamoxifen, compared to HIV-negative women (OR = 2.40, 95% CI = 1.11-5.20). CONCLUSION: High rates of non-adherence to adjuvant tamoxifen may limit the overall survival of black South African women with HR-positive breast cancer, especially among WLWH.

Determinants of utilization of malaria preventive measures during pregnancy among women aged 15 to 49 years in Kenya: an analysis of the Malaria Indicator Survey 2020.

BACKGROUND: Malaria is a significant cause of morbidity and mortality. Malaria infection in pregnancy can have severe consequences for the fetus and the mother. To fight against malaria infection in pregnancy, Kenya integrated the issuance of an insecticide-treated net (ITN) and intermittent preventive treatment with sulfadoxine-pyrimethamine (IPTpSP) with antenatal care (ANC) for pregnant women. However, the uptake of the ITN and IPTpSP is still low. Individual, social, or structural factors may influence the low uptake. It is, therefore, important to identify the determinants associated with the uptake of ITN and IPTpSP during pregnancy in Kenya. METHODS: Data were from the 2020 Kenya Malaria Indicator Survey (MIS). A total of 1779 women between the ages of 15 to 49 years who had a history of either being pregnant or having given birth within 5 years before the MIS survey were included. Survey-adjusted multinomial logistic regression was used in the analysis. RESULTS: During pregnancy, ITN use was more than half (54.9%). The use of at least one dose of IPTpSP was 43.5%, three or more doses of IPTpSP was 27.2%, and only 28.2% of the participants used both ITN and IPTpSP during pregnancy. The significant determinants of combined use of ITN and IPTpSP during pregnancy were maternal age (RR 3.57, CI 1.80-7.08; p=<0.001), maternal education (RRR 2.84, CI 1.33-6.06; p=0.007), wealth index (RR 2.14, CI 1.19-3.84; p=0.011) and living in the different malaria epidemiological zones: lake endemic (RRR 10.57 CI 5.65-19.76; p=<0.001), coastal endemic area (RRR 4.86 CI 1.86-12.67; p=0.001), seasonal (RRR 0.21 CI 0.10-0.39; p=<0.001) and low risk (RRR 0.07, CI 0.03-0.17; p=<0.001). CONCLUSION: The uptake of malaria preventive measures is still below 80% for both ITN and IPTpSP during pregnancy in Kenya. The significant results on determinants of the use of ITN and IPTpSP could be considered in implementing malaria prevention programmes during pregnancy. For example, sensitizing the community on the importance of antenatal care visits will provide a platform to teach the importance of malaria prevention in pregnancy. Moreover, the pregnant mothers receive an ITN and IPTpSP during the ANC visit.

Loss to Follow-Up Risk among HIV Patients on ART in Zimbabwe, 2009-2016: Hierarchical Bayesian Spatio-Temporal Modeling.

Loss to follow-up (LTFU) is a risk factor for poor outcomes in HIV patients. The spatio-temporal risk of LTFU is useful to identify hotspots and guide policy. Secondary data on adult HIV patients attending a clinic in provinces of Zimbabwe between 2009 and 2016 were used to estimate the LTFU risk in each of the 10 provinces. A hierarchical Bayesian spatio-temporal Poisson regression model was fitted using the Integrated Nested Laplace Approximation (INLA) package with LTFU as counts adjusting for age, gender, WHO clinical stage, tuberculosis coinfection and duration on ART. The structured random effects were modelled using the conditional autoregression technique and the temporal random effects were modelled using first-order random walk Gaussian priors. The overall rate of LTFU was 22.7% (95%CI: 22.6/22.8) with Harare (50.28%) and Bulawayo (31.11%) having the highest rates. A one-year increase in the average number of years on ART reduced the risk of LTFU by 35% (relative risk (RR) = 0.651; 95%CI: 0.592-0.712). In general, the provinces with the highest exceedance LTFU risk were Matabeleland South and Matabeleland North. LTFU is one of the drawbacks of HIV prevention. Interventions targeting high-risk regions in the southern and northern regions of Zimbabwe are a priority. Community-based interventions and programmes which mitigate LTFU risk remain essential in the global HIV prevention campaign.

Factors influencing the implementation of TB screening among PLHIV in selected HIV clinics in Ghana: a qualitative study.

BACKGROUND: Decreasing the burden of Tuberculosis (TB) among PLHIV through TB screening is an effective intervention recommended by the World Health Organization (WHO). However, after over a decade of implementation in Ghana, the intervention does not realize the expected outcomes. It is also not well understood whether this lack of success is due to implementation barriers. Our study, therefore, sought to examine the factors influencing the implementation of the intervention among people living with HIV (PLHIV) attending HIV clinics at district hospitals in Ghana. METHODS: This was a qualitative study conducted from 6th to 31 May 2019 in three regions of Ghana. We conducted 17 in-depth interviews (IDIs - comprising two regional, six districts and nine facility TB/HIV coordinators) and eight focus group discussions (FGD - consisting of a total of 65 participants) with HIV care providers. The Consolidated Framework for Implementation Research (CFIR) guided the design of interview guides, data collection and analysis. All responses were digitally audio-recorded and transcribed verbatim for coding and analysis using the Framework Approach. Participants consented to the interview and recording. RESULTS: The main barriers to TB screening relate to the low commitment of the implementers to screen for TB and limited facility infrastructure for the screening activities. Facilitators of TB screening include (1) ease in TB screening, (2) good communication and referral channels, (3) effective goals and feedback mechanisms, (4) health workers recognizing the need for the intervention and (5) the role of chemical sellers. CONCLUSIONS: Key barriers and facilitators to the intervention are revealed. The study has shown that there is a need to increase HIV care providers and institutional commitment towards TB screening interventions. In addition, cost issues need to be assessed as they are drivers of sustainability. Our study also advances the field of implementation science through CFIR to better understand the factors influencing the implementation.

Building knowledge, optimising physical and mental health and setting up healthier life trajectories in South African women (Bukhali): a preconception randomised control trial part of the Healthy Life Trajectories Initiative (HeLTI).

INTRODUCTION: South Africa's evolving burden of disease is challenging due to a persistent infectious disease, burgeoning obesity, most notably among women and rising rates of non-communicable diseases (NCDs). With two thirds of women presenting at their first antenatal visit either overweight or obese in urban South Africa (SA), the preconception period is an opportunity to optimise health and offset transgenerational risk of both obesity and NCDs. METHODS AND ANALYSIS: Bukhali is the first individual randomised controlled trial in Africa to test the efficacy of a complex continuum of care intervention and forms part of the Healthy Life Trajectories Initiative (HeLTI) consortium implementing harmonised trials in Canada, China, India and SA. Starting preconception and continuing through pregnancy, infancy and childhood, the intervention is designed to improve nutrition, physical and mental health and health behaviours of South African women to offset obesity-risk (adiposity) in their offspring. Women aged 18-28 years (n=6800) will be recruited from Soweto, an urban-poor area of Johannesburg. The primary outcome is dual-energy X-ray absorptiometry derived fat mass index (fat mass divided by height2) in the offspring at age 5 years. Community health workers will deliver the intervention randomly to half the cohort by providing health literacy material, dispensing a multimicronutrient supplement, providing health services and feedback, and facilitating behaviour change support sessions to optimise: (1) nutrition, (2) physical and mental health and (3) lay the foundations for healthier pregnancies and early child development. ETHICS AND DISSEMINATION: Ethical approval has been obtained from the Human Ethics Research Committee University of the Witwatersrand, Johannesburg, South Africa (M1811111), the University of Toronto, Canada (19-0066-E) and the WHO Ethics Committee (ERC.0003328). Data and biological sample sharing policies are consistent with the governance policy of the HeLTI Consortium (https://helti.org) and South African government legislation (POPIA). The recruitment and research team will obtain informed consent. TRIAL REGISTRATION: This trial is registered with the Pan African Clinical Trials Registry (https://pactr.samrc.ac.za) on 25 March 2019 (identifier: PACTR201903750173871). PROTOCOL VERSION: 20 March 2022 (version #4). Any protocol amendments will be communicated to investigators, Institutional Review Board (IRB)s, trial participants and trial registries.

Training and capacity building in medical statistics in Sub-Saharan Africa: Impact of the London School of Hygiene & Tropical Medicine MSc in Medical Statistics, 1969 to 2021.

Since its inception in 1969, the MSc in medical statistics program has placed a high priority on training students from Africa. In this article, we review how the program has shaped, and in turn been shaped by, two substantial capacity building initiatives: (a) a fellowship program, funded by the UK Medical Research Council, and run through the International Statistical Epidemiology Group at the LSHTM, and (b) the Sub-Saharan capacity building in Biostatistics (SSACAB) initiative, administered through the Developing Excellence in Leadership, Training and Science in Africa (DELTAS) program of the African Academy of Sciences. We reflect on the impact of both initiatives, and the implications for future work in this area.

Impact of HIV infection on survival among women with stage I-III breast cancer: Results from the South African breast cancer and HIV outcomes study.

In some countries of sub-Saharan Africa, the prevalence of HIV exceeds 20%; in South Africa, 20.4% of people are living with HIV. We examined the impact of HIV infection on the overall survival (OS) of women with nonmetastatic breast cancer (BC) enrolled in the South African Breast Cancer and HIV Outcomes (SABCHO) study. We recruited women with newly diagnosed BC at six public hospitals from 1 July 2015 to 30 June 2019. Among women with stages I-III BC, we compared those with and without HIV infection on sociodemographic, clinical, and treatment factors. We analyzed the impact of HIV on OS using multivariable Cox proportional hazard models. Of 2367 women with stages I-III BC, 499 (21.1%) had HIV and 1868 (78.9%) did not. With a median follow-up of 29 months, 2-year OS was poorer among women living with HIV (WLWH) than among HIV-uninfected women (72.4% vs 80.1%, P < .001; adjusted hazard ratio (aHR) 1.49, 95% confidence interval (CI) = 1.22-1.83). This finding was consistent across age groups ≥45 years and <45 years, stage I-II BC and stage III BC, and ER/PR status (all P < .03). Both WLWH with <50 viral load copies/mL and WLWH with ≥50 viral load copies/mL had poorer survival than HIV-uninfected BC patients [aHR: 1.35 (1.09-1.66) and 1.54 (1.20-2.00), respectively], as did WLWH who had ≥200 CD4+ cells/mL at diagnosis [aHR: 1.39 (1.15-1.67)]. Because receipt of antiretroviral therapy has become widespread, WLWH is surviving long enough to develop BC; more research is needed on the causes of their poor survival.

Comparison of statistical methods for the analysis of recurrent adverse events in the presence of non-proportional hazards and unobserved heterogeneity: a simulation study.

BACKGROUND: In preventive drug trials such as intermittent preventive treatment for malaria prevention during pregnancy (IPTp), where there is repeated treatment administration, recurrence of adverse events (AEs) is expected. Challenges in modelling the risk of the AEs include accounting for time-to-AE and within-patient-correlation, beyond the conventional methods. The correlation comes from two sources; (a) individual patient unobserved heterogeneity (i.e. frailty) and (b) the dependence between AEs characterised by time-dependent treatment effects. Potential AE-dependence can be modelled via time-dependent treatment effects, event-specific baseline and event-specific random effect, while heterogeneity can be modelled via subject-specific random effect. Methods that can improve the estimation of both the unobserved heterogeneity and treatment effects can be useful in understanding the evolution of risk of AEs, especially in preventive trials where time-dependent treatment effect is expected. METHODS: Using both a simulation study and the Chloroquine for Malaria in Pregnancy (NCT01443130) trial data to demonstrate the application of the models, we investigated whether the lognormal shared frailty models with restricted cubic splines and non-proportional hazards (LSF-NPH) assumption can improve estimates for both frailty variance and treatment effect compared to the conventional inverse Gaussian shared frailty model with proportional hazard (ISF-PH), in the presence of time-dependent treatment effects and unobserved patient heterogeneity. We assessed the bias, precision gain and coverage probability of 95% confidence interval of the frailty variance estimates for the models under varying known unobserved heterogeneity, sample sizes and time-dependent effects. RESULTS: The ISF-PH model provided a better coverage probability of 95% confidence interval, less bias and less precise frailty variance estimates compared to the LSF-NPH models. The LSF-NPH models yielded unbiased hazard ratio estimates at the expense of imprecision and high mean square error compared to the ISF-PH model. CONCLUSION: The choice of the shared frailty model for the recurrent AEs analysis should be driven by the study objective. Using the LSF-NPH models is appropriate if unbiased hazard ratio estimation is of primary interest in the presence of time-dependent treatment effects. However, ISF-PH model is appropriate if unbiased frailty variance estimation is of primary interest. TRIAL REGISTRATION: ClinicalTrials.gov; NCT01443130.

Effect of adverse events on non-adherence and study non-completion in malaria chemoprevention during pregnancy trial: A nested case control study.

BACKGROUND: In drug trials, adverse events (AEs) burden can induce treatment non-adherence or discontinuation. The non-adherence and discontinuation induce selection bias, affecting drug safety interpretation. Nested case-control (NCC) study can efficiently quantify the impact of the AEs, although choice of sampling approach is challenging. We investigated whether NCC study with incidence density sampling is more efficient than NCC with path sampling under conditional logistic or weighted Cox models in assessing the effect of AEs on treatment non-adherence and participation in preventive antimalarial drug during pregnancy trial. METHODS: Using data from a trial of medication to prevent malaria in pregnancy that randomized 600 women to receive chloroquine or sulfadoxine-pyrimethamine during pregnancy, we conducted a NCC study assessing the role of prospectively collected AEs, as exposure of interest, on treatment non-adherence and study non-completion. We compared estimates from NCC study with incidence density against those from NCC with path sampling under conditional logistic and weighted Cox models. RESULTS: Out of 599 women with the outcomes of interest, 474 (79%) experienced at least one AE before delivery. For conditional logistic model, the hazard ratio for the effect of AE occurrence on treatment non-adherence was 0.70 (95% CI: 0.42, 1.17; p = 0.175) under incidence density sampling and 0.68 (95% CI: 0.41, 1.13; p = 0.137) for path sampling. For study non-completion, the hazard ratio was 1.02 (95% CI: 0.56, 1.83; p = 0.955) under incidence density sampling and 0.85 (95% CI: 0.45, 1.60; p = 0.619) under path sampling. We obtained similar hazard ratios and standard errors under incidence density sampling and path sampling whether weighted Cox or conditional logistic models were used. CONCLUSION: NCC with incidence density sampling and NCC with path sampling are practically similar in efficiency whether conditional logistic or weighted Cox analytical methods although path sampling uses more unique controls to achieve the similar estimates. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01443130.