Impact of the first COVID-19 lockdown on male urethritis syndrome services in South Africa.

OBJECTIVES: Globally, there have been significant changes in utilisation of STI testing and treatment services during the period of the COVID-19 pandemic. The impact of COVID-19 in countries that use syndromic STI management is not documented. This study used routine STI surveillance data to evaluate the impact of COVID-19 on utilisation of STI syndromic management services during the first wave of the COVID-19 epidemic in South Africa. METHODS: We conducted a time-trend analysis of male urethritis syndrome (MUS) cases reported through routine national STI surveillance in South Africa and COVID-19 data available through the national dashboard. We defined three time periods (prelockdown, lockdown and postlockdown) based on COVID-19 response levels. Trends in MUS reporting was compared between these time periods at national and provincial level and with the number of positive COVID-19 tests in a district. RESULTS: An overall reduction of 27% in the national number of MUS cases reported (monthly average from 27 117 to 20 107) occurred between the pre-COVID-19 and COVID-19 lockdown periods (p<0.001), with a range of 18%-39% between the nine provinces. Postlockdown, case numbers returned almost to the prelockdown level (26 304; -3.0%). No significant difference was found in number of MUS cases between the prelockdown and postlockdown periods. A weak correlation (R2=0,21) was identified between the change in number of MUS reported and COVID-19 positive tests in a district. CONCLUSIONS: A strong reduction in reported MUS cases for syndromic management was observed during the first wave of the COVID-19 epidemic and lockdown across all provinces in South Africa. This is likely the result of various healthcare system and service delivery factors associated with lockdown measures. The observed return of MUS cases reported to prelockdown measures is reassuring.

From purists to pragmatists: a qualitative evaluation of how implementation processes and contexts shaped the uptake and methodological adaptations of a maternal and neonatal quality improvement programme in South Africa prior to, and during COVID-19.

BACKGROUND: Despite progress, maternal and neonatal mortality and still births remain high in South Africa. The South African National Department of Health implemented a quality improvement (QI) programme, called Mphatlalatsane, to reduce maternal and neonatal mortality and still births. It was implemented in 21 public health facilities, seven per participating province, between 2018 and 2022. METHODS: We conducted a qualitative process evaluation of the contextual and implementation process factors' influence on implementation uptake amongst the QI teams in 15 purposively selected facilities. Data collection included three interview rounds with the leaders and members of the QI teams in each facility; intermittent interviews with the QI advisors; programme documentation review; observation of programme management meetings; and keeping a fieldwork journal. All data were thematically analysed in Atlas.ti. Implementation uptake varied across the three provinces and between facilities within provinces. RESULTS: Between March and August 2020, the COVID-19 pandemic disrupted uptake in all provinces but affected QI teams in one province more severely than others, because they received limited pre-pandemic training. Better uptake among other sites was attributed to receiving more QI training pre-COVID-19, having an experienced QI advisor, and good teamwork. Uptake was more challenging amongst hospital teams which had more staff and more complicated MNH services, versus the primary healthcare facilities. We also attributed better uptake to greater district management support. A key factor shaping uptake was leaders' intrinsic motivation to apply QI methodology. We found that, across sites, organic adaptations to the QI methodology were made by teams, started during COVID-19. Teams did away with rapid testing of change ideas and keeping a paper trail of the steps followed. Though still using data to identify service problems, they used self-developed audit tools to record intervention effectiveness, and not the prescribed tools. CONCLUSIONS: Our study underscores the critical role of intrinsic motivation of team leaders, support from experienced technical QI advisors, and context-sensitive adaptations to maximise QI uptake when traditionally recognised QI steps cannot be followed.

Effect of Short, Animated Video Storytelling on Maternal Knowledge and Satisfaction in the Perinatal Period in South Africa: Randomized Controlled Trial.

BACKGROUND: Innovative mobile health (mHealth) interventions can improve maternal knowledge, thereby supporting national efforts to reduce preventable maternal and child mortality in South Africa. Studies have documented a potential role for mobile video content to support perinatal health messaging, enhance maternal satisfaction, and overcome literacy barriers. Short, animated storytelling (SAS) is an innovative, emerging approach to mHealth messaging. OBJECTIVE: We aimed to measure the effect of SAS videos on maternal knowledge and user satisfaction for mothers enrolled in antenatal care programs at 2 public health facilities in the Tshwane District of South Africa. METHODS: We used a randomized controlled trial with a nested evaluation of user satisfaction. Participants were randomized 1:1 into Standard-of-Care (SOC) Control, and SAS Intervention groups. The intervention videos were delivered through WhatsApp, and 1 month later, participants responded to telephone surveys assessing their knowledge. The intervention group then participated in a nested evaluation of user satisfaction. RESULTS: We surveyed 204 participants. Of them, 49.5% (101/204) were aged between 25 and 34 years. Almost all participants self-identified as Black, with the majority (190/204, 93.2%) having completed secondary school. The mean overall knowledge score was 21.92/28. We observed a slight increase of 0.28 (95% uncertainty interval [UI] -0.58 to 1.16) in the overall knowledge score in the intervention arm. We found that those with secondary education or above scored higher than those with only primary education by 2.24 (95% UI 0.76-4.01). Participants aged 35 years or older also scored higher than the youngest age group (18-24 years) by 1.83 (95% CI 0.39-3.33). Finally, the nested user satisfaction evaluation revealed high maternal satisfaction (4.71/5) with the SAS video series. CONCLUSIONS: While the SAS videos resulted in high user satisfaction, measured knowledge gains were small within a participant population that was already receiving perinatal health messages through antenatal clinics. The higher knowledge scores observed in older participants with higher education levels suggest that boosting maternal knowledge in younger mothers with lower education levels should continue to be a public health priority in South Africa. Given the high maternal satisfaction among the SAS video-users in this study, policy makers should consider integrating similar approaches into existing, broad-reaching perinatal health programs, such as MomConnect, to boost satisfaction and potentially enhance maternal engagement. While previous studies have shown the promise of animated video health education, most of this research has been conducted in high-income countries. More research in underresourced settings is urgently needed, especially as access to mobile technology increases in the Global South. Future studies should explore the effect of SAS videos on maternal knowledge in hard-to-reach populations with limited access to antenatal care, although real-world logistical challenges persist when implementing studies in underresourced South African populations. TRIAL REGISTRATION: Pan African Clinical Trials Registry PACTR202203673222680; https://tinyurl.com/362cpuny.

Optimizing knowledge and behavioral intention of women and their partners in the perinatal period in South Africa: a randomized control trial study protocol in the Tshwane district, Gauteng province, South Africa.

BACKGROUND: Maternal knowledge that motivates improvements in critical perinatal health behaviors has the potential to significantly reduce maternal and neonatal mortality. However, evidence-based health information often fails to reach mothers and their partners. mHealth video micro-messages, which disseminate evidence-based perinatal health messages, have the potential to address this gap. METHODS: The study will make use of a mixed method design, using both qualitative and quantitative methods. The study consists of two phases. During Phase 1, qualitative in-depth interviews will be used as part of a human-centered design approach to co-create 10 videos on priority perinatal behaviors. During Phase 2, quantitative methods (a randomized control trial) will be used to test the effectiveness of the videos in improving maternal knowledge and intended behavioral change. DISCUSSION: We hypothesize that by engaging mothers and their partners through emotive, resonant narratives and visuals, we can facilitate the delivery of evidence-based health messages at the foundation of perinatal health, thereby motivating life-saving improvements in health behaviors during the perinatal period. TRIAL REGISTRATION: This trial has been prospectively registered on the Pan African Clinical Trials Registry (PACTR), with the registration number PACTR202203673222680 . Registration date: 14 March 2022.  TRIAL REGISTRATION WHO DATA SET: Registry - Pan African Clinical Trials Registry (PACTR). Date: 14 March 2022. Secondary identification number - grant number: GCCSOAFMNH1. Source of support: Science for Africa Foundation. Primary sponsor - Clinton Health Access Initiative South Africa. Secondary sponsor - Stanford University School of Medicine and Heidelberg University. Contact for public & scientific queries: amandlamamasa@clintonhealthaccess.org ; +27 123,426,911; 1166 Francis Baard St, Hatfield, Pretoria, 0028. Public title - Amandla Mama. Scientific title - Optimizing knowledge and behavioral intention of women and their partners in the perinatal period in South Africa. Countries of recruitment - South Africa. Health conditions - antenatal care. Intervention - Amandla Mama mHealth videos, short 2D animated health promotional videos that promote healthy behavior in expectant mothers. Inclusion and exclusion criteria - Expectant mothers and their partners must be 18 years and older. Study type - randomized control trial. Date of first enrollment - 14 March 2021. Sample size - plan to enrol 450 participants, participants enrolled 29 participants. Recruitment Status - suspended. Primary outcome - improving knowledge. Secondary outcome - intended behavioral change. Ethics review - Approved on 24 January 2022 by Pharma-Ethics, contact Mrs. Marzelle Haskins, marzelle@pharma-ethics.co.za . Completion date - N/A. Summary results - N/A. IPD sharing statement - yes, through the publication of results in a journal article.

Investment case for malaria elimination in South Africa: a financing model for resource mobilization to accelerate regional malaria elimination.

BACKGROUND: Malaria continues to be a public health problem in South Africa. While the disease is mainly confined to three of the nine provinces, most local transmissions occur because of importation of cases from neighbouring countries. The government of South Africa has reiterated its commitment to eliminate malaria within its borders. To support the achievement of this goal, this study presents a cost-benefit analysis of malaria elimination in South Africa through simulating different scenarios aimed at achieving malaria elimination within a 10-year period. METHODS: A dynamic mathematical transmission model was developed to estimate the costs and benefits of malaria elimination in South Africa between 2018 and 2030. The model simulated a range of malaria interventions and estimated their impact on the transmission of Plasmodium falciparum malaria between 2018 and 2030 in the three endemic provinces of Limpopo, Mpumalanga and KwaZulu-Natal. Local financial, economic, and epidemiological data were used to calibrate the transmission model. RESULTS: Based on the three primary simulated scenarios: Business as Usual, Accelerate and Source Reduction, the total economic burden was estimated as follows: for the Business as Usual scenario, the total economic burden of malaria in South Africa was R 3.69 billion (USD 223.3 million) over an 11-year period (2018-2029). The economic burden of malaria was estimated at R4.88 billion (USD 295.5 million) and R6.34 billion (~ USD 384 million) for the Accelerate and Source Reduction scenarios, respectively. Costs and benefits are presented in midyear 2020 values. Malaria elimination was predicted to occur in all three provinces if the Source Reduction strategy was adopted to help reduce malaria rates in southern Mozambique. This could be achieved by limiting annual local incidence in South Africa to less than 1 indigenous case with a prediction of this goal being achieved by the year 2026. CONCLUSIONS: Malaria elimination in South Africa is feasible and economically worthwhile with a guaranteed positive return on investment (ROI). Findings of this study show that through securing funding for the proposed malaria interventions in the endemic areas of South Africa and neighbouring Mozambique, national elimination could be within reach in an 8-year period.

Adherence clubs and decentralized medication delivery to support patient retention and sustained viral suppression in care: Results from a cluster-randomized evaluation of differentiated ART delivery models in South Africa.

BACKGROUND: Differentiated antiretroviral therapy (ART) delivery models, in which patients are provided with care relevant to their current status (e.g., newly initiating, stable on treatment, or unstable on treatment) has become an essential part of patient-centered health systems. In 2015, the South African government implemented Chronic Disease Adherence Guidelines (AGLs), which involved five interventions: Fast Track Initiation Counseling for newly initiating patients, Enhanced Adherence Counseling for patients with an unsuppressed viral load, Early Tracing of patients who miss visits, and Adherence Clubs (ACs) and Decentralized Medication Delivery (DMD) for stable patients. We evaluated two of these interventions in 24 South African facilities: ACs, in which patients meet in groups outside usual clinic procedures and receive medication; and DMD, in which patients pick up their medication outside usual pharmacy queues. METHODS AND FINDINGS: We compared those participating in ACs or receiving DMD at intervention sites to those eligible for ACs or DMD at control sites. Outcomes were retention and sustained viral suppression (<400 copies/mL) 12 months after AC or DMD enrollment (or comparable time for controls). 12 facilities were randomly allocated to intervention and 12 to control arms in four provinces (Gauteng, North West, Limpopo, and KwaZulu Natal). We calculated adjusted risk differences (aRDs) with cluster adjustment using generalized estimating equations (GEEs) using difference in differences (DiD) with patients eligible for ACs/DMD prior to implementation (Jan 1, 2015) for comparison. For DMD, randomization was not preserved, and the analysis was treated as observational. For ACs, 275 intervention and 294 control patients were enrolled; 72% of patients were female, 61% were aged 30-49 years, and median CD4 count at ART initiation was 268 cells/µL. AC patients had higher 1-year retention (89.5% versus 81.6%, aRD: 8.3%; 95% CI: 1.1% to 15.6%) and comparable sustained 1-year viral suppression (<400 copies/mL any time ≤ 18 months) (80.0% versus 79.6%, aRD: 3.8%; 95% CI: -6.9% to 14.4%). Retention associations were apparently stronger for men than women (men RD: 13.1%, 95% CI: 0.3% to 23.5%; women RD: 6.0%, 95% CI: -0.9% to 12.9%). For DMD, 232 intervention and 346 control patients were enrolled; 71% of patients were female, 65% were aged 30-49 years, and median CD4 count at ART initiation was 270 cells/µL. DMD patients had apparently lower retention (81.5% versus 87.2%, aRD: -5.9%; 95% CI: -12.5% to 0.8%) and comparable viral suppression versus standard of care (77.2% versus 74.3%, aRD: -1.0%; 95% CI: -12.2% to 10.1%), though in both cases, our findings were imprecise. We also noted apparently increased viral suppression among men (RD: 11.1%; 95% CI: -3.4% to 25.5%). The main study limitations were missing data and lack of randomization in the DMD analysis. CONCLUSIONS: In this study, we found comparable DMD outcomes versus standard of care at facilities, a benefit for retention of patients in care with ACs, and apparent benefits in terms of retention (for AC patients) and sustained viral suppression (for DMD patients) among men. This suggests the importance of alternative service delivery models for men and of community-based strategies to decongest primary healthcare facilities. Because these strategies also reduce patient inconvenience and decongest clinics, comparable outcomes are a potential success. The cost of all five AGL interventions and possible effects on reducing clinic congestion should be investigated. CLINICAL TRIAL REGISTRATION: NCT02536768.

What will it take for the Global Plan priority countries in Sub-Saharan Africa to eliminate mother-to-child transmission of HIV?

BACKGROUND: The 2016 'Start Free, Stay Free, AIDS Free' global agenda, builds on the 2011-2015 'Global Plan'. It prioritises 22 countries where 90% of the world's HIV-positive pregnant women live and aims to eliminate vertical  transmission of HIV (EMTCT) and to keep mothers alive. By 2019, no Global Plan priority country had achieved EMTCT; however, 11 non-priority countries had. This paper synthesises the characteristics of the first four countries validated for EMTCT, and of the 21 Global Plan priority countries located in Sub-Saharan Africa (SSA). We consider what drives vertical transmission of HIV (MTCT) in the 21 SSA Global Plan priority countries. METHODS: A literature review, using PubMed, Science direct and the google search engine was conducted to obtain global and national-level information on current HIV-related context and health system characteristics of the first four EMTCT-validated countries and the 21 SSA Global Plan priority countries. Data representing only one clinic, hospital or region were excluded. Additionally, key global experts working on EMTCT were contacted to obtain clarification on published data. We applied three theories (the World Health Organisation's building blocks to strengthen health systems, van Olmen's Health System Dynamics framework and Baral's socio-ecological model for HIV risk) to understand and explain the differences between EMTCT-validated and non-validated countries. Additionally, structural equation modelling (SEM) and linear regression were used to explain associations between infant HIV exposure, access to antiretroviral therapy and two outcomes: (i) percent MTCT and (iii) number of new paediatric HIV infections per 100 000 live births (paediatric HIV case rate). RESULTS: EMTCT-validated countries have lower HIV prevalence, less breastfeeding, fewer challenges around leadership, governance within the health sector or country, infrastructure and service delivery compared with Global Plan priority countries. Although by 2016 EMTCT-validated countries and Global Plan priority countries had adopted a public health approach to HIV prevention, recommending lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and lactating women, EMCT-validated countries had also included contact tracing such as assisted partner notification, and had integrated maternal and child health (MCH) and sexual and reproductive health (SRH) services, with services for HIV infection, sexually transmitted infections, and viral hepatitis. Additionally, Global Plan priority countries have limited data on key SRH indicators such as unmet need for family planning, with variable coverage of antenatal care, HIV testing and triple antiretroviral therapy (ART) and very limited contact tracing. Structural equation modelling (SEM) and linear regression analysis demonstrated that ART access protects against percent MTCT (p<0.001); in simple linear regression it is 53% protective against percent MTCT. In contrast, SEM demonstrated that the case rate was driven by the number of HIV exposed infants (HEI) i.e. maternal HIV prevalence (p<0.001). In linear regression models, ART access alone explains only 17% of the case rate while HEI alone explains 81% of the case rate. In multiple regression, HEI and ART access accounts for 83% of the case rate, with HEI making the most contribution (coef. infant HIV exposure=82.8, 95% CI: 64.6, 101.1, p<0.001 vs coef. ART access=-3.0, 95% CI: -6.2, 0.3, p=0.074). CONCLUSION: Reducing infant HIV exposure, is critical to reducing the paediatric HIV case rate; increasing ART access is critical to reduce percent MTCT. Additionally, our study of four validated countries underscores the importance of contact tracing, strengthening programme monitoring, leadership and governance, as these are potentially-modifiable factors.

When donor funding leaves: an interrupted time-series analysis of the impact of integrating direct HIV care and treatment into public health services in a region of Johannesburg.

BACKGROUND: Early in South Africa's HIV response, donor-funded organizations directly provided HIV treatment through Comprehensive HIV Care, Management and Treatment sites (CCMTs), using their own and government staff. From 2012 to 2014 the donor-funded CCMT model was phased out, leaving nurses in South Africa's public clinics responsible for delivery of antiretroviral treatment (ART) services. We aimed to examine the impact on resources, staff workloads, and service delivery throughout this period of integration of HIV treatment into primary health clinics. METHODS: We conducted an Interrupted Time-Series Analysis (ITSA) using data from three public clinics, including one former CCMT site, in one administrative region of Johannesburg. The ITSA was complemented by visual inspection of the data in Excel. We compared trends in expenditure, clinical staffing levels, patient headcounts, and services rendered at the clinics during four periods: pre-CCMT (2004-2007), CCMT operational (2007-2012), CCMT closure (2012-2014), and post-CCMT (2014-2016). Data were drawn from the country's District Health Information System, a national HIV treatment database, local budget and expenditure reports, National Health Laboratory Service charge records, and staff records. RESULTS: Closure of the CCMT differentially impacted the study clinics. As expected, ART services decreased at Clinic 1, where the CCMT was co-located, and increased at Clinics 2 and 3 possibly reflecting redistribution of patients. Despite a reduction in patient headcounts post-CCMT, Clinic 1 experienced a decrease in staff and a large increase in patients seen per clinical staff member per month. In contrast, Clinics 2 and 3 increased or maintained stable workforces, and staff workloads post closure were similar to pre-closure levels. Other primary care services-contraception and immunisations-seemed largely unaffected at Clinics 1 and 2. At Clinic 3, service delivery reduced, but this was accompanied by lowered patient headcounts generally, likely due to clinic renovations. CONCLUSIONS: In this study, integration of HIV treatment into primary healthcare services did not result in large-scale reductions in overall service delivery. One facility did experience increased staff workloads, but we were unable to assess service quality. To mitigate potential problems, monitoring systems should be introduced in advance and acknowledge the disparate and decentralised management of various data sources.

Effectiveness of interventions for unstable patients on antiretroviral therapy in South Africa: results of a cluster-randomised evaluation.

BACKGROUND: As loss from HIV care is an ongoing challenge globally, interventions are needed for patients who don't achieve or maintain ART stability. The 2015 South African National Adherence Guidelines (AGL) for Chronic Diseases include two interventions targeted at unstable patients: early tracing of patients who miss visits (TRIC) and enhanced adherence counselling (EAC). METHODS: As part of a cluster-randomised evaluation at 12 intervention and 12 control clinics in four provinces, intervention sites implemented the AGL interventions, while control sites retained standard care. We report on outcomes of EAC for patients with an elevated viral load (>400 copies/ml) and for TRIC patients who missed a visit by >5 days. We estimated risk differences (RD) of 3 and 12-month viral resuppression (<400 copies/ml) and 12-month retention with cluster adjustment using generalised estimating equations and controlled for imbalances using difference-in-differences compared to all eligible in 2015, prior to intervention roll-out. RESULTS: For EAC, we had 358 intervention and 505 control site patients (61% female, median ART initiation CD4 count 154 cells/µl). We found no difference between arms in 3-month resuppression (RD: -1.7%; 95%CI: -4.3% to 0.9%), but <20% of patients had a repeat viral load within 3 months (19.8% intervention, 13.5% control). Including the entire clinic population eligible for EAC with a repeat viral load at all evaluation sites (n = 934), intervention sites showed a small increase in 3-month resuppression (28% vs. 25%, RD 3.0%; 95%CI: -2.7% to 8.8%). Adjusting for baseline differences increased the RD to 8.1% (95% CI: -0.1% to 17.2%). However, we found no differences in 12-month suppression (RD: 1.5%; 95% CI: -14.1% to 17.1% but suppression was low overall at 40%) or retention (RD: 2.8%; 95% CI: -7.5% to 13.2%). For TRIC, we enrolled 155 at intervention sites and 248 at control sites (44% >40 years, 67% female, median CD4 count 212 cells/µl). We found no difference between groups in return to care by 12 months (RD: -6.8%; 95% CI: -17.7% to 4.8%). During the study period, control sites continued to use tracing within standard care, however, potentially masking intervention effects. CONCLUSIONS: Enhanced adherence counselling showed no benefit over 12 months. Implementation of the tracing intervention under the new guidelines was similar to the standard of care. Interventions that aim to return unstable patients to care should incorporate active monitoring to determine if the interventions are effective.

The South African Tuberculosis Care Cascade: Estimated Losses and Methodological Challenges.

Background: While tuberculosis incidence and mortality are declining in South Africa, meeting the goals of the End TB Strategy requires an invigorated programmatic response informed by accurate data. Enumerating the losses at each step in the care cascade enables appropriate targeting of interventions and resources. Methods: We estimated the tuberculosis burden; the number and proportion of individuals with tuberculosis who accessed tests, had tuberculosis diagnosed, initiated treatment, and successfully completed treatment for all tuberculosis cases, for those with drug-susceptible tuberculosis (including human immunodeficiency virus (HIV)-coinfected cases) and rifampicin-resistant tuberculosis. Estimates were derived from national electronic tuberculosis register data, laboratory data, and published studies. Results: The overall tuberculosis burden was estimated to be 532005 cases (range, 333760-764480 cases), with successful completion of treatment in 53% of cases. Losses occurred at multiple steps: 5% at test access, 13% at diagnosis, 12% at treatment initiation, and 17% at successful treatment completion. Overall losses were similar among all drug-susceptible cases and those with HIV coinfection (54% and 52%, respectively, successfully completed treatment). Losses were substantially higher among rifampicin- resistant cases, with only 22% successfully completing treatment. Conclusion: Although the vast majority of individuals with tuberculosis engaged the public health system, just over half were successfully treated. Urgent efforts are required to improve implementation of existing policies and protocols to close gaps in tuberculosis diagnosis, treatment initiation, and successful treatment completion.

Human resource for health reform in peri-urban areas: a cross-sectional study of the impact of policy interventions on healthcare workers in Epworth, Zimbabwe.

BACKGROUND: The need to understand how healthcare worker reform policy interventions impact health personnel in peri-urban areas is important as it also contributes towards setting of priorities in pursuing the universal health coverage goal of health sector reform. This study explored the impact of post 2008 human resource for health reform policy interventions on healthcare workers in Epworth, a peri-urban community in Harare, Zimbabwe, and the implications towards health sector reform policy in peri-urban areas. METHODS: The study design was exploratory and cross-sectional and involved the use of qualitative and quantitative methods in data collection, presentation, and analysis. A qualitative study in which data were collected through a documentary search, five key informant interviews, seven in-depth interviews, and five focus group discussions was carried out first. This was followed by a quantitative study in which data were collected through a documentary search and 87 semi-structured sample interviews with healthcare workers. Qualitative data were analyzed thematically whilst descriptive statistics were used to examine quantitative data. All data were integrated during analysis to ensure comprehensive, reliable, and valid analysis of the dataset. RESULTS: Three main factors were identified to help interpret findings. The first main factor consisted policy result areas that impacted most successfully on healthcare workers. These included the deployment of community health workers with the highest correlation of 0.83. Policy result areas in the second main factor included financial incentives with a correlation of 0.79, training and development (0.77), deployment (0.77), and non-financial incentives (0.75). The third factor consisted policy result areas that had the lowest satisfaction amongst healthcare workers in Epworth. These included safety (0.72), equipment and tools of trade (0.72), health welfare (0.65), and salaries (0.55). CONCLUSIONS: The deployment of community health volunteers impacted healthcare workers most successfully. This was followed by salary top-up allowances, training, deployment, and non-financial incentives. However, health personnel were least satisfied with their salaries. This had negative implications towards health sector reform interventions in Epworth peri-urban community between 2009 and 2014.

HIV-Tat immunization induces cross-clade neutralizing antibodies and CD4(+) T cell increases in antiretroviral-treated South African volunteers: a randomized phase II clinical trial.

BACKGROUND: Although combined antiretroviral therapy (cART) has saved millions of lives, it is incapable of full immune reconstitution and virus eradication. The transactivator of transcription (Tat) protein is a key human immunodeficiency virus (HIV) virulence factor required for virus replication and transmission. Tat is expressed and released extracellularly by infected cells also under cART and in this form induces immune dysregulation, and promotes virus reactivation, entry and spreading. Of note, anti-Tat antibodies are rare in natural infection and, when present, correlate with asymptomatic state and reduced disease progression. This suggested that induction of anti-Tat antibodies represents a pathogenesis-driven intervention to block progression and to intensify cART. Indeed Tat-based vaccination was safe, immunogenic and capable of immune restoration in an open-label, randomized phase II clinical trial conducted in 168 cART-treated volunteers in Italy. To assess whether B-clade Tat immunization would be effective also in patients with different genetic background and infecting virus, a phase II trial was conducted in South Africa. METHODS: The ISS T-003 was a 48-week randomised, double-blinded, placebo-controlled trial to evaluate immunogenicity (primary endpoint) and safety (secondary endpoint) of B-clade Tat (30 µg) given intradermally, three times at 4-week intervals, in 200 HIV-infected adults on effective cART (randomised 1:1) with CD4(+) T-cell counts ≥200 cells/µL. Study outcomes also included cross-clade anti-Tat antibodies, neutralization, CD4(+) T-cell counts and therapy compliance. RESULTS: Immunization was safe and well-tolerated and induced durable, high titers anti-Tat B-clade antibodies in 97 % vaccinees. Anti-Tat antibodies were cross-clade (all vaccinees tested) and neutralized Tat-mediated entry of oligomeric B-clade and C-clade envelope in dendritic cells (24 participants tested). Anti-Tat antibody titers correlated positively with neutralization. Tat vaccination increased CD4(+) T-cell numbers (all participants tested), particularly when baseline levels were still low after years of therapy, and this had a positive correlation with HIV neutralization. Finally, in cART non-compliant patients (24 participants), vaccination contained viral load rebound and maintained CD4(+) T-cell numbers over study entry levels as compared to placebo. CONCLUSIONS: The data indicate that Tat vaccination can restore the immune system and induces cross-clade neutralizing anti-Tat antibodies in patients with different genetic backgrounds and infecting viruses, supporting the conduct of phase III studies in South Africa. Trial registration ClinicalTrials.gov NCT01513135, 01/23/2012.

Early Diagnosis of HIV Infection in Infants - One Caribbean and Six Sub-Saharan African Countries, 2011-2015.

Pediatric human immunodeficiency virus (HIV) infection remains an important public health issue in resource-limited settings. In 2015, 1.4 million children aged <15 years were estimated to be living with HIV (including 170,000 infants born in 2015), with the vast majority living in sub-Saharan Africa (1). In 2014, 150,000 children died from HIV-related causes worldwide (2). Access to timely HIV diagnosis and treatment for HIV-infected infants reduces HIV-associated mortality, which is approximately 50% by age 2 years without treatment (3). Since 2011, the annual number of HIV-infected children has declined by 50%. Despite this gain, in 2014, only 42% of HIV-exposed infants received a diagnostic test for HIV (2), and in 2015, only 51% of children living with HIV received antiretroviral therapy (1). Access to services for early infant diagnosis of HIV (which includes access to testing for HIV-exposed infants and clinical diagnosis of HIV-infected infants) is critical for reducing HIV-associated mortality in children aged <15 years. Using data collected from seven countries supported by the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), progress in the provision of HIV testing services for early infant diagnosis was assessed. During 2011-2015, the total number of HIV diagnostic tests performed among HIV-exposed infants within 6 weeks after birth (tests for early infant diagnosis of HIV), as recommended by the World Health Organization (WHO) increased in all seven countries (Cote d'Ivoire, the Democratic Republic of the Congo, Haiti, Malawi, South Africa, Uganda, and Zambia); however, in 2015, the rate of testing for early infant diagnosis among HIV-exposed infants was <50% in five countries. HIV positivity among those tested declined in all seven countries, with three countries (Cote d'Ivoire, the Democratic Republic of the Congo, and Uganda) reporting >50% decline. The most common challenges for access to testing for early infant diagnosis included difficulties in specimen transport, long turnaround time between specimen collection and receipt of results, and limitations in supply chain management. Further reductions in HIV mortality in children can be achieved through continued expansion and improvement of services for early infant diagnosis in PEPFAR-supported countries, including initiatives targeted to reach HIV-exposed infants, ensure access to programs for early infant diagnosis of HIV, and facilitate prompt linkage to treatment for children diagnosed with HIV infection.

Health personnel retention strategies in a peri-urban community: an exploratory study on Epworth, Zimbabwe.

BACKGROUND: The need to retain health personnel is a policy challenge undermining health system reform of the 21st century. The need to resolve this global health workforce crisis resulted in the First Global Forum on Human Resources for Health in 2008 from which the Kampala Declaration and Agenda for Global Action was formulated. However, whilst there have been several studies exploring the retention of health personnel towards this end, available literature does not provide a detailed narrative on strategies used in peri-urban communities. The aim of this study was to explore retention strategies implemented in a Zimbabwean peri-urban community between 2009 and 2014 and implications for peri-urban communities towards the health system reform agenda. METHODS: The study was carried out in Epworth, a peri-urban community in Harare, Zimbabwe. The research design was a cross-sectional survey, in which qualitative methods were used in sampling, data collection, reporting and analysis. Qualitative tools were used to collect data through in-depth interviews with purposively selected health personnel managers at 10 local clinics and sample interviews with purposively selected healthcare workers who included registered general nurses, state-certified nurses, midwives, environmental health technicians, nurse aids and community health volunteers at each clinic. Two focus group discussions were carried out with community health volunteers. Qualitative data was subjected to thematic analysis, with coding being performed manually. RESULTS: A programme-specific strategic partnership between the government and donor community contributed towards the mobilisation of more health personnel, health facilities, worker development and remuneration. To complement this, the Ministry of Health intervened through the review and payment of salaries, support towards post-basic training and development, and protection. The local board, mission and donors contributed through the payment of top-up allowances and provision of non-monetary incentives. CONCLUSIONS: The review of salaries, engagement of international strategic partners, payment of top-up allowances, support towards post-basic training and development, mobilisation of more health personnel, non-monetary incentives and healthcare worker protection were critical towards the retention of health personnel in the Epworth peri-urban community between 2009 and 2014.

From evidence to action to deliver a healthy start for the next generation.

Remarkable progress has been made towards halving of maternal deaths and deaths of children aged 1-59 months, although the task is incomplete. Newborn deaths and stillbirths were largely invisible in the Millennium Development Goals, and have continued to fall between maternal and child health efforts, with much slower reduction. This Series and the Every Newborn Action Plan outline mortality goals for newborn babies (ten or fewer per 1000 livebirths) and stillbirths (ten or fewer per 1000 total births) by 2035, aligning with A Promise Renewed target for children and the vision of Every Woman Every Child. To focus political attention and improve performance, goals for newborn babies and stillbirths must be recognised in the post-2015 framework, with corresponding accountability mechanisms. The four previous papers in this Every Newborn Series show the potential for a triple return on investment around the time of birth: averting maternal and newborn deaths and preventing stillbirths. Beyond survival, being counted and optimum nutrition and development is a human right for all children, including those with disabilities. Improved human capital brings economic productivity. Efforts to reach every woman and every newborn baby, close gaps in coverage, and improve equity and quality for antenatal, intrapartum, and postnatal care, especially in the poorest countries and for underserved populations, need urgent attention. We have prioritised what needs to be done differently on the basis of learning from the past decade about what has worked, and what has not. Needed now are four most important shifts: (1) intensification of political attention and leadership; (2) promotion of parent voice, supporting women, families, and communities to speak up for their newborn babies and to challenge social norms that accept these deaths as inevitable; (3) investment for effect on mortality outcome as well as harmonisation of funding; (4) implementation at scale, with particular attention to increasing of health worker numbers and skills with attention to high-quality childbirth care for newborn babies as well as mothers and children; and (5) evaluation, tracking coverage of priority interventions and packages of care with clear accountability to accelerate progress and reach the poorest groups. The Every Newborn Action Plan provides an evidence-based roadmap towards care for every woman, and a healthy start for every newborn baby, with a right to be counted, survive, and thrive wherever they are born.

A Political and Social History of HIV in South Africa.

For the past 25 years, South Africa has had to deal with the inexorable and monumental rise of HIV. From one or two isolated cases, in the late 1980s, South Africa now has an estimated 6.4 million people infected with HIV, with high rates of concomitant tuberculosis, which will profoundly affect the country for decades to come. For nearly 10 years, the South African government's response to the HIV epidemic was described as denialist, which was estimated to have resulted in the deaths of 330,000 people because lifesaving antiretroviral therapy (ART) was not provided (Chigwedere et al. J Acquir Immune Defic Syndr. 49:410-15, 2008; Heywood 2004). However, the story of the HIV and AIDS response in South Africa over the past 5 years is one of great progress after almost a decade of complex and tragic denialism that united civil society in a way not seen since the opposition to apartheid. Today, South Africa can boast of close to 3 million people on ART, by far the largest number in the world. Prevention efforts appear to be yielding results but there continues to be large numbers of new infections, with a profound peak in incidence in young women aged 15 to 24 years. In addition, infections occur across the gender spectrum in older age groups. As a result of the massive increase in access to ART after 2004 and particularly after 2008 as political will towards the HIV ART programme improved, there has been a marked increase in life expectancy, from 56 to 61 years in the period 2009-2012 alone; the aggressive expansion of the prevention of mother to child transmission (PMTCT) to HIV-positive pregnant women has been accompanied by dramatic decrease in HIV transmission to infants; and a 25 % decrease in child and infant mortality rates in the period 2009-2012. This progress in access is significantly due to a civil society movement that was prepared to pose a rights-based challenge to a governing party in denial and to brave health officials, politicians and clinicians working in a hostile system to bring about change.

Scale-up of HIV Viral Load Monitoring--Seven Sub-Saharan African Countries.

To achieve global targets for universal treatment set forth by the Joint United Nations Programme on human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) (UNAIDS), viral load monitoring for HIV-infected persons receiving antiretroviral therapy (ART) must become the standard of care in low- and middle-income countries (LMIC) (1). CDC and other U.S. government agencies, as part of the President's Emergency Plan for AIDS Relief, are supporting multiple countries in sub-Saharan Africa to change from the use of CD4 cell counts for monitoring of clinical response to ART to the use of viral load monitoring, which is the standard of care in developed countries. Viral load monitoring is the preferred method for immunologic monitoring because it enables earlier and more accurate detection of treatment failure before immunologic decline. This report highlights the initial successes and challenges of viral load monitoring in seven countries that have chosen to scale up viral load testing as a national monitoring strategy for patients on ART in response to World Health Organization (WHO) recommendations. Countries initiating viral load scale-up in 2014 observed increases in coverage after scale-up, and countries initiating in 2015 are anticipating similar trends. However, in six of the seven countries, viral load testing coverage in 2015 remained below target levels. Inefficient specimen transport, need for training, delays in procurement and distribution, and limited financial resources to support scale-up hindered progress. Country commitment and effective partnerships are essential to address the financial, operational, technical, and policy challenges of the rising demand for viral load monitoring.

HIV programme sustainability in Southern and Eastern Africa and the changing role of external assistance for health.

High human immunodeficiency virus (HIV)-prevalence countries in Southern and Eastern Africa continue to receive substantial external assistance (EA) for HIV programming, yet countries are at risk of transitioning out of HIV aid without achieving epidemic control. We sought to address two questions: (1) to what extent has HIV EA in the region been programmed and delivered in a way that supports long-term sustainability and (2) how should development agencies change operational approaches to support long-term, sustainable HIV control? We conducted 20 semi-structured key informant interviews with global and country-level respondents coupled with an analysis of Global Fund budget data for Malawi, Uganda, and Zambia (from 2017 until the present). We assessed EA practice along six dimensions of sustainability, namely financial, epidemiological, programmatic, rights-based, structural and political sustainability. Our respondents described HIV systems' vulnerability to donor departure, as well as how development partner priorities and practices have created challenges to promoting long-term HIV control. The challenges exacerbated by EA patterns include an emphasis on treatment over prevention, limiting effects on new infection rates; resistance to service integration driven in part by 'winners' under current EA patterns and challenges in ensuring coverage for marginalized populations; persistent structural barriers to effectively serving key populations and limited capacity among organizations best positioned to respond to community needs; and the need for advocacy given the erosion of political commitment by the long-term and substantive nature of HIV EA. Our recommendations include developing a robust investment case for primary prevention, providing operational support for integration processes, investing in local organizations and addressing issues of political will. While strategies must be locally crafted, our paper provides initial suggestions for how EA partners could change operational approaches to support long-term HIV control and the achievement of universal health coverage.

Eliminating mother-to-child HIV transmission in South Africa.

PROBLEM: The World Health Organization has produced clear guidelines for the prevention of mother-to-child transmission (PMTCT) of the human immunodeficiency virus (HIV). However, ensuring that all PMTCT programme components are implemented to a high quality in all facilities presents challenges. APPROACH: Although South Africa initiated its PMTCT programme in 2002, later than most other countries, political support has increased since 2008. Operational research has received more attention and objective data have been used more effectively. LOCAL SETTING: In 2010, around 30% of all pregnant women in South Africa were HIV-positive and half of all deaths in children younger than 5 years were associated with the virus. RELEVANT CHANGES: Between 2008 and 2011, the estimated proportion of HIV-exposed infants younger than 2 months who underwent routine polymerase chain reaction (PCR) tests to detect early HIV transmission increased from 36.6% to 70.4%. The estimated HIV transmission rate decreased from 9.6% to 2.8%. Population-based surveys in 2010 and 2011 reported transmission rates of 3.5% and 2.7%, respectively. LESSONS LEARNT: CRITICAL ACTIONS FOR IMPROVING PROGRAMME OUTCOMES INCLUDED: ensuring rapid implementation of changes in PMTCT policy at the field level through training and guideline dissemination; ensuring good coordination with technical partners, such as international health agencies and international and local nongovernmental organizations; and making use of data and indicators on all aspects of the PMTCT programme. Enabling health-care staff at primary care facilities to initiate antiretroviral therapy and expanding laboratory services for measuring CD4+ T-cell counts and for PCR testing were also helpful.

Résumé PROBLÈME: L'Organisation mondiale de la Santé a élaboré des lignes directrices claires pour la prévention de la transmission mère-enfant (PTME) du virus de l'immunodéficience humaine (VIH). S'assurer que tous les éléments du programme de PTME soient mis en œuvre de manière qualitative dans tous les établissements présente cependant des défis. APPROCHE: Bien que l'Afrique du Sud ait lancé son programme de PTME en 2002, plus tard que la plupart des autres pays, le soutien politique a augmenté depuis 2008. La recherche opérationnelle a reçu davantage d'attention, et les données objectives ont été utilisées plus efficacement. ENVIRONNEMENT LOCAL: En 2010, environ 30% de toutes les femmes enceintes en Afrique du Sud étaient séropositives, et la moitié de tous les décès d'enfants de moins de 5 ans étaient associée au virus. CHANGEMENTS SIGNIFICATIFS: Entre 2008 et 2011, la proportion estimée de nourrissons de moins de 2 mois exposés au VIH, ayant subi une réaction en chaîne par polymérase (PCR) de routine visant à détecter la transmission précoce du VIH, est passée de 36,6% à 70,4%. Le taux estimé de transmission du VIH a diminué, passant de 9,6% à 2,8%. Les enquêtes basées sur la population en 2010 et 2011 ont signalé des taux de transmission de 3,5% et 2,7%, respectivement. LEÇONS TIRÉES: Voici certaines actions essentielles pour améliorer les résultats du programme: assurer la mise en œuvre rapide des changements de politique de PTME sur le terrain, grâce à la formation et à la diffusion des lignes directrices; assurer une bonne coordination avec les partenaires techniques, comme les agences de santé internationales et locales et les organisations non gouvernementales; et utiliser les données et les indicateurs relatifs à tous les aspects du programme de PTME. Il est aussi utile de permettre au personnel soignant des établissements de soins de santé primaires d'initier un traitement antirétroviral et de développer les services de laboratoire pour les décomptes de cellules CD4 + T et les tests PCR.

Resumen SITUACIÓN: La Organización Mundial de la Salud ha presentado unas directrices claras para la prevención de la transmisión del virus de la inmunodeficiencia humana (VIH) de la madre al niño. No obstante, habrá que superar algunos desafíos para asegurar la puesta en marcha de todos los elementos del programa de prevención a fin de alcanzar un nivel de calidad elevado en todas las instalaciones. ENFOQUE: Aunque Sudáfrica inició su programa de prevención en el año 2002, más tarde que la mayoría de los países, el apoyo político ha aumentado desde 2008. Se ha prestado más atención a las investigaciones operativas y los datos objetivos se han utilizado con mayor eficacia. MARCO REGIONAL: En 2010, alrededor del 30% de las mujeres embarazadas en Sudáfrica eran seropositivas, y la mitad de todas las muertes en niños menores de cinco años estuvieron asociadas al virus. CAMBIOS IMPORTANTES: Entre los años 2008 y 2011, la proporción estimada de niños menores de dos meses expuestos al VIH que se sometió a las pruebas rutinarias de reacción en cadena de la polimerasa aumentó del 36,6% al 70,4%, y la tasa estimada de transmisión del VIH se redujo del 9,6% al 2,8%. Las encuestas de población de los años 2010 y 2011 reflejaron unas tasas de transmisión del 3,5% y el 2,7%, respectivamente LECCIONES APRENDIDAS: Las actividades fundamentales para mejorar los resultados del programa incluyeron: garantizar la implementación rápida de los cambios en la política de prevención de la transmisión a nivel de campo mediante cursos formativos y la difusión de las directrices; garantizar una coordinación adecuada entre los socios técnicos, tales como las agencias sanitarias internacionales y las ONG locales e internacionales; y utilizar los datos e indicadores acerca de todos los aspectos del programa de prevención de la transmisión del VIH de la madre al niño. También resultó muy útil permitir al personal sanitario de los centros de atención primaria iniciar terapias antirretrovirales y ampliar los servicios de laboratorio para realizar los recuentos de linfocitos T CD4+ y las pruebas de reacción en cadena de la polimerasa.

What will it take for an injectable ARV to change the face of the HIV epidemic in high-prevalence countries? Considerations regarding drug costs and operations.

INTRODUCTION: The proven effectiveness of injectable cabotegravir (CAB-LA) is higher than that of any other HIV prevention intervention ever trialled or implemented, surpassing medical male circumcision, condoms and combination antiretroviral treatment. Based on our own analyses and experience with the South African oral pre-exposure prophylaxis (PrEP) programme, we review the supply and demand side factors that would need to be in place for a successful rollout of CAB-LA, and delineate lessons for the launch of other long-acting and extended delivery (LAED) antiretroviral drugs. DISCUSSION: On the supply side, CAB-LA will have to be offered at a price that makes the drug affordable and cost-effective to low- and middle-income countries, especially those with high HIV prevalence. An important factor in lowering prices is a guaranteed market volume, which in turn necessitates the involvement of large funders, such as PEPFAR and the Global Fund, and a fairly rapid scale-up of the drug. Such a scale-up would have to involve speedy regulatory approval and WHO pre-qualification, swift integration of CAB-LA into national guidelines and planning for large enough manufacturing capacity, including the enabling of local manufacture. On the demand side, existing demand for HIV prevention products has to be harnessed and additional demand created, which will be aided by designing CAB-LA programmes at the primary healthcare or community level, and involving non-traditional outlets, such as private pharmacies and doctors' practices. CONCLUSIONS: CAB-LA could be the game changer for HIV prevention that we have been hoping for, and serve as a useful pilot for other LAEDs. A successful rollout would involve building markets of a guaranteed size; lowering the drug's price to a level possibly below the cost of production, while also lowering the cost of production altogether; harnessing, creating and sustaining demand for the product over the long term, wherever possible, in national programmes rather than single demonstration sites; and establishing and maintaining manufacturing capacity and supply chains. For this, all parties have to work together-including originator and generic manufacturers, donor organizations and other large funders, and the governments of low- and middle-income countries, in particular those with high HIV prevalence.