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Background The Avahan India AIDS Initiative was implemented to provide HIV prevention services to key populations including female sex workers (FSWs) who carry the burden of India’s concentrated HIV epidemic. Established in 2003 and handed over to the Indian government in 2009, the Initiative included peer-led outreach education, condom promotion and distribution and STI treatment. This study aimed to determine if HIV prevention cascades could be generated using routine monitoring and evaluation data from the Avahan program and to assess their value in identifying and responding to program gaps for FSWs. Methods Two data sources were used namely the Integrated Behavioural and Biological Assessment reports and the Centralized Management Information System dataset. Indicators selected for the cascades were: FSWs at risk, belief that HIV can be prevented, condom access and consistent condom use with an occasional partner. Six districts were selected and stratified by HIV prevalence at baseline and two cascades were generated per district reflecting changes over time. Results Consistent condom use with occasional partners in this population increased in all six districts during program implementation, with statistically significant increases in four of the six. No patterns in the cascades were detected according to HIV prevalence either at baseline (2005) or at follow-up (2009). Cascades were able to identify key programmatic bottlenecks at baseline that could assist with focusing program efforts and direct resources at district levels. In some districts the belief that HIV could not be prevented contributed to inconsistent condom use, while in others, low levels of condom access were a more important barrier to consistent condom use. Conclusion This HIV prevention cascade analysis among FSWs in India suggests that cascades could assist in identifying program gaps, focus intervention efforts and monitor their effect. However, cascades cannot replace a detailed understanding of the multiple factors at individual, community and structural levels that lead to consistent condom use in this key population. Careful indicator selection coupled with innovative data collection methods will be required. Pilot projects are proposed to formally evaluate the value of HIV prevention cascades at district level.

Background Voluntary medical male circumcision (VMMC) reduces the risk of male HIV acquisition by 60%. Programmes to provide VMMCs for HIV prevention have been introduced in sub-Saharan African countries with high HIV burden. Traditional circumcision is also a long-standing male coming-of-age ritual, but practices vary considerably across populations. Accurate estimates of circumcision coverage by age, type, and time at subnational levels are required for planning and delivering VMMCs to meet targets and evaluating their impacts on HIV incidence. Methods We developed a Bayesian competing risks time-to-event model to produce region-age-time-type specific probabilities and coverage of male circumcision with probabilistic uncertainty. The model jointly synthesises data from household surveys and health system data on the number of VMMCs conducted. We demonstrated the model using data from five household surveys and VMMC programme data to produce estimates of circumcision coverage for 52 districts in South Africa between 2008 and 2019. Results Nationally, in 2008, 24.1% (95% CI: 23.4–24.8%) of men aged 15–49 were traditionally circumcised and 19.4% (18.9–20.0%) were medically circumcised. Between 2010 and 2019, 4.25 million VMMCs were conducted. Circumcision coverage among men aged 15–49 increased to 64.0% (63.2–64.9%) and medical circumcision coverage to 42% (41.3–43.0%). Circumcision coverage varied widely across districts, ranging from 13.4 to 86.3%. The average age of traditional circumcision ranged between 13 and 19 years, depending on local cultural practices. Conclusion South Africa has made substantial, but heterogeneous, progress towards increasing medical circumcision coverage. Detailed subnational information on coverage and practices can guide programmes to identify unmet need to achieve national and international targets. Plain language summary Voluntary medical male circumcision reduces the risk of male HIV acquisition. Programmes to provide circumcisions for HIV prevention have been introduced in sub-Saharan African countries with high HIV burden. Estimates of circumcision coverage are needed for planning and delivering circumcisions to meet targets and evaluate their impacts on HIV incidence. We developed a model to integrate date from both household surveys and health systems on the number of circumcisions conducted, and applied it to understand how the practices and coverage of circumcision are changing in South Africa. National circumcision coverage increased considerably between 2008 and 2019, however, there remains a substantial subnational variation across districts and age groups. Further progress is needed to reach national and international targets. Thomas et al. present a model that integrates household survey and health system data to estimate subnational circumcision coverage in South Africa during scale-up for HIV prevention. Results show considerable, but heterogenous, progress towards increasing circumcision coverage, identifying priority ages and districts to reach national targets.

Voluntary medical male circumcision (VMMC) reduces the risk of male HIV acquisition by 60%. Programmes to provide male circumcision (MC) to prevent HIV infection have been introduced in sub-Saharan African countries with high HIV burden. While large-scale provision of MMC is recent, traditional MC has long been conducted as part of male coming-of-age practices. How and at what age traditional MC occurs varies by ethnic groups within countries. Accurate estimates of MC coverage by age and type of circumcision (traditional or medical) over time at sub-national levels are essential for planning and delivering VMMCs to meet targets and evaluating their impacts on HIV incidence. In this paper, we developed a Bayesian competing risks time-to-event model to produce region-age-time-type specific probabilities and coverage of MC with probabilistic uncertainty. The model jointly synthesises data from household surveys and health system data on the number of VMMCs conducted. We demonstrated the model using data from five household surveys and VMMC programme data to produce estimates of MC coverage for 52 districts in South Africa between 2008 and 2019. Nationally in 2008, 24.1% (CI: 23.4-24.8%) of men aged 15-49 were traditionally circumcised and 19.4% (CI: 18.9-20.0%) were medically circumcised. Between 2008 and 2019, five million VMMCs were conducted, and MC coverage among men aged 15-49 increased to 64.0% (CI: 63.2-64.9%) and medical MC coverage to 42% (CI: 41.3-43.0%). MC coverage varied widely across districts, ranging from 13.4-86.3%. The average age of traditional MC ranged between 13 to 19 years, depending on local cultural practices.

Background In Zambia's maternal and child health departments, midwives offer compulsory and free obstetric ultrasound scans during antenatal care (ANC). These scans monitor fetal growth and development and identify any possible pregnancy-related complications or abnormalities. However, the normalization of obstetric ultrasound scans (USS) by midwives in Zambia is still in progress. The study sought to assess the facilitators and barriers to the implementation of obstetric ultrasound scans by midwives during antenatal care within 11 healthcare facilities in Zambia: experiences of healthcare workers (HCWs). Methods This was an explorative qualitative study with 28 healthcare workers from 11 healthcare facilities in four districts of Zambia. In-depth interviews were conducted in English, guided by an interview guide. The interviews were recorded with audio recorders, transcribed in verbatim, coded with Nvivo version 12, and analysed using an inductive thematic analysis approach. Results Healthcare workers highlighted that pregnant women who accessed ultrasound scans during antenatal care within maternal and child health departments were more inclined to follow through with their ANC appointments. The availability of free ultrasound scans encouraged pregnant women to accept and utilize these services, leading to enhanced quality of ANC care provided by healthcare workers. Obstetric ultrasounds during ANC expedited decision-making processes about specialized pregnancy care by midwives. The main facility barriers were inadequate space in maternal and child health departments, heightened workloads for midwives leading to burnout, and lengthy waiting queues that discouraged pregnant women from utilizing ultrasound scan services. Conclusion The study underscores the significance of obstetric ultrasound scans in improving antenatal care within Zambia's healthcare facilities. Recommendations include prioritizing infrastructure upgrades to accommodate ultrasound services within MCH, implementing workload management strategies for midwives, and reducing waiting times for pregnant women to access the service. Furthermore, providing continuous training and support for midwives in ultrasound scanning technology will enhance the delivery of quality and normalisation of antenatal care in Zambia.

BackgroundThere are limited data on the epidemiology of sexually transmitted infections (STI) and their contribution to adverse birth outcomes (ABO) in sub-Saharan Africa (SSA). We performed a case–control study to assess the prevalence of STI and their association with ABO among women attending Queen Elizabeth Central Hospital, Blantyre, Malawi.MethodsA composite case definition for ABO included stillborn, preterm and low birthweight infants and infants admitted to neonatal intensive care unit within 24 hours of birth. Following recruitment of an infant with an ABO, the next born healthy infant was recruited as a control. Multiplex PCR for Neisseria gonorrhoeae (NG), Chlamydia trachomatis (CT) and Trichomonas vaginalis (TV) was performed on maternal vaginal swabs. HIV and syphilis status was determined on maternal and infant serum. For syphilis, we used combined treponemal/non-treponemal rapid point-of-care tests in parallel with rapid plasma reagin tests, PCR for Treponema pallidum and clinical parameters to diagnose and stage the infection. We compared STI positivity between cases and controls.ResultsWe included 259 cases and 251 controls. Maternal prevalence of STI was 3.1%, 2.7% and 17.1% for NG, CT and TV, respectively. Maternal prevalence of untreated syphilis was 2.0% and 6.1% for early stage and late/unknown stage, respectively; prevalence of treated syphilis was 2.7%. The HIV prevalence was 16.5%. HIV infection significantly increased the odds for ABO (OR=3.31; 95% CI 1.10 to 9.91) as did NG positivity (OR=4.30; 95% CI 1.16 to 15.99). We observed higher rates of ABO among women with untreated maternal syphilis (early: OR=7.13; 95% CI 0.87 to 58.39, late/unknown stage: OR=1.43; 95% CI 0.65 to 3.15). Maternal TV and CT infections were not associated with ABO.ConclusionSTI prevalence among pregnant women in Malawi is comparable to other SSA countries. HIV, NG and untreated syphilis prevalence was higher among women with ABO compared with women with healthy infants.

Abstract Background The adequacy of the World Health Organization’s Integrated Management of Childhood Illness (IMCI) antimicrobial guidelines for the treatment of suspected severe bacterial infections is dependent on a low prevalence of antimicrobial resistance (AMR). We describe trends in etiologies and susceptibility patterns of bloodstream infections (BSI) in hospitalized children in Malawi. Methods We determined the change in the population-based incidence of BSI in children admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi (1998–2017). AMR profiles were assessed by the disc diffusion method, and trends over time were evaluated. Results A total 89643 pediatric blood cultures were performed, and 10621 pathogens were included in the analysis. Estimated minimum incidence rates of BSI for those ≤5 years of age fell from a peak of 11.4 per 1000 persons in 2002 to 3.4 per 1000 persons in 2017. Over 2 decades, the resistance of Gram-negative pathogens to all empiric, first-line antimicrobials (ampicillin/penicillin, gentamicin, ceftriaxone) among children ≤5 years increased from 3.4% to 30.2% (P < .001). Among those ≤60 days, AMR to all first-line antimicrobials increased from 7.0% to 67.7% (P < .001). Among children ≤5 years, Klebsiella spp. resistance to all first-line antimicrobial regimens increased from 5.9% to 93.7% (P < .001). Conclusions The incidence of BSI among hospitalized children has decreased substantially over the last 20 years, although gains have been offset by increases in Gram-negative pathogens’ resistance to all empiric first-line antimicrobials. There is an urgent need to address the broader challenge of adapting IMCI guidelines to the local setting in the face of rapidly-expanding AMR in childhood BSI. Incidences of bloodstream infections in Malawian children declined significantly over 2 decades, but resistance of Gram-negative pathogens to empiric, first-line antimicrobials increased from 3.4% to 30.2% for children ≤5 years and 7.0% to 67.7% for young infants ≤60 days.

BackgroundThere are many proposed benefits of using learning health systems (LHSs), including improved patient outcomes. There has been little adoption of LHS in practice due to challenges and barriers that limit adoption of new data-driven technologies in healthcare. We have identified a more fundamental explanation: the majority of developments in LHS are not identified as LHS. The absence of a unifying namespace and framework brings a lack of consistency in how LHS is identified and classified. As a result, the LHS ‘community’ is fragmented, with groups working on similar systems being unaware of each other’s work. This leads to duplication and the lack of a critical mass of researchers necessary to address barriers to adoption.ObjectiveTo find a way to support easy identification and classification of research works within the domain of LHS.MethodA qualitative meta-narrative study focusing on works that self-identified as LHS was used for two purposes. First, to find existing standard definitions and frameworks using these to create a new unifying framework. Second, seeking whether it was possible to classify those LHS solutions within the new framework.ResultsThe study found that with apparently limited awareness, all current LHS works fall within nine primary archetypes. These findings were used to develop a unifying framework for LHS to classify works as LHS, and reduce diversity and fragmentation within the domain.ConclusionsOur finding brings clarification where there has been limited awareness for LHS among researchers. We believe our framework is simple and may help researchers to classify works in the LHS domain. This framework may enable realisation of the critical mass necessary to bring more substantial collaboration and funding to LHS. Ongoing research will seek to establish the framework’s effect on the LHS domain.

Pollution of aquatic ecosystems with heavy metals is now of global concern due to their dangers to human health and persistence in the environment. An investigation on the spatial distribution of heavy metals in water and sediments and the bioaccumulation potential of heavy metals by plant parts (i.e. roots, stems and leaves) of aquatic macrophyte Typha domingensis (Pers.) Steud in a tropical reservoir was carried out. The results showed no difference in spatial distribution of heavy metals (Fe, Cu, Cd, Cr, Pb, Zn, Mn) in water and sediments from the riverine to the dam wall. The concentration of heavy metals Fe, Cu, Cr and Zn in T. domingensis was of the order root > stem > leaves, but for Pb, Cd and Mn, it followed the order root > leaf > stem. The metal transfer between roots and shoots of T. domingensis followed the order Zn > Pb > Fe > Cu > Cd > Cr. The bio-concentration factor (BCF) was low (BCF < 1) for all the selected metals while the transfer factor (TF) varied among metals suggesting that T. domingensis is not an accumulator of the studied metals. The high concentration of heavy metals found in the water (0.7–16.14 mg L −1 ) and sediments (43.6–569.18 mg kg −1 ) present a potential risk to both ecological health and human health for the population living in the area. The results of metal concentration in water and sediments from this study are important as a baseline for future monitoring studies. Further studies on bioavailability of metals to other macrophytes and aquatic organisms are recommended.

Reducing preterm birth and stillbirth and improving outcomes for babies born too soon is essential to reduce under-5 mortality globally. In the context of a rapidly evolving evidence base and problems with extrapolating efficacy data from high- to low-income settings, an assessment of the evidence for maternal and newborn interventions specific to low- and middle-income countries (LMICs) is required. A systematic review of the literature was done. We included all studies performed in LMICs since the Every Newborn Action Plan, between 2013 - 2018, which reported on interventions where the outcome assessed was reduction in preterm birth or stillbirth incidence and/or a reduction in preterm infant neonatal mortality. Evidence was categorised according to maternal or neonatal intervention groups and a narrative synthesis conducted. 179 studies (147 primary evidence studies and 32 systematic reviews) were identified in 82 LMICs. 81 studies reported on maternal interventions and 98 reported on neonatal interventions. Interventions in pregnant mothers which resulted in significant reductions in preterm birth and stillbirth were (i) multiple micronutrient supplementation and (ii) enhanced quality of antenatal care. Routine antenatal ultrasound in LMICs increased identification of fetal antenatal conditions but did not reduce stillbirth or preterm birth due to the absence of services to manage these diagnoses. Interventions in pre-term neonates which improved their survival included (i) feeding support including probiotics and (ii) thermal regulation. Improved provision of neonatal resuscitation did not improve pre-term mortality rates, highlighting the importance of post-resuscitation care. Community mobilisation, for example through community education packages, was found to be an effective way of delivering interventions. Evidence supports the implementation of several low-cost interventions with the potential to deliver reductions in preterm birth and stillbirth and improve outcomes for preterm babies in LMICs. These, however, must be complemented by overall health systems strengthening to be effective. Quality improvement methodology and learning health systems approaches can provide important means of understanding and tackling implementation challenges within local contexts. Further pragmatic efficacy trials of interventions in LMICs are essential, particularly for interventions not previously tested in these contexts.

Melanoma possesses invasive metastatic growth patterns and is one of the most aggressive types of skin cancer. In 2021, it is estimated that 7180 deaths were attributed to melanoma in the United States alone. Once melanoma metastasizes, traditional therapies are no longer effective. Instead, immunotherapies, such as ipilimumab, pembrolizumab, and nivolumab, are the treatment options for malignant melanoma. Several biomarkers involved in tumorigenesis have been identified as potential targets for molecularly targeted melanoma therapy, such as tyrosine kinase inhibitors (TKIs). Unfortunately, melanoma quickly acquires resistance to these molecularly targeted therapies. To bypass resistance, combination treatment with immunotherapies and single or multiple TKIs have been employed and have been shown to improve the prognosis of melanoma patients compared to monotherapy. This review discusses several combination therapies that target melanoma biomarkers, such as BRAF, MEK, RAS, c-KIT, VEGFR, c-MET and PI3K. Several of these regimens are already FDA-approved for treating metastatic melanoma, while others are still in clinical trials. Continued research into the causes of resistance and factors influencing the efficacy of these combination treatments, such as specific mutations in oncogenic proteins, may further improve the effectiveness of combination therapies, providing a better prognosis for melanoma patients.