Setting up a state-of-the-art laboratory in resource limited settings: A case study of the biomedical science research and training centre in Northeast Nigeria.

African science has substantial potential, yet it grapples with significant challenges. Here we describe the establishment of the Biomedical Science Research and Training Centre (BioRTC) in Yobe State, Northeast Nigeria, as a case study of a hub fostering on-continent research and describe strategies to overcome current barriers. We detail the steps taken to establish BioRTC, emphasising the critical importance of stakeholder engagement, community involvement, resource optimisation and collaborations. With its state-of-the-art facilities and commitment to training African scientists, BioRTC is poised to significantly advance neuroscience research and training in the region. Although we are in the early stages of our journey, our model, emphasizing open access and inclusivity, offers a replicable blueprint for neuroscience research development in similar resource-limited settings, promising to enrich the global neuroscience community. We invite the support and collaboration of those who share our vision and believe in our potential.

Development of RPA-Cas12a assay for rapid and sensitive detection of Pneumocystis jirovecii.

Pneumocystis jirovecii is a prevalent opportunistic fungal pathogen that can lead to life-threatening Pneumocystis pneumonia in immunocompromised individuals. Given that timely and accurate diagnosis is essential for initiating prompt treatment and enhancing patient outcomes, it is vital to develop a rapid, simple, and sensitive method for P. jirovecii detection. Herein, we exploited a novel detection method for P. jirovecii by combining recombinase polymerase amplification (RPA) of nucleic acids isothermal amplification and the trans cleavage activity of Cas12a. The factors influencing the efficiency of RPA and Cas12a-mediated trans cleavage reaction, such as RPA primer, crRNA, the ratio of crRNA to Cas12a and ssDNA reporter concentration, were optimized. Our RPA-Cas12a-based fluorescent assay can be completed within  30-40 min, comprising a 25-30 min RPA reaction and a 5-10 min trans cleavage reaction. It can achieve a lower detection threshold of 0.5 copies/µL of target DNA with high specificity. Moreover, our RPA-Cas12a-based fluorescent method was examined using 30 artificial samples and demonstrated high accuracy with a diagnostic accuracy of 93.33%. In conclusion, a novel, rapid, sensitive, and cost-effective RPA-Cas12a-based detection method was developed and demonstrates significant potential for on-site detection of P. jirovecii in resource-limited settings.

Interests and Barriers to Medical Students Participation in a Dedicated Global Surgery Curriculum.

INTRODUCTION: Despite many institutions establishing global surgery (GS) programs to support clinical care and education in resource-limited settings, few have established a specific curriculum in GS. This study's objective was to assess medical student interest in such a curriculum and prospects for future careers in GS/global health (GH), and to define the barriers to pursuing an international rotation. METHODS: We conducted an anonymous online survey of all 495 medical students at a major academic medical center in the mid-South that collected demographic data, country of origin, interest in a GS/GH elective, and barriers to pursuing a GS/GH rotation abroad. The data were analyzed using SPSS software. RESULTS: Prior international experience increased the likelihood of a student's involvement in GS/GH and more preclinical (years 1 & 2) students (90%) than clinical students. (years 3 & 4) (70%) felt strongly about the value of a GS/GH experience. Of the 163 students who completed the survey, 80% expressed interest in a GS/GH elective, with preclinical students expressing more interest (90%) than clinical students (71%). This interest strongly correlated with an interest in pursuing a career in GH (94%) and/or GS (100%). Identified barriers to engagement in a GS/GH experience abroad included financing (74%), scheduling (58%), family obligations (23%), and personal safety (19%). CONCLUSIONS: The students we surveyed were very interested in a GS/GH curriculum that included a rotation abroad, especially if they were to receive financial support. Preclinical students expressed more willingness to self-fund such experiences. The findings of this survey further strengthen the need to incorporate GS/GH in medical school curricula.

Surgical aspects and outcomes after nephrectomy for Wilms tumour in sub-Saharan Africa: A report from Wilms Africa Phase II-CANCaRe Africa.

BACKGROUND: Wilms tumour (WT) is one of the common and curable cancer types targeted by the Global Initiative for Childhood Cancer. Tumour excision is essential for cure. This analysis focuses on surgical outcomes of patients with WT in sub-Saharan Africa. METHODS: We implemented a risk-stratified WT treatment guideline as a multicentre, prospective study across eight hospitals and six countries. Eligibility criteria were age 6 months to 16 years, unilateral WT, surgery performed after preoperative chemotherapy and diagnosed between 1 January 2021 and 31 December 2022. Data collection included a specific surgical case report form (CRF). RESULTS: The study registered 230 patients, among whom 164 (71.3%) had a nephrectomy. Ninety-eight percent of patients had a completed surgical CRF. Out 164 patients, 50 (30.5%) had distant metastases. Median tumour diameter at surgery was 11.0 cm. Lymph node sampling was done in 122 (74.3%) patients, 34 (20.7%) had intraoperative tumour rupture, and for 18 (10.9%), tumour resection involved en bloc resection of another organ. Tumour size at surgery was significantly correlated with tumour rupture (p < .01). With a median follow-up of 17 months (range: 2-33), 23 (14.0%) patients have relapsed. Twenty-two (13.4%) patients abandoned treatment post nephrectomy. Two-year event-free survival was 60.4% ± 4.7% with treatment abandonment as an event. CONCLUSION: Survival post nephrectomy is challenged by treatment abandonment, treatment-related mortality and relapse. Large tumours after preoperative chemotherapy were associated with a higher risk of tumour rupture. Earlier diagnosis and access to radiotherapy are expected to improve survival.

Effectiveness of a Wilms tumour treatment guideline adapted to local circumstances in sub-Saharan Africa: A report from Wilms Africa Phase II-CANCaRe Africa.

BACKGROUND: Wilms tumour (WT) is one of the cancer types targeted by the Global Initiative for Childhood Cancer (GICC). The objective of this study was to describe the outcomes of Wilms Africa Phase II in sub-Saharan Africa. METHODS: Wilms Africa Phase II used a comprehensive WT treatment protocol in a multi-centre, prospective study conducted in eight hospitals in Ethiopia (2), Ghana (2), Malawi, Cameroon, Zimbabwe and Uganda. Eligibility criteria were: age younger than 16 years, unilateral WT, diagnosed between 1 January 2021 and 31 December 2022. RESULTS: We included 230 WT patients, median age 3 years, 53% male. Median maximum tumour diameter at diagnosis was 13.6 cm and 33% of patients had metastatic disease. Nephrectomy was performed in 71% of patients, of whom 21% had a tumour rupture. Two-year event-free survival (EFS) was 41.3% ± 3.9% after a median follow-up of 17 months (range: 1-33 months), with treatment abandonment considered an event. Treatment abandonment occurred in 26% and death during treatment in 14%. Disease relapse occurred in 10%. Two-year EFS of the 26 patients who received radiotherapy was 64.5% ± 9.7% with no reported disease relapse. CONCLUSION: Patients continue to present late with advanced WT in sub-Saharan Africa, and their survival is below the 60% GICC target. Prevention of treatment abandonment and treatment-related mortality remain important. Earlier diagnosis and access to radiotherapy are expected to decrease disease-related mortality.

Reflections on 20 years of the Wilms Africa project: Lessons learned and the way forward.

Wilms tumour (WT) is one of the common and curable childhood cancer types included in the Global Initiative for Childhood Cancer (GICC) to monitor progress. Local evidence is key to finding effective and sustainable solutions to local challenges to improve care and survival. Local evidence generated by the Wilms Africa project is summarised with recommendations for the future.

Prevention of treatment abandonment remains an important challenge to increase survival of Wilms tumor in sub-Saharan Africa: A report from Wilms Africa-CANCaRe Africa.

BACKGROUND: The Wilms Africa studies implemented an adapted Wilm's tumor (WT) treatment protocol in sub-Saharan Africa in two phases. Phase I began with four sites and provided out-of-pocket costs. Phase II expanded the number of sites, but lost funding provision. Objective is to describe the outcomes of Phase II and compare with Phase I. METHODS: Wilms Africa Phase I (n = 4 sites; 2014-2018) and Phase II (n = 8 sites; 2021-2022) used adapted treatment protocols. Funding for families' out-of-pocket costs was provided during Phase I but not Phase II. Eligibility criteria were age less than 16 years and newly diagnosed unilateral WT. We documented patients' outcome at the end of planned first-line treatment categorized as treatment abandonment, death during treatment, and disease-related events (death before treatment, persistent disease, relapse, or progressive disease). Sensitivity analysis compared outcomes in the same four sites. RESULTS: We included 431 patients in Phase I (n = 201) and Phase II (n = 230). The proportion alive without evidence of disease decreased from 69% in Phase I to 54% in Phase II at all sites (p = .002) and 58% at the original four sites (p = .04). Treatment abandonment increased overall from 12% to 26% (p < .001), and was 20% (p = .04) at the original four sites. Disease-related events (5% vs. 6% vs. 6%) and deaths during treatment (14% vs. 14% vs. 17%) were similar. CONCLUSION: Provision of out-of-pocket costs was important to improve patient outcomes at the end of planned first-line treatment in WT. Prevention of treatment abandonment remains an important challenge.

Local evidence in sub-Saharan Africa; the CANCaRe Africa experience-Lessons learned and shared thoughts about the way forward.

Collaborative research generating local evidence is key to closing the research and survival gap between sub-Saharan Africa and high-income countries. Lessons learned by CANCaRe Africa, the Collaborative African Network for Childhood Cancer Care and Research while pioneering such research are being discussed together with recommendations for the future.

Integrated assessment of malignancy in IDH-mutant astrocytoma with p16 and methylthioadenosine phosphorylase immunohistochemistry.

In the fifth edition of the World Health Organization's (WHO) classification of tumors of the central nervous system (CNS), molecular analysis is required for not only determining each tumor type but assessing its prognosis based on malignancy (CNS WHO grade). A notable example is the loss of tumor suppressor gene cyclin-dependent kinase inhibitor 2A (CDKN2A), and CDKN2A homozygous deletion (HD) is a novel CNS WHO grade 4 marker in isocitrate dehydrogenase gene (IDH)-mutant astrocytoma. However, incorporating molecular workup into the "routine diagnostics" of each brain tumor type remains a major challenge, especially in resource-limited settings, including low- and middle-income countries. We herein validated the usefulness of p16 and methylthioadenosine phosphorylase (MTAP) immunohistochemistry (IHC) as potential surrogates for the assessment of CDKN2A status in 20 IDH-mutant astrocytoma cases. Of note, loss or retention of p16 and MTAP could accurately predict CDKN2A HD (p16: 87.5%, MTAP: 88.9%) or non-HD (p16: 100%, MTAP: 100%) with a single marker alone. Importantly, we revealed contributing factors to gray-zone IHC results (p16: 5-20%, MTAP: mosaic), including (1) hemizygous deletion of CDKN2A, (2) degenerative findings, and (3) intratumoral CDKN2A HD heterogeneity, the detailed histologic and molecular assessment of which would be a key to achieving integrated assessment of malignancy in IDH-mutant astrocytoma. We characterized the pitfalls of each method and provided for the first time a practical flowchart of astrocytoma grading, contributing to a normalization of WHO2021-based molecular diagnostics in resource-limited settings.

Experiences of membership in munno mubulwadde (your friend indeed) - a novel community-based health insurance scheme in Luwero district in rural central Uganda.

BACKGROUND: Community-Based Health Insurance (CBHI) schemes are recognized as an important health financing pathway to achieving universal health coverage (UHC). Although previous studies have documented CBHIs in low-income countries, the majority of these have been provider-based. Non-provider based schemes have received comparatively less empirical attention. We sought to describe a novel non-provider based CBHI munno mubulwadde (your friend indeed) comprising informal sector members in rural central Uganda to understand the structure of the scheme, the experiences of scheme members in terms of the perceived benefits and barriers to retention in the scheme. METHODS: We report qualitative findings from a larger mixed-methods study. We conducted in-depth interviews with insured members (n = 18) and scheme administrators (n = 12). Four focus groups were conducted with insured members (38 participants). Data were inductively analyzed by thematic approach. RESULTS: Munno mubulwadde is a union of ten CBHI schemes coordinated by one administrative structure. Members were predominantly low-income rural informal sector households who pay annual premiums ranging from $17 and $50 annually and received medical care at 13 scheme-contracted private health facilities in Luwero District in Central Uganda. Insured members reported that scheme membership protected them from catastrophic health expenditure during episodes of sickness among household members, and especially so among households with children under-five who were reported to fall sick frequently, the scheme enabled members to receive perceived better quality health care at private providers in the study district relative to the nearest public facilities. The identified barriers to retention in the scheme include inconvenient dates for premium payment that are misaligned with harvest periods for cash crops (e.g. maize corn) on which members depended for their agrarian livelihoods, long distances to insurance-contracted private providers, falling prices of cash crops which diminished real incomes and affordability of insurance premiums in successive years after initial enrolment. CONCLUSION: Munno mubulwadde was perceived by as a valuable financial cushion during episodes of illness by rural informal sector households. Policy interventions for promoting price stability of cash crops in central Uganda could enhance retention of members in this non-provider CBHI which is worthy of further research as an additional funding pathway for realizing UHC in Uganda and other low-income settings.

The Urban-Rural Divide in Neurocritical Care in Low-Income and Middle-Income Countries.

The term "urban-rural divide" encompasses several dimensions and has remained an important concern for any country. The economic disparity; lack of infrastructure; dearth of medical specialists; limited opportunities to education, training, and health care; lower level of sanitation; and isolating effect of geographical location deepens this gap, especially in low-income and middle-income countries (LMICs). This article gives an overview of the rural-urban differences in terms of facilities related to neurocritical care (NCC) in LMICs. Issues related to common clinical conditions such as stroke, traumatic brain injury, myasthenia gravis, epilepsy, tubercular meningitis, and tracheostomy are also discussed. To facilitate delivery of NCC in resource-limited settings, proposed strategies include strengthening preventive measures, focusing on basics, having a multidisciplinary approach, promoting training and education, and conducting cost-effective research and collaborative efforts. The rural areas of LMICs bear the maximum impact because of their limited access to preventive health services, high incidence of acquired brain injury, inability to have timely management of neurological emergencies, and scarcity of specialist services in a resource-deprived health center. An increase in the health budget allocation for rural areas, NCC education and training of the workforce, and provision of telemedicine services for rapid diagnosis, management, and neurorehabilitation are some of the steps that can be quite helpful.

Focused cardiac ultrasound: Competency among pre-internship medical officers in diagnosing cardiac causes of dyspnea.

BACKGROUND: Differentiating cardiovascular causes of dyspnea in resource-limited healthcare settings can be challenging. The use of easy-to-train, point-of-care, focused cardiac ultrasound (FoCUS) protocols may potentially alleviate this challenge. RESEARCH QUESTION: Can novices attain competency in FoCUS use after training using the cardiac ultrasound for resource-limited settings (CURLS) protocol? METHODS: A quasi-experimental study was conducted at the Kenyatta National Hospital in Nairobi, Kenya. Forty-five graduate medical pre-interns, novices in cardiac ultrasound, received simulated didactic and hands-on FoCUS skills training using the CURLS protocol and 2018 European Association of Cardiovascular Imaging (EACVI) FoCUS training and competence assessment recommendations. Competency was assessed in image interpretation, image acquisition, and image quality. RESULTS: Aggregate image interpretation competency was attained by n = 38 (84%) of trainees with a median score of 80%. The proportion of trainees attaining category-specific image interpretation competency was as follows: pericardial effusion n = 44 (98%), left atrial enlargement n = 40 (89%), cardiomyopathy n = 38 (84%), left ventricular hypertrophy n = 37 (82%), and right ventricular enlargement n = 29 (64%). Image acquisition skills competency was attained by n = 36 (80%) of trainees. Three-quarters of trainee-obtained images were of good quality. CONCLUSION: Majority of the trainees attained competency. Training constraints limit the generalizability of our findings.

The Indian Society of Critical Care Medicine Position Statement on the Management of Sepsis in Resource-limited Settings.

Sepsis poses a significant global health challenge in low- and middle-income countries (LMICs). Several aspects of sepsis management recommended in international guidelines are often difficult or impossible to implement in resource-limited settings (RLS) due to issues related to cost, infrastructure, or lack of trained healthcare workers. The Indian Society of Critical Care Medicine (ISCCM) drafted a position statement for the management of sepsis in RLS focusing on India, facilitated by a task force of 18 intensivists using a Delphi process, to achieve consensus on various aspects of sepsis management which are challenging to implement in RLS. The process involved a comprehensive literature review, controlled feedback, and four iterative surveys conducted between 21 August 2023 and 21 September 2023. The domains addressed in the Delphi process included the need for a position statement, challenges in sepsis management, considerations for diagnosis, patient management while awaiting an intensive care unit (ICU) bed, and treatment of sepsis and septic shock in RLS. Consensus was achieved when 70% or more of the task force members voted either for or against statements using a Likert scale or a multiple-choice question (MCQ). The Delphi process with 100% participation of Task Force members in all rounds, generated consensus in 32 statements (91%) from which 20 clinical practice statements were drafted for the management of sepsis in RLS. The clinical practice statements will complement the existing international guidelines for the management of sepsis and provide valuable insights into tailoring sepsis interventions in the context of RLS, contributing to the global discourse on sepsis management. Future international guidelines should address the management of sepsis in RLS. How to cite this article: Juneja D, Nasa P, Chanchalani G, Cherian A, Jagiasi BG, Javeri Y, et al. The Indian Society of Critical Care Medicine Position Statement on the Management of Sepsis in Resource-limited Settings. Indian J Crit Care Med 2024;28(S2):S4-S19.

Five-year results of a treatment program for chronic hepatitis B in Ethiopia.

BACKGROUND: In sub-Saharan Africa, less than 1% of treatment-eligible chronic hepatitis B (CHB) patients receive antiviral therapy. Experiences from local CHB programs are needed to inform treatment guidelines and policies on the continent. Here, we present 5-year results from one of the first large-scale CHB treatment programs in sub-Saharan Africa. METHODS: Adults with CHB were enrolled in a pilot treatment program in Addis Ababa, Ethiopia, in 2015. Liver enzymes, viral markers, and transient elastography were assessed at baseline and thereafter at 6-month intervals. Tenofovir disoproxil fumarate was initiated based on the European Association for the Study of the Liver (EASL) criteria, with some modifications. Survival analysis was performed using the Kaplan-Meier method. RESULTS: In total, 1303 patients were included in the program, of whom 291 (22.3%) started antiviral therapy within the initial 5 years of follow-up. Among patients on treatment, estimated 5-year hepatocellular carcinoma-free survival was 99.0% in patients without cirrhosis at baseline, compared to 88.8% in patients with compensated cirrhosis, and 54.2% in patients with decompensated cirrhosis (p < 0.001). The risk of death was significantly higher in patients with decompensated cirrhosis at baseline (adjusted hazard ratio 44.6, 95% confidence interval 6.1-328.1) and in patients older than 40 years (adjusted hazard ratio 3.7, 95% confidence interval 1.6-8.5). Liver stiffness declined significantly after treatment initiation; the median change from baseline after 1, 3, and 5 years of treatment was - 4.0 kPa, - 5.2 kPa, and - 5.6 kPa, respectively. CONCLUSIONS: This pilot program demonstrates the long-term benefits of CHB therapy in a resource-limited setting. The high mortality in patients with cirrhosis underscores the need for earlier detection of CHB and timely initiation of antiviral treatment in sub-Saharan Africa. TRIAL REGISTRATION: The study was registered at ClinicalTrials.gov (NCT02344498) on January 26, 2015.

Outcomes of Wilms tumor therapy in Lilongwe, Malawi, 2016-2021: Successes and ongoing research priorities.

INTRODUCTION: Wilms tumor therapy in low- and middle-income countries (LMICs) relies on treatment protocols adapted to resource limitations, but these protocols have rarely been evaluated in real-world settings. Such evaluations are necessary to identify high-impact research priorities for clinical and implementation trials in LMICs. The purpose of this study was to identify highest priority targets for future clinical and implementation trials in sub-Saharan Africa by assessing outcomes of a resource-adapted treatment protocol in Malawi. METHODS: We conducted a retrospective cohort study of children treated for Wilms tumor with an adapted SIOP-backbone protocol in Lilongwe, Malawi between 2016 and 2021. Survival analysis assessed variables associated with poor outcome with high potential for future research and intervention. RESULTS: We identified 136 patients, most commonly with stage III (n = 35; 25.7%) or IV disease (n = 35; 25.7%). Two-year event-free survival (EFS) was 54% for stage I/II, 51% for stage III, and 13% for stage IV. A single patient with stage V disease survived to 1 year. Treatment abandonment occurred in 36 (26.5%) patients. Radiotherapy was indicated for 55 (40.4%), among whom three received it. Of these 55 patients, 2-year EFS was 31%. Of 14 patients with persistent metastatic pulmonary disease at the time of nephrectomy, none survived to 2 years. Notable variables independently associated with survival were severe acute malnutrition (hazard ratio [HR]: 1.9), increasing tumor stage (HR: 1.5), and vena cava involvement (HR: 3.1). CONCLUSION: High-impact targets for clinical and implementation trials in low-resource settings include treatment abandonment, late presentation, and approaches optimized for healthcare systems with persistently unavailable radiotherapy.

Drivers of retention of the HIV workforce transitioned from PEPFAR support to the Uganda government payroll.

BACKGROUND: Health worker (HW) retention in the public health sector in Uganda is an enduring health system constraint. Although previous studies have examined the retention of in-service HWs, there is little research focusing on donor-recruited HWs. The objective of this study was to explore drivers of retention of the HIV workforce transitioned from PEPFAR support to the Uganda government payroll between 2015 and 2017. METHODS: We conducted ten focus group discussions with HWs (n = 87) transitioned from PEPFAR support to the public sector payroll in 10 purposively selected districts across Uganda. In-depth interviews were conducted with national-level stakeholders (n = 17), district health and personnel officers (n = 15) and facility in-charges (n = 22). Data were analyzed by a hybrid approach of inductive and deductive thematic development based on the analytical framework by Schaefer and Moos regarding individual-level and organizational-context drivers. RESULTS: At the individual level, job security in the public sector was the most compelling driver of health worker retention. Community embeddedness of HWs in the study districts, opportunities for professional development and career growth and the ability to secure salary loans due to 'permanent and pensionable' terms of employment and the opportunity to work in 'home districts', where they could serve their 'kinsmen' were identified as enablers. HWs with prior private sector backgrounds perceived public facilities as offering more desirable challenging professional work. Organizational context enablers identified include perceptions that public facilities had relaxed supervision regimes and more flexible work environments. Work environment barriers to long-term retention include frequent stock-out of essential commodities, heavy workloads, low pay and scarcity of rental accommodation, particularly in rural Northern Uganda. Compared to mid-cadres (such as nurses and midwives), higher calibre cadres, such as physicians, pharmacists and laboratory technologists, expressed a higher affinity for seeking alternative employment in the private sector in the immediate future. CONCLUSIONS: Overall, job security was the most compelling driver of retention in public service for the health workforce transitioned from PEPFAR support to the Uganda government payroll. Monetary and non-monetary policy strategies are needed to enhance the retention of upper cadre HWs, particularly physicians, pharmacists and laboratory technologists in rural districts of Uganda.

Affordable drug resistance genotyping of HIV-1 reverse transcriptase, protease and integrase genes, for resource limited settings.

BACKGROUND: As use of dolutegravir (DTG) becomes more common in resource limited settings (RLS), the demand for integrase resistance testing is increasing. Affordable methods for genotyping all relevant HIV-1 pol genes (i.e., protease (PR), reverse transcriptase (RT) and integrase (IN)) are required to guide choice of future antiretroviral therapy (ART). We designed an in-house HIV-1 drug resistance (HIVDR) genotyping method that is affordable and suitable for use in RLS. METHODS: We obtained remnant plasma samples from CAPRISA 103 study and amplified HIV-1 PR, RT and IN genes, using an innovative PCR assay. We validated the assay using remnant plasma samples from an external quality assessment (EQA) programme. We genotyped samples by Sanger sequencing and assessed HIVDR mutations using the Stanford HIV drug resistance database. We compared drug resistance mutations with previous genotypes and calculated method cost-estimates. RESULTS: From 96 samples processed, we obtained sequence data for 78 (81%), of which 75 (96%) had a least one HIVDR mutation, with no major-IN mutations observed. Only one sample had an E157Q INSTI-accessory mutation. When compared to previous genotypes, 18/78 (23%) had at least one discordant mutation, but only 2/78 (3%) resulted in different phenotypic predictions that could affect choice of subsequent regimen. All CAPRISA 103 study sequences were HIV-1C as confirmed by phylogenetic analysis. Of the 7 EQA samples, 4 were HIV-1C, 2 were HIV-1D, and 1 was HIV-1A. Genotypic resistance data generated using the IDR method were 100% concordant with EQA panel results. Overall genotyping cost per sample was estimated at ~ US$43-$US49, with a processing time of ~ 2 working days. CONCLUSIONS: We successfully designed an in-house HIVDR method that is suitable for genotyping HIV-1 PR, RT and IN genes, at an affordable cost and shorter turnaround time. This HIVDR genotyping method accommodates changes in ART regimens and will help to guide HIV-1 treatment decisions in RLS.

Enhancement of paediatric oncology pharmacy practices in a low-middle-income country through teaching and training using the My Child Matters Grant.

The development of a successful oncology pharmacy system includes competency training, cost-efficient procurement, proper storage, preparation and administration of chemotherapy, and appropriate waste disposal. Low-middle-income countries such as Pakistan face several challenges within the realm of oncology pharmacy such as the unavailability of training programmes, resources and financial support, and inconsistencies in the safe handling of cytotoxic drugs. The Indus Hospital and Health Network (IHHN) is among the pioneers of oncology pharmacy practices in Pakistan, with a well-established Oncology Pharmacy Team and chemotherapy preparation in accordance with the United States Pharmacopeia 797 and 800 safety guidelines. The My Child Matters Grant was awarded by the Sanofi Espoir Foundation to the Department of Paediatric Hematology and Oncology at IHHN for holistic improvement in childhood cancer care through teaching, training and capacity building. Partnerships were formed with five public-sector paediatric oncology units nationwide. Initiatives were taken to improve oncology pharmacy practices including teaching and training courses, in-person assessment visits, and mentorship and liaison efforts. Despite prevailing challenges, promising improvements were noted at each centre. However, Pakistan needs to establish a national plan for childhood cancer with the creation of regional organisations for the training and monitoring of oncology pharmacists. Centralisation of pharmacy operations within hospitals is essential to maintain the availability, storage, preparation and administration standards of chemotherapy.

Community health workers can be trained to identify patients eligible for tuberculosis preventive therapy, but encounter barriers to programme implementation in KwaZulu-Natal, South Africa.

Tuberculosis (TB) remains one of the top 10 causes of death worldwide, ranking as the leading cause of death from infectious disease, above HIV and AIDS. South Africa has the sixth highest TB incidence rate in the world and the world's largest HIV epidemic. This study sought to demonstrate the feasibility of community health workers (CHWs) contributing to the implementation of tuberculosis preventive therapy (TPT) among people living with HIV and AIDS. Twelve community health workers were trained to test for communicable and non-communicable diseases and screen for TPT eligibility. They visited a select number of homes monthly to conduct screening for HIV, TB and non-communicable diseases. We recorded screening results, rates of referral for TPT, linkage to care - defined as being seen in the clinic for TPT - and treatment initiation. Among the 1 279 community members screened, 248 were identified as living with HIV, 99 (39.9%) individuals were identified as eligible for TPT, and 46 (46.5%) were referred to care. Among those referred, the median age was 39 (IQR 30-48) and 29 (63%) linked to care; 11 (37.9%) of those linked subsequently initiated treatment. In rural South Africa, it is feasible to train CHWs to identify and refer patients eligible for TPT, but losses occurred at each step of the cascade. CHWs can facilitate TPT implementation, although further implementation research exploring and addressing barriers to TPT (on an individual, provider and systems level) should be prioritised to optimise their role in rural resource-limited settings.

Symptoms of depression, anxiety, and thoughts of suicide/self-injury in adolescents and young adults living with HIV in Botswana.

Globally, mental health problems have been reported to be more common in youth living with HIV (YLWH) than in the general population, but routine mental health screening is rarely done in high-volume HIV clinics. In 2019, YLWH in a large HIV clinic in Botswana were screened using the Generalized Anxiety Scale-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) in a pilot standard-of-care screening programme. Two-way ANOVA was used to describe the effects of age group (12-<16, 16-<20 and 20-25 years old) and sex on GAD-7 and PHQ-9 scores. Chi-square statistics were used to compare characteristics of YLWH with and without potential suicidality/self-harm symptoms based on question 9 in the PHQ-9. Among 1 469 YLWH, 33.1%, 44.3% and 15.0% had anxiety, depression and potential suicidality/self-harm symptoms respectively. YLWH of 20-25 years old and 16-<20 years old had higher GAD-7 scores compared to 12-<16-year-olds (p = 0.014 and p = <0.001 respectively). Female YLWH of 20-25 years old had higher PHQ-9 scores compared to 12-<16-year-olds (p = 0.002). There were no other sex-age dynamics that were statistically significant. Female YLWH endorsed more thoughts of suicidality/self-harm than males (17% versus 13%, p = 0.03 respectively). Given the proportion of YLWH with mental health symptoms, Botswana should enhance investments in mental health services for YLWH, especially for young female adults who bear a disproportionate burden.