BACKGROUND:International support for surgery and healthcare in low-resource settings is primarily channeled through partnerships. To be truly impactful, such partnerships must endure long enough to mature, however longevity appears to be rare. Analysis of the challenges faced by successful long-term partnerships and how they were overcome may offer useful lessons for newer and aspiring global health partnerships. METHODS:The surgical training collaboration between the Royal College of Surgeons in Ireland and the College of Surgeons of East, Central, and Southern Africa has continued for 18 years and has delivered significant benefits for both partner institutions. Challenges faced by the collaboration and solutions to these challenges were elicited from key stakeholders in each college through an inductive approach. RESULTS:Challenges and solutions reported were grouped under four domains: power, operational capacity, changing needs, and maximizing impact. A set of governance structures are proposed to mitigate power disparities between partners and between individuals. Leveraging nonclinical staff members to support development of back-office systems increases local operational capacity to effectively engage in partnership activities. Constant change is a challenge for partnerships, which must both be accepted and planned for. The impact of work done through partnerships can be multiplied by expanding the collaboration to other comparable or synergistic institutions and making resources available open access. CONCLUSIONS:The RCSI/COSECSA collaboration program demonstrates that, over time, global health partnerships can play a transformational role in improving health outcomes in low-resource settings, while also benefitting high-income partners. Analysis of the development of the collaboration offers practical strategies for the development of other global health partnerships.

BACKGROUND:Access to surgery across sub-Saharan Africa faces persistent challenges with substantial disparity between disease burden and the surgical workforce. This updated situational analysis of specialist surgeons was undertaken to monitor progress toward global surgery development goals and address workforce deficits. METHODS:A cross-sectional analysis of the surgeon workforce across 12 of the 14 member countries of The College of Surgeons of East, Central and Southern Africa (COSECSA) was conducted between 2021 and 2022. The data was validated by at least two sources, including medical council registers and direct contact with surgeons via COSECSA Country representatives. Results were compared to data collection undertaken in 2015. RESULTS:2555 surgeons were identified as practising within the region, a 42% increase since 2015. This represents a rise of only 0.06 surgeons per 100,000. Surgeon density varies widely, with an 18-fold difference between the lowest (Mozambique, 0.22/100,000) and the highest surgeon densities (Namibia, 3.97/100,000). Women surgeons constitute one-tenth of the surgical workforce, a figure stagnant since 2015. Most surgeons (58%) practice in highly populated areas, and 78% work in their country of primary qualification. CONCLUSION:Currently there is a higher rate of population growth relative to surgical workforce expansion. Innovative approaches in surgical training are crucial to meet 2030 workforce targets. The non-progression in the ratio of female to male surgeons demands attention. Future workforce planning should recognize the growing impact of female doctors on the healthcare workforce and prioritize strategies to support women in surgical careers.

Burkitt lymphoma (BL) is a B-cell malignancy that disproportionately affects children in sub-Saharan Africa. We performed a genome-wide association study (GWAS) in a combined set of 800 childhood cases and 3865 controls in East Africa, controlling for age, sex, country, population-specific principal components, and a genetic relationship matrix. This analysis identified a BL-protective region within chromosome 21q22.12 tagged by the rs111457485-T allele (odds ratio [OR] = 0.57; p = 5.7 × 10−9). The results were robust in standard meta-analysis (OR = 0.57, p < 1.6 × 10−8), sensitivity analyses (removing genomic outliers and related individuals), and after adjustment for Epstein-Barr virus (EBV) status. Genomic analyses revealed long-range (over ~700 kb) chromatin interactions between the chr21q22.12 locus and the RUNX1-P1 promoter region. The African-specific rs2242780-C allele (r2 = 0.69 with the rs111457485-T allele in the study controls) showed increased enhancer activity in in-vitro Luciferase reporter assays (p = 4.5 × 10−10), nominating it as the likely functional variant for the BL-associated loci. In addition to the association with reduced BL risk in GWAS (OR = 0.62, p = 2.24 × 10−8), the rs2242780-C allele was also associated with better survival in patients with abdominal-only BL in exploratory analyses (hazard ratio = 0.39, p = 0.038, 106 patients, 59 deaths). Our GWAS uncovered novel BL-protective loci near RUNX1, offering insights into the genetic etiology of BL in African children.

BackgroundThe College of Surgeons of East, Central, and Southern Africa (COSECSA) comprises 14 countries, many of which currently grapple with an increasing burden of cardiothoracic surgical (CTS) diseases. Health and economic implications of unaddressed CTS conditions are profound and require a robust regional response. This study aimed to define the status of CTS specialist training in the region (including the density of specialists, facilities, and active training posts), examine implications, and proffer recommendations.MethodsA desk review of COSECSA secretariat documents and program accreditation records triangulated with information from surgical societies was performed in May 2022 and September 2023 as part of education quality improvement. A modified nominal group process involving contextual experts was used to develop a relevant action framework.ResultsOnly 6 of 14 (43%) of COSECSA countries offered active training programs with annual intake of only 18 trainees. Significant training gaps existed in Burundi, Botswana, Malawi, Rwanda, South Sudan, Zambia, and Zimbabwe. Country specialist density ranged from 1 per 400,000 (Namibia) to 1 per 8,000,000 (Ethiopia). Overall, the region had 0.2 CTS specialists per million population as compared with 7.15 surgeons per million in High-Income Countries. Surgical education experts proposed an action framework to address the training crisis including increasing investments in CTS education, establishing regional centers of excellence, retention incentives and opportunities for women, and leveraging international partnerships.ConclusionProactive investments in infrastructure, human resources, training, and collaborative efforts by national governments, regional intergovernmental organizations, and international partners are critical to expanding regional CTS training.

Annually more than 1 million newly diagnosed cancer cases and 500,000 cancer-related deaths occur in Sub Saharan Africa (SSA). By 2030, the cancer burden in Africa is expected to double accompanied by low survival rates. Surgery remains the primary treatment for solid tumours especially where other treatment modalities are lacking. However, in SSA, surgical residents lack sufficient training in cancer treatment. In 2022, Malawian and Dutch specialists co-designed a training course focusing on oncologic diseases and potential treatment options tailored to the Malawian context. The aim of this study was to describe the co-creation process of a surgical oncology education activity in a low resource setting, at the same time attempting to evaluate the effectiveness of this training program. The course design was guided and evaluated conform Kirkpatrick’s requirements for an effective training program . Pre-and post-course questionnaires were conducted to evaluate the effectiveness. Thirty-five surgical and gynaecological residents from Malawi participated in the course. Eighty-six percent of respondents ( n = 24/28) were highly satisfied at the end of the course. After a 2-month follow-up, 84% ( n = 16/19) frequently applied the newly acquired knowledge, and 74% ( n = 14/19) reported to have changed their patient care. The course costs were approximately 119 EUR per attendee per day. This course generally received generally positively feedback, had high satisfaction rates, and enhanced knowledge and confidence in the surgical treatment of cancer. Its effectiveness should be further evaluated using the same co-creation model in different settings. Integrating oncology into the regular curriculum of surgical residents is recommended.

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.

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.

INTRODUCTION:The College of Surgeons of East, Central, and Southern Africa (COSECSA) has been expanding surgical training in sub-Saharan Africa to respond to the shortage in the region. However, acquiring surgical skills requires rigorous training, and these skills are repeatedly assessed throughout training. Therefore, understanding the factors influencing these assessments is crucial. Previous research has identified individual characteristics, educational background, curriculum structure and previous exam outcomes to influence performance. However, COSECSA's Membership of the College of Surgeons (MCS) exam has not been investigated for factors influencing performance, which this study aims to investigate. METHODS:Data from MCS trainees who took the exam between 2015 and 2021 were analyzed. Trainee demographics, institutional affiliation, operative experience, and exam performance were considered. Linear regression models were used to analyze the factors related to written and clinical exam performance. RESULTS:Out of 354 trainees, 228 were included in the study. Factors such as training duration, the ratio of emergency surgeries, institutional funding source, and country language were associated with written exam performance. Training duration, funding source, exposure to major surgeries, and the ratio of performing operations were significant factors for the clinical exam. DISCUSSION:Operative experience, institutional affiliation, training duration, and language proficiency influence exam performance. Hospitals funded by faith-based organizations or nongovernmental organizations had trainees with higher scores. Prolonged training did not guarantee improved performance. Lastly, having English as an official language improved written exam scores. Gender and country of training did not significantly impact performance. CONCLUSION:This study highlights the importance of operative experience, institutional affiliation, and language proficiency in the exam performance of surgical trainees in COSECSA. Interventions to enhance surgical training and improve exam outcomes in sub-Saharan Africa should consider these factors. Further research is needed to explore additional outcome measures and gather comprehensive data on trainee and hospital characteristics.

BackgroundIncreasing surgical specialist workforce density in sub-Saharan Africa is essential for improving access to surgical care. However, out-migration creates a significant challenge to attaining provider targets. We aimed to determine the rates and trends of retention of surgeons in the College of Surgeons of East Central and Southern Africa (COSECSA) regions.MethodologyAn online, web-based survey was distributed to COSECSA surgeons who graduated from 2004 to 2020. Current practice and migration patterns were visualized using descriptive analyses and logistic regression models.ResultsResponse rate was 48% (270/557). Most respondents trained as general surgeons and practiced in Ethiopia, Kenya, Zimbabwe, and Zambia. Majority practiced in public hospitals (74%), and were active in research (81%), teaching (84%) and leadership (55%). Overall country (85%), regional (92%) and Africa retention rates (99%) were high with 100% country retention in Rwanda, Botswana, Lesotho, and Namibia. Tanzania had the lowest retention (61%). Highest inter-regional migration occurred from East to Southern Africa (26%), and continental out-migration occurred from Zambia, Zimbabwe, and Kenya. On bivariate analysis, out-migration from training country and region was associated working with a non-governmental organization (p = 0.002 and 0.0003) or a specialized hospital (p = 0.046 and 0.011). A multiple regression model with type of institution and leadership was a poor fit (McFadden R2 = 0.055; p = 0.082).ConclusionRetention rates of surgeons trained by COSECSA in the region remain remarkably high. This can be taken as an indicator of success of the training model to increase surgical workforce density, however, contributory factors need to be qualitatively explored.

Burkitt lymphoma (BL) is responsible for many childhood cancers in sub-Saharan Africa, where it is linked to recurrent or chronic infection by Epstein-Barr virus or Plasmodium falciparum . However, whether human leukocyte antigen ( HLA ) polymorphisms, which regulate immune response, are associated with BL has not been well investigated, which limits our understanding of BL etiology. Here we investigate this association among 4,645 children aged 0-15 years, 800 with BL, enrolled in Uganda, Tanzania, Kenya, and Malawi. HLA alleles are imputed with accuracy >90% for HLA class I and 85-89% for class II alleles. BL risk is elevated with HLA-DQA1*04:01 (adjusted odds ratio [OR] = 1.61, 95% confidence interval [CI] = 1.32-1.97, P = 3.71 × 10 −6 ), with rs2040406(G) in HLA-DQA1 region (OR = 1.43, 95% CI = 1.26-1.63, P = 4.62 × 10 −8 ), and with amino acid Gln at position 53 versus other variants in HLA-DQA1 (OR = 1.36, P = 2.06 × 10 −6 ). The associations with HLA-DQA1*04:01 (OR = 1.29, P = 0.03) and rs2040406(G) (OR = 1.68, P = 0.019) persist in mutually adjusted models. The higher risk rs2040406(G) variant for BL is associated with decreased HLA-DQB1 expression in eQTLs in EBV transformed lymphocytes. Our results support the role of HLA variation in the etiology of BL and suggest that a promising area of research might be understanding the link between HLA variation and EBV control.

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.

BackgroundIn 2017 the SURG-Africa project set out to institute a surgical, obstetric, trauma and anesthesia (SOTA) care capacity-building intervention focused on non-specialist providers at district hospitals in Zambia, Malawi and Tanzania. The aim was to scale up quality-assured SOTA care for rural populations. This paper reports the process of developing the intervention and our experience of initial implementation, using a participatory approach.MethodsParticipatory Action Research workshops were held in the 3 countries in July-October 2017 and in October 2018-July 2019, involving representatives of key local stakeholder groups: district hospital (DH) surgical teams and administrators, referral hospital SOTA specialists, professional associations and local authorities. Through semi-structured discussions, qualitative data were collected on participants' perceptions and experiences of barriers to the provision of SOTA care at district level, and on the training and supervision needs of district surgical teams. Data were compared for themes across countries and across surgical team cadres.ResultsAll groups reported a lack of in-service training to develop essential skills to manage common SOTA cases; use and care of equipment; essential anesthesia care including resuscitation skills; and infection prevention and control. Very few district surgical teams had access to supervision. SOTA providers at DHs reported a demand for more feedback on referrals. Participants prioritized training needs that could be addressed through regular in-service training and supervision visits from referral hospital specialists to DHs. These data were used by participants in an action-planning cycle to develop site-specific training plans for each research site.ConclusionThe inclusive, participatory approach to stakeholder involvement in SOTA system strengthening employed by this study supported the design of a locally relevant and contextualized intervention. This study provides lessons on how to rebalance power dynamics in Global Surgery, through giving a voice to district surgical teams.

Introduction: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma with hallmark somatic IG::MYC chromosomal translocations. BL is responsible for a significant proportion of childhood cancers in equatorial Africa, where exposure to Epstein Barr Virus (EBV) and P. falciparum are established risk factors. Host genetic factors are suspected to modify risk but are currently undefined, with exception of the sickle cell trait that is protective against severe malaria and childhood BL in Africa. Discovery of novel host genetic susceptibility in BL would suggest new directions to understand the biology of BL, particularly the link between host and environmental cofactors. Methods: We conducted the first genome-wide association study (GWAS) of BL among 4,645 children (800 with BL) aged 0–15 years enrolled in the Epidemiology of Burkitt lymphoma in East African Children and Minors (EMBLEM) study in Uganda, Kenya, and Tanzania (2010–2016) and the Childhood Infections and Cancer case-control study in Malawi (2005–2008). Genotypes at approximately 4.6 million sites were determined using the Infinium Omni5Exome-4 v1.3 BeadChip (Illumina) and imputation was performed using the African Genome Resources reference panel (Sanger Imputation Service), with rigorous quality control to filter unreliable calls. GWAS based on logistic mixed model was performed in SAIGE, adjusting for age, sex, and ancestry using population-specific principal components, and country of origin. Additional analyses were performed using genomic, epigenomic and expression data from the BL and ICGC MMML-Seq genome sequencing projects to provide insight into the potential mechanisms by which the novel loci may influence BL risk in African children. Results: Considering variants with a minor allele frequency threshold of ≥5%, we identified one genome-wide significant locus at 21q22.12 (Figure 1A) upstream of RUNX1. The index SNP (rs111457485, ref/effect: C/T, effect size: −0.57; p-value = 5.7 × 10−9; Figure 1B) is common in Africans (frequency of allele T: 10.2%) and rare in Europeans (allele frequency of T: 0.7%) in the 1000 Genomes populations. Fine mapping in this locus using the Sum of Single Effects (SuSiE) model revealed a credible set of 17 variants spanning 76 kb including the causal variant at the locus with 95% probability (Figure 1C). This associated region contains enhancer elements linked to RUNX1 expression that are differentially methylated in BL as compared to follicular lymphoma. Moreover, mining of RNA-seq data identified a novel spliced transcript expressed in BL and germinal center B cells. In secondary transcriptome-wide analyses in whole blood and spleen, we identified statistically significant association with additional loci at 19p13.2 in region previously identified to harbor somatic mutations in BL. The research was funded by: National Cancer Institute, National Institutes of Health, US Department of Health and Human Services Keywords: Aggressive B-cell non-Hodgkin lymphoma, Cancer Health Disparities, Genomics, Epigenomics, and Other-Omics No conflicts of interests pertinent to the abstract.

Introduction: Coronavirus disease-19 led to a significant reduction in surgery worldwide. Studies, however, of the effect on surgical volume for pediatric patients in low-income and middle-income countries (LMICs) are limited.Methods: A survey was developed to estimate waitlists in LMICs for priority surgical con-ditions in children. The survey was piloted and revised before it was deployed over email to 19 surgeons. Pediatric surgeons at 15 different sites in eight countries in sub-Saharan Af-rica and Ecuador completed the survey from February 2021 to June 2021. The survey included the total number of children awaiting surgery and estimates for specific condi-tions. Respondents were also able to add additional procedures.Results: Public hospitals had longer wait times than private facilities. The median waitlist was 90 patients, and the median wait time was 2 mo for elective surgeries.Conclusions: Lengthy surgical wait times affect surgical access in LMICs. Coronavirus disease-19 had been associated with surgical delays around the world, exacerbating existing surgical backlogs. Our results revealed significant delays for elective, urgent, and emergent cases across sub-Saharan Africa. Stakeholders should consider approaches to scale the limited surgical and perioperative resources in LMICs, create mitigation strategies for future pandemics, and establish ways to monitor waitlists on an ongoing basis. 2023 Elsevier Inc. All rights reserved.

Abstract Background The EU Global Health Strategy recognises that a skilled workforce is critical to advance universal health coverage. In response, our consortium brought together researchers, academics and clinicians from Ireland, the UK, the Netherlands, Malawi, Zambia and Tanzania to co-design a surgical workforce training and supervision intervention for district hospital teams aimed at scaling-up access to essential surgery in rural East Africa. Participatory action research (PAR) informed intervention design, incorporating the needs of frontline surgical providers and tailoring the training to meet identified gaps. This is the first study of this type in global surgery. Methods PAR workshops were held in Malawi, Zambia and Tanzania in 2017-2019 with key stakeholder groups: local authorities, professional associations, hospital managers and multi-disciplinary representatives of surgical teams from 67 district and referral hospitals. Through semi-structured discussions, qualitative data were collected on participants’ perceptions and experiences of barriers to safe and timely surgical and anaesthesia care, challenges in referral systems, and district surgical teams’ training and supervision needs. Data were compared for themes across sites and cadres. Results District surgical providers reported: a lack of in-service training, lack of access to mentoring and a demand for feedback on referrals. Participants prioritised training needs that could be addressed through regular in-service training and supervision visits from referrals to district hospitals to be delivered over the intervention period. Participants used findings in an action-planning cycle to develop country- and site-specific training plans for each research site. Conclusions Our approach to surgical capacity building, utilising both European and African expertise, has resulted in a demand-driven in-service training and supervision programme, now included in the participating countries’ national health strategies. Key messages • The inclusive, participatory approach to surgical system strengthening employed by our study enabled the co-design of a locally relevant, contextualised intervention. • Our study generated lessons on how to rebalance power dynamics in European-African health partnerships.

OBJECTIVES:Dedicated PICUs are slowly starting to emerge in sub-Saharan Africa. Establishing these units can be challenging as there is little data from this region to inform which populations and approaches should be prioritized. This study describes the characteristics and outcome of patients admitted to the first PICU in Malawi, with the aim to identify factors associated with increased mortality. DESIGN:Review of a prospectively constructed PICU database. Univariate analysis was used to assess associations between demographic, clinical and laboratory factors, and mortality. Univariate associations (p < 0.1) for mortality were entered in two multivariable models. SETTING:A recently opened PICU in a public tertiary government hospital in Blantyre, Malawi. PATIENTS:Children admitted to PICU between August 1, 2017, and July 31, 2019. INTERVENTIONS:None. MEASUREMENT AND MAIN RESULTS:Of 531 included PICU admissions, 149 children died (28.1%). Mortality was higher in neonates (88/167; 52.7%) than older children (61/364; 16.8%; p <= 0.001). On univariate analysis, gastroschisis, trachea-esophageal fistula, and sepsis had higher PICU mortality, while Wilms tumor, other neoplasms, vocal cord papilloma, and foreign body aspiration had higher survival rates compared with other conditions. On multivariable analysis, neonatal age (adjusted odds ratio [AOR], 4.0; 95% CI, 2.0-8.3), decreased mental state (AOR, 5.8; 95 CI, 2.4-13.8), post-cardiac arrest (AOR, 2.0; 95% CI, 1.0-8.0), severe hypotension (AOR, 6.3; 95% CI, 2.0-19.1), lactate greater than 5 mmol/L (AOR, 4.2; 95% CI, 1.5-11.2), pH less than 7.2 (AOR, 3.1; 95% CI, 1.2-8.0), and platelets less than 150 x 10(9)/L (AOR, 2.4; 95% CI, 1.1-5.2) were associated with increased mortality. CONCLUSIONS:In the first PICU in Malawi, mortality was relatively high, especially in neonates. Surgical neonates and septic patients were identified as highly vulnerable, which stresses the importance of improvement of PICU care bundles for these groups. Several clinical and laboratory variables were associated with mortality in older children. In neonates, severe hypotension was the only clinical variable associated with increased mortality besides blood gas parameters. This stresses the importance of basic laboratory tests, especially in neonates. These data contribute to evidence-based approaches establishing and improving future PICUs in sub-Saharan Africa.

Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be expressed only by carriers of the genetic variant rs368234815-dG within the first exon of the IFNL4 gene. Genetic inability to produce IFN-λ4 (in carriers of the rs368234815-TT/TT genotype) has been associated with improved clearance of hepatitis C virus (HCV) infection. The IFN-λ4-expressing rs368234815-dG allele (IFNL4-dG) is most common (up to 78%) in West sub-Saharan Africa (SSA), compared to 35% of Europeans and 5% of individuals from East Asia. The negative selection of IFNL4-dG outside Africa suggests that its retention in African populations could provide survival benefits, most likely in children. To explore this hypothesis, we conducted a comprehensive association analysis between IFNL4 genotypes and the risk of childhood Burkitt lymphoma (BL), a lethal infection-associated cancer most common in SSA. We used genetic, epidemiologic, and clinical data for 4,038 children from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) and the Malawi Infections and Childhood Cancer case-control studies. Generalized linear mixed models fit with the logit link controlling for age, sex, country, P. falciparum infection status, population stratification, and relatedness found no significant association between BL risk and 3 coding genetic variants within IFNL4 (rs368234815, rs117648444, and rs142981501) and their combinations. Because BL occurs in children 6-9 years of age who survived early childhood infections, our results suggest that additional studies should explore the associations of IFNL4-dG allele in younger children. This comprehensive study represents an important baseline in defining the health effects of IFN-λ4 in African populations.

IntroductionWilms 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. MethodsWe 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. ResultsWe 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). ConclusionHigh-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.