Sickle cell allele HBB-rs334(T) is associated with decreased risk of childhood Burkitt lymphoma in East Africa.

Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that significantly contributes to childhood cancer burden in sub-Saharan Africa. Plasmodium falciparum, which causes malaria, is geographically associated with BL, but the evidence remains insufficient for causal inference. Inference could be strengthened by demonstrating that mendelian genes known to protect against malaria-such as the sickle cell trait variant, HBB-rs334(T)-also protect against BL. We investigated this hypothesis among 800 BL cases and 3845 controls in four East African countries using genome-scan data to detect polymorphisms in 22 genes known to affect malaria risk. We fit generalized linear mixed models to estimate odds ratios (OR) and 95% confidence intervals (95% CI), controlling for age, sex, country, and ancestry. The ORs of the loci with BL and P. falciparum infection among controls were correlated (Spearman's ρ = 0.37, p = .039). HBB-rs334(T) was associated with lower P. falciparum infection risk among controls (OR = 0.752, 95% CI 0.628-0.9; p = .00189) and BL risk (OR = 0.687, 95% CI 0.533-0.885; p = .0037). ABO-rs8176703(T) was associated with decreased risk of BL (OR = 0.591, 95% CI 0.379-0.992; p = .00271), but not of P. falciparum infection. Our results increase support for the etiological correlation between P. falciparum and BL risk.

The unmet need for treatment of children with musculoskeletal impairment in Malawi.

BACKGROUND: More than a billion people globally are living with disability and the prevalence is likely to increase rapidly in the coming years in low- and middle-income countries (LMICs). The vast majority of those living with disability are children residing in LMICs. There is very little reliable data on the epidemiology of musculoskeletal impairments (MSIs) in children and even less is available for Malawi. Previous studies in Malawi on childhood disability and the impact of musculoskeletal impairment (MSI) on the lives of children have been done but on a small scale and have not used disability measurement tools designed for children. Therefore in this study, we aimed to estimate the MSI prevalence, causes, and the treatment need among children aged 16 years or less in Malawi. METHODS: This study was carried out as a national cross sectional survey. Clusters were selected across the whole country through probability proportional to size sampling with an urban/rural and demographic split that matched the national distribution of the population. Clusters were distributed around all 27-mainland districts of Malawi. Population of Malawi was 18.3 million from 2018 estimates, based on age categories we estimated that about 8.9 million were 16 years and younger. MSI diagnosis from our randomized sample was extrapolated to the population of Malawi, confidence limits was calculated using normal approximation. RESULTS: Of 3792 children aged 16 or less who were enumerated, 3648 (96.2%) were examined and 236 were confirmed to have MSI, giving a prevalence of MSI of 6.5% (CI 5.7-7.3). Extrapolated to the Malawian population this means as many as 576,000 (95% CI 505,000-647,000) children could be living with MSI in Malawi. Overall, 46% of MSIs were due to congenital causes, 34% were neurological in origin, 8.4% were due to trauma, 7.8% were acquired non-traumatic non-infective causes, and 3.4% were due to infection. We estimated a total number of 112,000 (80,000-145,000) children in need of Prostheses and Orthoses (P&O), 42,000 (22,000-61,000) in need of mobility aids (including 37,000 wheel chairs), 73,000 (47,000-99,000) in need of medication, 59,000 (35,000-82,000) in need of physical therapy, and 20,000 (6000-33,000) children in need of orthopaedic surgery. Low parents' educational level was one factor associated with an increased risk of MSI. CONCLUSION: This survey has uncovered a large burden of MSI among children aged 16 and under in Malawi. The burden of musculoskeletal impairment in Malawi is mostly unattended, revealing a need to scale up both P&O services, physical & occupational therapy, and surgical services in the country.

Starting a spine surgery service in a low-resource setting: a look back over twenty five years of spine surgery in Malawi.

PURPOSE: This is a short historical narrative of the development of spine surgery in Malawi. METHODS: The authors communicated and both drew on memories and anecdotes over the last 25 years. RESULTS: This is not a scientific paper, so there are no results. CONCLUSION: The short paper outlines the development of spine surgery in Malawi over the last 25 years. This develops in association with the overall increase in the number of surgeons in the country.

Evaluation of a Managed Surgical Consultation Network in Malawi.

BACKGROUND: Access to surgery is a challenge for low-income countries like Malawi due to shortages of specialists, especially in rural areas. District hospitals (DH) cater for the immediate surgical needs of rural patients, sending difficult cases to central hospitals (CH), usually with no prior communication. METHODS: In 2018, a secure surgical managed consultation network (MCN) was established to improve communication between specialist surgeons and anaesthetists at Queen Elizabeth and Zomba Central Hospitals, and surgical providers from nine DHs referring to these facilities. RESULTS: From May to December 2018, DHs requested specialist advice on 249 surgical cases through the MCN, including anonymised images (52% of cases). Ninety six percent of cases received advice, with a median of two specialists answering. For 74% of cases, a first response was received within an hour, and in 68% of the cases, a decision was taken within an hour from posting the case on MCN. In 60% of the cases, the advice was to refer immediately, in 26% not to refer and 11% to possibly refer at a later stage. CONCLUSION: The MCN facilitated quick access to consultations with specialists on how to manage surgical patients in remote rural areas. It also helped to prevent unnecessary referrals, saving costs for patients, their guardians, referring hospitals and the health system as a whole. With time, the network has had spillover benefits, allowing the Ministry of Health closer monitoring of surgical activities in the districts and to respond faster to shortages of essential surgical resources.

Cost utility analysis of intramedullary nailing and skeletal traction treatment for patients with femoral shaft fractures in Malawi.

Background and purpose - In Malawi, both skeletal traction (ST) and intramedullary nailing (IMN) are used in the treatment of femoral shaft fractures, ST being the mainstay treatment. Previous studies have found that IMN has improved outcomes and is less expensive than ST. However, no cost-effectiveness analyses have yet compared IMN and ST in Malawi. We report the results of a cost-utility analysis (CUA) comparing treatment using either IMN or ST.Patients and methods - This was an economic evaluation study, where a CUA was done using a decision-tree model from the government healthcare payer and societal perspectives with an 1-year time horizon. We obtained EQ-5D-3L utility scores and probabilities from a prospective observational study assessing quality of life and function in 187 adult patients with femoral shaft fractures treated with either IMN or ST. The patients were followed up at 6 weeks, and 3, 6, and 12 months post-injury. Quality adjusted life years (QALYs) were calculated from utility scores using the area under the curve method. Direct treatment costs were obtained from a prospective micro costing study. Indirect costs included patient lost productivity, patient transportation, meals, and childcare costs associated with hospital stay and follow-up visits. Multiple sensitivity analyses assessed model uncertainty.Results - Total treatment costs were higher for ST ($1,349) compared with IMN ($1,122). QALYs were lower for ST than IMN, 0.71 (95% confidence interval [CI] 0.66-0.76) and 0.77 (CI 0.71-0.82) respectively. Based on lower cost and higher utility, IMN was the dominant strategy. IMN remained dominant in 94% of simulations. IMN would be less cost-effective than ST at a total procedure cost exceeding $880 from the payer's perspective, or $1,035 from the societal perspective.Interpretation - IMN was cost saving and more effective than ST in the treatment of adult femoral shaft fractures in Malawi, and may be an efficient use of limited healthcare resources.

Anesthesia Capacity of District-Level Hospitals in Malawi, Tanzania, and Zambia: A Mixed-Methods Study.

BACKGROUND: District-level hospitals (DLHs) are the main providers of surgical services for rural populations in Sub-Saharan Africa (SSA). Skilled teams are essential for surgical care, and gaps in anesthesia impact negatively on surgical capacity and outcomes. This study, from a baseline of a project scaling-up access to safe surgical and anesthesia care in Malawi, Tanzania, and Zambia, illustrates the deficit of anesthesia care in DLHs. METHODS: We undertook an in-depth investigation of anesthesia capacity in 76 DLHs across the 3 countries, July to November 2017, using a mixed-methods approach. The quantitative component assessed district-level anesthesia capacity using a standardized scoring system based on an adapted and extended Personnel, Infrastructure, Procedures, Equipment and Supplies (PIPES) Index. The qualitative component involved semistructured interviews with providers from 33 DLHs, exploring how weaknesses in anesthesia impacted district surgical team practices and quality, volume, and scope of service provision. RESULTS: Anesthesia care at the district level in these countries is provided only by nonphysician anesthetists, some of whom have no formal training. Ketamine anesthesia is widely used in all hospitals, compensating for shortages of other forms of anesthesia. Pediatric size supplies/equipment were frequently missing. Anesthesia PIPES index scores in Malawi (M = 8.0), Zambia (M = 8.3), and Tanzania (M = 8.4) were similar (P = .59), but an analysis of individual PIPES components revealed important cross-country differences. Irregular availability of reliable equipment and supply is a particular priority in Malawi, where only 29% of facilities have uninterrupted access to electricity and 23% have constant access to water, among other challenges. Zambia is mostly affected by staffing shortages, with 30% of surveyed hospitals lacking an anesthesia provider. The challenge that stood out in Tanzania was nonavailability of functioning anesthesia machines among frequent shortages of staff and other equipment. CONCLUSIONS: Tanzania, Malawi, and Zambia are falling far short of ensuring universal access to safe and affordable surgical and anesthesia care for district and rural populations. Mixed-methods situation analyses, undertaken in collaboration with anesthesia specialists-measuring and understanding deficits in district hospital anesthetic staff, equipment, and supplies-are needed to address the critical neglect of anesthesia that is essential to providing surgical responses to the needs of rural populations in SSA.

Deaths from surgical conditions in Malawi - a randomised cross-sectional Nationwide household survey.

BACKGROUND: Relatively little is known about deaths from surgical conditions in low- and middle- income African countries. The prevalence of untreated surgical conditions in Malawi has previously been estimated at 35%, with 24% of the total deaths associated with untreated surgical conditions. In this study, we wished to analyse the causes of deaths related to surgical disease in Malawi and where the deaths took place; at or outside a health facility. METHODS: The study is based on data collected in a randomised multi-stage cross-sectional national household survey, which was carried out using the Surgeons Overseas Assessment of Surgical Need (SOSAS) tool. Randomisation was done on 48,233 settlements, using 55 villages from each district as data collection sites. Two to four households were randomly selected from each village. Two members from each household were interviewed. A total of 1479 households (2909 interviewees) across the whole country were visited as part of the survey. RESULTS: The survey data showed that in 2016, the total number of reported deaths from all causes was 616 in the 1479 households visited. Data related to cause of death were available for 558 persons (52.7% male). Surgical conditions accounted for 26.9% of these deaths. The conditions mostly associated with the 150 surgical deaths were body masses, injuries, and acute abdominal distension (24.3, 21.5 and 18.0% respectively). 12 women died from child delivery complications. Significantly more deaths from surgical conditions or injuries (55.3%) occurred outside a health facility compared to 43.6% of deaths from other medical conditions, (p = 0.0047). 82.3% of people that died sought formal health care and 12.9% visited a traditional healer additionally prior to their death. 17.7% received no health care at all. Of 150 deaths from potentially treatable surgical conditions, only 21.3% received surgical care. CONCLUSION: In Malawi, a large proportion of deaths from possible surgical conditions occur outside a health facility. Conditions associated with surgical death were body masses, acute abdominal distention and injuries. These findings indicate an urgent need for scale up of surgical services at all health care levels in Malawi.

Outcome at 1 year in patients with femoral shaft fractures treated with intramedullary nailing or skeletal traction in a low-income country: a prospective observational study of 187 patients in Malawi.

Background and purpose - Intramedullary nailing (IMN) is underutilized in low-income countries (LICs) where skeletal traction (ST) remains the standard of care for femoral shaft fractures. This prospective study compared patient-reported quality of life and functional status after femoral shaft fractures treated with IMN or ST in Malawi. Patients and methods - Adult patients with femoral shaft fractures managed by IMN or ST were enrolled prospectively from 6 hospitals. Quality of life and functional status were assessed using EQ-5D-3L, and the Short Musculoskeletal Function Assessment (SMFA) respectively. Patients were followed up at 6 weeks, 3, 6, and 12 months post-injury. Results - Of 248 patients enrolled (85 IMN, 163 ST), 187 (75%) completed 1-year follow-up (55 IMN, 132 ST). 1 of 55 IMN cases had nonunion compared with 40 of 132 ST cases that failed treatment and converted to IMN (p < 0.001). Quality of life and SMFA Functional Index Scores were better for IMN than ST at 6 weeks, 3 and 6 months, but not at 1 year. At 6 months, 24 of 51 patients in the ST group had returned to work, compared with 26 of 37 in the IMN group (p = 0.02). Interpretation - Treatment with IMN improved early quality of life and function and allowed patients to return to work earlier compared with treatment with ST. Approximately one-third of patients treated with ST failed treatment and were converted to IMN.

TRANSPORTATION BARRIERS TO ACCESS HEALTH CARE FOR SURGICAL CONDITIONS IN MALAWI a cross sectional nationwide household survey.

BACKGROUND: It is estimated that nearly five billion people worldwide do not have access to safe surgery. This access gap disproportionately affects low-and middle-income countries (LMICs). One of the barriers to healthcare in LMICs is access to transport to a healthcare facility. Both availability and affordability of transport can be issues delaying access to health care. This study aimed to describe the main transportation factors affecting access and delay in reaching a facility for health care in Malawi. METHODS: This was a multi-stage, clustered, probability sampling with systematic sampling of households for transportation access to general health and surgical care. Malawi has an estimated population of nearly 18 million people, with a total of 48,233 registered settlements spread over 28 administrative districts. 55 settlements per district were randomly selected for data collection, and 2-4 households were selected, depending on the size. Two persons per household were interviewed. The Surgeons Overseas Assessment of Surgical need (SOSAS) tool was used by trained personnel to collect data during the months of July and August 2016. Analysis of data from 1479 households and 2958 interviewees was by univariate and multivariate methods. RESULTS: Analysis showed that 90.1% were rural inhabitants, and 40% were farmers. No formal employment was reported for 24.9% persons. Animal drawn carts prevailed as the most common mode of transport from home to the primary health facility - normally a health centre. Travel to secondary and tertiary level health facilities was mostly by public transport, 31.5 and 43.4% respectively. Median travel time from home to a health centre was 1 h, and 2.5 h to a central hospital. Thirty nine percent of male and 59% of female head of households reported lack financial resources to go to a hospital. CONCLUSION: In Malawi, lack of suitable transport, finances and prolonged travel time to a health care centre, all pose barriers to timely access of health care. Improving the availability of transport between rural health centres and district hospitals, and between the district and central hospitals, could help overcome the transportation barriers to health care.

Cost-Effectiveness of Two Government District Hospitals in Sub-Saharan Africa.

BACKGROUND: District hospitals in sub-Saharan Africa are in need of investment if countries are going to progress towards universal health coverage, and meet the sustainable development goals and the Lancet Commission on Global Surgery time-bound targets for 2030. Previous studies have suggested that government hospitals are likely to be highly cost-effective and therefore worthy of investment. METHODS: A retrospective analysis of the inpatient logbooks for two government district hospitals in two sub-Saharan African hospitals was performed. Data were extracted and DALYs were calculated based on the diagnosis and procedures undertaken. Estimated costs were obtained based on the patient receiving ideal treatment for their condition rather than actual treatment received. RESULTS: Total cost per DALY averted was 26 (range 17-66) for Thyolo District Hospital in Malawi and 363 (range 187-881) for Bo District Hospital in Sierra Leone. CONCLUSION: This is the first published paper to support the hypothesis that government district hospitals are very cost-effective. The results are within the same range of the US$32.78-223 per DALY averted published for non-governmental hospitals.

Demographics of patients affected by surgical disease in rural hospitals in two sub-Saharan African countries: a retrospective analysis.

BACKGROUND: Awareness is growing of both the importance of surgical disease as a major cause of death and disability in low-income and middle-income countries (LMICs) and the cost-effectiveness of fairly simple surgical interventions. We hypothesised that surgical disease predominantly affects young adults and is therefore significant in both the macroeconomic effect of untreated disease and the microeconomic effects on patients and families in low-resource settings. METHODS: We retrospectively reviewed all admission data from two rural government district hospitals, Bo District Hospital in Sierra Leone and Thyolo District Hospital in Malawi. Both hospitals serve a rural population of roughly 600 000. We analysed data from 3 months in the wet season and 3 months in the dry season for each hospital by careful analysis of all hospital logbook data. For the purposes of this study, a surgical diagnosis was defined as a diagnosis in which the patient should be managed by a surgically trained provider. We analysed all surgical admissions with respect to patient demographics (age and sex), diagnoses, and the procedures undertaken. FINDINGS: In Thyolo, 835 (12·9%) of 6481 hospital admissions were surgical admissions. In Bo, 427 (19·8%) of 2152 hospital admissions were surgical admissions. In Thyolo, if all patients who had undergone a procedure in theatre were admitted overnight, the total number of admissions would have been 6931, with 1344 (19·4%) hospital admissions being surgical and 1282 (18·5%) hospital patients requiring a surgical procedure. In Bo, 133 patients underwent a surgical procedure. This corresponded to 6·18% of all hospital admissions; although notably many of the obstetric admissions were referred to a nearby Médecins Sans Frontières (MSF) hospital for treatment. Analysis of the admission data showed that younger than 16-year-olds accounted for 10·5% of surgical admissions in Bo, and 17·9% of surgical admissions in Thyolo. 16-35-year-olds accounted for 57·3% of all surgical admissions in Bo and 53·5% of all surgical admissions in Thyolo. Men accounted for 53·7% of surgical admissions in Bo and 46·0% of surgical admissions in Thyolo. Analysis of the procedure data showed that younger than 16-year-olds accounted for 7·0% of procedures in Bo and 4·5% of procedures in Thyolo, with 16-35-year-olds accounting for 65·6% of all procedures in Bo and 84·4% of all procedures in Thyolo. Men underwent 63% of all surgical procedures in Bo, but only 7·7% of surgical procedures in Thyolo. This discrepancy is explained by the high rate of maternal surgery in Thyolo, which was not present in Bo because this service was provided at the nearby MSF hospital. INTERPRETATION: Most people affected by disease requiring surgery are young adults. It would be expected that failure to provide surgical care could have long-term adverse effects on both individual and national wealth. FUNDING: The Sir Ratanji Dalal Scholarship from the Royal College of Surgeons of England.

Critical Care in a Tertiary Hospital in Malawi.

BACKGROUND: The provision of critical care services is essential to healthcare systems and increasingly a global health focus, but many hospitals in sub-Saharan Africa are unable to meet this need. Intensive care unit (ICU) mortality in this region is high, but studies describing the provision of critical care services are scarce. METHODS: This was a retrospective cohort study of all patients admitted to the ICU at Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi, between September 1, 2013, and October 17, 2014. We summarized demographics, clinical characteristics, and outcomes, and analyzed factors associated with mortality. RESULTS: Of 390 patients admitted to ICU during the study, 44.9 % of patients were male, and the median age was 22 years (IQR 6-35) years. Although most patients (73.1 %) were admitted with surgical diagnoses, the highest mortality was among patients admitted with sepsis (59.3 %), or obstetric (44.7 %) or medical (40.0 %) diagnoses. Overall ICU mortality was high (23.6 %). CONCLUSIONS: There is a shortage of data describing critical care in low-resource settings, particularly in sub-Saharan Africa. Surgical disease comprises the majority of ICU utilization in this study site, but medical and obstetric illness carried higher ICU mortality. These data may guide strategies for improving critical care in the region.

The Specialist Surgeon Workforce in East, Central and Southern Africa: A Situation Analysis.

BACKGROUND: In East, Central and Southern Africa accurate data on the current surgeon workforce have previously been limited. In order to ensure that the workforce required for sustainable delivery of surgical care is put in place, accurate data on the number, specialty and distribution of specialist-trained surgeons are crucial for all stakeholders in surgery and surgical training in the region. METHODS: The surgical workforce in each of the ten member countries of the College of Surgeons of East, Central and Southern Africa (COSECSA) was determined by gathering and crosschecking data from multiple sources including COSECSA records, medical council registers, local surgical societies records, event attendance lists and interviews of Members and Fellows of COSECSA, and validating this by direct contact with the surgeons identified. This data was recorded and analysed in a cloud-based computerised database, developed as part of a collaboration programme with the Royal College of Surgeons in Ireland. RESULTS: A total of 1690 practising surgeons have been identified yielding a regional ratio of 0.53 surgeons per 100,000 population. A majority of surgeons (64 %) practise in the main commercial city of their country of residence and just 9 % of surgeons are female. More than half (53 %) of surgeons in the region are general surgeons. CONCLUSIONS: While there is considerable geographic variation between countries, the regional surgical workforce represents less than 4 % of the equivalent number in developed countries indicating the magnitude of the human resource challenge to be addressed.

Essential surgery: the way forward.

INTRODUCTION: Very little surgical care is performed in low- and middle-income countries (LMICs). An estimated two billion people in the world have no access to essential surgical care, and non-surgeons perform much of the surgery in remote and rural areas. Surgical care is as yet not recognized as an integral aspect of primary health care despite its self-demonstrated cost-effectiveness. We aimed to define the parameters of a public health approach to provide surgical care to areas in most need. METHODS: Consensus meetings were held, field experience was collected via targeted interviews, and a literature review on the current state of essential surgical care provision in Sub-Saharan Africa (SSA) was conducted. Comparisons were made across international recommendations for essential surgical interventions and a consensus-driven list was drawn up according to their relative simplicity, resource requirement, and capacity to provide the highest impact in terms of averted mortality or disability. RESULTS: Essential Surgery consists of basic, low-cost surgical interventions, which save lives and prevent life-long disability or life-threatening complications and may be offered in any district hospital. Fifteen essential surgical interventions were deduced from various recommendations from international surgical bodies. Training in the realm of Essential Surgery is narrow and strict enough to be possible for non-physician clinicians (NPCs). This cadre is already active in many SSA countries in providing the bulk of surgical care. CONCLUSION: A basic package of essential surgical care interventions is imperative to provide structure for scaling up training and building essential health services in remote and rural areas of LMICs. NPCs, a health cadre predominant in SSA, require training, mentoring, and monitoring. The cost of such training is vastly more efficient than the expensive training of a few polyvalent or specialist surgeons, who will not be sufficient in numbers within the next few generations. Moreover, these practitioners are used to working in the districts and are much less prone to gravitate elsewhere. The use of these NPCs performing "Essential Surgery" is a feasible route to deal with the almost total lack of primary surgical care in LMICs.

Moving from data collection to application: a systematic literature review of surgical capacity assessments and their applications.

BACKGROUND: Over the past decade, assessments of surgical capacity in low- and middle-income countries (LMICs) have contributed to our understanding of barriers to the delivery of surgical services in a number of countries. It is yet unclear, however, how the findings of these assessments have been applied and built upon within the published literature. METHODS: A systematic literature review of surgical capacity assessments in LMICs was performed to evaluate current levels of understanding of global surgical capacity and to identify areas for future study. A reverse snowballing method was then used to follow-up citations of the identified studies to assess how this research has been applied and built upon in the literature. RESULTS: Twenty-one papers reporting the findings of surgical capacity assessments conducted in 17 different LMICs in South Asia, East Asia and Pacific, Latin America and the Caribbean, and sub-Saharan Africa were identified. These studies documented substantial deficits in human resources, infrastructure, equipment, and supplies. Only seven additional papers were identified which applied or built upon the studies. Among these, capacity assessment findings were most commonly used to develop novel tools and intervention strategies, but they were also used as baseline measurements against which updated capacity assessments were compared. CONCLUSIONS: While the global surgery community has made tremendous progress in establishing baseline values of surgical capacity in LMICs around the world, further work is necessary to build upon and apply the foundational knowledge established through these efforts. Capacity assessment data should be coordinated and used in ongoing research efforts to monitor and evaluate progress in global surgery and to develop targeted intervention strategies. Intervention strategy development may also be further incorporated into the evaluation process itself.

Cost-effectiveness of surgery in low- and middle-income countries: a systematic review.

BACKGROUND: There is increasing interest in provision of essential surgical care as part of public health policy in low- and middle-income countries (LMIC). Relatively simple interventions have been shown to prevent death and disability. We reviewed the published literature to examine the cost-effectiveness of simple surgical interventions which could be made available at any district hospital, and compared these to standard public health interventions. METHODS: PubMed and EMBASE were searched using single and combinations of the search terms "disability adjusted life year" (DALY), "quality adjusted life year," "cost-effectiveness," and "surgery." Articles were included if they detailed the cost-effectiveness of a surgical intervention of relevance to a LMIC, which could be made available at any district hospital. Suitable articles with both cost and effectiveness data were identified and, where possible, data were extrapolated to enable comparison across studies. RESULTS: Twenty-seven articles met our inclusion criteria, representing 64 LMIC over 16 years of study. Interventions that were found to be cost-effective included cataract surgery (cost/DALY averted range US$5.06-$106.00), elective inguinal hernia repair (cost/DALY averted range US$12.88-$78.18), male circumcision (cost/DALY averted range US$7.38-$319.29), emergency cesarean section (cost/DALY averted range US$18-$3,462.00), and cleft lip and palate repair (cost/DALY averted range US$15.44-$96.04). A small district hospital with basic surgical services was also found to be highly cost-effective (cost/DALY averted 1 US$0.93), as were larger hospitals offering emergency and trauma surgery (cost/DALY averted US$32.78-$223.00). This compares favorably with other standard public health interventions, such as oral rehydration therapy (US$1,062.00), vitamin A supplementation (US$6.00-$12.00), breast feeding promotion (US$930.00), and highly active anti-retroviral therapy for HIV (US$922.00). CONCLUSIONS: Simple surgical interventions that are life-saving and disability-preventing should be considered as part of public health policy in LMIC. We recommend an investment in surgical care and its integration with other public health measures at the district hospital level, rather than investment in single disease strategies.

Human leukocyte antigen-DQA1*04:01 and rs2040406 variants are associated with elevated risk of childhood Burkitt lymphoma.

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.

The Socioeconomic consequences of femoral shaft fracture for patients in Malawi.

Background: Femoral shaft fractures are common in Malawi, with an annual incidence of 44 per 100,000 people. Inadequate treatment and delayed presentation often result in functional, biopsychosocial, and financial challenges for patients. The purpose of this study was to examine the socioeconomic consequences of femoral shaft fractures for patients in Malawi. Methods: This study of 42 patients was part of a larger study that prospectively examined quality of life. Questionnaires were distributed to patients at 1-year follow-up following femoral shaft fracture treatment. Patients reported pre- and post-injury standard of living and financial well-being. Results: Patients reported relatively high transportation costs to and from the hospital. One year after injury, 17 patients (40%) had not returned to work. Of the 25 (60%) who had returned, 5 (20%) changed jobs due to their injury, all reported decreased productivity. Household income decreased for 29% of patients. 20 (49%) of 41 patients reported food insecurity in the week prior to questionnaire completion. Many patients reported changing their residence, borrowing money, selling personal property, and unenrolling children from school due to financial hardship caused by their injury. Conclusion: While the Malawian public healthcare system is free at the point of care, it lacks the financial risk protection that is essential to universal health coverage (UHC). In this study, we found that the indirect costs of care due to femoral shaft fractures had substantial socioeconomic consequences on the majority of patients and their families. Increased investment of financial and human capital should be made into capacity building and preventative measures to decrease the burden of injury, increase access to care, improve care delivery, and provide financial risk protection for patients with traumatic injuries in Malawi.

IFNL4 Genotypes and Risk of Childhood Burkitt Lymphoma in East 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.

Mosaic chromosomal alterations in peripheral blood leukocytes of children in sub-Saharan Africa.

In high-income countries, mosaic chromosomal alterations in peripheral blood leukocytes are associated with an elevated risk of adverse health outcomes, including hematologic malignancies. We investigate mosaic chromosomal alterations in sub-Saharan Africa among 931 children with Burkitt lymphoma, an aggressive lymphoma commonly characterized by immunoglobulin-MYC chromosomal rearrangements, 3822 Burkitt lymphoma-free children, and 674 cancer-free men from Ghana. We find autosomal and X chromosome mosaic chromosomal alterations in 3.4% and 1.7% of Burkitt lymphoma-free children, and 8.4% and 3.7% of children with Burkitt lymphoma (P-values = 5.7×10-11 and 3.74×10-2, respectively). Autosomal mosaic chromosomal alterations are detected in 14.0% of Ghanaian men and increase with age. Mosaic chromosomal alterations in Burkitt lymphoma cases include gains on chromosomes 1q and 8, the latter spanning MYC, while mosaic chromosomal alterations in Burkitt lymphoma-free children include copy-neutral loss of heterozygosity on chromosomes 10, 14, and 16. Our results highlight mosaic chromosomal alterations in sub-Saharan African populations as a promising area of research.