Variation in the Human Leukocyte Antigen system and risk for endemic Burkitt lymphoma in northern Uganda.

Endemic Burkitt lymphoma (eBL) is an aggressive childhood B-cell lymphoma associated with Plasmodium falciparum (Pf) malaria and Epstein-Barr virus (EBV) infections. Variation in the Human Leukocyte Antigen (HLA) system is suspected to play a role, but assessments using less accurate serology-based HLA typing techniques in small studies yielded conflicting results. We studied 200 eBL cases and 400 controls aged 0-15 years enrolled in northern Uganda and typed by accurate high-resolution HLA sequencing methods. HLA results were analyzed at one- or two-field resolution. Odds ratios and 95% confidence intervals (aOR, 95% CI) for eBL risk associated with common HLA alleles versus alleles that were rare (<1%) or differed by <2% between the cases and controls as the reference category, were estimated using multiple logistic regression adjusting for age, sex, microgeography, region, malaria positivity and treatment history, and genetic variants associated with eBL. Compared to the controls, eBL cases had a lower frequency of HLA-A*02 (aOR = 0·59, 95% CI 0·38-0·91), HLA-B*41 (aOR = 0·36, 95% CI 0·13-1·00), and HLA-B*58 alleles (aOR = 0·59, 95% CI 0·36-0·97). eBL cases had a lower frequency of HLA-DPB1 homozygosity (aOR = 0·57, 95% CI 0·40-0·82) but a higher frequency of HLA-DQA1 homozygosity (aOR = 2·19, 95% CI 1·42-3·37). Our results suggest that variation in HLA may be associated with eBL risk.

Evaluating the cost-effectiveness of combination antiretroviral therapy for the prevention of mother-to-child transmission of HIV in Uganda.

OBJECTIVE: To model the cost-effectiveness in Uganda of combination antiretroviral therapy (ART) to prevent mother-to-child transmission of human immunodeficiency virus (HIV). METHODS: The cost-effectiveness of ART was evaluated on the assumption that ART reduces the risk of an HIV-positive pregnant woman transmitting HIV to her baby from 40% (when the woman is left untreated) to 25.8%, 17.4% and 3.8%, respectively, when the woman is given: (i) single-dose nevirapine (at an estimated total drug cost of 0.06 United States dollars [US$]); (ii) dual therapy with zidovudine and lamivudine for 7 weeks (at a total drug cost of US$ 15.63); or (iii) ART for 18 months (at a total annual cost of US$ 469.77). Lifetime ART (US$ 6883), recommended for pregnant women with < 350 CD4+ T lymphocytes per mm(3), was assumed to give the same reduction in transmission risk in each subsequent pregnancy. FINDINGS: Compared with single-dose nevirapine, dual therapy and no therapy, 18 months of ART averted 5.21, 3.22 and 8.58 disability-adjusted life years (DALYs), respectively, at a cost of US$ 46, US$ 99 and US$ 34 per DALY averted. The corresponding figures for lifetime ART are, respectively, 19.20, 11.87 and 31.60 DALYs averted, at a cost of US$ 205, US$ 354 and US$ 172 per DALY averted. CONCLUSION: In Uganda, ART appears highly cost-effective for the prevention of mother-to-child HIV transmission, even if continued over the patients' lifetimes. Given the additional public health benefits of ART, efforts to ensure that all HIV-positive pregnant women have access to lifelong ART should be intensified.

Cause of death distribution with InterVA and physician coding in a rural area of Burkina Faso.

OBJECTIVES: To compare the cause of death distribution using the Physician Coded Verbal Autopsy approach versus the Interpreting Verbal Autopsy model, based on information from a French verbal autopsy questionnaire, in rural north-western Burkina Faso. METHODS: Data from 5649 verbal autopsy questionnaires reviewed by local physicians at the Nouna Health and Demographic Surveillance Site between 1998 and 2007 were considered for analyses. Information from VA interviews was extracted to create a set of standard indicators needed to run the Interpreting Verbal Autopsy model. Cause-specific mortality fractions were used to compare Physician Coded Verbal Autopsy and Interpreting Verbal Autopsy results. RESULTS: At the population level, 62.5% of causes of death using the Interpreting Verbal Autopsy model corresponded with those determined by two or three physicians. Although seven of the 10 main causes of death were present in both approaches, the comparison of percentages of single causes of death shows discrepancies, dominated by higher malaria rates found in the Physician Coded Verbal Autopsy approach. CONCLUSION: Our results confirm that national mortality statistics, which are partly based on verbal autopsies, must be carefully interpreted. Difficulties in determining malaria as cause of death in holoendemic malaria regions might result in higher discrepancies than those in non-endemic areas. As neither Physician Coded Verbal Autopsy nor Interpreting Verbal Autopsy results represent a gold standard, uncertainty levels with either procedure are high.

Cost-effectiveness of early initiation of first-line combination antiretroviral therapy in Uganda.

BACKGROUND: Ugandan national guidelines recommend initiation of combination antiretroviral therapy (cART) at CD4+ T cell (CD4) count below 350 cell/µl, but the implementation of this is limited due to availability of medication. However, cART initiation at higher CD4 count increases survival, albeit at higher lifetime treatment cost. This analysis evaluates the cost-effectiveness of initiating cART at a CD4 count between 250-350 cell/µl (early) versus <250 cell/µl (delayed). METHODS: Life expectancy of cART-treated patients, conditional on baseline CD4 count, was modeled based on published literature. First-line cART costs $192 annually, with an additional $113 for patient monitoring. Delaying initiation of cART until the CD4 count falls below 250 cells/µl would incur the cost of the bi-annual CD4 count tests and routine maintenance care at $85 annually. We compared lifetime treatment costs and disability adjusted life-expectancy between early vs. delayed cART for ten baseline CD4 count ranges from 250-350 cell/µl. All costs and benefits were discounted at 3% annually. RESULTS: Treatment delay varied from 6-18 months. Early cART initiation increased life expectancy from 1.5-3.5 years and averted 1.33-3.10 disability adjusted life years (DALY's) per patient. Lifetime treatment costs were $4,300-$5,248 for early initiation and $3,940-$4,435 for delayed initiation. The cost/DALY averted of the early versus delayed start ranged from $260-$270. CONCLUSIONS: In HIV-positive patients presenting with CD4 count between 250-350 cells/µl, immediate initiation of cART is a highly cost-effective strategy using the recommended one-time per capita GDP threshold of $490 reported for Uganda. This would constitute an efficient use of scarce health care funds.

Improving Iron and Folic Acid Supplementation Among Pregnant Women: An Implementation Science Approach in East-Central Uganda.

INTRODUCTION: To address maternal iron-deficiency anemia and low uptake of iron and folic acid supplementation (IFAS) among antenatal care (ANC) clinic attendees in East-Central Uganda, the Anemia Implementation Science Initiative embedded enhanced quality improvement (QI) activities into an integrated health project utilizing QI methodologies. METHODS: To address 2 bottlenecks of stock-outs and inadequate health education for pregnant women during ANC, an enhanced QI intervention was implemented from July 2019 to September 2020 in 2 districts. We conducted a mixed-methods effectiveness quasi-experimental study to assess whether the intervention increased the availability of IFAS in the intervention districts. We used longitudinal facility-level data from 2 treatment districts and 1 comparison district for the quantitative results. Difference-in-difference estimation was used to measure the impact of the intervention on IFAS health education and IFA availability at the health facility. We used logistic regression modeling to control for factors associated with IFAS uptake and potential differences in baseline values. Researchers conducted exit interviews with ANC clients and in-depth interviews with providers and district managers for greater insights into the implementation process. RESULTS: The intervention increased the probability, at a statistically significant level, of pregnant women both receiving IFAS and receiving health education on IFAS during ANC. According to inter-viewees, the intervention approach improved stakeholder engagement and buy-in, which brought about change at all levels of the health system. DISCUSSION: The intervention successfully addressed the 2 main bottlenecks to availability of IFAS for pregnant women attending ANC-inadequate provision of IFAS education and a weak drug quantification process. Even without additional funds to purchase commodities, this approach improved district capacity to advocate for and manage IFAS commodities. It could also be used to strengthen overall ANC quality.