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.
View Article and Find Full Text PDFUnlabelled: The genetic subtypes of Burkitt lymphoma have been defined, but the role of epigenetics remains to be comprehensively characterized. We searched genomic DNA from 218 patients across four continents for recurrent DNA methylation patterns and their associations with clinical and molecular features. We identified DNA methylation patterns that were not fully explained by the Epstein-Barr virus status or mutation status, leading to two epitypes described here as HypoBL and HyperBL.
View Article and Find Full Text PDFThe addition of rituximab to the chemotherapy backbone was shown to significantly improve outcomes of children with aggressive high-grade lymphomas in high-income countries. However, data on its safety and efficacy in children with Epstein-Barr virus (EBV)-positive Burkitt lymphoma (BL) are limited. We conducted a prospective nonrandomized observational study in East African patients aged ≤25 years with confirmed BL.
View Article and Find Full Text PDFIntroduction: Burkitt lymphoma (BL) is an aggressive non-Hodgkin lymphoma associated with Plasmodium falciparum and Epstein-Barr virus, both of which affect metabolic pathways. The metabolomic patterns of BL is unknown.
Materials And Methods: We measured 627 metabolites in pre-chemotherapy treatment plasma samples from 25 male children (6-11 years) with BL and 25 cancer-free area- and age-frequency-matched male controls from the Epidemiology of Burkitt Lymphoma in East African Children and Minors study in Uganda using liquid chromatography-tandem mass spectrometry.
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.
View Article and Find Full Text PDFJ Interferon Cytokine Res
September 2023
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 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 (-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.
View Article and Find Full Text PDFJ Acquir Immune Defic Syndr
October 2023
Objectives: Adolescent girls and young women younger than 25 years (AGYW) account for disproportionate HIV infections in sub-Saharan Africa. Impacts of war in Northern Uganda continue to affect HIV-related health and wellbeing of young people postconflict. Prevalence and incidence of HIV infection were estimated, and factors associated with HIV prevalence among sexually active AGYW in Northern Uganda were investigated.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
January 2023
Endemic Burkitt lymphoma (eBL) is a pediatric cancer coendemic with malaria in sub-Saharan Africa, suggesting an etiological link between them. However, previous cross-sectional studies of limited geographic areas have not found a convincing association. We used spatially detailed data from the Epidemiology of Burkitt Lymphoma in East African Children and Minors (EMBLEM) study to assess this relationship.
View Article and Find Full Text PDFNat Rev Dis Primers
December 2022
Burkitt lymphoma (BL) is an aggressive form of B cell lymphoma that can affect children and adults. The study of BL led to the identification of the first recurrent chromosomal aberration in lymphoma, t(8;14)(q24;q32), and subsequent discovery of the central role of MYC and Epstein-Barr virus (EBV) in tumorigenesis. Most patients with BL are cured with chemotherapy but those with relapsed or refractory disease usually die of lymphoma.
View Article and Find Full Text PDFBackground: From 1986 to 2006, Northern Uganda experienced an atrocious civil war between the Lord's Resistance Army (LRA) and the Ugandan government. Acholi people living in the region continue to be impacted by trauma sequelae of the war and a wide range of daily stressors including poverty, hunger, and high rates of HIV infection. To date, there is a dearth of gender-differentiated mental health research in this post-conflict setting.
View Article and Find Full Text PDFBackground: The capacity for invasive tissue biopsies followed by histopathology diagnosis in sub-Saharan Africa is severely limited. Consequently, many cancer patients are diagnosed late and outcomes are poor. Here, we propose to evaluate circulating tumour (ct) DNA analysis ("liquid biopsy"), a less invasive and faster approach to diagnose endemic EBV-driven lymphomas (EBVL) in East Africa.
View Article and Find Full Text PDFUnlabelled: Epstein-Barr virus (EBV) is associated with endemic Burkitt lymphoma (eBL), but the contribution of EBV variants is ill-defined. Studies of EBV whole genome sequences (WGS) have identified phylogroups that appear to be distinct for Asian versus non-Asian EBV, but samples from BL or Africa, where EBV was first discovered, are under-represented. We conducted a phylogenetic analysis of EBV WGS and sequences obtained primarily from BL patients in Africa and representative non-African EBV from other conditions or regions using data from GenBank, Sequence Read Archive, or Genomic Data Commons for the Burkitt Lymphoma Genome Sequencing Project (BLGSP) to generate data to support the use of a simpler biomarker of geographic or phenotypic associations.
View Article and Find Full Text PDFFront Oncol
December 2021
Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in regions of equatorial Africa where malaria is holoendemic. The tumor is consistently associated with Epstein-Barr virus (EBV). Screening for EBV DNA in plasma in a high-risk population in Hong Kong has been shown to be useful in facilitating the early diagnosis of nasopharyngeal carcinoma, another EBV-associated tumor.
View Article and Find Full Text PDFCholecystocolonic fistula is a rare condition often diagnosed intraoperatively, requiring an adequate set of knowledge and skills to allow safe intraoperative change of prior planned surgery and alleviate significant morbidity.
View Article and Find Full Text PDFEClinicalMedicine
June 2020
Background: Civil war in Northern Uganda resulted in widespread atrocities, human rights violations, and death, and caused millions to flee to internally displaced persons camps. War-related traumas combined with difficulties accessing HIV prevention and health services has led to extreme HIV-related vulnerability among conflict-affected people who survived the war. Objectives were to (1) determine HIV incidence among conflict-affected people in Northern Uganda and (2) identify vulnerabilities associated with HIV infection.
View Article and Find Full Text PDFPlatelet counts are decreased in Plasmodium falciparum malaria, which is aetiologically linked with endemic Burkitt lymphoma (eBL). However, the pattern of platelet counts in eBL cases is unknown. We studied platelet counts in 582 eBL cases and 2 248 controls enrolled in a case-control study in Uganda, Tanzania and Kenya (2010-2016).
View Article and Find Full Text PDFEndemic 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.
View Article and Find Full Text PDFWe studied our 30-day postoperative outcomes in patients with non-traumatic gastroduodenal perforation (NTGDP) in Mbarara Regional Referral Hospital, southwestern Uganda. We conducted a one-year prospective study of patients who underwent exploratory laparotomy for suspected NTGDP between June 2016 and July 2017. Twenty-nine patients had NTGDP, the male-to-female ratio was 3:1 and median age was 60 years (range = 13-80 years).
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