Assessment of mixed plasmodium falciparum sera5 infection in endemic burkitt lymphoma : A case-control study in Malawi

Background: Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in Africa and is linked to Plasmodium falciparum (Pf) malaria infection, one of the most common and deadly childhood infections in Africa; however, the role of Pf genetic diversity is unclear. A potential role of Pf genetic diversity in eBL has been suggested by a correlation of age-specific patterns of eBL with the complexity of Pf infection in Ghana, Uganda, and Tanzania, as well as a finding of significantly higher Pf genetic diversity, based on a sensitive molecular barcode assay, in eBL cases than matched controls in Malawi. We examined this hypothesis by measuring diversity in Pf-serine repeat antigen-5 (Pfsera5), an antigenic target of blood-stage immunity to malaria, among 200 eBL cases and 140 controls, all Pf polymerase chain reaction (PCR)-positive, in Malawi. Methods: We performed Pfsera5 PCR and sequencing (~3.3 kb over exons II–IV) to determine single or mixed PfSERA5 infection status. The patterns of Pfsera5 PCR positivity, mixed infection, sequence variants, and haplotypes among eBL cases, controls, and combined/pooled were analyzed using frequency tables. The association of mixed Pfsera5 infection with eBL was evaluated using logistic regression, controlling for age, sex, and previously measured Pf genetic diversity. Results: Pfsera5 PCR was positive in 108 eBL cases and 70 controls. Mixed PfSERA5 infection was detected in 41.7% of eBL cases versus 24.3% of controls; the odds ratio (OR) was 2.18, and the 95% confidence interval (CI) was 1.12–4.26, which remained significant in adjusted results (adjusted odds ratio [aOR] of 2.40, 95% CI of 1.11–5.17). A total of 29 nucleotide variations and 96 haplotypes were identified, but these were unrelated to eBL. Conclusions: Our results increase the evidence supporting the hypothesis that infection with mixed Pf infection is increased with eBL and suggest that measuring Pf genetic diversity may provide new insights into the role of Pf infection in eBL

Impact of infection with human immunodeficiency virus-1 (HIV) on the risk of cancer among children in Malawi - preliminary findings

<p>Abstract</p> <p>Background</p> <p>The impact of infection with HIV on the risk of cancer in children is uncertain, particularly for those living in sub-Saharan Africa. In an ongoing study in a paediatric oncology centre in Malawi, children (aged ≤ 15 years) with known or suspected cancers are being recruited and tested for HIV and their mothers or carers interviewed. This study reports findings for children recruited between 2005 and 2008.</p> <p>Methods</p> <p>Only children with a cancer diagnosis were included. Odds ratios (OR) for being HIV positive were estimated for each cancer type (with adjustment for age (<5 years, ≥ 5 years) and sex) using children with other cancers and non-malignant conditions as a comparison group (excluding the known HIV-associated cancers, Kaposi sarcoma and lymphomas, as well as children with other haematological malignancies or with confirmed non-cancer diagnoses).</p> <p>Results</p> <p>Of the 586 children recruited, 541 (92%) met the inclusion criteria and 525 (97%) were tested for HIV. Overall HIV seroprevalence was 10%. Infection with HIV was associated with Kaposi sarcoma (29 cases; OR = 93.5, 95% CI 26.9 to 324.4) and with non-Burkitt, non-Hodgkin lymphoma (33 cases; OR = 4.4, 95% CI 1.1 to 17.9) but not with Burkitt lymphoma (269 cases; OR = 2.2, 95% CI 0.8 to 6.4).</p> <p>Conclusions</p> <p>In this study, only Kaposi sarcoma and non-Burkitt, non-Hodgkin lymphoma were associated with HIV infection. The endemic form of Burkitt lymphoma, which is relatively frequent in Malawi, was not significantly associated with HIV. While the relatively small numbers of children with other cancers, together with possible limitations of diagnostic testing may limit our conclusions, the findings may suggest differences in the pathogenesis of HIV-related malignancies in different parts of the world.</p

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

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

Associations between Burkitt Lymphoma among Children in Malawi and Infection with HIV, EBV and Malaria: Results from a Case-Control Study

Background: Burkitt lymphoma, a childhood cancer common in parts of sub-Saharan Africa, has been associated with Epstein Barr Virus (EBV) and malaria, but its association with human immunodeficiency virus (HIV) is not clear.Methodology/Principal Findings: We conducted a case-control study of Burkitt lymphoma among children (aged <= 15 years) admitted to the pediatric oncology unit in Blantyre, Malawi between July 2005 and July 2006. Cases were 148 children diagnosed with Burkitt lymphoma and controls were 104 children admitted with non-malignant conditions or cancers other than hematological malignancies and Kaposi sarcoma. Interviews were conducted and serological samples tested for antibodies against HIV, EBV and malaria. Odds ratios for Burkitt lymphoma were estimated using unconditional logistic regression adjusting for sex, age, and residential district. Cases had a mean age of 7.1 years and 60% were male. Cases were more likely than controls to be HIV positive (Odds ratio (OR)) = 12.4, 95% Confidence Interval (CI) 1.3 to 116.2, p = 0.03). ORs for Burkitt lymphoma increased with increasing antibody titers against EBV (p = 0.001) and malaria (p = 0.01). Among HIV negative participants, cases were thirteen times more likely than controls to have raised levels of both EBV and malaria antibodies (OR = 13.2; 95% CI 3.8 to 46.6; p = 0.001). Reported use of mosquito nets was associated with a lower risk of Burkitt lymphoma (OR = 0.2, 95% CI, 0.03 to 0.9, p = 0.04).Conclusions: Our findings support prior evidence that EBV and malaria act jointly in the pathogenesis of Burkitt lymphoma, suggesting that malaria prevention may decrease the risk of Burkitt lymphoma. HIV may also play a role in the etiology of this childhood tumor

The demographics of patients affected by surgical disease in district hospitals in two sub-Saharan African countries:a retrospective descriptive analysis

BACKGROUND: There is a growing awareness of the importance of surgical disease within global health. We hypothesised that surgical disease in low income countries predominantly affects young adults and may therefore have a significant economic impact. METHODS: We retrospectively reviewed all surgical admission data from two rural government district hospitals in two different sub-Saharan African countries over a 6-month period. We analysed all surgical admissions with respect to patient demographics (age and gender), diagnosis, and procedure performed. RESULTS: Surgical admissions accounted for 12.9 and 19.8 % of all hospital admissions in Malawi and Sierra Leone respectively. 18.5 and 6.2 % of all hospital patients required a surgical procedure in Malawi and Sierra Leone respectively, with the low number in Sierra Leone accounted for in that many of the obstetric admissions were referred to a nearby Medicins Sans Frontiers (MSF) hospital for treatment. 17.9 and 10.5 % of surgical admissions were under the age of 16 in Malawi and Sierra Leone respectively, with 16–35 year olds accounting for 57.3 % of surgical admissions in Sierra Leone and 53.5 % in Malawi. Men accounted for 53.7 and 46.0 % of surgical admissions in Sierra Leone and Malawi respectively. An unexpected finding was the high level of patients who absconded from hospital in Sierra Leone after diagnosis but before treatment. This involved 11.8 % of all surgical patients, including 38 % with a bowel obstruction, 39 % with peritonitis and 20 % with ectopic pregnancy. CONCLUSIONS: Most people affected by disease requiring surgery are young adults and this may have significant economic implications

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

Nontraumatic Myelopathy in Malawi: A Prospective Study in an Area with High HIV Prevalence

Nontraumatic myelopathy causes severe morbidity and is not uncommon in Africa. Clinically, patients often present with paraplegia, and extrinsic cord compression and transverse myelitis are most common causes. Data on exact pathogenesis are scanty because of limitations in diagnostic methods. In Queen Elizabeth Central Hospital, Blantyre, Malawi, we recorded consecutive patients presenting with nontraumatic paraplegia for maximally 6 months between January and July 2010 and from March to December 2011. The diagnostic workup included imaging and examining blood, stool, urine, sputum, and cerebrospinal fluid (CSF) samples for infection. After discharge, additional diagnostic tests, including screening for virus infections, borreliosis, syphilis, and schistosomiasis, were carried out in the Netherlands. The clinical diagnosis was, thus, revised in retrospect with a more accurate final differential diagnosis. Of 58 patients included, the mean age was 41 years (range, 12-83 years) and the median time between onset and presentation was 18 days (range, 0-121 days), and of 55 patients tested, 23 (42%) were HIV positive. Spinal tuberculosis (n = 24, 41%), tumors (n = 16, 28%), and transverse myelitis (n = 6, 10%) were most common; in six cases (10%), no diagnosis could be made. The additional tests yielded evidence for CSF infection with Schistosoma, Treponema pallidum, Epstein-Barr virus (EBV), HHV-6, HIV, as well as a novel cyclovirus. The diagnosis of the cause of paraplegia is complex and requires access to an magnetic resonance imaging (MRI) scan and other diagnostic (molecular) tools to demonstrate infection. The major challenge is to confirm the role of detected pathogens in the pathophysiology and to design an effective and affordable diagnostic approach

Use of mosquito nets in Burkitt lymphoma cases and controls.

1<p>Adjusted for child age, sex and residence.</p>2<p>Numbers reduced towards end of study because questions introduced later.</p

Burkitt lymphoma cases and controls recruitment flow chart.

<p>Burkitt lymphoma cases and controls recruitment flow chart.</p