Eric Borgstein

Spectrum and presentation of pediatric malignancies in the HIV era: Experience from Blantyre, Malawi, 1998–2003

Data on childhood cancers in Africa are sparse, particularly since the spread of HIV. We aimed to document the frequency of pediatric cancers presenting to a large central hospital in Malawi, detailing the presenting features, initial investigations, and HIV status of these children.

Promiscuous expression of Epstein-Barr virus genes in Burkitt's lymphoma from the central African country Malawi

Primary BL in Malawian children has a very high frequency association, approaching 100%, with the human herpesvirus EBV. A detailed study carried out on viral gene expression in these tumours, using both fresh material and methanol‐fixed FNAs, showed, contrary to prediction, that most belong to a variant “class II” latency category, with lytic cycle–related genes also expressed. That is, in addition to EBNA1 expression, membrane proteins (LMP1/2A), immediate early (BZLF1) and early (IR2 and IR4) genes, a putative viral oncogene (BARF1), CST (BART) antisense transcripts and the viral bcl‐2 homologue are expressed in a high proportion of the BLs. Most, but not all, express the small viral (EBER) RNAs. Two other significant observations were made: (i) in addition to expression of cellular cytokine (IL‐10) transcripts in all tumours investigated, the normally silent viral IL‐10 homologue was expressed in some tumours; (ii) whereas EBNA1 expression from its restricted Qp promoter was generally observed, the nonrestricted Cp/Wp promoter was also active in some tumours. Viral gene expression in the Malawian [endemic (e)] BLs appears to be more promiscuous than predicted from other studies, but expression accords with the cytopathologic picture of eBLs as a rapidly proliferating cell population accompanied by considerable necrosis, and a clinically diverse disease. A small‐scale study of relapse Malawian BLs revealed a different picture of viral association, more akin to systemic BL than eBL, where EBV appears to be absent or present only at very low levels. The significance of these findings is considered.

Systematic Review of Met and Unmet Need of Surgical Disease in Rural Sub-Saharan Africa

BackgroundLittle is known about the burden of surgical disease in rural sub-Saharan Africa, where district and rural hospitals are the main providers of care. The present study sought to analyze what is known about the met and unmet need of surgical disease.MethodsThe PubMed and EMBASE databases were searched for studies of surveys in rural areas, information on surgical admissions, and operations performed within rural and district hospitals. Data were extrapolated to calculate the amount of surgical disease per 100,000 population and the number of operations performed per 100,000 population. These extrapolations were used to estimate the total, the met, and the unmet need of surgical disease.ResultsThe estimated overall incidence of nonfatal injury is at least 1,690/100,000 population per year. Morbidity as a result of injury is up to 190/100,000 population per year, and the annual mortality from injury is 53–92/100,000. District hospitals perform 6 fracture reductions (95% CI: 0.1–12)/100,000 population per year and 14 laparotomies (95% CI: 7–21)/100,000 per year. The incidence of peritonitis and bowel obstruction is unknown, although it may be as high as 1,364/100,000 population for the acute abdomen. The annual total need for inguinal hernia repair is estimated to be a minimum of 205/100,000 population. The average district hospital performs 30 hernia repairs (95% CI: 18–41)/100,000 population per year, leaving an unmet need of 175/100,000 population annually.ConclusionsDistrict hospitals are not meeting the surgical needs of the populations they serve. Urgent intervention is required to build up their capacity, to train healthcare personnel in safe surgery and anesthesia, and to overcome obstacles to timely emergency care.

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 2000 Burkitt lymphoma trial in Malawi.

We previously reported 57% 12‐month event free survival (EFS) in Malawian children with stage I to III Burkitt lymphoma (BL) with an intermediate dose chemotherapy protocol lasting 77 days. This protocol was shortened to 42 days and evaluated in children with stage I to IV disease for EFS and toxicity.

Mixed patterns of transmission of human herpesvirus-8 (Kaposi's sarcoma-associated herpesvirus) in Malawian families.

To study transmission patterns of human herpesvirus-8 (HHV-8) (Kaposis sarcoma-associated herpesvirus) in families in Malawi, nucleotide sequences derived from two hypervariable loci of the HHV-8 genome, the V1 and V2 regions of open reading frame K1 (K1/V1 and K1/V2, respectively), were amplified from blood and mouth rinse samples of 22 patients with treated and untreated Kaposis sarcoma (KS) and their first-degree relatives (n=67). In patients with KS, vincristine therapy was significantly associated with non-detectability of circulating, but not oral, K1/V1 DNA. Intra-familial K1/V1 phylogenetic comparisons of eight families were possible. Both identical and non-identical sequences were observed between family members, suggesting transmission of HHV-8 along both intra- and extra-familial transmission routes.

SIOP PODC: Clinical Guidelines for the Management of Children With Wilms Tumour in a Low Income Setting

Wilms tumour is a relatively common and curable paediatric tumour. Known challenges to cure in low income countries are late presentation with advanced disease, malnutrition, failure to complete treatment and limited facilities. In this article, management recommendations are given for a low income setting where only the minimal requirements for treatment with curative intent are available (setting 1). These include general management, supportive care, social support and registration of patients. Recommendations specific for Wilms tumour care include diagnostic procedures with emphasis on the role of ultrasonography, preoperative chemotherapy with a reduced dosage for malnourished children and postoperative chemotherapy based on surgical staging. Pediatr Blood Cancer 2013; 60: 5–11.

Surgical and anaesthetic capacity of hospitals in Malawi: key insights

Background Surgery is increasingly recognized as an important driver for health systems strengthening, especially in developing countries. To facilitate quality improvement initiatives, baseline knowledge of capacity for surgical, anaesthetic, emergency and obstetric care is critical. In partnership with the Malawi Ministry of Health, we quantified government hospitals’ surgical capacity through workforce, infrastructure and health service delivery components. Methods From November 2012 to January 2013, we surveyed district and mission hospital administrators and clinical staff onsite using a modified version of the Personnel, Infrastructure, Procedures, Equipment and Supplies (PIPES) tool from Surgeons OverSeas. We calculated percentage of facilities demonstrating adequacy of the assessed components, surgical case rates, operating theatre density and surgical workforce density. Results Twenty-seven government hospitals were surveyed (90% of the district hospitals, all central hospitals). Of the surgical workforce surveyed (n = 370), 92.7% were non-surgeons and 77% were clinical officers (COs). Of the 109 anaesthesia providers, 95.4% were non-physician anaesthetists (anaesthesia COs or ACOs). Non-surgeons and ACOs were the only providers of surgical services and anaesthetic services in 85% and 88.9% of hospitals, respectively. No specialists served the district hospitals. All of the hospitals experienced periods without external electricity. Most did not always have a functioning generator (78.3% district, 25% central) or running water (82.6%, 50%). None of the district hospitals had an Intensive Care Unit (ICU). Cricothyroidotomy, bowel resection and cholecystectomy were not done in over two-thirds of hospitals. Every hospital provided general anaesthesia but some did not always have a functioning anaesthesia machine (52.2%, 50%). Surgical rate, operating theatre density and surgical workforce density per 100 000 population was 289.48–747.38 procedures, 0.98 and 5.41 and 3.68 surgical providers, respectively. Conclusion COs form the backbone of Malawi’s surgical and anaesthetic workforce and should be supported with improvements in infrastructure as well as training and mentorship by specialist surgeons and anaesthetists.

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

BackgroundThe 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.MethodsOnly 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).ResultsOf 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).ConclusionsIn 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.

Acute malnutrition is common in Malawian patients with a Wilms tumour: a role for peanut butter

Children with cancer in resource limited countries are often malnourished at diagnosis. Acute malnutrition is associated with more infectious complications and an increased risk of morbidity and mortality in major surgery.