Risk factors for Burkitt lymphoma in East African children and minors: A case-control study in malaria-endemic regions in Uganda, Tanzania and Kenya.

Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in sub-Saharan African countries, however, few epidemiologic studies have been undertaken and none attempted enrolling cases from multiple countries. We therefore conducted a population-based case-control study of eBL in children aged 0-15 years old in six regions in Northern Uganda, Northern Tanzania and Western Kenya, enrolling 862 suspected cases and 2,934 population controls (response rates 98.5-100%), and processing ~40,000 vials of samples using standardized protocols. Risk factor questionnaires were administered, and malaria period prevalence was measured using rapid diagnostic tests (RDTs). A total of 80.9% of the recruited cases were diagnosed as eBL; 61.4% confirmed by histology. Associations with eBL risk were computed using logistic regression models adjusted for relevant confounders. Associations common in at least two countries were emphasized. eBL risk was decreased with higher maternal income and paternal education and elevated with history of inpatient malaria treatment >12 months before enrollment. Reporting malaria-attributed fever up to 6 months before enrollment and malaria-RDT positivity at enrollment were associated with decreased eBL risk. Conversely, reporting exposure to mass malaria suppression programs (e.g., indoor residual insecticide) was associated with elevated risk. HIV seropositivity was associated with elevated eBL risk, but the relative impact was small. The study shows that it is feasible to conduct networked, multisite population-based studies of eBL in Africa. eBL was inversely associated with socioeconomic status, positively associated with inpatient malaria treatment 12 months ago and with living in areas targeted for malaria suppression, which support a role of malaria in eBL.

Nonparametric evaluation of dynamic disease risk: a spatio-temporal kernel approach.

Quantifying the distributions of disease risk in space and time jointly is a key element for understanding spatio-temporal phenomena while also having the potential to enhance our understanding of epidemiologic trajectories. However, most studies to date have neglected time dimension and focus instead on the "average" spatial pattern of disease risk, thereby masking time trajectories of disease risk. In this study we propose a new idea titled "spatio-temporal kernel density estimation (stKDE)" that employs hybrid kernel (i.e., weight) functions to evaluate the spatio-temporal disease risks. This approach not only can make full use of sample data but also "borrows" information in a particular manner from neighboring points both in space and time via appropriate choice of kernel functions. Monte Carlo simulations show that the proposed method performs substantially better than the traditional (i.e., frequency-based) kernel density estimation (trKDE) which has been used in applied settings while two illustrative examples demonstrate that the proposed approach can yield superior results compared to the popular trKDE approach. In addition, there exist various possibilities for improving and extending this method.

Prevalence of Epstein-Barr viral sequences and EBV LMP1 oncogene deletions in Burkitt's lymphoma from Pakistan: epidemiological correlations.

To investigate the potential relationship of socioeconomic status with the prevalence of Epstein-Barr virus (EBV) and to understand the significance of del-LMP-1 within EBV+ cases of Burkitt's lymphoma (BL), we studied 10 cases of BL, 30 cases of diffuse large cell lymphoma (DLCL) arising in nonimmunocompromised patients, and 30 reactive tonsillar biopsy specimens from Pakistan. Each lymphoma was analyzed for EBV by EBER1 RNA in situ hybridization (EBV-RISH). Cases showing hybridization signal within neoplastic cells and all reactive tonsillar tissues were analyzed for EBV strain type by EBNA-2 polymerase chain reaction (PCR) and for the presence of a del-LMP-1 by PCR. Eight of 10 (80%) of BL were EBV+, each containing EBV strain A and a wild-type LMP-1 gene. In contrast, only 4 of 30 DLCL (13%) cases were EBV positive (three strain A, one strain B), each containing a wild-type LMP-1 gene. Fifteen of 30 tonsillar biopsy specimens contained EBV, all of which were strain A and wild-type for LMP1. The prevalence of EBV in BL from Pakistan is slightly lower than in BL in endemic regions, but significantly higher than in BL in North America. EBV positivity probably reflects the socioeconomic status of the patient population and age at seroconversion. The absence of del-LMP-1 within all EBV+ BL cases is consistent with the view that del-LMP-1 is not involved in the pathogenesis of BL, and the presence of del-LMP-1 in EBV+ cases of BL reported in other studies may likely reflect the prevalence of a viral strain containing the 30-bp deletion within the respective population studied.

International variations in the incidence of childhood lymphomas.

The International Agency for Research on Cancer has coordinated a worldwide study of childhood cancer incidence, with data provided by contributors from over 50 countries. We present here the results on lymphomas from this study and other sources. Hodgkin's disease had a relatively high incidence in North Africa and West Asia and a low incidence throughout East Asia. In populations of predominantly European origin, the highest rates tended to be in warmer countries of lower latitude. In industrialised Western countries, the incidence increased steeply with age and was low in childhood compared with that in young adults whereas elsewhere the increase in incidence between childhood and adults aged 20-34 was much less marked. The age-distribution of Hodgkin's disease in childhood appears to be related to levels of socio-economic development but the total incidence seems to be determined more by ethnic and environmental factors. The highest incidence of Burkitt's lymphoma occurred in tropical Africa and Papua New Guinea. Elsewhere, Burkitt's lymphoma was rare, though the incidence was higher in Spain, North Africa and the Middle East than in other areas. In most Western countries, a third of all non-Hodgkin lymphomas may be Burkitt's. There was no consistent pattern in the incidence of other non-Hodgkin lymphomas except for a tendency towards higher rates around the Mediterranean and in some Latin American registries.