Burkitt lymphoma risk shows geographic and temporal associations with Plasmodium falciparum infections in Uganda, Tanzania, and Kenya.

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. EMBLEM is a case-control study of eBL from 2010 through 2016 in six regions of Kenya, Uganda, and Tanzania. To measure the intensity of exposure to the malaria parasite, Plasmodium falciparum, among children in these regions, we used high-resolution spatial data from the Malaria Atlas Project to estimate the annual number of P. falciparum infections from 2000 through 2016 for each of 49 districts within the study region. Cumulative P. falciparum exposure, calculated as the sum of annual infections by birth cohort, varied widely, with a median of 47 estimated infections per child by age 10, ranging from 4 to 315 infections. eBL incidence increased 39% for each 100 additional lifetime P. falciparum infections (95% CI: 6.10 to 81.04%) with the risk peaking among children aged 5 to 11 and declining thereafter. Alternative models using estimated annual P. falciparum infections 0 to 10 y before eBL onset were inconclusive, suggesting that eBL risk is a function of cumulative rather than recent cross-sectional exposure. Our findings provide population-level evidence that eBL is a phenotype related to heavy lifetime exposure to P. falciparum malaria and support emphasizing the link between malaria and eBL.

Distance to Health Care Facilities, Lifestyle Risk Factors, and Stage at Diagnosis in relation to Geographic Pattern of Esophageal Cancer in Tanzania, 2006-2016.

Esophageal cancer is an aggressive, often deadly disease globally that represents a significant health problem in Tanzania. The WHO reported 604,100 new esophageal cancer cases worldwide during 2020 and 544,076 deaths (Sung, 2021; World Health Organization, 2020). In Eastern Africa, 16,137 cases and 15,188 deaths were related to this disease in 2020. Esophageal cancer is associated with various etiologic risk factors, and access to the disease treatment is a major barrier to survival. This study examined associations between the prevalence of four geographically stratified, population-level, etiologic risk factors (tobacco use, unprotected water use, solid fuel source use, and poverty), as well as two access-to-care predictors (persons per hospital and distance from residence to where esophageal cancer treatment occurs). Regional- and coarser-scale zonal incidence rates were calculated for 2006 through 2016 and evaluated for geographic differences in relation to risk factors and access to care predictors using Poisson regression. Differences in the geographic distribution of esophageal cancer were observed. Distance from the region of residence to the treatment center (Ocean Road Cancer Institute) was statistically associated with the geographic pattern of esophageal cancer incidence. Further research into etiologic risk factors, dietary practices, and nutrition is needed to better understand the associations with esophageal cancer in Tanzania and other parts of Eastern Africa.

A behavior change communication intervention, but not livelihood interventions, improves diet diversity and animal-source food consumption among Ghanaian women.

Background: Women of reproductive age (WRA), especially in sub-Saharan Africa, are vulnerable to micronutrient deficiencies driven largely by poor quality diets. Intervening into food value chains, on which many households in low- and middle-income countries depend for their livelihood, may be a promising approach to improving diets in these contexts. Objective: In this pilot-scale randomized trial, we evaluated whether a multisectoral, food value chain intervention improved the diet diversity and the consumption of animal-source foods (ASFs) among WRA in Ghana. Design: Twelve fish-smoking communities in two regions of Ghana with 296 eligible women were randomly assigned to one of three 9-month treatment arms: 1) behavior change communication (BCC) to promote improved diet quality through twice-weekly audio messages and bi-weekly peer-to-peer learning sessions; 2) BCC with microcredit to increase women's incomes; or 3) BCC with provision of new smoke-oven technology. We assessed baseline-endline and between-treatment arm differences using a 10-food group diet diversity score (DDS), the Minimum Dietary Diversity for Women (MDD-W) indicator, and 7-day frequency of ASF consumption. Results: Among 118 participants (39 in both treatment arm 1 and treatment arm 3, and 40 in treatment arm 2, with no participant refusals), DDS increased from a mean (SD) of 4.0 (1.3) at baseline to 5.1 (0.9) at endline (P-value < 0.0001). The proportion of women achieving the MDD-W indicator nearly doubled from baseline (35.6%) to endline (69.5%) (P-value < 0.0001). Frequency of ASF consumption similarly increased for meat and poultry (2.7 (4.1) to 4.7 (5.3); P-value < 0.0001) and eggs (1.5 (3.1) to 2.3 (4.9); P-value = 0.02). Few differences in these outcomes were observed among treatment arms. Conclusions: A BCC intervention improved diet diversity and consumption of ASFs among participants. However, neither a group-based microcredit nor improved smoke oven intervention, both of which increased women's income, led to additional dietary improvements.

Associations of bacterial enteropathogens with systemic inflammation, iron deficiency, and anemia in preschool-age children in southern Ghana.

Anemia remains a pervasive public health problem among preschool-age children in Ghana. Recent analyses have found that anemia in Ghanaian children, particularly in Southern regions, is largely attributable to infectious causes, rather than nutritional factors. Infections with enteropathogens can reduce iron absorption and increase systemic inflammation, but few studies have examined direct links between enteropathogens and anemia. This study investigated associations between detection of individual bacterial enteropathogens and systemic inflammation, iron deficiency, and anemia among 6- to 59-month-old children in Greater Accra, Ghana. Serum samples were analyzed from a cross-sectional sample of 262 children for concentrations of hemoglobin (Hb), biomarkers of systemic inflammation [C-reactive protein (CRP) and α-1-acid glycoprotein (AGP)], and biomarkers of iron status [serum ferritin (SF) and serum transferrin receptor (sTfR)]. Stool samples were analyzed for ten bacterial enteropathogens using qPCR. We estimated associations between presence of each enteropathogen and elevated systemic inflammation (CRP > 5 mg/L and AGP > 1 g/L), iron deficiency (SF < 12 µg/L and sTfR > 8.3 mg/L) and anemia (Hb < 110 g/L). Enteropathogens were detected in 87% of children's stool despite a low prevalence of diarrhea (6.5%). Almost half (46%) of children had anemia while one-quarter (24%) had iron deficiency (low SF). Despite finding no associations with illness symptoms, Campylobacter jejuni/coli detection was strongly associated with elevated CRP [Odds Ratio (95% CI): 3.49 (1.45, 8.41)] and elevated AGP [4.27 (1.85, 9.84)]. Of the pathogens examined, only enteroinvasive Escherichia coli/Shigella spp. (EIEC/Shigella) was associated with iron deficiency, and enteroaggregative Escherichia coli (EAEC) [1.69 (1.01, 2.84)] and EIEC/Shigella [2.34 (1.15, 4.76)] were associated with anemia. These results suggest that certain enteroinvasive pathogenic bacteria may contribute to child anemia. Reducing exposure to enteropathogens through improved water, sanitation, and hygiene practices may help reduce the burden of anemia in young Ghanaian children.

School-Based Malaria Screening and Treatment Reduces Plasmodium falciparum Infection and Anemia Prevalence in Two Transmission Settings in Malawi.

BACKGROUND: In areas highly endemic for malaria, Plasmodium falciparum infection prevalence peaks in school-age children, adversely affecting health and education. School-based intermittent preventive treatment reduces this burden but concerns about cost and widespread use of antimalarial drugs limit enthusiasm for this approach. School-based screening and treatment is an attractive alternative. In a prospective cohort study, we evaluated the impact of school-based screening and treatment on the prevalence of P. falciparum infection and anemia in 2 transmission settings. METHODS: We screened 704 students in 4 Malawian primary schools for P. falciparum infection using rapid diagnostic tests (RDTs), and treated students who tested positive with artemether-lumefantrine. We determined P. falciparum infection by microscopy and quantitative polymerase chain reaction (qPCR), and hemoglobin concentrations over 6 weeks in all students. RESULTS: Prevalence of infection by RDT screening was 37% (9%-64% among schools). An additional 9% of students had infections detected by qPCR. Following the intervention, significant reductions in infections were detected by microscopy (adjusted relative reduction [aRR], 48.8%; P < .0001) and qPCR (aRR, 24.5%; P < .0001), and in anemia prevalence (aRR, 30.8%; P = .003). Intervention impact was reduced by infections not detected by RDT and new infections following treatment. CONCLUSIONS: School-based screening and treatment reduced P. falciparum infection and anemia. This approach could be enhanced by repeating screening, using more-sensitive screening tests, and providing longer-acting drugs. CLINICAL TRIALS REGISTRATION: NCT04858087.

School-based screening and treatment may reduce P. falciparum transmission.

In areas where malaria remains entrenched, novel transmission-reducing interventions are essential for malaria elimination. We report the impact screening-and-treatment of asymptomatic Malawian schoolchildren (n = 364 in the rainy season and 341 in the dry season) had on gametocyte-the parasite stage responsible for human-to-mosquito transmission-carriage. We used concomitant household-based surveys to predict the potential reduction in transmission in the surrounding community. Among 253 students with P. falciparum infections at screening, 179 (71%) had infections containing gametocytes detected by Pfs25 qRT-PCR. 84% of gametocyte-containing infections were detected by malaria rapid diagnostic test. While the gametocyte prevalence remained constant in untreated children, treatment with artemether-lumefantrine reduced the gametocyte prevalence (p < 0.0001) from 51.8 to 9.7% and geometric mean gametocyte density (p = 0.008) from 0.52 to 0.05 gametocytes/microliter. In community surveys, 46% of all gametocyte-containing infections were in school-age children, who comprised only 35% of the population. Based on these estimates six weeks after the intervention, the gametocyte burden in the community could be reduced by 25-55% depending on the season and the measure used to characterize gametocyte carriage. Thus, school-based interventions to treat asymptomatic infections may be a high-yield approach to not only improve the health of schoolchildren, but also decrease malaria transmission.

Evaluating the incidence of inflammatory breast cancer using population- and hospital-based cancer registries in Casablanca, Morocco.

BACKGROUND: Inflammatory breast cancer (IBC) is a rare and aggressive type of breast cancer (BC). Physicians have difficulty diagnosing it correctly given its clinical nature. Previous studies have shown that North Africa compared to the United States has a higher proportion of IBC relative to all BC. PURPOSE: The purpose of this study was to calculate a corrected IBC incidence rate using the population-based registry of Casablanca and other, local hospital-based data sources and to characterize the clinical presentation and basis of diagnosis of IBC. METHODS: We retrieved the Casablanca registry data from 2009-2012, and matched its data with demographic and clinical data from the medical records, logbooks and a local epidemiologic IBC case-control study. A corrected incidence was calculated after accounting for missed cases in the registry. RESULTS: The data showed that the incidence of IBC in the registry was significantly underestimated when the population-based and hospital data were combined. CONCLUSIONS: Population-based registries should focus on specific measures for verifying the diagnosis of IBC since physicians may miss documenting the disease in medical records. This study may have implications for better reporting and documentation of IBC in hospital- and population-based cancer registries in Morocco and other similar countries.

Forecasted impacts of a sofosbuvir-based national hepatitis C treatment programme on Egypt's hepatocellular cancer epidemic: simulation of alternatives.

BACKGROUND: Egypt is experiencing a hepatocellular cancer (HCC) epidemic due to widespread hepatitis C virus (HCV) transmission. The use of sofosbuvir-related therapies producing improved treatment success has permitted an updated, nationwide, HCV treatment programme with expanded coverage. This study simulated the multidecade impacts of the new treatment programme on hepatitis and HCC. METHODS: A Markov model of HCV infection and treatment analysed the HCV-related HCC epidemic between 2009 and 2050, using parameters based on peer-reviewed studies and expert opinion. Comparing the 'new' and 'old' scenarios, and with the old treatment programme being replaced or not by the new programme in 2015, the annual number, prevalence and incidence of HCC were simulated for representative Egypt populations including HCV-infected patients aged 15-59 years in 2008, healthy people aged 5-59 years in 2008 and 5-year-old children cohorts entering the population each year beginning in 2009. Averted HCC cases were calculated, and sensitivity analyses were performed. RESULTS: Compared with the old scenario, the estimated number, prevalence and incidence of future HCC cases in the new scenario would peak earlier and at lower levels in 2025 (~29 000), 2023 (~28/100 000) and 2022 (~14/100 000), respectively. The new treatment programme is estimated to avert ~956 000 HCC cases between 2015 and 2050. DISCUSSION: By reducing cancer cases and shortening the peak epidemic period, the new programme should substantially diminish the HCC epidemic across Egypt. Our timeline forecast for Egypt's HCC epidemic, and evaluation of various disease and programme components, should be useful to other countries that are developing policies to address HCV-related liver cancer prevention.

Malaria control in Malawi: current status and directions for the future.

The last decade has seen an increase in investment and concerted efforts by the Malawi Ministry of Health and partners to control malaria disease. This report summarizes what is known about the burden of malaria and the strategies being implemented to control it in Malawi. Over the past 5 years, roll out of treatment and prevention efforts have been successful in the country, as demonstrated by increased use of insecticide treated nets, improved access to prompt and effective treatment and the initiation of pilot studies of indoor residual spraying. However, unlike other countries in the region, the recent data have not suggested a decrease in the burden of disease. We describe the environment in which the activities of Malawi's International Center for Excellence in Malaria Research (ICEMR) will be carried out and provide the rationale for the clinical, entomological and molecular studies. Our approach is to establish consistent, stainable data collection systems that are embedded within the public health sector. Through standardized and long-term studies of hosts, parasites and vectors, we hope to contribute to assessment of malaria disease burden, the appropriate application of interventions and policies and provide both the data collection and the health care infrastructure to ultimately eliminate the disease.

Urban-rural differences in breast cancer incidence in Egypt (1999-2006).

OBJECTIVE: To describe urban-rural differences in breast cancer incidence in Gharbiah, Egypt and to investigate if these differences could be explained by known risk factors of breast cancer. METHODS: We used data from the population-based cancer registry of Gharbiah, Egypt to assess breast cancer incidence from 1999 through 2006. The Egyptian census provided data on district-specific population, age, and urban-rural classification. Incidence patterns of breast cancer by district and age-specific urban-rural differences were analyzed. RESULTS: Overall, incidence rate of breast cancer was three to four times higher in urban areas than in rural areas (60.9/10(5)-year for urban areas versus 17.8/10(5)-year for rural areas; IRR=3.73, 95% CI=3.30, 4.22). Urban areas had consistently higher incidence of breast cancer across all age-groups for all years. Higher incidence of breast cancer was also seen in the more developed districts of Tanta and El-Mehalla. CONCLUSIONS: Higher incidence of breast cancer in urban and more developed populations might be related to higher exposure to xenoestrogens, as well as other endocrine disruptors and genotoxic substances.

Lifetime exposure to arsenic in drinking water and bladder cancer: a population-based case-control study in Michigan, USA.

OBJECTIVE: Arsenic in drinking water has been linked with the risk of urinary bladder cancer, but the dose-response relationships for arsenic exposures below 100 microg/L remain equivocal. We conducted a population-based case-control study in southeastern Michigan, USA, where approximately 230,000 people were exposed to arsenic concentrations between 10 and 100 microg/L. METHODS: This study included 411 bladder cancer cases diagnosed between 2000 and 2004, and 566 controls recruited during the same period. Individual lifetime exposure profiles were reconstructed, and residential water source histories, water consumption practices, and water arsenic measurements or modeled estimates were determined at all residences. Arsenic exposure was estimated for 99% of participants' person-years. RESULTS: Overall, an increase in bladder cancer risk was not found for time-weighted average lifetime arsenic exposure >10 microg/L when compared with a reference group exposed to <1 microg/L (odds ratio (OR) = 1.10; 95% confidence interval (CI): 0.65, 1.86). Among ever-smokers, risks from arsenic exposure >10 microg/L were similarly not elevated when compared to the reference group (OR = 0.94; 95% CI: 0.50, 1.78). CONCLUSIONS: We did not find persuasive evidence of an association between low-level arsenic exposure and bladder cancer. Selecting the appropriate exposure metric needs to be thoughtfully considered when investigating risk from low-level arsenic exposure.

Urban-rural differences in breast cancer incidence by hormone receptor status across 6 years in Egypt.

Breast cancer incidence is higher in developed countries with higher rates of estrogen receptor positive (ER+) tumors. ER+ tumors are caused by estrogenic exposures although known exposures explain approximately 50% of breast cancer risk. Unknown risk factors causing high breast cancer incidence exist that are estrogenic and development-related. Xenoestrogens are such risk factors but are difficult to study since developed countries lack unexposed populations. Developing countries have urban-rural populations with differential exposure to xenoestrogens. This study assessed urban-rural breast cancer incidence classified by hormone receptor status using data from Gharbiah population-based cancer registry in Egypt from 2001 to 2006. Urban ER+ incidence rate (per 100,000 women) was 2-4 times (IRR = 3.36, 95% CI = 4.84, 2.34) higher than rural incidence rate. ER-incidence rate was 2-3 times (IRR = 1.86, 95% CI = 2.38, 1.45) higher in urban areas than in rural areas. Our findings indicate that urban women may probably have a higher exposure to xenoestrogens.

Incidence analyses of bladder cancer in the Nile delta region of Egypt.

Bladder cancer is the most common malignancy among Egyptian males and previously has been attributed to Schistosoma infection, a major risk factor for squamous cell carcinoma (SCC). Recently, transitional cell carcinoma (TCC) incidence has been increasing while SCC has declined. To investigate this shift, we analyzed the geographical patterns of all bladder cancers cases recorded in Egypt's Gharbiah Population-Based Cancer Registry from 1999 through 2002. Data on tumor grade, stage, and morphology, as well as smoking, community of residence, age and sex, were collected on 1209 bladder cancer cases. Age-adjusted incidence rates were calculated for males, females, and the total population for the eight administrative Districts and 316 communities in Gharbiah. Incidence Rate Ratios (IRR) and 95% confidence intervals (CI) were computed using Poisson Regression. The male age-adjusted incidence rate (IR) in Gharbiah Province was 13.65/100,000 person years (PY). The District of Kotour had the highest age-adjusted IR 28.96/100,000 among males. The District of Kotour also had the highest IRR among all Districts, IRR=2.15 95% CI (1.72, 2.70). Kotour's capital city had the highest bladder cancer incidence among the 316 communities (IR=73.11/100,000 PY). Future studies on sources and types of environmental pollution and exposures in relation to the spatial patterns of bladder cancer, particularly in Kotour District, may improve our understating of risk factors for bladder cancer in the region.

Epidemiology of hepatitis viruses among hepatocellular carcinoma cases and healthy people in Egypt: a systematic review and meta-analysis.

Liver cancers are strongly linked to hepatitis B virus (HBV) and hepatitis C virus (HCV). Egypt has the highest prevalence of HCV worldwide and has rising rates of hepatocellular carcinoma (HCC). Egypt's unique nature of liver disease presents questions regarding the distribution of HBV and HCV in the etiology of HCC. Accordingly, a systematic search of MEDLINE, ISI Web of Science, ScienceDirect and World Health Organisation databases was undertaken for relevant articles regarding HBV and HCV prevalence in Egypt among healthy populations and HCC cases. We calculated weighted mean prevalences for HBV and HCV among the populations of interest and examined differences in prevalence by descriptive features, including age, year and geographic region. Prevalences for HBV and HCV were 6.7% and 13.9% among healthy populations, and 25.9% and 78.5% among HCC cases. Adults had higher prevalences of both infections (Adult HBV=8.0%, Child HBV=1.6%; Adult HCV=15.7%, Child HCV=4.0%). Geographically, HBV was higher in the south, whereas HCV was greater in the north (North HBV=4.6%, South HBV=11.7%; North HCV=15.8%, South HCV=6.7%). Among HCC cases, HBV significantly decreased over time (p=0.001) while HCV did not, suggesting a shift in the relative influences of these viruses in HCC etiology in Egypt. Our results highlight large amounts of heterogeneity among the epidemiological factors associated with liver disease in Egypt and underscore the necessity of an integrated strategy for the successful prevention of viral hepatitis infections and chronic liver disease.

Family environment is associated with endemic Burkitt lymphoma: a population-based case-control study.

Endemic Burkitt's lymphoma (eBL) has been linked to Epstein-Barr virus and holoendemic Plasmodium falciparum malaria. These co-infections, however, are insufficient to explain the non-random occurrence of Endemic Burkitt's lymphoma within Equatorial Africa. To explore whether this distribution could be explained by household characteristics and family environment, we conducted a case-control study using 41 hospitalized incident endemic Burkitt's lymphoma cases and 91 healthy controls identified through a population-based multistage cluster-sampling scheme in Nyanza Province, Kenya. In a multivariate analysis, odds ratios associated with having one, two, and three or more younger siblings compared with none were 0.28 (90% CI: 0.09, 0.83), 0.59 (90% CI: 0.16, 2.23) and 0.15 (90% CI: 0.03, 0.67) respectively, suggesting that children with endemic Burkitt's lymphoma were more likely than controls to be last-born. Children with endemic Burkitt's lymphoma were also more likely to live in non-monogamous families (OR=3.12, 90% CI:1.19, 8.17) and to have at least one deceased parent (OR=3.38, 90% CI: 1.18, 9.64). Household characteristics, especially sibship relationships, may contribute to endemic Burkitt's lymphoma and therefore warrant further study.

The changing patterns of bladder cancer in Egypt over the past 26 years.

OBJECTIVE: To evaluate temporal changes in histopathological types of bladder cancer and to assess associated changes in demographic, epidemiologic, and lifestyle risk factors. METHODS: We abstracted data from all available medical records from the National Cancer Institute of Cairo University (NCI-Cairo). Six calendar years representing 5-year periods between 1980 and 2005 were evaluated. Information on demographics, schistosomal infection, clinical symptoms of bladder cancer, and tumor pathology was abstracted. RESULTS: During this 26-year period, important changes in the frequency of histopathological types of bladder cancer occurred. We found a statistically significant association between time period of diagnosis and histopathological type. Patients diagnosed in 2005 had a sixfold higher odds associated with transitional cell carcinoma compared to those patients diagnosed in 1980 (odds ratio (OR) 6.00 (95% CI 4.00-8.97)). CONCLUSIONS: These data strongly suggest that the histopathological profile of bladder cancer in Egypt has changed significantly over the past 26 years. Historically, squamous cell carcinoma was the predominant form of bladder cancer in Egypt; however transitional cell carcinoma has become the most frequent type. These results corroborate findings from a few small-scale hospital-based studies which conclude that the etiology of bladder cancer in Egypt has changed significantly over the past 26 years.

Patterns of hepatocellular carcinoma incidence in Egypt from a population-based cancer registry.

AIM: Hepatocellular carcinoma (HCC) is increasing worldwide, and is frequently attributed to rising rates of hepatitis C virus infection and interactions between viral and environmental risk factors. Because of Egypt's unique risk factor profile, we analyzed data from the Gharbiah Population-Based Cancer Registry for the period 1999-2003 to characterize demographic and geographic patterns of cases in this province. METHODS: We calculated age- and sex-specific and age- and sex-standardized HCC incidence rates for the eight districts in Gharbiah. We also compared rates from Gharbiah with the USA (US Surveillance Epidemiology and End RESULTS [SEER] database). RESULTS: The analysis revealed a higher incidence in males than in females, significant geographic variations among districts, and a higher incidence in Gharbiah than that reported by SEER. CONCLUSION: The findings of this study document the heterogeneous distribution of HCC at regional and international levels. This population-based registry offers the opportunity for careful representative studies of various etiologies, particularly infectious and/or environmental factors that may contribute to risk.

Spatial distribution of Burkitt's lymphoma in Kenya and association with malaria risk.

Endemic Burkitt's lymphoma (BL) is the most common paediatric malignancy in equatorial Africa and was originally shown to occur at high-incidence rates in regions where malaria transmission is holoendemic. New ecological models of malaria that are based on both parasite prevalence and disease have been described. In this study, we examined district level data collected from paediatric BL cases in Kenya from 1988 through 1997 and assessed whether the distribution of district level incidence rates could be explained by new ecologic estimates of malaria risk. Chi-square tests and log-linear regression models were used to evaluate these associations. An association with tribe of origin as a factor also was examined. The 10-year average annual incidence rate (IR) for Kenya was 0.61 per 100,000 children. Incidence rates varied by malaria transmission intensity as follows: low malaria risk (BL IR = 0.39), arid/seasonal (0.25), highland (0.66), endemic coast (0.68), and endemic lake (1.23) (chi(2) = 11.32, P = 0.002). In a log-linear model, BL rates were 3.5 times greater in regions with chronic and intense malaria transmission intensity than in regions with no or sporadic malaria transmission (odds ratio = 3.47, 95% confidence interval = 1.30-9.30), regardless of tribe. Although crude tribe-specific incidence rates ranged between 0.0 and 3.26, tribe was not associated with BL after controlling for malaria. These findings support the aetiologic role of intense malaria transmission intensity in BL.

Spatial clustering of endemic Burkitt's lymphoma in high-risk regions of Kenya.

Endemic Burkitt's lymphoma (eBL), the most common childhood cancer in sub-Saharan Africa, occurs at a high incidence in western Kenya, a region that also experiences holoendemic malaria. Holoendemic malaria has been identified as a co-factor in the etiology of this cancer. We hypothesized that eBL may cluster spatially within this region. Medical records for all eBL cases diagnosed from 1999 through 2004 at Nyanza Provincial General Hospital were reviewed for case residential information to examine this hypothesis. Two cluster detection methods, Anselin's Local Moran test for spatial autocorrelation and a spatial scan test statistic, were applied to this residential data to determine whether statistically significant high- and low-risk areas were present in the Province. During the 6-year study period, 272 children were diagnosed with eBL, with an average annual incidence of 2.15 cases per 100,000 children. Using Empirical Bayes smoothed rates, the Local Moran test identified 1 large multi-centered area of low eBL risk (p-values < 0.01) and 2 significant multi-centered clusters of high eBL risk (p-values < 0.001). The spatial scan detected 3 small independent low-risk areas (p-values < 0.02) and 2 high-risk clusters (p-values = 0.001), both similar in location to those identified from the Local Moran analysis. Significant spatial clustering of elevated eBL risk in high-malaria transmission regions and of reduced incidence where malaria is infrequent suggests that malaria plays a role in the complex eBL etiology, but that additional factors are also likely involved.

Case-control geographic clustering for residential histories accounting for risk factors and covariates.

BACKGROUND: Methods for analyzing space-time variation in risk in case-control studies typically ignore residential mobility. We develop an approach for analyzing case-control data for mobile individuals and apply it to study bladder cancer in 11 counties in southeastern Michigan. At this time data collection is incomplete and no inferences should be drawn - we analyze these data to demonstrate the novel methods. Global, local and focused clustering of residential histories for 219 cases and 437 controls is quantified using time-dependent nearest neighbor relationships. Business address histories for 268 industries that release known or suspected bladder cancer carcinogens are analyzed. A logistic model accounting for smoking, gender, age, race and education specifies the probability of being a case, and is incorporated into the cluster randomization procedures. Sensitivity of clustering to definition of the proximity metric is assessed for 1 to 75 k nearest neighbors. RESULTS: Global clustering is partly explained by the covariates but remains statistically significant at 12 of the 14 levels of k considered. After accounting for the covariates 26 Local clusters are found in Lapeer, Ingham, Oakland and Jackson counties, with the clusters in Ingham and Oakland counties appearing in 1950 and persisting to the present. Statistically significant focused clusters are found about the business address histories of 22 industries located in Oakland (19 clusters), Ingham (2) and Jackson (1) counties. Clusters in central and southeastern Oakland County appear in the 1930's and persist to the present day. CONCLUSION: These methods provide a systematic approach for evaluating a series of increasingly realistic alternative hypotheses regarding the sources of excess risk. So long as selection of cases and controls is population-based and not geographically biased, these tools can provide insights into geographic risk factors that were not specifically assessed in the case-control study design.