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Query: UMLS:C0024530 (malaria)
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Burkitt's lymphoma is the most common childhood cancer in Africa. Most prevalent in areas endemic for malaria, the disease, a malignant growth of lymphoid tissue, usually presents itself as a large tumour of the jaw. When first characterized in the 1950s, the lymphoma was thought to spread by some infectious agent. Subsequent research indicates that the frequent involvement of an infectious agent is but one factor in a more complex aetiology. Today, Burkitt's lymphoma is considered an example of multistep carcinogenesis. Each step in the process results from a different agent. The agent in the first step is the Epstein-Barr virus, which infects B cells of the immune system causing a proliferation of these cells. The second step, malarial infection, furthers the proliferation of B cells providing a large population of cells available for a chromosomal translocation which represents the third step in the formation of the lymphoma. The chromosomal translocation places a cancer causing gene, c-myc, in close proximity to an active antibody-encoding its proliferation resulting in a cell capable of unlimited growth which serves as the nucleus of a B cell lymphoma.
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PMID:Burkitt's lymphoma and the role of Epstein-Barr virus. 216 60

The total incidence of childhood cancer varies rather little between different regions of the world, with cumulative risk to age 15 nearly always in the range 1.0-2.5 per thousand. Acute lymphoblastic leukaemia, especially in early childhood, is most common in populations of high socio-economic status and is the most frequent childhood cancer in all industrialised countries. The risk of Burkitt's lymphoma is highest in tropical Africa and Papua New Guinea; it is strongly associated with Epstein-Barr virus infection and intense immune stimulation by malaria. Other lymphomas are also relatively common in developing countries. Non-heritable retinoblastoma has a higher incidence among less affluent populations, suggesting an association with poor living conditions and maybe an infectious aetiology. In contrast, the incidence of Wilms' tumour and Ewing's sarcoma varies largely on ethnic lines, indicating a strong role for genetic predisposition. Much of the variation in recorded incidence of brain tumours and neuroblastoma may be due to varying levels of case ascertainment. Recently the incidence of childhood Kaposi's sarcoma has risen substantially in parts of Africa severely affected by the AIDS epidemic.
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PMID:Geographic and ethnic variations in the incidence of childhood cancer. 903 26

Burkitt's lymphoma has the highest incidence of any childhood cancer in equatorial Africa. Geographic distribution appears to be related to climatic conditions and coincides with areas of endemic malaria. These tumors are characterized by reciprocal translocation from chromosome 8 at or near the c-myc locus to either the immunoglobulin chain locus on chromosome 14 (80 p. 100 of cases) or one of the light chain loci on chromosome 2 or 22. As a result of this translocation, transcription of the protooncogene c-myc is activated. Deregulation of c-myc could play a major role in onset and development of the tumor. Study of Burkitt's lymphoma led to the discovery of the first association between viral infection and tumor development in humans. The Epstein-Barr virus is contained in all endemic Burkitt's lymphoma cells, thus implicating it as a likely etiologic factor. Viral expression is reduced essentially to small non-coding RNA, non-polyadenilates, and EBERs (10(6) copies per cell) and a nuclear protein EBNA1 which is indispensable for maintenance of the Epstein-Barr virus genome in infected cells. Expression of EBNA in transgenes leads to lymphoma in mice and could play a role in the expression of the c-myc gene involved in translocations.
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PMID:[Epstein-Barr virus and Burkitt's lymphoma]. 1090 54

Child mortality has declined remarkably during the last decades. While neonatal disorders, diarrhoea, pneumonia, and malaria as well as being underweight account for most of the child deaths worldwide, children's health discussions in Europe and the USA focus on other issues such as asthma, neurodevelopmental disorders, male genital malformations, and childhood cancer. There is clear evidence of increasing rates of asthma in various countries during the last decades, although rates in some countries may now have stabilised or even decline as recent UK data indicate. Although an increase in the frequency of neurodevelopmental disorders such as autism and attention deficit disorder has frequently been discussed, the limited data in this field does not justify such a conclusion. While geographic heterogeneity regarding reproductive outcomes is apparent, global trends have not been identified. Interpretation of the available information on asthma, neurodevelopmental disorders and reproductive outcomes is hampered by inconstant diagnostic criteria over place and time and the lack of good and comprehensive population-based surveillance data, which makes it impossible to ascertain trends in actual disease frequency. Data indicate that developed countries have a gradually increasing incidence in leukaemia with a corresponding drop in the incidence of lymphoma. Increases in brain tumour frequency may be related to the development and wide application of new diagnostic capabilities, rather than a true change in the incidence of malignant disease. With a better prognosis for childhood cancer survival, secondary cancers following chemotherapy appear to be increasing. A wide range of environmental factors is thought to have an impact on children's health. These factors include nutrition (protein, vitamins, antioxidants), lifestyle and behaviour choices such as tobacco and alcohol use, parental health, socio-economic status, choice of living environment (urban versus rural, etc.), and parent-sibling behaviour. From the available data, no general conclusions on the contribution of specific chemicals can be drawn.
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PMID:Trends in childhood disease. 1685 14

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.
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PMID:Spatial clustering of endemic Burkitt's lymphoma in high-risk regions of Kenya. 1701 6

Burkitt lymphoma, a childhood tumor common in parts of sub-Saharan Africa, has been directly associated with Epstein-Barr virus (EBV) and indirectly with prevalence of malaria. We studied antibodies to both EBV and malaria in children diagnosed with this cancer in Uganda. We performed a case-control study of HIV-seronegative children (<or=15 years) admitted to hospital. Cases were diagnosed with Burkitt lymphoma and controls with non-malignant conditions or non-lymphatic cancers. Interviews were conducted and serological samples collected and, when possible, tested for both EBV and malaria. Adjusted odds ratios (ORs) for Burkitt lymphoma were estimated using unconditional logistic regression adjusting for sex, age, residential district, household income and tribe. The mean age of cases was 7 years and 61% were male. Compared to controls, cases were more likely to be reported having received more frequent treatment for malaria in the past year (OR = 2.0; p = 0.001) and less likely to be living in a home where insecticides were used (OR = 0.2; p < 0.0001). Odds ratios for Burkitt lymphoma in children increased with increasing antibody levels against EBV (p < 0.0001) and malaria (p = 0.05). Findings were similar for children residing in districts close to the capital city and in remote areas. Cases were 5 times more likely than controls to have raised levels of both EBV and malaria antibodies (OR = 5.0; p = 0.003). Our findings suggest that EBV and malaria may act synergistically in the pathogenesis of childhood Burkitt lymphoma. Malaria prevention measures may also prevent this childhood cancer.
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PMID:Antibodies against malaria and Epstein-Barr virus in childhood Burkitt lymphoma: a case-control study in Uganda. 1800 Aug 23

Despite increasing globalisation, international mobility and economic interdependence, 9.7 million children aged less than 5 years in low income countries will die this year, almost all from preventable or treatable diseases. Diarrhoea, pneumonia and malaria account for 5 million of these deaths each year, compared to about 150,000 deaths from childhood cancer in low- and middle-income countries. In high-income countries, 80% of the 50,000 children diagnosed with cancer each year survive, yet cancer remains the leading disease-related cause of childhood death. In low- and middle-income countries, where 80% of children live, the 200,000 children diagnosed with cancer each year have limited access to curative treatment, and only about 25% survive. Some might argue that death from paediatric cancer in poor countries is insignificant compared to death from other causes, and that scarce health resources may be better used in other areas of public health. Is there a role for the treatment of children with cancer in these regions? Do international partnerships or 'twinning' programmes enhance local health care or detract from other public health priorities? What is ethical and what is possible? This review examines the health challenges faced by infants and children in low-income countries, and assesses the role and impact of international paediatric oncology collaboration to improve childhood cancer care worldwide.
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PMID:Global child health priorities: what role for paediatric oncologists? 1879 6

Endemic Burkitt lymphoma (eBL) is the most common childhood cancer in equatorial Africa and is linked to Epstein-Barr virus (EBV) and Plasmodium falciparum coinfections early in life. Epstein-Barr nuclear antigen 1 (EBNA1) is the sole viral latent antigen expressed in BL tumors. Loss of EBNA1-specific immune surveillance could allow eBL emergence. Therefore, EBNA1-specific T cell responses were analyzed by IFN-gamma ELISPOT in Kenyan children with eBL and compared to healthy children with divergent malaria exposure. Significantly fewer children with eBL, 16% (7/44) had EBNA1-specific IFN-gamma responses in contrast to healthy children living in a malaria holoendemic area or in an area with sporadic malaria transmission, 67% (40/60) and 72% (43/60) responders, respectively (p < 0.003). Children with eBL maintained IgG(1) dominated antibody responses to EBNA1 similar to healthy children suggesting a selective loss of IFN-gamma secreting EBNA1-specific T cells in the presence of intact humoral immunity. CD8(+) T cell responses to EBV lytic and latent antigens not expressed in the tumors were similarly robust in eBL patients compared to healthy children. In addition, CD4(+) T cell responses to a malaria protein, merozoite surface protein 1, were present in lymphoma patients. This study demonstrates a selective loss of EBNA1-specific T cell responses in children with eBL and suggests a potential immunotherapeutic target for this EBV-associated lymphoma.
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PMID:Children with endemic Burkitt lymphoma are deficient in EBNA1-specific IFN-gamma T cell responses. 1908 27

Despite the well-established relationship between endemic Plasmodium falciparum malaria and Epstein-Barr virus (EBV) infection in the genesis of endemic Burkitt's lymphoma (eBL), very little research has examined the interaction between these two pathogens. eBL, the most prevalent childhood cancer in equatorial Africa where malaria is holoendemic, is a high-grade B cell lymphoma characterized by a c-myc translocation and the consistent presence of EBV. After primary infection, EBV establishes a life-long persistent infection characterized by virus shedding into saliva. African children are infected early in life and most have sero-converted by 3 years of age while sero-conversion tends to occur later in developed countries. Acute and chronic malaria infections profoundly affect the B cell compartment, inducing polyclonal activation, hyper-gammaglobulinemia and a dramatic increase in the levels of circulating EBV. In this review we present and discuss recent data suggesting a molecular link between the parasite, the B cell and EBV and provide evidence that adds to the concept of polymicrobial disease pathogenesis in eBL. Following the observation of EBV reactivation in children living in malaria endemic areas and its relationship with acute malaria infection, we identified the cystein-rich inter-domain region 1 alpha (CIDR1 alpha) of the Plasmodium falciparum membrane protein 1 as a polyclonal B cell activator. CIDR1 alpha increases B cell survival and preferentially activates the memory compartment where EBV is known to persist. Analysis of the mechanisms of interaction between CIDR1 alpha and EBV in the context of B cells demonstrated that CIDR1 alpha induces virus production in the EBV-infected B cell line Akata and in latently infected primary B cells derived from the peripheral blood of healthy carriers and children with eBL. This is the first demonstration that EBV can be reactivated directly by another pathogen. Our results suggest that P. falciparum antigens such as PfEMP1 can directly induce EBV reactivation during malaria infections. The increased viral load and the concomitant polyclonal B cell activation with enhanced B cell survival may augment the risk of eBL development in children living in malaria-endemic areas.
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PMID:Endemic Burkitt's lymphoma as a polymicrobial disease: new insights on the interaction between Plasmodium falciparum and Epstein-Barr virus. 1989 39

Burkitt's lymphoma (BL) is the most common childhood cancer in Africa and is most prevalent in areas endemic for malaria. The disease, a malignant growth of lymphoid tissue, usually presents itself as a large tumor of the jaw. It is however, a rarity in the Indian subcontinent. Through an extensive literary survey, it is seen that only a few cases of BL have been reported, accounting for only 0.76% of solid malignant tumors among Indian children. Here we present a case of BL of mandible extending to maxilla in a 13-year-old boy of Indian origin.
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PMID:Burkitt's lymphoma in leukemic phase in an Indian boy. 2189 10


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