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Query: UMLS:C0024530 (malaria)
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From 1977 to 1982, the authors attempted a malaria suppression trial in North Mara District, Tanzania, to see whether the incidence of Burkitt's lymphoma (BL) could be lowered by reducing the level of malarial infection in a child population below 10 years of age. Immediately after initiation of the suppression trial, the prevalence of malaria fell drastically in the Mara children; however, soon after, the rate of malarial infection rose again in the trial area in spite of continued chloroquine distribution, and by 1981 the prevalence of malarial infection again reached the high levels that had prevailed in the North Mara lowlands before 1977. However, during the period of chloroquine distribution in North Mara, the level of malarial infection there was constantly lower than that observed in a comparison area in South Mara, although the two areas had been similar with respect to malaria endemicity prior to the intervention. During the years of chloroquine distribution in North Mara, the incidence rate of BL there fell considerably, from about 4 per 100,000 population to about 1 per 100,000 population, and it rose again to pretrial levels in 1984, that is, about two years after the chloroquine distribution had been terminated. This apparent association between malaria suppression and decline in BL incidence at first seemed to indicate that malaria is a causal factor in BL production. A close scrutiny of the survey data revealed, however, that the decline in BL incidence might have started several years before the chloroquine distribution began; thus it appears that the malaria suppression could not have been the sole cause of the BL decline.
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PMID:Effect of a malaria suppression program on the incidence of African Burkitt's lymphoma. 292 22

The Epstein-Barr virus (EBV), a B lymphotropic virus, is involved in a growing number of immunopathological disorders benign or malignant. The X-linked lymphoproliferative syndrome and its multifaceted clinical expression in a unique situation described in this issue by Purtilo. Among recent findings, the association between EBV and idiopathic interstitial pneumopathy (also named cryptogenic fibrosing alveolitis), is to be noted (6). From a molecular biology view-point, in vitro immortalization of B lymphocytes by EBV is under a pluri-genic (EBNA 2, EBNA 1, LYDMA) control. The role of EBV in oncogenesis appears different in Burkitt's Lymphoma (BL) and in nasopharyngeal carcinoma (NPC). In development of African BL, EBV appears to initiate the multistage carcinogenic event, through an early and massive infection. Other events include specific depression of T-cell immunity by hyperendemic malaria and c-myc onc-gene activation through chromosome translocation. In the genesis of NPC, the role of EBV still remain to be clarified although the strong and consistent association between EBV and the undifferentiated carcinoma of the nasopharyngeal (NPC) around the world favours an etiological relationship. The simple detection of IgA antibodies to VCA and EA allows early detection of the NPC, thus permitting a 95% cure rate at 5 years post-radiotherapy. Such an early diagnostic is of paramount public health importance. Furthermore, IgA/VCA and IgA/EA antibodies characterize precancerous conditions, giving the theoretical possibility of preventive interventions.
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PMID:The Epstein-Barr virus (EBV): a Rosetta Stone for understanding the role of viruses in immunopathological disorders and in human carcinogenesis. 299 May 89

Burkitt's lymphoma (BL) in tropical Africa represents by far the most common tumour in children between 0 and 14 years of age, 97% of the tumours being associated with Epstein-Barr virus (EBV). In North Africa, the tumour is about ten times less frequent than in equatorial Africa, but, according to reports from Algeria, 85% of the cases appear to be associated with EBV. In Western countries, BL represents about 3% of childhood tumours, 10 to 15% of them EBV-associated. Thus, from the northern industrialized countries to the equatorial developing countries, increasing incidences of lymphomas of the BL type are paralleled by an increasing proportion of EBV-associated cases. The Ugandan BL prospective study showed that high antibody titres to viral capsid antigen (VCA) preceded BL development by many years, with a quantifiable relationship between the level of VCA antibodies and tumour risk. If an early and/or massive EBV primary infection seems to represent the critical event for BL development in equatorial Africa, the favourable conditions for EBV-associated tumours in North Africa and in Europe remain to be investigated. Malaria appears to favour BL development through an EBV-specific T-cell immune deficiency. Chromosomal translocations and oncogene activation, considered as the final step in lymphoma development, do not appear to be related to EBV. Intervention against the virus may represent the ultimate proof of a causal relationship between EBV and the majority of BL cases around the world.
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PMID:Epstein-Barr virus and Burkitt's lymphoma worldwide: the causal relationship revisited. 299 87

Burkitt's lymphoma, characterized by jaw and abdominal tumors, is the most common early childhood malignancy in Central Africa and well-known in the United States, with only sporadic reports coming from other countries. Considered to be the fastest growing tumor in man, it is thought to be of viral etiology with warm, humid climate and malaria regarded as co-factors. This is the first case of Burkitt's lymphoma reported from Greece.
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PMID:Non-endemic Burkitt's lymphoma. 308 11

Pre- and post syndrome sera from five Burkitt's lymphoma patients who partook in the Ugandan prospective study (A. Geser et al., Int. J. Cancer 29 (1982) 397-400) were investigated with respect to autoantibodies. Neighbours and siblings of these patients served as controls and all of these groups were compared with sera from 50 Caucasian normal controls (CNC). Antibody levels significantly higher than those in CNC were found in all African groups for actin, desmin, vimentin, tubulin, keratin, laminin, and collagen type I. Polyclonal B-cell activation, as measured by antibodies to DNP, and high levels of antibodies to P. falciparum were also found. Anti-DNP and antibodies to malaria were also present in sera from our earlier study on Burkitt's lymphoma (E. Vainio et al., Clin. exp. Immunol. 54 (1983) 387-396). Whereas EBV infected B cells do produce autoantibodies, there is a potentiation of autoantibody formation as a result of infection with malaria, which seems to provide an independent trigger of polyclonal B cell activation. This latter event might be one of the factors which results in a correlation of Burkitt's lymphoma with malaria endemic regions.
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PMID:Autoantibodies in Burkitt's lymphoma patients from the Ugandan prospective study. 351 27

Nearly all epidemiological characteristics of Burkitt's lymphoma (BL) can be explained on the basis of relationships of BL to the intensity of the host response to Plasmodium falciparum. The major epidemiological associations are: the high degree of geographic correlation between the incidence rate of BL and the intensity of P. falciparum transmission, both at a global level and within individual countries; the close correlation between the age incidence of BL and the age of acquiring maximum levels of antimalarial immunoglobulin; the relative protection from BL by residence in urban areas, where levels of malaria transmission are lower, compared with rural areas; the decline in BL incidence in areas where death rates due to malaria have declined and, within such areas, a differential decline in BL incidence in people making better use of health facilities; the older age of onset in patients who have migrated from low-intensity to high-intensity malaria areas as compared with patients born in the high-intensity areas - the higher absolute age-specific incidence rate in those above age ten in this immigrant group being consistent with the hypothesis that intense malaria infection and consequent host defence response serve as the major triggering event in the pathogenesis of the lymphoma; the inverse geographic correlation between the average age of onset of BL and the intensity of falciparum malaria infection. An inverse association of BL with sickle-cell trait (AS haemoglobin) would provide strong evidence for the role of intense falciparum malaria, but most studies to date have not achieved statistical significance. Time-space clustering and reports of seasonal variation in BL incidence would indicate that a precipitating factor operates over a relatively short time-span, at least in some areas. Combining the evidence concerning cytogenetics, Epstein-Barr virus (EBV) and falciparum malaria, the following three-phase model for the oncogenesis of BL could account for virtually all the currently known facts and be tested by further laboratory and field studies: Primary infection with EBV, perhaps early and intense, leads to the immortalization of large numbers of B lymphocytes. Severe falciparum malaria then leads to an intense host response with particular proliferation of the EBV-infected B lymphocytes. Finally, the great increase in the B lymphocytes provides a much higher statistical opportunity for the emergence of the cytogenetically abnormal BL cell.
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PMID:Epidemiological evidence for the role of falciparum malaria in the pathogenesis of Burkitt's lymphoma. 390 88

Antibodies with different spectra of reactivity are produced during malarial infections and marked changes in IgG and IgM levels occur. In addition malaria elicits serological changes that are usually associated with connective tissue disease. The excessive anaemia associated with malaria may, in part, be an autoimmune phenomenon. Transient nephritis accompanies many plasmodial infections but chronic malarial nephrotic syndrome is specifically associated with quartan malaria. Malarial infection leads to splenomegaly, the most extreme form of which is idiopathic tropical splenomegaly, which probably represents an aberrant immune response to the infection. Malaria can affect the humoral immune response to unrelated antigens and infectious agents. This may be relevant to the etiology of Burkitt's lymphoma. During pregnancy there is some loss of acquired immunity to P. falciparum and the placenta appears to be an immunologically privileged site for the multiplication of this parasite.
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PMID:Immunopathology of malaria. 421 8

The clinical picture and local epidemiology in 65 cases of Burkitt's lymphoma seen in Ilesha, Western Nigeria, over a 16-year period is presented. Incidence figures have been calculated and comparison made with other Nigerian and East African reports. Ilesha is the centre of a high tumour density area. A changing pattern of presentation over the years has evolved. Its possible relationship to the treatment of malaria and immunization facilities is suggested and discussed.
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PMID:Burkitt's lymphoma in Ilesha, Western Nigeria. 558 2

Epstein-Barr virus (EBV), although not an indispensable factor for the development of Burkitt lymphoma, is apparently associated with the 20-fold higher incidence of the disease in Equatorial Africa compared to the incidence in other parts of the world. To determine whether different EBV subtypes are associated with the appearance of the malignant phenotype, we have compared the EBV genomes carried in the Burkitt tumor cells with those carried in the nonmalignant lymphoblastoid cells from the same individuals. From three patients with EBV -associated Burkitt lymphoma, tumor cell lines as well as spontaneously established lymphoblastoid cell lines representing the nonmalignant counterparts were obtained. The viral DNA in these cell lines was analyzed by Southern blot hybridization, using a set of cloned EBV DNA fragments as probes that recognize polymorphic regions in the viral genome. Using a number of different polymorphic markers to distinguish one isolate from another, the virus genome found in the tumor cells could also be identified in the nonmalignant cells of the same patient. In one case, in which two independent lymphoblastoid cell lines were established, evidence was obtained that this patient was infected by at least two distinct EBV subtypes. These results strongly suggest that in Burkitt lymphoma, the risk associated with EBV is related to cofactors such as chronic malaria and the mode of infection rather than to peculiar viral subtypes. The situation seems to be totally different from papillomavirus-associated diseases, in which the risk of progression to malignancy appears to be associated with particular viral strains.
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PMID:No evidence for differences in the Epstein-Barr virus genome carried in Burkitt lymphoma cells and nonmalignant lymphoblastoid cells from the same patients. 608 53

Endemic Burkitt's lymphoma, a tumour of children in which B lymphocytes are infected with Epstein-Barr virus (EBV), is common in areas of Africa where malaria is holoendemic. The tumour is characterized by chromosome translocations; usually the terminal portion of chromosome 8 containing the c-myc gene is translocated to chromosome 14, near the enhancer of the immunoglobulin heavy-chain locus. Less frequent are translocations of chromosome 8 to the kappa light-chain locus of chromosome 2 or to the lambda light-chain locus of chromosome 22. In vitro, EBV induces B cells to proliferate and secrete immunoglobulin and antibody. However, in vivo the infected B lymphocytes are under immunological control, so that abnormal proliferation is found only in immunosuppressed patients. Such patients are subsequently liable to develop lymphomas. Burkitt believed that the tumour he had described resulted from interaction between a virus(es) and a "reticuloendothelial system altered by chronic and heavy infection by malarial or other parasites". We report here that during an attack of Plasmodium falciparum malaria, T-cell subpopulations are radically altered so that, in vitro, B lymphocytes infected with EBV proliferate abnormally to secrete large amounts of immunoglobulin and antibody. This phenomenon offers some explanation for the increased incidence of Burkitt's tumour and the high levels of immunoglobulin found in people living in areas where P. falciparum malaria is common.
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PMID:T-cell control of Epstein-Barr virus-infected B cells is lost during P. falciparum malaria. 609 4


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