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Query: UMLS:C0024530 (malaria)
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The association between EBV and two human tumours (BL and NPC) is presented. The BL prospective study conducted by the International Agency for Research on Cancer is progressing well, and up to date 10 pre-BL sera have been available and tested. The results show that not only every serum has VCA antibodies 7 to 31 months prior to tumour development, but that the VCA titres of such pre-BL sera appear higher than that of various age-sex matched controls. These preliminary results would favour a chronic and heavy EBV infection as a risk factor for BL. The role of co-factors, such as malaria, is discussed together with proposals of anti-malaria partial suppression scheme. The association between HSV-2 and cervical carcinoma is weaker, and HSV-2 infection could become an epidemiological marker, rather than an etiological agent for the tumour.
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PMID:[Epidemiology and nature of the association between herpesviruses (EBV and herpes simplex) and several human tumors. Recent results]. 18 71

The genesis of Burkitt's lymphoma is visualized as proceeding in three steps: I. Primary EBV infection affects the young child, probably at a relatively high multiplicity. It immortalizes a certain number of B-lymphocytes in vivo. II. This is followed by the impact of an environmental promoting agent, perhaps chronic holoendemic malaria, providing a chronic stimulus to the proliferation of the EBV-carrying preneoplastic cells. III. Chromosomally abnormal variants appear in the stimulated tissue by chance. After certain types of changes, particularly the 8 to 14 translocation that leads to the 14q+ marker, the affected B lymphocyte would no longer obey the negative feedback controls that would otherwise restrict its proliferation in vivo.
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PMID:Cancer, viruses and environmental factors. 23 49

The epidemiology of Epstein-Barr virus (EBV) infection in populations at different risk for EBV-associated diseases indicates significant differences between the populations. EBV infection takes place much earlier in Uganda, where all children are infected before the age of 2 to 3 years, than in Southeast Asia, where nasopharyngeal carcinoma is prevalent. It is proposed that such early infection in Equatorial Africa is related to the risk for Burkitt's lymphoma. Four possible interventions to control EBV-associated diseases are presented: (a) simple hygienic measures to delay natural primary infection by EBV; (b) EBV vaccine; (c) intervention against cofactors such as malaria in Burkitt's lymphoma; and (d) characterization of high-risk groups to allow early detection and successful treatment.
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PMID:Epstein-Barr virus behavior in different populations and implications for control of Epstein-Barr virus-associated tumors. 125 56

Recent investigations indicate that Burkitt's lymphoma consists of several subtypes, defined by their clinical and molecular features. Each geographical region so far studied appears to consist of a different mixture of subtypes. Interestingly, there appear to be geographic 'gradients' with respect to the fraction of tumors associated with EBV and the type of 8;14 chromosomal translocation. The rate of EBV association is highest in Equatorial Africa, lowest in North America and intermediate in South America. The fraction of tumors with breakpoints far upstream of the c-myc gene follows a similar pattern. These findings strongly suggest that the subtypes of Burkitt's lymphoma are environmentally determined, and we propose that the pattern of infection (e.g. malaria) to which the young child is exposed influences the tumor subtype distribution by altering the relative and absolute numbers of various B cell precursors at sites of B cell ontogeny (the bone marrow, and possibly mesentery). These B cell precursors are the cells which are susceptible to the specific chromosomal translocations associated with Burkitt's lymphoma. We further propose that immunoglobulin enhancers (recognized and unrecognized) both influence the likelihood of the translocation occurring, and in at least a fraction of cases, contribute to the deregulation of a c-myc. EBV, via EBNA-1, the only invariably expressed latent-gene in Burkitt's lymphoma, probably influences c-myc expression in Burkitt's lymphoma by increasing immunoglobulin enhancer function. Thus, in effect, EBV collaborates with the translocations associated with Burkitt's lymphoma in causing c-myc deregulation. This collaboration is independent of the breakpoint location. While other molecular abnormalities must be able to contribute to myc deregulation in the same way, EBV association in Burkitt's lymphoma is probably determined by the age at which EBV infection occurs (being more likely when infection occurs in very young children) and perhaps also by other infectious diseases that numerically influence the fraction, and predominant stage of differentiation (and hence translocation breakpoint sites) of immature B cells infected by EBV. The presence of EBV in many such cells greatly increases the incidence rate of Burkitt's lymphoma, since one of the genetic lesions needed to deregulate c-myc is already present.
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PMID:Epstein-Barr virus and Burkitt's lymphoma. 133 92

Eighteen tissue samples from lymphoproliferative lesions and lymphomas in immunodeficiency states were investigated for their content of Epstein-Barr virus (EBV) genome by dot blotting and for the distribution of EBV in tissue sections by in situ hybridization. Fourteen lymphomas from AIDS patients and four children with disorders of the immune system were available. For control reasons, six cases of infectious mononucleosis (IM) and eight Burkitt's lymphomas (BL) from malaria-free regions of Africa were included in the study. Two different patterns of EBV distribution are described: 1) heterogeneous scattered EBV-positive cells, as originally seen in IM and therefore called the IM-type pattern, 2) and a BL-type pattern seen in endemic Burkitt's lymphoma with homogeneous EBV-positive cells all over the tumor. In lymphomas in patients with inborn immunodeficiencies, an IM-type pattern was found. In lymphomas from AIDS patients, the two different patterns were found. There were lymphomas with the IM-type pattern as well as some with the BL-type pattern. In some AIDS-associated lymphomas, both patterns occurred in one tumor. The findings suggest that it is not the disease process that is the distinguishing feature between the two patterns of EBV infection but rather the patient's underlying disease and the extent of this disease.
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PMID:Different Epstein-Barr virus expression in lymphomas from immunocompromised and immunocompetent patients. 169 92

Epstein-Barr virus and HTLV-1 are both lymphotropic viruses, capable of immortalizing lymphocytes in vitro (Fig. 1). Both viruses have been sequenced and subjected to intense molecular biologic scrutiny, and in both cases genes believed to be important in lymphocyte immortalization have been identified. These viral genes are not homologues of cellular oncogenes, nor is there any evidence to suggest insertional mutagenesis. Rather, these genes alter the expression of a variety of cellular genes and, in so doing, alter the growth characteristics of the host cell. Infection with either virus is most likely to be asymptomatic, associated with a benign self-limited lymphoproliferation, or both, but in a small fraction of instances these benign lymphoproliferations give rise to a lymphoma or leukemia. In the case of the Epstein-Barr virus, a variety of cofactors have been identified that are important to the evolution of malignancy. These cofactors include immunosuppression in transplant recipients, cogenital immunodeficiency in the X-linked lymphoproliferative syndrome, human immunodeficiency virus infection in AIDS patients, and malaria in patients with endemic Burkitt's lymphoma. In the case of HTLV-1, cofactors have not been identified. Nonetheless, the importance of cofactors is suggested by the small fraction of the population infected by the virus who actually develop lymphoproliferative disease, and the long latency period between infection and the development of frank lymphoproliferative disease. In organ transplant recipients with lymphomas associated with Epstein-Barr virus infection, the EBV immortalizing/transforming genes are expressed in the malignant tissue. But in Burkitt's lymphoma and in adult T-cell leukemia/lymphoma, the EBV and HTLV-1 immortalizing/transforming genes are not detectably expressed. In Burkitt's lymphoma, it is suggested that the dysregulated myc gene renders the growth effects of Epstein-Barr virus latency genes superfluous. No comparable proto-oncogene translocation or activation has yet been identified in HTLV-1 lymphoma/leukemia.
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PMID:Human lymphotropic viruses associated with lymphoid malignancy: Epstein-Barr and HTLV-1. 217 3

A demographic and serological survey of Epstein-Barr virus infection was carried out in 5 geographically representative regions of Ethiopia. 80% of the 500 people studied were under 15 years of age. 82% of children under 5 years of age and 94% under 10 years of age were positive for IgG anti-viral capsid antigen (VCA) antibody. 51 of 100 children under 12 months of age and from 5 different provinces were positive for anti-VCA antibody. Of these, 23 were under 6 months. The distribution of anti-VCA antibody positivity was comparable in both sexes, in each age group and in the different provinces at different altitudes. Economic status, expressed in terms of estimated income, type of water supply, mode of excreta disposal and family size, did not significantly influence the distribution of anti-VCA antibody. Thus, early exposure to Epstein-Barr virus, with asymptomatic or subclinical presentation, probably accounts for the rarity of typical infectious mononucleosis in young adult Ethiopians. The lack of a relationship between Epstein-Barr virus infection and Burkitt's lymphoma, nasopharyngeal carcinoma, malaria as well as liver diseases is briefly discussed.
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PMID:Serological and demographic survey of Epstein-Barr virus infection in Ethiopia. 283 81

Both Epstein-Barr virus and malaria have been implicated as possible factors in Burkitt's lymphoma. To examine this implication a cross-sectional serological survey of an urban and a rural population in Ghana was conducted. Malaria was more prevalent in the rural areas, but there was no difference in antiviral capsid antigen (VCA) antibody titres between urban and rural dwellers. There was also no correlation between anti-malaria antibody titres and anti-VCA antibody titres. Thus malaria does not seem to influence immunological response to Epstein-Barr virus infection, as measured by anti-VCA antibodies. These results suggest that if Epstein-Barr virus infection and malaria are important in the aetiology of Burkitt's lymphoma, they produce their effects independently. The survey also showed that those in rural areas seroconverted earlier than those in urban areas, and that antibody levels were consistently higher in females than in males in every age-group. Case-control studies and screening programmes involving anti-VCA levels will therefore have to take these two findings into account.
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PMID:Malaria, sex, and place of residence as factors in antibody response to Epstein-Barr virus in Ghana, West Africa. 611 82

The Epstein-Barr Virus (EBV) is consistently found in tumor cells of Burkitt's lymphoma (BL) endemic in central Africa and malaria is considered a pathogenic cofactor. In contrast, fewer than 20% of BL cases occurring in Western countries are EBV-associated. We have investigated 54 BL cases from Bahia, a tropical region of Northeast Brazil, for expression of EBV gene products by in situ hybridization and immunohistology and performed typing of the EBV by polymerase chain reaction. Ten pediatric BL cases from Germany served as controls. New cases of malaria were not observed in the period and area of our study. Small nuclear EBV encoded transcripts, EBER, were found in tumor cells of 47 of 54 Brazilian cases (87%) but in only 2 of 10 German cases (20%). Type I latency of the EBV infection with absence of EBV-encoded proteins LMP1 and EBNA2 was found in 45 of 47 of the EBER-positive Brazilian cases. In two cases, occasional LMP1-containing tumor cells were found in the neighborhood of small Schistosoma mansoni granulomas and scars. BHLF1 transcripts associated with lytic EBV infection could be detected in few cells in 3 of the 40 EBER-positive Brazilian cases investigated. EBV type A was found in the majority of Brazilian BL cases (20 of 30 A-type, 7 of 30 B-type, and 3 of 30 not amplifiable). Our results indicate that the association of Bahian BL with EBV, but not the regional prevalence of malaria, is similar to endemic African BL. In two cases, type II latency was found in association with schistosomiasis, suggesting a role of this parasitosis in the induction of an EBV expression pattern that is unusual for BL. Because chronic schistosomiasis is associated with elevated Th2 cytokine expression resulting in reduced cell-mediated cytotoxicity, it seems possible that altered local immunity is responsible for this peculiar phenotype.
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PMID:Expression of Epstein-Barr virus-gene products in Burkitt's lymphoma in Northeast Brazil. 973 Oct 79

Epstein-Barr virus (EBV) has been linked to several undifferentiated carcinomas of the aerodigestive tract, especially the nasopharynx, but has not been reported in the biliary tract. We here presented a case of an unusual cholangiocarcinoma harboring EBV genome in a 47-year-old Chinese woman. Physical examination in 1988 in Taiwan, including abdominal sonography of the liver, was essentially negative. She experienced three episodes of malaria in 1990 when she worked in Ghana, Africa, and felt a tumor mass in the epigastrium in October 1992. She received an extended left lobectomy for a huge hepatic tumor of 12 x 10 x 5.5 cm in February 1993. Light microscopy revealed a cholangiocarcinoma composed of both well-differentiated adenocarcinoma and lymphoepitheliomatous undifferentiated carcinoma components. Abundant EBV EBER1 was shown in both tumor components, but not in the nontumor liver. Southern blot analysis and polymerase chain reaction showed a monoclonal episomal form of EBV, with a genotype characteristic for Chinese EBV strain type 1. This finding suggests that the EBV infection preceded monoclonal EBV-harboring tumor cell expansion in this case.
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PMID:Clonal Epstein-Barr virus associated cholangiocarcinoma with lymphoepithelioma-like component. 876 21


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