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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Chloroquine (CHL) has been suggested to play an important role in the development of Burkitt's lymphoma by enhancing Epstein-Barr virus expression. Herpes zoster virus incidence is markedly increased following malaria infection in children being treated with CHL. Recently, CHL has also been shown to dramatically increase the transactivation of Tat protein purified from human immunodeficiency virus. These previous studies indirectly suggest that CHL may be involved in the enhancement of virus replication. This study demonstrates for the first time that CHL indeed enhances Semliki Forest virus and encephalomyocarditis virus replication in mice. These results raise the possible connection between the increased spread of AIDS in endemic malaria areas and the wide use of CHL in those areas for the chemotherapy of malaria.
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PMID:Chloroquine enhances replication of Semliki Forest virus and encephalomyocarditis virus in mice. 184 12

Children living in hyperendemic malarious regions have high immunoglobulin levels and an increased frequency of Burkitt's lymphoma. In a study of Gambian children which endeavours to explain these findings we showed that acute P. falciparum malaria caused spontaneous activation and growth of their B lymphocytes in vitro. A high proportion of these cells contained Epstein-Barr nuclear antigen (EBNA). In ancillary experiments aimed at explaining these findings. CD4 helper cells from adult donors were destroyed with monoclonal antibody and complement. This manoeuvre resulted in loss of cytotoxic T cell control of their B lymphocytes when infected with Epstein-Barr virus (EBV). In children with acute malaria, both spontaneous immunoglobulin and antibody production by B cells was increased yet CD4 helper cell control over these cells, as measured by responses to pokeweed mitogen, was found to be intact. Spontaneous and concanavalin A-driven lymphocyte proliferation was depressed. We infer from these findings that in patients with P. falciparum malaria loss of cytotoxic T cell control of the EBV in B cells, possibly due to destruction or dysfunction of a subset of CD4 cells responsible for induction of suppressor/cytotoxic CD8 cells, leads to activation and proliferation of foci of B cells containing EBV. The expanded pool and rapid turnover of these cells may increase chances of malignant transformation leading to the genesis of Burkitt's tumor. Partial loss of suppressor mechanisms coupled with normal CD4 helper/inducer activity may result in high serum levels of immunoglobulin which are characteristic of persons living in malarious regions.
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PMID:The effects of Plasmodium falciparum malaria on immune control of B lymphocytes in Gambian children. 197 71

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

Peripheral blood lymphocytes from healthy, Epstein-Barr virus (EB-virus)-seropositive donors and from patients with acute Plasmodium falciparum malaria were tested for their cytotoxicity towards autologous EB-virus-infected B-cells using an in vitro regression assay. Of the 18 cultures from control donors, 88.8% showed the normal pattern of regression. Of the 20 malaria patients in the study, 40% failed to exhibit the normal pattern observed in the control group. Analysis of the lymphocyte subsets showed a high incidence of inverted CD4:CD8 ratios in the patient group due to an absolute rise in the CD8 population. This data suggests that the immunosuppressive effects of acute malaria extend to defective control over EB-virus. The relevance of the observations to the aetiology of EB-virus-associated, endemic Burkitt's lymphoma (eBL) is discussed.
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PMID:In vitro analysis of Epstein-Barr virus: host balance in patients with acute Plasmodium falciparum malaria. I. Defective T-cell control. 216 84

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

Biopsies of malignant lymphomas collected from all districts of Uganda, filed in the Kampala Cancer Registry for the 8-year period 1966-1973, were reviewed. This review confirmed a relatively low frequency of follicle-centre-cell lymphomas with a follicular growth pattern and the geographical co-distribution between malaria and Burkitt's lymphoma (BL). It also showed a similar, though less marked, association between non-Burkitt, non-Hodgkin's lymphoma (NBNHL) and malarial endemicity, and a correlation in the regional incidence between BL and NBNHL. In both comparisons, these associations were strong for high-grade lymphomas and weak for low-grade neoplasms. BL and other NHL may therefore share, to a varying degree, some common pathogenesis. The excess in frequency of NBNHL of high-grade malignancy in malarial endemic areas appears to be in contrast to Western countries where most non-Hodgkin's lymphomas are of low-grade malignancy.
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PMID:The distribution of non-Burkitt, non-Hodgkin's lymphomas in Uganda in relation to malarial endemicity. 232 41

Burkitt's lymphoma is characterized by particular epidemiological features. It is a frequent childhood tumor in children in tropical Africa and occurs at a much lesser frequency all over the world. Chromosomal translocation affecting the long arm of chromosome 8 (band 8q24) and one of the chromosomes carrying the immunoglobulin loci (chromosomes 2, 14 or 22) are regularly observed in Burkitt's lymphoma, regardless of whether the tumor occurred in high or low incidence areas. The prevalence of Burkitt's lymphoma in Africa appears to be related to two factors: holo- or hyperendemic malaria and presence of Epstein-Barr virus genomes in the tumor cells. We present a model of pathogenesis, in which stimulation of B cells by malaria is the primary event in the development of the disease. The risk of the chromosomal translocation should be increased by increasing the number of new B cells generated per time. According to our model, the translocation leads to constitutive c-myc activation and makes the cells responsive to growth factors without inducing proliferation on its own. Infection of a translocation-carrying cell with EBV may provide an additional growth advantage and drive the cell further towards a fully malignant state.
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PMID:[Chromosome translocations and Epstein-Barr virus in Burkitt's lymphoma]. 282 99

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

The recognition of Burkitt lymphoma (BL) as a clinical syndrome and a pathological entity in African children resulted from astute clinical observations (bedside epidemiology), the availability of cancer registry data and accurate pathological interpretation. Following the early studies in Africa, it soon became evident that this tumor occurred worldwide and the excess of cases in Africa was an incidence phenomenon associated with specific environmental factors. The sentinel discovery of the Epstein Barr virus (EBV) and its association with BL stimulated a wide variety of scientific investigations which have had an impact of virtually every discipline and biology. Epidemiological observations linked to modern laboratory techniques have provided etiological insights which implicate specific environmental factors and genetic events in the pathogenesis of BL and other immunoproliferative diseases. Early infection with EBV and holoendemic malaria are clearly of paramount importance in the development of endemic BL (eBL). These factors do not play a role in the majority of sporadic BL (sBL) cases, but immunosuppression and T-cell deregulation almost certainly are common denominators. The final or principle genetic event in both instances would appear to be the chromosome 8 translocation involving the c-myc oncogene and structural alteration. It is expected that the BL model will continue to be a useful one for identifying basic mechanisms in carcinogenesis which may be applicable as well to a variety of non-neoplastic diseases.
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PMID:Malignant lymphoma in African children: three decades of discovery. 285 87

The ubiquitous, DNA herpesvirus, EBV, has B cell tropism and the geographically restricted RNA retrovirus, ATLV/HTLV-I has T cell tropism. Clinical descriptions by Burkitt and Takatsuki led to discovery of these viruses which infect silently early in life; however, ATLV is also transmitted to a spouse or by blood transfusion. In normal seropositive persons both viruses infect only 1 in about 10,000 B or T cells, respectively. EBV is associated with Burkitt's lymphoma, nasopharyngeal carcinoma, and infectious mononucleosis. ATLV is associated with adult T cell leukemia/lymphoma and smoldering T cell lymphoma. EBV infects polyclonally and is controlled by multiple cellular and humoral control mechanisms. Escape from immune surveillance as in immune deficient African children with malaria, males with x-linked lymphoproliferative syndrome, organ transplant recipients, and AIDS patients permits conversion from polyclonal to oligoclonal and finally, monoclonal malignancy. T cell immune defects permit proliferation of cells which undergo molecular and/or cytogenetic alterations. In contrast to EBV, which is integrated and nonintegrated in B cells, ATLV is monoclonally integrated. Viral transforming proteins and immune suppressive substances are produced. Immune deficiency in silent carriers of ATLV and in those with smoldering ATL suggest that immune surveillance deters emergence of ATL. Prevention of primary infection by vaccination against these lymphotropic viruses, and use of immunotherapy and antiviral drugs may potentially retard conversion of infected B or T cells to monoclonal malignancy.
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PMID:Lymphotropic viruses, Epstein-Barr virus (EBV) and human T-cell lymphotropic virus-I (HTLV-I)/adult T-cell leukemia virus (ATLV), and HTLV-III/human immune deficiency virus (HIV) as etiological agents of malignant lymphoma and immune deficiency. 288 52


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