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Query: UMLS:C0024530 (malaria)
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Burkitt lymphoma (BL), a tumor occurring in endemic, sporadic and AIDS-associated forms, is the classic example of a human malignancy whose pathogenesis involves a specific cellular genetic change, namely, a chromosomal translocation deregulating expression of the c-myc oncogene, complemented in many cases by the action of an oncogenic virus, the Epstein-Barr virus (EBV). Here we review recent work in two complementary areas of research: (1) on cellular genetic changes that occur in addition to the c-myc translocation in BL, in particular the capacity of p53/ ARF pathway breakage or of c-myc mutation to decouple the pro-proliferative effects of c-myc deregulation from its pro-apoptotic effects; and (2) on a postulated role for EBV in BL pathogenesis, through adopting restricted forms of virus latent gene expression that remain compatible with the c-myc-driven growth program but offer the tumor additional protection from apoptosis. We stress the many fundamental questions that remain to be resolved and, in that regard, highlight the general lessons that might be learned through understanding how two other infectious agents, malaria and HIV, dramatically enhance BL incidence.
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PMID:Burkitt lymphoma: revisiting the pathogenesis of a virus-associated malignancy. 1802 41

Burkitt lymphoma (BL) is an aggressive B-cell malignancy with endemic, sporadic and immunodeficiency-associated variants. It has been known for many years that the fundamental transforming event in BL is the translocation of the MYC gene, and the events that bring about this translocation and those that allow cells to survive with the constitutive expression of MYC have been the subject of intense investigation. Epstein-Barr virus (EBV) infection, malaria, immunodeficiency and spontaneous, somatic mutation can all contribute to the origin and maintenance of this cancer and their mechanisms are the subject of this review.
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PMID:Epstein-Barr virus and Burkitt lymphoma. 1804 96

Burkitt's lymphoma (BL) was first described in Eastern Africa, initially thought to be a sarcoma of the jaw. Shortly it became well known that this was a distinct form of Non Hodgkin's lymphoma. The disease has given insight in all aspects of cancer research and care. Its peculiar epidemiology has led to the discovery of Epstein Barr virus (EBV) and its importance in the cause of several viral illnesses and malignancies. The highest incidence and mortality rates of BL are seen in Eastern Africa. BL affects mainly children, and boys are more susceptible than girls. Evidence for a causal relationship between EBV and BL in the endemic form is fairly strong. Frequency of association between EBV and BL varies between different patient groups and different parts of the world. EBV may play a role in the pathogenesis of BL by deregulation of the oncogene c-MYC by chromosomal translocation. Although several studies suggest an association between malaria and BL, there has never been a conclusive population study in support of a direct role of malaria in causation of BL. The emergence of HIV and a distinct subtype of BL in HIV infected have brought a new dimension to the disease particularly in areas where both HIV and BL are endemic. BL has been reported as a common neoplasmin HIV infected patients, but not in other forms of immuno-depression, and the occurrence of BL seems to be higher amongst HIV positive adults, while the evidence of an association amongst children is still disputed. The role of other possible risk factors such as low socio-economical status, exposure to a plant species common in Africa called Euphorbiaceae, exposure to pesticies and to other infections such as schistosomiasis and arbovirus (an RNA virus transmitted by insect vectors) remain to be elucidated.
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PMID:Burkitt's lymphoma in Africa, a review of the epidemiology and etiology. 1805 71

We reviewed the scientific literature on Burkitt's lymphoma (BL) in Africa in order to provide information on the current status of clinical care and the existing research challenges. BL epidemiology led to the discovery of the Epstein Barr virus, an important cause of several viral illnesses and malignancies. The incidence of BL has increased in the endemic areas of Africa, overlapping with the epidemic of HIV and increase of malaria. The impact of this on the clinical care of BL in the region is therefore of interest, especially in HIV-infected children. Rapid methods must be developed which enable the correct diagnosis to be made. It is important to improve supportive care to allow fairly aggressive treatment, to research into salvage therapy for those who fail first-line treatment, and to develop less toxic drug combinations for HIV-infected patients. Documentation of HIV status through counselling should be offered to all patients.
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PMID:Current investigations and treatment of Burkitt's lymphoma in Africa. 1830 50

Burkitt lymphoma (BL) is an aggressive B-cell malignancy with endemic, sporadic and immunodeficiency-associated variants. It has been known for many years that the fundamental transforming event in BL is the translocation of the MYC gene, and the events that bring about this translocation and those that allow cells to survive with the constitutive expression of MYC have been the subject of intense investigation. Epstein-Barr virus (EBV) infection, malaria, immunodeficiency and spontaneous, somatic mutation can all contribute to the origin and maintenance of this cancer and their mechanisms are the subject of this review.
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PMID:Epstein-Barr virus and Burkitt lymphoma. 1871 17

Burkitt's lymphoma (BL) was first described 50 years ago, and the first human tumour virus Epstein-Barr virus (EBV) was discovered in BL tumours soon after. Since then, the role of EBV in the development of BL has become more and more enigmatic. Only recently have we finally begun to understand, at the cellular and molecular levels, the complex and interesting interaction of EBV with B cells that creates a predisposition for the development of BL. Here, we discuss the intertwined histories of EBV and BL and their relationship to the cofactors in BL pathogenesis: malaria and the MYC translocation.
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PMID:The curious case of the tumour virus: 50 years of Burkitt's lymphoma. 1900 91

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

The epidemiology of Burkitt lymphoma (BL) has never been documented in Cameroon. Data were collected from 16 hospitals, the Delegation of Public Health and the regional pathologist in the Northwest province of Cameroon on all BL cases. The incidence of BL in this region is 5.9/100,000 children aged <15 years/year - the second highest incidence documented to date. Significant clustering was also identified in Ndop, a low-lying region with a high malaria endemicity, at 21.5 cases/100,000 children aged <15 year/year (P < 0.001).
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PMID:The incidence, clustering and characteristics of Burkitt lymphoma in the Northwest province of Cameroon. 1967 77

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

Great progress has been made in the care of children with cancer in recent decades. Worldwide, more than 80% of children with cancer live in resource-limited countries where access to care is poor. Sub-Saharan Africa is the world's poorest region. Child mortality is high, caused by largely preventable and treatable conditions. Paediatric cancer accounts for only a small fraction of deaths and understandably receives little attention from local policy makers or global health agencies. The survival of children with cancer is very poor. Challenges to improving survival include advanced-stage disease at presentation, failure to start or complete treatment (abandonment), inadequate hospital infrastructure and medications, lack of trained health care providers, lack of cancer registration and follow-up and lack of treatment guidelines adapted to local medical facilities. We propose a stepwise approach that integrates paediatric cancer treatment with existing general paediatric care. Priority is given to interventions (improvement of supportive care, diagnostic facilities) that also improve general paediatric care. Minimal requirements for diagnostic procedures include complete blood counts, HIV and malaria tests, blood cultures, histopathology and simple imaging (X-ray and ultrasonography). Feasible interventions include adequate palliative care, curative treatment for Burkitt lymphoma and Wilms tumour and symptomatic treatment for Kaposi sarcoma.
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PMID:Strategies to improve care for children with cancer in Sub-Saharan Africa. 2040 85


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