Chikungunya fever as a risk factor for endemic Burkitt's lymphoma in Malawi

Abstract

The geographical and age distributions of endemic Burkitt's lymphoma (eBL), in Africa, parallel those of certain arboviruses, which include chikungunya fever. Increased incidences of antibodies to assorted arboviruses, including chikungunya, have been found in eBL sera compared to controls. An increased incidence and space-time case-clusters of eBL occurred during a chikungunya fever epidemic which were confirmed by serology and clinical observation. The present study, conducted in 1987-89, involved 108 eBL patients, and 97 local and 111 hospital controls. We examined, as hospital controls, patients with afebrile, non-malignant conditions admitted to Kamuzu Central Hospital, Malawi, during the eBL patients' first admission there. Analyses were for hospital controls and eBL patients at the end of their first admission and for local controls and eBL patients at the beginning of their third admission, about 8 weeks after the day of first admission, because of the local controls' temporal bias. Patients in case-clusters were among those seropositive for chikungunya virus, with a history compatible with arbovirus infection preceding the lymphoma, suggesting involvement of chikungunya virus in the case-clusters and a possible association between recent infection with this virus and development of the lymphoma. eBL patients were significantly more likely to be seropositive for chikungunya virus antibody (68x5%) than either hospital controls (46.8%) or local controls (50x5%) (P = 0x002 and 0x009, respectively), raising the possibility of an association between infection with an arbovirus and developing eBL in children already primed by holoendemic malaria and Epstein-Barr virus infection.

A Role for RNA Viruses in the Pathogenesis of Burkitt's Lymphoma: The Need for Reappraisal

“…A statistically significant association between infection with the arbovirus, CHIKV and the onset of eBL was observed in Malaŵi, at the time of a CHIKV epidemic, when space-time case clusters were also being observed [12]. BL patients were significantly more likely to be CHIKV seropositive on first admission or to have seroconverted three weeks afterwards than either hospital or local controls ( P = 0.002 and 0.009, resp.)…”

“…BL patients were significantly more likely to be CHIKV seropositive on first admission or to have seroconverted three weeks afterwards than either hospital or local controls ( P = 0.002 and 0.009, resp.) [12]. A majority of BL patients, irrespective of CHIKV seropositivity, gave a history of signs and symptoms typical of arboviral infection, such as rashes, oral lesions, and bleeding tendencies, occurring shortly before the appearance of BL, as summarized in Table 3 [12, 22, 56].…”

“…[12]. A majority of BL patients, irrespective of CHIKV seropositivity, gave a history of signs and symptoms typical of arboviral infection, such as rashes, oral lesions, and bleeding tendencies, occurring shortly before the appearance of BL, as summarized in Table 3 [12, 22, 56]. Rashes and oral lesions preceding BL onset had been seen previously in Uganda and attributed to Herpes or Measles infection [110].…”

“…They are the DNA Herpes viruses, the Epstein-Barr virus [2] and Kaposi Sarcoma Herpesvirus [2, 3], the retroviruses Human Immunodeficiency Virus type 1 and Human T Cell Lymphotropic Virus Type 1 [4], the Hepatitis viruses, Hepatitis B , a DNA virus, and Hepatitis C , an RNA virus [5], and the bacterium, Helicobacter pylori [6]. In addition, the bacteria Campylobacter jejuni [7], Chlamydia psittaci and pneumoniae [8, 9], Borrelia burgdorferi [10, 11] and the RNA Alphavirus Chikungunya virus [12], an arbovirus, have been found to be associated with various different forms of lymphoma. The Epstein-Barr virus (EBV) [2], the protozoon, Malaria [13], and the vector-borne Alphavirus, Chikungunya virus (CHIKV), have been linked specifically with endemic Burkitt's Lymphoma (eBL), perhaps the best studied of all lymphomas.…”

“…It will discuss, drawing on research into lymphomagenesis in HCV infection, how the arbovirus, CHIKV, shown to be associated with the onset of eBL [12, 22], might contribute to lymphomagenesis.…”