Biography

Dr. Biggar received an M.D. from Baylor Medical School, and is a physician epidemiologist. He is board certified in pediatrics and worked previously at the Centers for Disease Control and Prevention. Dr. Biggar joined the NCI in 1975, and was stationed for four years in Ghana, West Africa, where he studied children with lymphoma. He transferred to the Epidemiology and Biostatistics Program in 1980. Dr. Biggar's research focuses mainly on retroviruses and herpesviruses, immunity-related conditions, and cancer related to immunity, especially NHL and Kaposi's sarcoma. He serves as the Branch's International AIDS Coordinator.

Research Interests

Persons infected with human immunodeficiency virus (HIV) or human T cell lymphotropic virus (HTLV) are at significantly increased risk of cancer. Our research is focusing on the biology and epidemiology of these viruses, including their transmission routes, natural history, and population distribution.

Perinatal Transmission Studies

Principal routes for the spread of HIV are sexual contact and exchange of blood products. However, perinatal transmission is a major contributor to risk of infection in Africa and other areas of the world with high HIV prevalence among young women. In Africa, infants are frequently infected and the natural history of transmission has been the focus of many of his studies. Recently, he has shown that girls have higher risks of acquiring perinatal infection than boys. In conjunction with this, he has also found that infants sharing HLA alleles with their mothers are more likely to acquire HTLV infection when mothers are infected. These findings argue that the immunity interactions between mother and foetus are important health parameters. Our studies of twins born to HIV-infected mothers are continuing, in an effort to better understand the factors that influence viral transmission. However, he has already examined risk of infection and divergence of strains in co-infected twins in whom the source must have been the mother. These findings indicate that factors intrinsic to the virus, not just the host, bear on rapidity of mutation.

Cancer Risk in HIV-infected Individuals

Risks for Kaposi's sarcoma and non-Hodgkin's lymphoma are markedly increased in HIV- infected persons, and Hodgkin's disease is also increased by as much as eight-fold. To determine which other malignancies are associated with HIV infection or its sequelae and to quantify risks, we linked population-based AIDS and cancer registry data in 15 locations in the United States. Registry data were matched for over 500,000 AIDS patients. Compared with adults, the data show a lower risk (2.5% versus 6%) of cancer in children with AIDS, but non-Hodgkin's lymphoma still dominates the increased risk. Most of the non-Hodgkin's lymphoma are B-cell types, but within this catch-all group, different types appear to have differing pathogenesis. Kapposi's sarcoma and non-Hodgkin's incidence have both declined in the general population in recent years because of the decline in AIDS cases and improved therapies for those with AIDS. Underlying this change is a great improvement in immunity in persons with AIDS and with immunology strengthening, NHL and Kaposi's risks have declined by varying amounts. Hodgkin lymphoma risk, for example, actually declines when people become profounded immunosuppressed, possibly because symptoms are related to recruitment of the host's own immune system. These findings have interesting pathogenesis implications.

Kaposi's Sarcoma-Associated Herpesvirus Studies

In extensive studies, we evaluated testing methods for Kaposi's sarcoma-associated herpesvirus (KSHV), a recently described virus etiologically linked to Kaposi's sarcoma. In Brazilian Amerindians, we found a remarkably high prevalence of KSHV, suggesting that it is an ancient virus associated with man. In Africa, his studies have found prevalence to be very high, and poverty/cleanliness/lack of water access may be risk factors for transmission. Recent studies in Uganda have shown blood transfusion transmission, albeit at only a low level. In Uganda, primary infections occur in mid childhood, and thus, most are not directly transmitted perinatally. Children appear to develop infection via salivary exposure, which may occur within families or from playmates. Viral level appear to be high, which may account for the high risk of Kaposi's sarcoma in Uganda.

Keywords

HIV, human papillomavirus, human T cell lymphotropic virus type (HTLV), immune deficiency, Kaposi's sarcoma, Kaposi's sarcoma-associated herpesvirus (KSHV), non-Hodgkin's lymphoma, registry studies, retroviruses, twins

Selected Publications

• Mbulaiteye SM, Biggar RJ, Pfeiffer RM, Bakaki PM, Gamache C, Owor AM, Katongole-Mbidde E, Ndugwa CM, Goedert JJ, Whitby D, Engels EA. "Water, socioeconomic factors, and human herpesvirus 8 in Ugandan children and their mothers." J Acquir Immune Defic Syndr. 38:474-9, 2005.
• Biggar RJ, Engels EA, Ly S, Kahn A, Schymura MJ, Sackoff J, Virgo P, Pfeiffer RM. "Survival following cancer diagnosis in persons with AIDS." JAIDS 39:293-9, 2005.
• Biggar RJ, Ng J, Kim N, Hisada M, Cranston B, Hanchard B, Maloney EM. "HLA concordance and the risk of breast-feeding transmission of human T-cell lymphotropic virus type I (HTLV-I)." J Infect Dis. 193:277-82, 2006.
• Mbulaiteye SM, Walters M, Engels EA, Bakaki PM, Ndugwa CM, Owor AM, Goedert JJ, Whitby D, Biggar RJ. "High levels of Epstein-Barr virus DNA in saliva and peripheral blood from Ugandan mother-child pairs." J Infect Dis. 193:422-6, 2006.
• Biggar RJ, Taha TE, Hoover D, Yellin F, Kumwenda N, Broadhead R. "Higher HIV infection risk in girls than boys infected in utero or perinatally." JAIDS 41:509-13, 2006.

Collaborators

DCEG Collaborators

• Anil Chaturvedi, Ph.D., Eric Engels, M.D.; James Goedert, M.D.; Michie Hisada, M.D., Sc.D.; Elizabeth Maloney, Dr.P.H.; Sam Mbulaiteye, M.D.; Ruth Pfieffer, Ph.D.

Other NIH Collaborators

• Denise Whitby and colleagues, Viral Epidemiology Section, SAIC, Frederick Cancer Research Center, Frederick, MD

Other Scientific Collaborators

• Tim McNeel, IMS, Rockville, MD; Phil Viro, CSC, Rockville, MD: Fran Yellin, Rockville, MD
• Robin Broadhead, M.D., Queen Elizabeth Central Hospital, Blantyre, Malawi
• Jennifer Ng, Ph.D., Georgetown University Hospital, Washington, DC
• Norma Kim, Research Triangle Institute, Rockville, MD
• Morten Frisch, M.D., Henrik Hjalgrim, and Mads Melbye, M.D., Danish Epidemiology Science Center, Copenhagen, Denmark
• Elizabeth Maloney, Centers for Disease Control, Atlanta, GA
• Taha Taha, M.D., The Johns Hopkins Bloomberg School of Hygiene and Public Health, Baltimore, MD