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Leukemia

photo: disease

Infection with human T cell leukemia virus-1 (HTLV-I) may have multiple disease outcomes. It can cause adult T cell leukemia/lymphoma (ATLL), a cancer of the blood; tropical spastic paraparesis (TSP) or HTLV associated myelopathy (HAM), a neurologic disease, primarily of the lower extremities; and any of a series of inflammatory diseases, such as dermatitis, uveitis, arthritis, thyroditis, or polymyositis.

  • At significant risk are babies born to infected mothers, especially in endemic regions of the world, persons receiving blood transfusions in countries without screening programs, sexually promiscuous individuals, intravenous drug users, and people with AIDS or compromised immune systems.
  • Ten to 20 million people are thought to be infected worldwide.
  • HTLV-I infection is life long, and patients are usually asymptomatic. One to 4% of those infected will progress to disease after a long infection period, with ATLL developing late in life following 30-50 years of infection, and HAM/TSP or any of the other possible inflammatory diseases developing within 3 months to 10 years.
  • Annual mortality due to HTLV-I is undetermined.
  • HTLV-I is endemic to Japan, the Caribbean basin, northeastern South America, Central Africa, and regions in the Pacific. More recent clusters of infected individuals are found in large metropolitan areas in the United States and Europe.

Infectious Agent

Human T cell leukemia virus I (HTLV-I) infects T lymphocytes, a population of circulating white blood cells. Although the levels of virus in the circulation will vary, infection is never fully cleared and remains throughout life.

Transmission

Mother to child transmission occurs either by passage of virus-infected cells through the placenta to the fetus or through milk to the infant during breast feeding.

Sexual transmission, usually by infected men to a partner.

Blood transfusions with unscreened blood.

Sharing of blood-contaminated needles, usually during intravenous (IV) drug abuse.

Disease

ATLL is a highly malignant cancer with high numbers of abnormal cancer cells circulating in the blood. Many individuals develop widespread skin lesions, lymph node, spleen, bone and lung complications, and finally, opportunistic bacterial and fungal infections often leading to death. The median survival for acute ATLL is less than a year, while chronic cases may survive longer. The risk of ATLL is greater in patients infected with HTLV-I during infancy.

TSP/HAM is a chronic disease of the nervous system that affects the lower extremities, similar to multiple sclerosis. It is a progressive, debilitating disease with leg-muscle weakness, uncontrolled movement in the legs, lower back pain, urinary incontinence, and sexual impotence. It is thought to be an autoimmune reaction to the cells of the central nervous system. TSP/HAM is most common in older children and adults infected with HTLV-I.

Infective dermatitis, uveitis, arthritis, thyroditis, and polymyositis are all inflammatory diseases associated with HTLV-I that result in varying amounts of rash, swelling, and inflammation in the skin, eye, joint, and muscle, respectively.

Co-infection of HTLV and HIV in AIDS patients is widespread and is thought to increase the incidence and progression to HTLV disease.

Treatment

No vaccine is available for treatment.

Standard chemotherapy for non-Hodgkin lymphoma is ineffective for ATLL. A combination of interferon-alpha and the AIDS drug AZT has been found minimally effective.

Early symptoms of TSP/HAM may be treated with corticosteroids, cyclophosphamide or interferon; however, those have had limited success. No treatments for chronic symptoms have been found.

Our Research

We have developed a monkey model of HTLV-I infection using the closely related monkey virus, simian T cell lymphotropic virus, (STLV-I). We can grow and study these viruses in the laboratory.

Monkeys infected with HTLV-I have produced some disease signs including early ATLL, arthritis, uveitis and polymyositis. Co-infection experiments with HTLV-I and SIV were performed and also produced disease related signs.

Experiments in monkeys are able to answer questions related to infection, disease, and potential vaccine and treatment methods.

We have developed a molecular diagnostic real-time polymerase chain reaction (PCR) assay that can quantitate the virus load in the circulation or in tissues.

The TNPRC is a division of Tulane University (985) 871-6201 tnprc@tulane.edu