Mother-to-Child HTLV-1 Transmission: Unmet Research Needs

Abstract

Mother-to-child transmission (MTCT) of Human T-cell lymphotropic virus type 1 (HTLV-1) causes lifelong infection. At least 5–10 million individuals worldwide are currently living with HTLV-1. Studies of regional variation are required to better understand the contribution of MTCT to the global burden of infection. Although most infected individuals remain asymptomatic ∼10% develop high morbidity, high mortality disease. Infection early in life is associated with a higher risk of disease development. Adult T-cell leukemia (ATL), which is caused by HTLV-1 and has a median survival of 8 months is linked to MTCT, indeed evidence of ATL following infection as an adult is sparse. Infective dermatitis also only occurs following neonatal infection. Whilst HTLV-1-associated myelopathy (HAM) follows sexual and iatrogenic infection approximately 30% of patients presenting with HAM/TSP acquired the infection through their mothers. HAM/TSP is a disabling neurodegenerative disease that greatly impact patient’s quality of life. To date there is no cure for HTLV-1 infection other than bone marrow transplantation for ATL nor any measure to prevent HTLV-1 associated diseases in an infected individual. In this context, prevention of MTCT is expected to contribute disproportionately to reducing both the incidence of HTLV-1 and the burden of HTLV-1 associated diseases. In order to successfully avoid HTLV-1 MTCT, it is important to understand all the variables involved in this route of infection. Questions remain regarding frequency and risk factors for in utero peri-partum transmission whilst little is known about the efficacy of pre-labor cesarean section to reduce these infections. Understanding the contribution of peripartum infection to the burden of disease will be important to gauge the risk-benefit of interventions in this area. Few studies have examined the impact of HTLV-1 infection on fertility or pregnancy outcomes nor the susceptibility of the mother to infection during pregnancy and lactation. Whilst breast-feeding is strongly associated with transmission and avoidance of breast-feeding a proven intervention little is known about the mechanism of transmission from the breast milk to the infant and there have been no clinical trials of antiretroviral therapy (ARV) to prevent this route of transmission.

Epidemiology and survival trend of adult T‐cell leukemia/lymphoma in the United States

“…However, it is important to note that 22.6% of patients with ATLL in New York City are born in North America because ATLL is often missed in American‐born patients as it is not expected, and this has potential implications for treatment. This low‐level endemicity of HTLV‐1 can likely be explained by vertical transmission from infected mothers in the United States or horizontal transmission through sexual intercourse to people born in the United States …”

The challenge of describing the epidemiology of HTLV in the Amazon region of Brazil

“…Viral dispersion in the human body leads to the infection of several biological fluids, including the blood, semen, vaginal fluid, and milk and results in its vertical transmission from mother to child (via the placenta and perinatal breast feeding), the injection of drugs, the transfusion of blood and its components, the transplantation of organs and the engagement in sexual relations [29,[33][34][35][36][37][38]. Each of these plays an important role in viral maintenance.…”

Dichotomy in Fatal Outcomes in a Large Cohort of People Living with HTLV-1 in São Paulo, Brazil

“…After the adoption of mandatory national blood screening tests in 1993 and the observed behavioral change from intravenous to inhalation drug abuse, parental exposure to HTLV dropped [4][5][6]. However, our group has documented rates of 40 percent of sexual transmission [7] and of 13 percent of vertical transmission [8,9].…”