Milk Transmission of HTLV-1 and the Need for Innovative Prevention Strategies

Abstract

Breastfeeding is recommended by the World Health Organization for at least 6 months up to 2 years of age, and breast milk protects against several diseases and infections. Intriguingly, few viruses are transmitted via breastfeeding including Human T-cell leukemia virus Type 1 (HTLV-1). HTLV-1 is a highly oncogenic yet neglected retrovirus, which primarily infects CD4+ T-cells in vivo and causes incurable diseases like HTLV-1-associated inflammatory conditions or Adult T-cell leukemia/lymphoma (ATLL) after lifelong viral persistence. Worldwide, at least 5–10 million people are HTLV-1-infected and most of them are unaware of their infection posing the risk of silent transmissions. HTLV-1 is transmitted via cell-containing body fluids such as blood products, semen, and breast milk, which constitutes the major route of mother-to-child transmission (MTCT). Risk of transmission increases with the duration of breastfeeding, however, abstinence from breastfeeding as it is recommended in some endemic countries is not an option in resource-limited settings or underrepresented areas and populations. Despite significant progress in understanding details of HTLV-1 cell-to-cell transmission, it is still not fully understood, which cells in which organs get infected via the oral route, how these cells get infected, how breast milk affects this route of infection and how to inhibit oral transmission despite breastfeeding, which is an urgent need especially in underrepresented areas of the world. Here, we review these questions and provide an outlook how future research could help to uncover prevention strategies that might ultimately allow infants to benefit from breastfeeding while reducing the risk of HTLV-1 transmission.

HTLV-1/2 in Indigenous Peoples of the Brazilian Amazon: Seroprevalence, Molecular Characterization and Sociobehavioral Factors Related to Risk of Infection

“…Three important epidemiological markers were shown to be associated with sexual transmission as follows: condom use, age at first sexual intercourse and number of pregnancies. It was evident that individuals who do not use condoms are more affected, since there is still a great rejection by Indigenous men of condom use, reinforcing the greater risk of transmission from men to women [ 6 , 9 , 12 , 14 , 27 ], as well as the number of children being positively correlated with the increase in the prevalence of the infection. Although the significance of prolonged breastfeeding and cross-breastfeeding has not been shown, these procedures are common in these communities and may be important forms of transmission of the virus [ 12 , 41 ].…”

“…Among the HTLV-1/2 transmission routes, mother-to-child transmission is important for the maintenance and endemicity of the virus, particularly HTLV-2 among Indigenous peoples, which is commonly associated with prolonged breastfeeding and cross-breastfeeding (when a woman breastfeeds a child who is not her child). The sexual route is also important, since condom use is uncommon in these people, and the infection is more likely to be transmitted from men to women [ 12 , 13 , 14 ].…”

Milk Transmission of Mammalian Retroviruses

“…The risk factors for MTCT upon breastfeeding have been reviewed earlier, including amongst others high proviral load in milk and blood as well as prolonged breastfeeding periods for more than 6 months [ 176 , 177 ]. Yet, the molecular details of the oral route of HTLV-1 transmission are only partially understood, e.g., it is unknown which cells in breast milk are crucial for HTLV-1 MTCT and which cells in the infant are infected first [ 178 ]. However, abandoning breastfeeding is not an option, especially in developing countries [ 178 ].…”

“…Yet, the molecular details of the oral route of HTLV-1 transmission are only partially understood, e.g., it is unknown which cells in breast milk are crucial for HTLV-1 MTCT and which cells in the infant are infected first [ 178 ]. However, abandoning breastfeeding is not an option, especially in developing countries [ 178 ]. To make matters worse, only a few countries screen pregnant women for HTLV antenatally.…”

How Can We Prevent Mother-to-Child Transmission of HTLV-1?

“…According to a review article by Millen et al, avoidance of breastfeeding is not an option in resource-limited areas or populations with few infected individuals [ 105 ]. In particular, in developing countries with high morbidity and mortality rates of serious gastrointestinal and other infections due to poor sanitation, which do not provide a stable supply of formula, baby bottles, and clean water, the advantages of the immunological benefits of breast milk may outweigh the disadvantages of the MTCT of HTLV-1.…”