Establishment of the milk-borne transmission as a key factor for the peculiar endemicity of human T-lymphotropic virus type 1 (HTLV-1): the ATL Prevention Program Nagasaki

Abstract

In late 2010, the nation-wide screening of pregnant women for human T-lymphotropic virus type 1 (HTLV-1) infection was implemented in Japan to prevent milk-borne transmission of HTLV-1. In the late 1970s, recognition of the adult T-cell leukemia (ATL) cluster in Kyushu, Japan, led to the discovery of the first human retrovirus, HTLV-1. In 1980, we started to investigate mother-to-child transmission (MTCT) for explaining the peculiar endemicity of HTLV-1. Retrospective and prospective epidemiological data revealed the MTCT rate at ∼20%. Cell-mediated transmission of HTLV-1 without prenatal infection suggested a possibility of milk-borne transmission. Common marmosets were successfully infected by oral inoculation of HTLV-1 harboring cells. A prefecture-wide intervention study to refrain from breast-feeding by carrier mothers, the ATL Prevention Program Nagasaki, was commenced in July 1987. It revealed a marked reduction of HTLV-1 MTCT by complete bottle-feeding from 20.3% to 2.5%, and a significantly higher risk of short-term breast-feeding (<6 months) than bottle-feeding (7.4% vs. 2.5%, P < 0.001).

Figure 1.

Histogram of cell concentrations in breast milk from carrier mothers. Morphologically, 90% of them were macrophages. Roughly 1% of Ficoll/Conray-purified mononuclear cells were producing HTLV-1 antigens after culture for 4 weeks.

Figure 2.

Concentrated fresh human-milk cells donated by carrier mothers were inoculated orally in separate doses to common marmosets by plastic syringes without needle. Abscissa: months after first inoculation, Ordinate: total numbers of cells inoculated (bars); antibody titers against HTLV-1 antigen determined by the indirect immunofluorescence test (dots).

Figure 3.

Screening of pregnant women for the anti-HTLV-1 antibody by the ATL Prevention Program Nagasaki commenced in 1987. Numbers of deliveries in the Nagasaki Prefecture, pregnant women screened, carriers detected and the prevalence of carrier women in each year are shown. Data were taken from the reference²⁶⁾ with permission of the Prefecture and authors.

Figure 4.

Birth-cohort effect on the prevalence of HTLV-1 carriers among pregnant women in the Nagasaki Prefecture. The dotted line estimates sharper decline of the prevalence after the start of APP Nagasaki.