Quantifying how multiple transmission routes contribute to the spread of HTLV-1 in different endemic foci: a...

Human T-lymphotropic virus 1 (HTLV-1) infection is estimated to affect at least 5-10 million people globally and can cause adult T-cell leukaemia/lymphoma. The global distribution of HTLV-1 is characterised by endemic foci (prevalence confined to specific populations) in Japan, Africa, the Americas, the Middle East, and Oceania. Transmission occurs through vertical, sexual, bloodborne, and zoonotic routes, but their relative contributions are poorly characterised and depend on the setting. This study aims to quantify the relative contributions of vertical, sexual, bloodborne, and zoonotic transmission routes across HTLV-1 endemic foci.

Following a systematic literature review, we analysed seven age-stratified and sex-stratified HTLV-1 seroprevalence surveys including nine subpopulations in French Guiana, rural Gabon, rural Cameroon, Japan (Miyazaki, Iriomote, and Ishigaki), and central Australia; Bantu and Pygmy participants in Gabon and Cameroon were considered as distinct subpopulations. We used a multiroute serocatalytic model incorporating vertical, sexual, and hospital-related (transfusion-anchored) routes of transmission in all settings, with additional non-human-primate (NHP) bite-related transmission in central Africa, and a male-specific route in central Australia. The primary outcome was the model-estimated route-specific force of infection by age, sex, and subpopulation, from which we derived the attributable fraction of infections due to each transmission route.

The estimated vertical transmission probability, conditional on a mother with HTLV-1 infection, was 17% (95% credible interval 15-20). Sexual infection probabilities in males ranged from 0·02% to 0·68% per year, and were 1·6 times (1·4-1·8) higher in females. Hospital admission infection probability ranged from 0·05 (in central Australia) to 125 (in Miyazaki, Japan) per 100 000 hospital admissions. NHP bites in males in central Africa carried a 7% (3-13) infection probability per bite. In adults aged 25-69 years, sexual transmission accounted for 85% (79-87) and vertical transmission for 8% (7-9) of infections across populations. Hospital-related transmission contributed to around 2% of all infections in Japan (pre-HTLV-1 blood-safety measures), around 5% in Cameroonian Bantu communities, and less than 1% elsewhere. NHP bite-related transmission accounted for up to 26% of adult male infections in Cameroonian Bantu rural communities and up to 9% elsewhere in central Africa. In central Australia, most adult male infections could not be accounted for by sexual or vertical transmission.

Sexual and vertical transmission dominate HTLV-1 spread, but context-specific exposures add substantial local burdens in central Africa and central Australia. These route-specific estimates support intervention prioritisation and the design of setting-specific control strategies.

EU and Agence Nationale de la Recherche.

For the French translation of the abstract see Supplementary Materials section.