Clinical and Public Health Implications of Human T-Lymphotropic Virus Type 1 Infection

Abstract

Human T-lymphotropic virus type 1 (HTLV-1) is estimated to affect 5 to 10 million people globally and can cause severe and potentially fatal disease, including adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The burden of HTLV-1 infection appears to be geographically concentrated, with high prevalence in discrete regions and populations. While most high-income countries have introduced HTLV-1 screening of blood donations, few other public health measures have been implemented to prevent infection or its consequences. Recent advocacy from concerned researchers, clinicians, and community members has emphasized the potential for improved prevention and management of HTLV-1 infection. Despite all that has been learned in the 4 decades following the discovery of HTLV-1, gaps in knowledge across clinical and public health aspects persist, impeding optimal control and prevention, as well as the development of policies and guidelines. Awareness of HTLV-1 among health care providers, communities, and affected individuals remains limited, even in countries of endemicity. This review provides a comprehensive overview on HTLV-1 epidemiology and on clinical and public health and highlights key areas for further research and collaboration to advance the health of people with and at risk of HTLV-1 infection.

Keywords: clinical methods; clinical therapeutics; diagnostics; epidemiology; human T-cell leukemia virus; oncogenic virus; pathogenesis; public health; sexually transmitted diseases; virology.

FIG 1

Global distribution of HTLV-1 seroprevalence among blood donors. These data were extracted from 65 critically appraised peer-reviewed publications reporting original prevalence data subject to confirmatory testing.

FIG 2

Global distribution of HTLV-1 seroprevalence among pregnant women. These data were extracted from 37 critically appraised peer-reviewed publications reporting original prevalence data subject to confirmatory testing.

FIG 3

Global distribution of HTLV-1 seroprevalence in general populations. These data were extracted from 37 critically appraised peer-reviewed publications reporting original prevalence data subject to confirmatory testing.

FIG 4

Sensitivity and specificity of 165 HTLV-1 diagnostic assays. Data were extracted from 65 peer-reviewed publications. Gray dots indicate data extracted pre-2009 and black circles post-2009, highlighting improved sensitivity and specificity of more recent assays. EIA, enzyme immunoassay; IF, immunofluorescence assay; INNO-LIA, line immunoassay; PA, particle agglutination; RIA, radioimmunoassay; WB, Western blot.

FIG 5

HTLV-1 testing algorithm. Testing algorithms for HTLV-1 have generally required two or three assays. An EIA-based method is used for screening plasma or sera given high sensitivity, simplicity, and potential for high throughput. Positive samples are then retested, either with the same EIA or an alternative. Finally, repeatedly reactive plasma or serum samples are confirmed by another assay type, either Western blot, INNO-LIA, or PCR. EIA, enzyme immunoassay; IFA, immunofluorescence assay; IMMO-LIA, line immunoassay; PA, particle agglutination; RIA, radioimmunoassay; WB, Western blot.

FIG 6

Age-standardized incidence rates of ATL worldwide per 100,000 population. Age-standardized incidence rates are reported for the general population and are not specific for people with HTLV-1 infection. (Adapted from references and .)

FIG 7

ATL incidence by age and sex in 2018. (Adapted from references and .)