We used “human T-lymphotropic virus 1” (MeSH major topic) as the search term in PubMed and considered journal articles in English, Spanish, Portuguese, French, and Dutch. Reference lists of these articles were also reviewed and many articles were identified through searches of the files of the authors. We selected clinical and basic science articles related to prevalence, pathogenesis, diagnosis, clinical management, and prevention of HTLV-1 infection and associated diseases. For the selection
ReviewHuman T-lymphotropic virus 1: recent knowledge about an ancient infection
Introduction
In 1979, the human T-lymphotropic virus 1 (HTLV-1) was isolated from a patient with a T-cell malignancy.1 This discovery was the first formal proof that human retroviruses exist and suggested their aetiological role in human cancer, a hypothesis that had been proposed decades before.2 It is estimated that 10 to 20 million people worldwide are infected with HTLV-1,3 and although the majority of infected people remain asymptomatic, the virus is associated with exceptionally severe diseases, such as adult T-cell leukaemia/lymphoma (ATL) and an inflammatory disease of the central nervous system called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).4, 5 The growing insight into the pathogenesis of these diseases sheds light upon the functioning of human T cells, the major target of HTLV-1. Nonetheless, it is not yet fully understood why some infected individuals develop associated diseases whereas others do not.6
Section snippets
HTLV-1 and T cells
HTLV-1 is a type C virus belonging to the family of Retroviridae and classified into the genus of Deltaretrovirus. It is a round-shaped, enveloped virus of approximately 100 nm diameter (figure 1A).7 The virion is surrounded by a proteolipid envelope bilayer of host cell membrane origin, equipped with viral transmembrane and surface proteins. The inner envelope contains the matrix layer, which helps to organise the viral components at the inner cell membrane. The icosahedral capsid protects the
Diagnosis of HTLV-1 infection
Serological screening for the presence of HTLV antibodies can either be done by an enzyme immunoassay (EIA) or by a particle agglutination test. The first generation EIAs were based on viral lysate and frequently resulted in false-positive reactions.21 Second generation EIAs using recombinant proteins and/or synthetic HTLV-1 peptides perform better, but confirmatory testing is still recommended to eliminate false-positive reactions and to discriminate between the different HTLV types.22
There
Transmission
HTLV-1 can be transmitted from mother to child through breastfeeding. The risk of infection in children of seropositive mothers correlates with the provirus load in breastmilk, the concordance of HLA class I type between mother and child, and the duration of breastfeeding.33, 34 In several reports from endemic populations, the overall rate of vertical transmission ranged between 15% and 25%, and in subgroups of children who received prolonged breastfeeding, these rates were even higher.35, 36,
Origin, spread, and prevalence
To estimate the global prevalence of HTLV-1 on the basis of published reports is difficult because there are few population-based studies. HTLV-1 prevalence estimates are usually based on serological screening of blood donors, pregnant women, and other selected population groups. Studying the prevalence in healthy donors might underestimate the population prevalence.54 Data from pregnant women may better reflect the general population, although reports from endemic areas suggest that HTLV-1
HTLV-1-associated diseases
Most people infected with HTLV-1 remain asymptomatic throughout life. How many people eventually develop any of the associated diseases depends on several factors, including age and the route of infection.99 Additionally, the incidence of HTLV-1-associated diseases is not uniform across geographical areas.100
Among HTLV-1 carriers, the lifetime risk of developing HAM/TSP ranges from between 0·3% and 4%.101 For ATL, this risk is calculated as 1% to 5% and for HTLV-1-associated diseases in
History
In the 1970s, clinicians in Japan felt that the haematological malignancies they observed did not fit the pattern described in the literature of that time.4 They diagnosed, for instance, few cases of chronic lymphocytic leukaemia on one hand and many acute, aggressive T-cell malignancies on the other, particularly among patients from southwestern Japan. The impression of an autochthonous pathology led to the description of a clinical entity: adult T-cell leukaemia/lymphoma.4, 115
Pathogenesis
ATL is a
History
Long before HTLV-1 was discovered, neurologists had reported the frequent occurrence of a myelopathy of unknown origin in tropical areas. The first descriptions of this syndrome go back to the 19th century.139 The association with HTLV-1 was recognised independently in the Caribbean and in Japan in 1985–1986.5, 140 Soon thereafter, it was agreed to refer to this disease as HTLV-1-associated myelopathy/tropical spastic paraparesis.
Pathogenesis
The main pathological feature of HAM/TSP is a chronic
Strongyloidiasis
Strongyloides stercoralis is an intestinal nematode of tropical regions that can replicate within the human host, an unusual characteristic among helminths. In the normal strongyloides cycle, filariform larvae from the soil penetrate the human skin and migrate to the lungs. The larvae ascend the bronchi and are swallowed. Adult females stay and lay eggs in the intestinal mucosa. Rhabditiform larvae hatch, migrate to the intestinal lumen and pass with the faeces into soil. An autoinfection cycle
Conclusion
A quarter of a century after its first description, HTLV-1 is still a poorly recognised infection. Many carriers remain asymptomatic, which contributes to the silent transmission of the virus. Since several associated diseases can also occur in uninfected people, the role of underlying HTLV-1 often passes unnoticed. Even though important knowledge about the pathogenesis is emerging, there are no clear surrogate markers for follow-up and the proviral lifestyle of HTLV-1 complicates the
Search strategy and selection criteria
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Comparison of immunofluorescence, enzyme immunoassay, and Western blot (immunoblot) methods for detection of antibody to human T-cell leukemia virus type I
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