Übersicht
The human T-lymphotropic virus type 1 (HTLV-1) was the first oncogenic human retrovirus to be discovered. It was first studied in 1977. The virus can cause adult T-cell leukaemia/lymphoma (ATL) and progressive nervous system condition known as HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP).
The current best estimates for the total number of people living with HTLV-1 infection range from 5 million to 10 million. The scarcity of reliable data indicates that is likely an underestimation of actual global numbers.
Transmission
HTLV-1 is understood to be transmitted primarily through direct contact via cell-containing bodily fluids including blood, breast milk and semen. Transmission via direct contact is also considered feasible, although the virus usually exists in the intra-cellular form.
Mothers can pass the virus to children through breastfeeding, and there is limited evidence of transmission before or during birth. The estimated mother to child transmission rate has ranged from 3.9% to 27%.
HTLV-1 has been detected in cervical secretions and semen. The elevated presence of the virus has been reported among the sexual partners of people with HTLV-1 infection, which supports evidence of sexual transmission. A history of unprotected sex, earlier age at first sex and a higher number of partners increase the risk of transmission.
Several studies have reported transmission rates of up to 63% from transfusions of blood from a donor with HTLV-1. One study reported transmission rate of 87% from tissue transplants from positive donors.
Injecting drug use is also a risk factor for HTLV-1 infection.
Screening and diagnosis
Following current practices, screening tests for HTLV-1 should be followed by confirmatory tests for the diagnosis of HTLV-1. Most screening tests use immunoassays, which rely on detecting anti-HTLV-1 antibodies. Commonly used confirmatory tests detect antibody responses to specific HTLV-1 antigens. Test types include the western blot, radioimmunoprecipitation assay (RIA) and line immunoassay; however, the western blot test has been found to give unreliable results. Several studies have proposed transitioning from using western blot for confirmation in routine testing to using line immunoassay or NAT.
Testing can be made more complicated due to the length of time between contracting the virus and the seroconversion required for the virus to appear on tests. This period has been reported to be as long as 65 days. Delayed seroconversion lasting several years has also been reported. Infants born to seropositive mothers have been reported to seroconvert within 1–3 years of age.
Symptoms
Most people with HTLV-1 infection are asymptomatic and do not develop conditions that can be causally linked to the infection. However, several serious diseases are thought to be caused by or strongly associated with the virus. These diseases each show specific symptoms that may point to the presence of HTLV-1.
For example, the lifetime risk of developing adult T-cell leukaemia/lymphoma (ATL) among people with an HTLV-1 infection is about 5% (although this may be conservative due to unreported cases). ATL presents as four clinical subtypes: acute, lymphomatous, chronic and smouldering, with the more aggressive subtypes (acute and lymphomatous) representing the majority of cases. Clinical presentation depends on the subtype. People may present with lymphadenopathy, hepatosplenomegaly, hypercalcaemia through involvement of the skin, lung, bones and other organs.
Another disease is HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP). This is a chronic inflammatory disease of the central nervous system, characterized by progressive spastic weakness of the lower limbs, lower back pain and bowel and bladder dysfunction. Clinical findings can include muscle weakness, hyperreflexia and clonus in the lower limbs, along with extensor plantar responsive and a spastic gait. Estimates of the lifetime risk of HAM/TSP among people with HTLV-1 infection have ranged from 0.18% to 1.8%.
Other diseases connected to HTLV-1 infection include HTLV-1-associated uveitis (HAU), infective dermatitis, bronchiectasis, bronchitis and bronchiolitis, seborrheic dermatitis, Sjögren’s syndrome, rheumatoid arthritis, fibromyalgia and ulcerative colitis. There is little evidence that HTLV-1 infections cause other forms of cancer.
Prevention
Few observational studies have investigated specific preventions for HTLV-1. There are no reports related to preventing sexual transmission nor to prevention among people who inject drugs. Currently studied strategies include:
Cessation of breast feeding: Based on observational studies of mother-to-child transmission, it was determined that shortening the duration of breastfeeding or even eliminating it altogether could enable women with HTLV-1 to limit the extent of exposure to their infants.
Breast milk freeze thaw method: The freeze-thaw method effectively eliminates the cells in breast milk that are infected with HTLV-1 and hence the source of transmission.
Antibody screening amongst blood donors: Mandatory HTLV-1 antibody screening of all blood donations has been implemented in 23 countries.
Leukoreduction: Because HTLV-1 is almost always cell associated, leukoreduction may be as effective as blood donation screening in preventing transmission.
There is currently no vaccine for HTLV-1, although development of a vaccine is considered feasible. However, animal models may not be suitable to study vaccine effects in HTLV-1. No candidate HTLV-1 vaccine has proceeded to a clinical trial with an efficacy endpoint so far.
Treatment
No treatment is currently recommended for people with asymptomatic HTLV-1 infection. Treatment should instead focus on the symptoms of associated diseases, namely ATL and HAM/TSP, and screening for comorbidities and coinfection.
Currently, no single biological marker or clinical feature accurately predicts the development of or quantifies the risk of diseases associated with HTLV-1, although the levels of HTLV-1 proviral load has been suggested as a possible indicator. Improvements in risk prediction would assist in clinical management.
WHO Response
In collaboration with Member States and partners, WHO works to develop guidance on HTLV-1 surveillance methods, including methods to determine prevalence and methods for monitoring interventions. This includes rapid assessment methods and burden of disease estimates. Specific guidance is also needed for low-resource settings on testing approaches and strategies for HTLV-1 detection that are appropriate to the setting and the purpose.
Further testing and analysis will determine whether there is a level of proviral load below which transmission risk is negligible, as well as specific data to better define the risk of mother-to-child HTLV-1 transmission and the effectiveness of prevention strategies.