Key Facts

  • Human T-lymphotropic virus type 1, often abbreviated as HTLV-1, is also referred to as human T-cell leukemia virus type 1.
  • This virus is linked to a cancer type called adult T-cell leukemia/lymphoma (ATL).
  • HTLV-1 spreads mainly through bodily fluids like blood, breast milk, and semen.
  • Risk factors for infection include unprotected sexual activity, injecting drug use, and receiving tissue or blood transfusions.
  • It is estimated that 5–10 million people worldwide are infected with HTLV-1, although this figure is likely higher due to insufficient data.

Overview

HTLV-1, identified as the first oncogenic human retrovirus, was discovered in 1977. It can lead to adult T-cell leukemia/lymphoma (ATL) and a neurological condition known as HTLV-1-associated myelopathy or tropical spastic paraparesis (HAM/TSP).

Current estimates suggest that between 5 and 10 million people globally are living with HTLV-1. However, due to a lack of reliable data, these numbers likely underestimate the true global infection rates.

Transmission

HTLV-1 is primarily transmitted through direct contact with infected bodily fluids such as blood, breast milk, and semen. Although the virus usually exists intracellularly, direct contact transmission is possible.

Mother-to-Child Transmission

Mothers can pass HTLV-1 to their children through breastfeeding, with transmission rates ranging from 3.9% to 27%.

Sexual Transmission

HTLV-1 is present in cervical secretions and semen, and sexual partners of infected individuals show higher transmission rates. Risks increase with unprotected sex, early sexual debut, and multiple partners.

Blood and Tissue Transmission

Blood transfusions from HTLV-1-positive donors have shown transmission rates up to 63%, while tissue transplants have reported rates as high as 87%.

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Drug Use

Sharing needles for injecting drugs is a significant risk factor for HTLV-1 infection.

Screening and Diagnosis

Screening for HTLV-1 involves initial tests followed by confirmatory diagnostics. Most screening tests utilize immunoassays to detect anti-HTLV-1 antibodies. Common confirmatory tests include the western blot, radioimmunoprecipitation assay (RIA), and line immunoassay, with the latter two being preferred due to the unreliability of the western blot.

Testing can be challenging due to the long period between infection and detectable seroconversion, which can take up to 65 days or even years. Infants of seropositive mothers typically seroconvert within 1–3 years.

Symptoms

Most HTLV-1-infected individuals are asymptomatic, but some may develop severe diseases linked to the virus. These diseases have distinct symptoms that may indicate HTLV-1 presence:

Adult T-cell Leukemia/Lymphoma (ATL)

Affects about 5% of infected individuals. It manifests in four subtypes: acute, lymphomatous, chronic, and smoldering, with the aggressive acute and lymphomatous types being most common. Symptoms may include lymphadenopathy, hepatosplenomegaly, hypercalcemia, and involvement of the skin, lungs, bones, and other organs.

HTLV-1-associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP)

A chronic inflammatory condition of the central nervous system. Symptoms include progressive weakness in the lower limbs, lower back pain, and bladder and bowel dysfunction. The lifetime risk ranges from 0.18% to 1.8%.

Other conditions associated with HTLV-1 include HTLV-1-associated uveitis (HAU), infective dermatitis, bronchiectasis, bronchitis, bronchiolitis, seborrheic dermatitis, Sjögren’s syndrome, rheumatoid arthritis, fibromyalgia, and ulcerative colitis. There is limited evidence of HTLV-1 causing other cancers.

Prevention

While specific prevention measures for HTLV-1 have not been extensively studied, current strategies include:

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Breastfeeding Cessation

Limiting or stopping breastfeeding may reduce mother-to-child transmission based on observational studies.

Freeze-Thaw Method

This technique can eliminate HTLV-1-infected cells from breast milk, reducing transmission risk.

Blood Donor Screening

Mandatory HTLV-1 antibody screening for blood donations is in place in 23 countries.

Leukoreduction

Since HTLV-1 is usually cell-associated, leukoreduction might be as effective as blood screening in preventing transmission.

No vaccine exists for HTLV-1, but vaccine development is considered feasible. However, the lack of suitable animal models has hindered progress, and no vaccine candidates have reached clinical trials.

Treatment

There is no specific treatment recommended for asymptomatic HTLV-1 infection. Management focuses on treating symptoms of related diseases like ATL and HAM/TSP and screening for comorbidities and coinfections.

No single biomarker or clinical feature accurately predicts HTLV-1-associated disease development. However, measuring HTLV-1 proviral load may serve as an indicator. Improved risk prediction could enhance clinical management.

WHO Response

The World Health Organization (WHO), in collaboration with member states and partners, is working on developing guidelines for HTLV-1 surveillance, including prevalence estimation and intervention monitoring. This includes rapid assessment methods and burden of disease estimation. Specific guidance for low-resource settings on appropriate testing approaches is also needed.

Further research is needed to determine if a proviral load level exists below which transmission risk is negligible and to refine the understanding of mother-to-child transmission risks and prevention efficacy.

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