What are the signs and symptoms of human T-lymphotropic virus type II (HTLV‑2) infection?

Signs and Symptoms of HTLV-II Infection

HTLV-II infection has not been clearly associated with any specific disease and most infected individuals remain asymptomatic throughout their lives. 1

Clinical Disease Association

No Definitive Disease Link

• HTLV-II infection has not been definitively linked to any clinical syndrome, unlike HTLV-I which causes adult T-cell leukemia/lymphoma (ATL) and HAM/TSP. 1
• The virus was initially isolated from two patients with hairy-cell leukemia, but subsequent studies found no evidence of HTLV-II in 21 additional hairy-cell leukemia patients, disproving this association. 1
• In New Mexico, where HTLV-II is endemic in American Indian populations, rates of lymphoproliferative illnesses were not increased compared to uninfected populations. 1

Rare Reported Neurological Cases

While extremely uncommon, isolated case reports have described neurological syndromes in HTLV-II-infected individuals:

• Rare HAM/TSP-like neurologic illnesses have been reported, presenting with progressive lower-extremity weakness, spasticity, hyperreflexia, sensory disturbances, and urinary incontinence—clinically indistinguishable from HTLV-I-associated myelopathy. 1, 2, 3
• These cases progressed to a non-ambulatory state in less than 5 years, with MRI demonstrating white matter disease in cerebrum and spinal cord. 3
• Critical caveat: The etiological link between HTLV-II and these neurological disorders remains unproven and controversial. 4, 5
• Many reported cases were confounded by concomitant HIV-1 infection and/or active injection drug use, making causality impossible to establish. 4
• In at least one investigated case, a family member with identical neurological symptoms tested negative for HTLV-II, undermining the disease association. 5

Other Rare Reported Associations

• Isolated cases of mycosis fungoides (cutaneous T-cell lymphoma) have been reported. 1
• Large granular lymphocyte leukemia has been described in rare HTLV-II-infected individuals. 1
• Erythrodermatitis and bacterial skin infections have been reported specifically in HIV-1 and HTLV-II co-infected persons, not in HTLV-II mono-infection. 1

Asymptomatic Carrier State

The overwhelming majority of HTLV-II-infected individuals are asymptomatic carriers who will never develop clinical disease. 1, 4

Epidemiologic Context

• HTLV-II is prevalent among injection drug users in the United States and Europe, with more than 80% of HTLV-I/II seropositivity in U.S. drug users due to HTLV-II. 1
• The virus is endemic in American Indian populations including Guaymi Indians in Panama and North American Indians in Florida and New Mexico. 1
• Approximately half of U.S. volunteer blood donors seropositive for HTLV-I/II are infected with HTLV-II. 1

Clinical Approach to HTLV-II-Positive Patients

What to Monitor

Since no definitive disease association exists, management focuses on:

• Distinguishing HTLV-II from HTLV-I is essential because HTLV-I carries significant disease risk (2-4% develop ATL, <1% develop HAM/TSP) while HTLV-II does not. 6, 7
• Perform confirmatory testing with Western blot or radioimmunoprecipitation to differentiate HTLV-I from HTLV-II, as screening assays cannot reliably distinguish between them. 1, 7
• If neurological symptoms develop (progressive weakness, spasticity, sensory changes, urinary dysfunction), consider the rare possibility of HTLV-II-associated myelopathy, but investigate other more common etiologies first. 2, 4, 3
• Rule out HIV co-infection and other confounding factors before attributing any neurological syndrome to HTLV-II. 4

Prevention Counseling

• Counsel on transmission prevention: avoid sharing needles, use barrier contraception, and do not donate blood, organs, or tissues. 8, 7
• Regarding breastfeeding: while HTLV-II provirus has been detected in breast milk, no data exist on transmission to breast-fed infants, and one study of 20 non-breast-fed children showed no transmission. 1

Key Clinical Pitfalls

• Do not assume HTLV-II causes disease simply because it is present—the association remains unproven despite decades of surveillance. 1, 4
• Do not confuse HTLV-II with HTLV-I, which has well-established disease associations requiring specific monitoring and management. 6, 7
• Be skeptical of reported HTLV-II disease associations in the literature, as most are confounded by co-infections or represent coincidental findings. 4, 5
• In the rare event of progressive myelopathy in an HTLV-II-positive patient, pursue comprehensive neurological workup for alternative diagnoses before attributing symptoms to HTLV-II. 4, 5