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      Drugs & Diseases > Infectious Diseases

      Human T-Cell Lymphotropic Viruses (HTLV) Clinical Presentation

      Updated: Feb 07, 2023
      • Author: Joseph M Yabes, Jr, MD, FACP; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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      History

      Acute HTLV infection is rarely seen or diagnosed, as most infections are asymptomatic. Infection might be diagnosed after an attempted blood donation, a familial history of the infection, or workup of a disease caused by the virus (eg, a recent diagnosis of ATL or HAM/TSP). Suspected cases may prompt investigation for a history of a recent blood-product transfusion or a nursing mother from an endemic area.

      When considering HTLV infection, the most important historical information pertains to risk assessment. Because detecting accurate seroprevalence in low-endemic populations is inherently problematic, it is important to stratify a patient's risk. Screening enzyme immunoassays (EIAs) are more likely to yield false-positive results in areas of low prevalence. [48] Therefore, a high-risk individual is anyone with any of the following characteristics:

      • Has lived or lives in an endemic area (ie, Japan, the Caribbean, Central or West Africa, South America)
      • Is a Native American Indian
      • Has parents or sexual partners from an endemic area
      • Received blood-product transfusions in the United States before 1988
      • Has received blood transfusions anywhere that lacks active blood-bank screening
      • Has a history of injection drug use
      • Has sexual partners with a history of injection drug use
      • Has multiple sexual partners and does not use barrier protection
      • Has strongyloidiasis hyperinfection

      Patients with HAM/TSP may present with weakness and stiffness in the lower limbs (first presenting symptom in 60% of cases [49] ), urinary incontinence, and/or severe lower back pain radiating to the legs. In some cases, urinary frequency, urgency, incontinence, or retention precedes the paraparesis by many years. Infected patients may also have symptoms of autonomic dysfunction leading to constipation and, in some cases, sexual dysfunction.

      Symptoms of ATL are clinically broad and can manifest as fatigue, overt lymphadenopathy, thirst (due to hypercalcemia), nausea, vomiting, fever, and/or abdominal pain. [50] A comprehensive review of the signs/symptoms of HAM/TSP and ATL is beyond the scope of this article.

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      Physical

      Physical examination should be comprehensive, evaluating all major organ systems. Special attention should be paid to the neurologic examination, evaluation for lymphadenopathy, and signs of hematologic abnormalities. There are no strict criteria established for physical findings of HAM/TSP; however, the following constellation of physical findings are typical and invariably worsen [22] :

      • Motor and sensory changes in the lower extremities
      • Clonus (may be evident); involuntary muscular contractions upon stretching of the muscles
      • Spastic gait in combination with weakness of the lower limbs
      • Detrusor insufficiency leading to bladder dysfunction
      • Preserved cognitive and upper-extremity neurological functions

      The following isolated neurologic symptoms have been also described in patients with HTLV-1 or HTLV-2 infection [22] :

      • Sensory neuropathies
      • Gait abnormalities
      • Bladder dysfunction
      • Erectile dysfunction
      • Mild cognitive defects
      • Motor abnormalities
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      Causes

      HTLV-1 and HTLV-2 have similar transmission patterns, although the transmission efficiency of HTLV-2 is uncertain because of a lack of unbiased data gathering. Both can be transmitted via breast milk, sexual contact, and intravenous drug use and can be introduced directly into the vascular system. HTLV-3 and HTLV-4 seem to be transmitted through direct human contact with primates (eg, through hunting, butchering, keeping them as pets), but data are lacking. [51]

      Breastfeeding

      HTLV-infected T cells in human milk pass from mother to child. The risk of HTLV-1 transmission reaches 20% and is affected by the duration of breastfeeding, the proviral load, and the quantity of maternal antibodies. Intrauterine infection is less common, about 5%. [52, 53, 54]

      For HTLV-2, the quantitative risk remains uncertain for both breastfeeding and intrauterine transmission.

      Sexual intercourse

      Increased exposure and increased proviral load increase the risk for sexual transmission of both HTLV-1 and HTLV-2. [39, 55]

      Transfusion/transplantation

      The risk of seroconversion due to contaminated blood transfusion has been reported to be 40%-60% and increases in immunosuppressed recipients. [56]

      Screening of blood products is standard policy in the United States and many other countries. The United States has been screening donated blood since 1988. [48]

      Reports have documented kidney, liver, and lung transplant transmission of HTLV-1. [57, 58]

      Intravenous drug use

      Transmission via intravenous drug use is mostly linked to HTLV-2. The prevalence of HTLV-2 infection in North American injection drug users ranges from 8%-17%. [24]

      Self-flagellation

      A report described ten heterosexual males without additional risk factors for HTLV infection who were found to be asymptomatically infected, presumably from using shared knives in religious self-flagellation. [59]

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      Complications

      Complications of HTLV infection result mostly from end-stage diseases rather than the infection itself, as the vast majority of individuals with this infection are asymptomatic.

      HTLV-1 is a risk factor for the development of severe strongyloidiasis; close follow-up after treatment for strongyloidiasis is recommended. [60, 61]

      Coinfection of either HTLV-1 or HTLV-2 with HIV remains controversial. Conclusive and reproducible data of such coinfections are not yet available, as most of the data are limited by the testing methodology. Theoretically, HTLV-1 and HIV affect the same cell type, and the additive result might be detrimental to the immune system, leading to faster progression to AIDS. Future research might lead to recommendations concerning coinfections (eg, starting HAART or prophylaxis for opportunistic infections); however, no specific guidelines exist at this time.

      A 2009 retrospective cohort study of Peruvian men with HIV/HTLV-1 coinfection did not show that coinfection increased the risk for death. [62] This area remains controversial, as some studies show an unfavorable outcome for HIV/HTLV-1 coinfection, whereas others do not. No evidence has shown that HIV/HTLV-2 coinfection leads to a faster progression to AIDS; in fact, coinfection might have some protective effects based on in vitro studies. [63, 64]

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