Human T-Cell Lymphotropic Viruses (HTLV) Workup

Updated: Dec 05, 2018
  • Author: Ewa Maria Szczypinska, MD; Chief Editor: Pranatharthi Haran Chandrasekar, MBBS, MD  more...
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Laboratory Studies

HTLV-1 and HTLV-2 infections are detected with enzyme-linked immunosorbent assay (ELISA), which then must be confirmed with Western blot, immunofluorescence assay (IFA), or polymerase chain reaction (PCR).

HTLV ELISA yields very high false-positive rates in areas of low prevalence. For example, confirmatory testing rules out HTLV infection in 60%-80% of blood donors in whom ELISA is initially positive in nonendemic areas.

PCR or EIA with virus-specific synthetic peptides is necessary to distinguish between HTLV-1 and HTLV-2. PCR is also necessary in infants who may have false-positive results because of circulating maternal anti-HTLV antibodies.

PCR also quantifies the proviral load, which is frequently used as a marker for progression, especially in HTLV-1–associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is expressed as “the number of HTLV-1 DNA copies per fixed number of peripheral blood mononuclear cells.” As an example, the mean proviral copy number per 10,000 peripheral blood mononuclear cells was found to be 798 in patients with HAM/TSP versus 120 in asymptomatic HTLV-1 carriers. [40]

Patients diagnosed with HTLV-1 or HTLV-2 infection should also undergo the following tests:

  • Screening for HIV should be strongly considered.

  • Routine blood work should include a CBC count with differential and peripheral blood smear, complete chemistry with calcium level, liver function tests, and lactate dehydrogenase.

  • Also recommended are viral hepatitis serology (A, B, C), rapid plasma reagin (RPR), purified protein derivative (PPD), Strongyloides stercoralis serology, and stool examination for ova and parasites.


Imaging Studies

No specific imaging studies are recommended for asymptomatic HTLV infections. However, the following might be considered in aiding in diagnoses/evaluation of HAM/TSP or adult T-cell leukemia (ATL).


Brain MRI reveals nonspecific periventricular and subcortical white matter lesions in 50%-80% of patients with HAM/TSP; however, these lesions also occur in patients with asymptomatic HTLV-1 infections, and comparisons with controls have not been adequate. [40]


Chest radiography is important, particularly in patients with ATL, to assess for pulmonary complications, opportunistic infections, and lytic bone lesions.

CT scanning of the neck, thorax, abdomen, and pelvis is crucial in assessing for nodal involvement. [46] It can also aid in further assessment for opportunistic infections (ie, abscess formation, pneumonia, intestinal infections).



Lumbar puncture to evaluate CSF for anti–HTLV-1 antibodies (and/or HTLV-1 proviral load) might be beneficial in establishing a diagnosis of HAM/TSP. The laboratory results often show a mild lymphocyte pleocytosis and increased protein levels. A proviral load ratio of CSF to peripheral blood that exceeds 1 supports a diagnosis of HAM/TSP. [40]

Serology for HTLV-1, along with histologically (ie, lymph node biopsy) or cytologically proven peripheral T-cell malignancy, is diagnostic of ATL. Furthermore, in indolent ATL (chronic or smoldering), when the cause of the lesion is unknown, a biopsy of a suspicious lesion can be performed for analysis of HTLV-1 provirus integration. [46]


Histologic Findings

HAM/TSP histopathology of the spinal cord shows perivascular and parenchymal infiltration of T cells, which worsens with the development of atrophy during progression of the disease. [40]

Peripheral blood smear is required for definitive diagnosis and categorization of ATL. ATL peripheral blood lymphocytes are found to have convoluted nuclei (cloverleaf or flower lymphocytes); provirus can be detected within these malignant cells.