Human T-cell Lymphotropic Virus

What is HTLV and how is it distributed in the world?
HTLV is a virus that infects humans and persists in the body for life. The virus infects the T-lymphocytes of the human host. T-lymphocytes are a type of white blood cell. Following infection there are three differing events, each of which contribute to the persistence of the virus in the host: 1) the virus spreads from the infected cell to other uninfected cells; 2) the virus causes the infected cells to multiply; 3) the virus persists in the infected cell silently for long periods.

Thus far four types of HTLV have been discovered which infect humans namely HTLV-1, HTLV-2, HTLV-3 and HTLV-4. HTLV-1 is the virus of major concern with the widest global distribution and the most disease complications. HTLV-2 is also relatively common in some regions/population groups but rarely causes disease. These two are therefore the HTLVs of principle concern. HTLV-3 and HTLV-4 are rare infections with no associated diseases yet reported.

On a global perspective, 5 to 10 million people are estimated to be infected with HTLV-1 with an uneven geographic distribution. There is only an incomplete picture of the prevalence of HTLV-1 infection but the existing data suggest that it is endemic with a high prevalence (considered as more than 1% of the population infected) in certain regions of the world: Japan, Caribbean islands, some African countries (especially West Africa), most countries of South America and certain regions of Oceania particularly Melanesia and the Northern Territory of Australia. HTLV-1 has also been reported in Romania and in some countries of the Middle-East. In Western Europe and North America the prevalence of HTLV-1 is considered low, but there are multiple pockets with higher prevalence within these low prevalence regions, which makes HTLV screening within them a higher priority.

The prevalence of HTLV-2 is estimated to be around 800,000 globally with the highest number in the United States followed by Brazil. The European HTLV-2 population is estimated to be between 20,000 and 40,000. HTLV-2 is endemic among the Amerindian populations and the pygmy populations in Central Africa.

Less is known about the epidemiology of the recently discovered HTLV-3 and HTLV-4, but these are simian viruses transmitted from monkeys to humans via bites or scratched in Central African (e.g. Cameroon). They have only been identified in a few subjects and have not yet been associated with human disease.

How is HTLV infection transmitted?
HTLV infection can be transmitted via 3 main routes.
1. Via unprotected sexual contact.
2. Via contaminated blood transfusions or blood products1, sharing contaminated needles and other injection equipment, or receiving an organ transplant from an infected donor.
3. HTLV virus can be passed from an infected mother to her baby mainly via breast feeding (predominantly with prolonged breast feeding beyond 6 months of age) and less commonly during the pregnancy (intra-uterine transmission).

1UK blood and tissue services test all blood donations and tissues for HTLV using serological techniques to ensure they are free of the infection. However, such screening is not mandatory in all countries including some European countries which may put recipients at risk. Additionally in the UK all blood products are subjected to removal of white blood cells (universal leucodepletion). This has been enforced since 1999, and further reduces the risk of transmission of infectious agents such as HTLV and cytomegalovirus to recipients.

What diseases does HTLV cause?
In the majority of infected individuals there is an asymptomatic carrier state (silent but ongoing infection), with only a small proportion (about 5 to 9%) developing disease associated with HTLV-1 during their lifetime.

HTLV-1 infection gives rise to two main disease entities: Adult T-cell leukaemia/lymphoma (ATLL) which is a form of blood cancer, and HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) which is a chronic inflammatory degenerative disease of the spinal cord leading to weakness of the lower limbs. ATLL occurs in 2 – 6% and HAM/TSP in approximately 3% of carriers.

In a smaller number of patients, other inflammatory conditions such as uveitis (inflammation of the eye), arthritis (inflammation of joints), myositis (inflammation of muscles), alveolitis (inflammation of lungs) and dermatitis (inflammation of skin) can be seen.

The HTLV-2 disease spectrum is less clear, but lung conditions, myelopathy (inflammation of the spinal cord) and dermatitis, have been reported.

Sometimes, as HTLV causes mild immunosuppression, patients may develop diseases caused by other infectious agents that are able to thrive in a host with a suppressed immune system (e.g. parasitic infections such as Strongyloides stercoralis).

What tests are performed?

• Serology: Once individuals are infected with HTLV, their immune system starts producing antibodies that are specifically directed against the virus. By detection of these antibodies using laboratory tests, whether or not a person is infected with this virus can be determined. Using the development of antibodies to detect infection is called serology.
• Molecular: Sometimes a test to detect the genetic material of the virus is used. This can be useful in situations such as having indeterminate serology (inconclusive antibody) test results or when antibodies to both HTLV-1 and HTLV-2 are detected. The measurement of HTLV-1 viral load in patients found to be infected is also useful to determine risk of disease and sometimes to aid with the diagnosis and treatment of an HTLV-1-associated disease. Detection and quantification of HTLV-genetic material is called molecular diagnostics.

How is the sample collected for testing?

Blood via venepuncture (inserting a needle into a vein of the arm).

Cerebrospinal fluid is collected via a lumbar puncture (inserting a needle into the lower back) to help with the diagnosis of HAM/TSP. This is only performed if HAM/TSP is suspected and is not required for the diagnosis of HTLV-1 or HTLV-2 infection per se.

Tissue for molecular test is obtained from a biopsy under local anaesthetic or at the time of an operation. This is only required if molecular testing of tissue is important to help with diagnosis of inflammation or ATLL.

Is any test preparation needed to ensure the quality of the sample?

No special preparations are needed for serology.

Blood samples for serological investigation can be sent to the laboratory in plain blood collection tubes or gel tubes (clotted blood).

The blood sample collected for molecular investigations needs to be collected into an EDTA (Ethylenediaminetetraacetic acid) blood tube. A minimum of 4mls should be obtained (adults).

CSF samples are collected into a plain universal container. Ideally at least 1ml is sent for HTLV diagnostic tests.

CSF samples and whole blood EDTA samples collected for molecular analysis must not be refrigerated or frozen, and must be sent to the laboratory within 24 hours, while being maintained at ambient temperature. Freezing CSF or whole blood kills the lymphocytes whilst refrigeration may also increase the rate of death of lymphocytes. Both can reduce the reliability of the molecular diagnostic tests.