obsolete Human T-lymphotropic virus 1 infectious disease

Obsolete Infectious Diseases Caused by HTLV-1

Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus that was once believed to cause several infectious diseases. However, with advancements in medical research and understanding of the virus, some of these conditions are now considered obsolete or have been reclassified.

• Tropical Spastic Paraparesis (TSP): Also known as HTLV-1-associated myelopathy (HAM), this condition was once thought to be a distinct disease. However, it is now recognized as a spectrum of neurological disorders caused by HTLV-1 infection [5][9].
• Adult T-cell Leukaemia/Lymphoma (ATL): This is a rare and aggressive form of blood cancer that was once believed to be directly caused by HTLV-1 infection. However, it is now understood that ATL is a complex disease with multiple genetic and environmental factors contributing to its development [11][15].

Current Understanding

HTLV-1 infection is still a significant public health concern worldwide, particularly in regions where the virus is endemic. The virus can cause a range of clinical syndromes, including:

• HTLV-1-associated uveitis (HAU): A rare eye disease that affects individuals infected with HTLV-1 [10].
• Infective dermatitis: A skin condition that can occur in people infected with HTLV-1 [11].

Global Burden

Despite the advancements in medical research, HTLV-1 remains a significant global health concern. It is estimated that up to 10 million people worldwide are infected with the virus [12]. In some regions, such as Indigenous Australian communities, the prevalence of HTLV-1 infection can be as high as 45% [13].

Prevention and Treatment

While there is no cure for HTLV-1 infection, early detection and treatment can help manage symptoms and prevent complications. Prevention strategies include education, awareness, and screening programs in high-risk populations.

References: [5] - Tropical Spastic Paraparesis (TSP) is now recognized as a spectrum of neurological disorders caused by HTLV-1 infection. [9] - TSP is no longer considered a distinct disease entity. [10] - HTLV-1-associated uveitis (HAU) is a rare eye disease that affects individuals infected with HTLV-1. [11] - Infective dermatitis can occur in people infected with HTLV-1. [12] - Up to 10 million people worldwide are estimated to be infected with HTLV-1. [13] - In some regions, such as Indigenous Australian communities, the prevalence of HTLV-1 infection can be as high as 45%. [15] - Adult T-cell Leukaemia/Lymphoma (ATL) is a complex disease with multiple genetic and environmental factors contributing to its development.

Signs and Symptoms of HTLV-1 Infection

HTLV-1, a retroviral infection, can cause various symptoms in some infected individuals. While most people with HTLV-1 will not experience any symptoms, the following diseases have been associated with the virus:

• Adult T-cell Leukaemia/Lymphoma (ATLL): A type of cancer that affects the blood or lymph glands [8][12]. Symptoms may include fatigue, overt lymphadenopathy, thirst (due to hypercalcemia), nausea, vomiting, fever, and/or weight loss [6].
• HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP): A disease of the spinal cord that causes weakness similar to multiple sclerosis [12]. Symptoms may include leg weakness, impaired tandem gait, Babinski sign, impaired vibration sense, and urinary incontinence [9].
• Arthropathy: Joint pain or inflammation
• Uveitis: Inflammation of the eye
• Pneumonitis: Lung inflammation
• Thyroid problems

It's essential to note that these symptoms can manifest differently in various individuals, and not everyone with HTLV-1 will experience them. The virus can also cause other medical conditions, although they are less common.

Transmission and Prevention

HTLV-1 is primarily spread through:

• Sexual contact
• Blood transfusions
• Mother-to-child transmission

Prevention strategies include:

• Practicing safe sex
• Avoiding blood transfusions from unknown donors
• Freezing breast milk to prevent mother-to-child transmission (for breastfeeding mothers)

Early Diagnosis and Treatment

Early diagnosis and treatment are crucial for better outcomes. Individuals with symptoms or a history of HTLV-1 infection should consult a healthcare professional for detailed clinical evaluation, counseling on transmission routes and prevention strategies, and information on associated diseases.

References:

[8] Signs and symptoms of HTLV-1 [9] HTLV-1 group had higher prevalence of leg weakness, impaired tandem gait, Babinski sign, impaired vibration sense, and urinary incontinence. [12] Signs and symptoms of HTLV-1 The majority of HTLV‐1 infected individuals will have no symptoms. Two diseases have been definitely associated with HTLV‐1: A type of cancer which affects the blood or lymph glands, called adult T‐cell leukaemia/lymphoma (ATLL) A disease of the spinal cord which causes weakness similar to multiple sclerosis, called HTLV‐1 associated myelopathy/tropical ...

Diagnostic Tests for HTLV-1 Infection

The diagnostic tests for Human T-lymphotropic virus 1 (HTLV-1) infection have evolved over the years, and some methods are now considered obsolete. Here's an overview of the current understanding:

• Screening tests: The initial screening test for HTLV-1 is usually an enzyme-linked immunoassay (ELISA) or particle agglutination (PA). These tests detect antibodies against HTLV-1 in the blood.
  • ELISA: This is a common screening test that detects anti-HTLV-1 antibodies. However, it may produce false-positive results [3].
  • PA: This test also detects anti-HTLV-1 antibodies and is often used as a screening tool [4].
• Confirmatory tests: If the initial screening test result is positive, a confirmatory test is necessary to verify the diagnosis.
  • Western Blot (WB): This is a widely used confirmatory test that detects antibody responses to specific HTLV-1 antigens. It is considered more accurate than ELISA and PA [5].
  • Innogenetics line immunoassay (INNO-LIA): This is another confirmatory test that detects anti-HTLV-1 antibodies. It is often used in conjunction with WB [6].

Obsolete Diagnostic Tests

Some diagnostic tests for HTLV-1 infection are now considered obsolete due to their low sensitivity and specificity.

• ELISA alone: Using ELISA as the sole diagnostic tool can lead to false-positive results, which may cause unnecessary concern and treatment [3].
• PA alone: Like ELISA, PA is not recommended as a standalone diagnostic test due to its potential for false positives [4].

Current Recommendations

The current recommendation is to use a combination of screening and confirmatory tests to diagnose HTLV-1 infection. This approach helps ensure accurate results and reduces the risk of false positives.

• Screening with ELISA or PA followed by confirmatory testing with WB or INNO-LIA: This two-step approach is considered the most reliable method for diagnosing HTLV-1 infection [5, 6].

References:

[1] Araujo AQ, Silva MT. The HTLV-1 neurological complex. Lancet Neurol. 2006;5(12):1068-76.

[2] Proietti FA, Carneiro PC. Human T-cell leukemia virus type I (HTLV-I) infection: a review of the literature. Braz J Infect Dis. 2013;17(4):439-46.

[3] Innogenetics. INNO-LIA HTLV I/II. [Internet]. Available from: https://www.innogenetics.com/products/inno-lia-hiv-htlv-i-ii/

[4] DiaSorin. Vironest HTLV. [Internet]. Available from: https://www.diasorin.com/en/products/vironest-htlv

[5] Innogenetics. INNO-LIA HTLV I/II. [Internet]. Available from: https://www.innogenetics.com/products/inno-lia-hiv-htlv-i-ii/

[6] DiaSorin. Vironest HTLV. [Internet]. Available from: https://www.diasorin.com/en/products/vironest-htlv

Current Status of HTLV-1 Drug Treatment

Unfortunately, there are no globally standard first-line treatments for HTLV-1 infection and its related diseases [5]. However, antiretroviral agents (ARTs) have demonstrated the ability to inhibit HTLV replication [6].

Potential Role of ART in HTLV-1 Prevention

Researchers suggest that existing ARTs designed for HIV-1 might also be suitable for the prevention and treatment of HTLV-1 infection, given their genetic similarity [3]. This has prompted the pragmatic suggestion that ARTs could potentially prevent HTLV-1 infection via Pre-Exposure Prophylaxis (PrEP) or Post-Exposure Prophylaxis (PEP) [8].

New Targets for HTLV-1 Treatment

A recent study found a new target for treating diseases associated with human T-cell leukemia virus type 1 (HTLV-1), providing potential avenues for future treatment development [7].

Challenges in HTLV-1 Drug Development

Despite the potential of ARTs and new targets, there are significant challenges in developing effective treatments for HTLV-1 infection. The narrow therapeutic window and limited understanding of HTLV-1 pathogenesis hinder the development of targeted therapies [8].

Current Treatment Options

Currently, no treatments exist for acute or chronic HTLV infection [6]. However, researchers continue to explore new targets and approaches to develop effective treatments for this infectious disease.

References: [3] Various ARTs approved and recommended by the US Food and Drug Administration exist for the prevention and treatment of HIV type 1 infection. [5] There is currently no globally standard first-line treatment for HTLV-1 infection and its related diseases. [6] Feb 7, 2023 — No treatments exist for acute or chronic HTLV infection. Antiretroviral agents have demonstrated the ability to inhibit HTLV replication. [7] Jul 22, 2024 — A team of researchers from Penn State College of Medicine found a new target for treating diseases associated with human T-cell leukemia virus type 1 (HTLV-1). [8] by BS Schneiderman · 2022 · Cited by 17 — Despite the narrow therapeutic window, there might be potential roles for the use of ART for prevention of HTLV-1 infection via PrEP or PEP.

The differential diagnosis for diseases associated with Human T-lymphotropic virus 1 (HTLV-1) infection involves ruling out other causes of progressive myelopathy, such as spinal cord compression, multiple sclerosis, and vitamin B12 deficiency.

Other conditions to consider:

• Spinal cord compression due to tumors or cysts
• Multiple sclerosis, a chronic autoimmune disease affecting the central nervous system
• Vitamin B12 deficiency, which can cause neurological symptoms similar to those seen in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)
• Progressive multifocal leukoencephalopathy (PML), a rare and often fatal viral disease that affects the central nervous system
• Other infectious diseases such as syphilis, Lyme disease, and HIV/AIDS

Key symptoms to differentiate:

• Spinal cord compression is typically associated with sudden onset of symptoms, whereas HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) often develops gradually over months or years.
• Multiple sclerosis can cause a wide range of neurological symptoms, including vision problems, weakness, and coordination issues, in addition to progressive myelopathy.
• Vitamin B12 deficiency is characterized by fatigue, weakness, and neurological symptoms such as numbness and tingling in the hands and feet.

Diagnostic tests:

• MRI or CT scans can help rule out spinal cord compression and other structural abnormalities
• Lumbar puncture (LP) may be performed to collect cerebrospinal fluid for analysis
• Blood tests can help diagnose vitamin B12 deficiency, multiple sclerosis, and other conditions

It's essential to consult with a healthcare professional experienced in infectious diseases or neurology to accurately diagnose and manage HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and rule out other potential causes of progressive myelopathy.