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HTLV-1: Incurable Sexually Transmitted Virus Threatens Aboriginal Communities

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A virus with ties to HIV is on the rise in aboriginal communities in Australia. The blood-borne virus is sexually transmitted and can also be passed from mother to child.

HTLV-1

Just like its cousin HIV, which over time causes AIDS, the T-cell lymphotropic virus type 1 (HTLV-1) has no cure and causes deadly complications. Unlike HIV, however, the symptoms of HTLV-1 takes longer to appear. Some people may have the virus for decades before chronic complications emerge.

HTLV-1 can cause inflammation of the skin, lungs, and eyes and those infected by it are at risk of becoming disabled through spinal injuries. They are also at risk of developing leukemia. Up to 10 percent of all who are infected will develop a rapidly deadly form of leukemia and those who do die within a year of diagnosis.

The virus is becoming more prevalent in remote regions affecting indigenous communities. Cases can be found in Africa, South America, and southern Japan but researchers said that Australia has the highest rate of HTLV-1 infection in the world.

Researchers from the Baker Heart and Diabetes Institute revealed that 45 percent of indigenous adults in central Australia carry the virus. The most common complication observed in these communities is a severe lung disease called bronchiectasis.

 

Neglected Virus

Researchers think that the virus likely arrived in Australia from Indonesia thousands of years ago. Unfortunately, it continues to affect aboriginal communities.

One of the challenges in dealing with the virus is that most of the people infected by it are not aware they have it and a large number of aboriginal communities have not been tested.

The virus is also spreading with population movement. It is estimated that 5 to 10 million people worldwide are affected.

"It's very suggestive that we have a major problem and it really pays no attention to borders, these very artificial constructs of Europeans," said Lloyd Einsiedel, of the Baker Heart and Diabetes Institute.

HTLV-1 was discovered as early as the 1980s alongside HIV but the global research community appears to have neglected it. Health experts cited the importance raising awareness about the seriousness of the disease.

"We need to stimulate more governmental involvement, we need to push the importance of the disease, the seriousness of it. We could do much better. We need to do significantly more with HTLV-1," said Robert Gallo, director of the Institute of Human Virology at the University of Maryland's school of medicine.

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An ancient virus infecting residents across Australia’s Northern Territory is leaving death and despair in its path, and doctors are now calling for greater efforts to stop the spread of infections.

The rates of human T-cell leukemia virus type 1, or HTLV-1, infection are exceeding 40% among adults in remote regions of central Australia, with indigenous communities being the hardest hit, especially in the town of Alice Springs.

Many doctors — including the man who discovered the virus nearly four decades ago — are raising the alarm about how little has been done to prevent, test for and treat HTLV-1, which can cause leukemia and lymphoma.

“The prevalence is off the charts” in Australia, said Dr. Robert Gallo, co-founder and director of the Institute of Human Virology at the University of Maryland School of Medicine, whose laboratory was the first to detect HTLV-1 in 1979 and publish the finding in 1980.

Yet “nobody that I know of in the world has done anything about trying to treat this disease before,” said Gallo, who is also co-

 

“There’s little to almost no vaccine efforts, outside of some Japanese research,” he said. “So prevention by vaccine is wide open for research.”

HTLV-1 — an ancient virus whose DNA can be found in 1,500-year-old Andean mummies — can spread from mother to child, particularly through breastfeeding; between sexual partners, through unprotected sex; and by blood contact, such as through transfusions. Because it can be transmitted through sex, it’s considered a sexually transmitted infection, or STI.

The virus is associated with myriad serious health problems, such as diseases of the nervous system and a lung-damaging condition called bronchiectasis, and it weakens the immune system. HTLV-1 is sometimes called the cousin of the human immunodeficiency virus, HIV.

An ‘extraordinary’ prevalence in remote Australia

The focus has come about now because of the high prevalence among indigenous Australians, “which is probably the highest-ever reported prevalence in any population,” said Dr. Graham Taylor, a clinician and professor at Imperial College London who runs the United Kingdom’s HTLV clinical service based at St. Mary’s Hospital.

“But if we look globally, we know about HTLV-1 in a number of countries,” he added.

HTLV-1 is present throughout the world, but there are certain areas where it is highly endemic, such as the rare isolated cluster in central Australia.

 

 

The main highly endemic areas are the southwestern part of Japan; some parts of the Caribbean; areas in South America including parts of Brazil, Peru, Colombia and French Guyana; some areas of intertropical Africa, such as south Gabon; some areas in the Middle East, such as the Mashhad region in Iran; a region in Romania; and a rare isolated cluster in Melanesia, according to the European Centre for Disease Prevention and Control.

Elsewhere in the world, such as in the United States and the UK, prevalence remains low.

“The interesting thing about central Australia, of course, is you can go back 25 years, and the high rates of HTLV-1 were published 25 years ago in that community,” Taylor said.

Indeed, a study published in the Medical Journal of Australia in 1993 found that HTLV-1 was endemic among natives in inland Australia, with a high 13.9% prevalence in the Alice Springs area.

 

 

It’s unclear whether the sample in that old study was of the same population currently experiencing a higher prevalence rate, and it’s unclear whether that previous rate was measured with similar methods used to assess prevalence today.

Nonetheless, the current prevalence rate, exceeding 40%, is “extraordinary,” Taylor said.

“It’s causing a problem of bronchiectasis. People are dying of bronchiectasis in association with HTLV-1 infection, and what is the response? If you can’t see a response, then you might say it’s neglected,” he said. “The virus is neglected, and the diseases that it causes are neglected.”

The reason why HTLV-1 prevalence in an already endemic area is exceeding 40% remains something of a mystery, Gallo said.

While musing on possible reasons, he questioned whether the HTLV-1 seen among indigenous communities in central Australia could be a variant that transmits more easily.

“Nobody knows that either,” he said. “That’s possible.”

However, he added, there is no reason for the rest of the world to be concerned about the virus spreading more widely.

Likely, “this virus, I don’t care what the variation is, will not transmit casually,” Gallo said.

“In short, I would not be afraid to use towels, drink out of the same glass, be part of the family, et cetera,” of an HTLV-1 positive person, he said. But he added that the virus certainly can transmit through breastfeeding, blood contact and sex.

‘We have to make up for what we didn’t do before’

On the other hand, why the HTLV-1 virus has been neglected in certain regions — especially Australia’s indigenous communities — appears to be not as mysterious.

Many regions around the world impacted by HTLV-1 are poorer communities that often go overlooked by the medical establishment and don’t have as many health care resources, Gallo said.

Around the world, there appear to be not many efforts to screen for HTLV-1, Taylor said. For instance, few countries have antenatal screening programs for it.

“The only country which has a national antenatal screening program is Japan,” he said. Screening and recommendations of formula feeding have been practiced in Nagasaki, Japan, since about 1987 and are being discussed in other parts of the world, including England and Jamaica.

“Then, you have the situation where blood which is infected with HTLV-1 can be given to a recipient, an organ can be given to a recipient,” he said. “So there are public health issues.”

Additionally, just a few years after HTLV-1 was discovered, Gallo and his colleagues also identified HIV for the first time. Between HTLV-1 and HIV, the latter got the most attention, Gallo said, partly because HIV is more efficient at transmitting.

Now, “we have to make up for what we didn’t do before,” he said. “We have to get attention to HTLV-1 quick.”

In other words, the high prevalence of HTLV-1 in central Australia has become something of a wakeup call for the world to do more to prevent and reduce infections from the virus.

“There’s a lack of knowledge about HTLV-1,” Taylor said.

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Doctors raise alarm about ancient HTLV-1 virus: 'Prevalence is off the charts' in Australia

AUDIO HERE

(CNN)An ancient virus infecting residents across Australia's Northern Territory is leaving death and despair in its path, and doctors are now calling for greater efforts to stop the spread of infections.

The rates of human T-cell leukemia virus type 1, or HTLV-1, infection are exceeding 40% among adults in remote regions of central Australia, with indigenous communities being the hardest hit, especially in the town of Alice Springs.
Many doctors -- including the man who discovered the virus nearly four decades ago -- are raising the alarm about how little has been done to prevent, test for and treat HTLV-1, which can cause leukemia and lymphoma.
    "The prevalence is off the charts" in Australia, said Dr. Robert Gallo, co-founder and director of the Institute of Human Virology at the University of Maryland School of Medicine, whose laboratory was the first to detect HTLV-1 in 1979 and publish the finding in 1980.
    Yet "nobody that I know of in the world has done anything about trying to treat this disease before," said Gallo, who is also co-founder and scientific director of the Global Virus Network and chairs the network's HTLV-1 Task Force.
    "There's little to almost no vaccine efforts, outside of some Japanese research," he said. "So prevention by vaccine is wide open for research."
    HTLV-1 -- an ancient virus whose DNA can be found in 1,500-year-old Andean mummies -- can spread from mother to child, particularly through breastfeeding; between sexual partners, through unprotected sex; and by blood contact, such as through transfusions. Because it can be transmitted through sex, it's considered a sexually transmitted infection, or STI.
    The virus is associated with myriad serious health problems, such as diseases of the nervous system and a lung-damaging condition called bronchiectasis, and it weakens the immune system. HTLV-1 is sometimes called a cousin of the human immunodeficiency virus, HIV.

    An 'extraordinary' prevalence in remote Australia

    The focus has come about now because of the high prevalence among indigenous Australians, "which is probably the highest-ever reported prevalence in any population," said Dr. Graham Taylor, a clinician and professor at Imperial College London who runs the United Kingdom's HTLV clinical service based at St. Mary's Hospital.
    "But if we look globally, we know about HTLV-1 in a number of countries," he added.
     
    Investigating the world's deadliest diseases
     

     

     

       
       
       

       

      Investigating the world's deadliest diseases 06:46
      HTLV-1 is present throughout the world, but there are certain areas where it is highly endemic, such as the rare isolated cluster in central Australia.
      The main highly endemic areas are the southwestern part of Japan; some parts of the Caribbean; areas in South America including parts of Brazil, Peru, Colombia and French Guyana; some areas of intertropical Africa, such as south Gabon; some areas in the Middle East, such as the Mashhad region in Iran; a region in Romania; and a rare isolated cluster in Melanesia, according to the European Centre for Disease Prevention and Control.
      Elsewhere in the world, such as in the United States and the UK, prevalence remains low.
      "The interesting thing about central Australia, of course, is you can go back 25 years, and the high rates of HTLV-1 were published 25 years ago in that community," Taylor said.
       
      Indeed, a study published in the Medical Journal of Australia in 1993 found that HTLV-1 was endemic among natives in inland Australia, with a high 13.9% prevalence in the Alice Springs area.
      It's unclear whether the sample in that old study was of the same population currently experiencing a higher prevalence rate, and it's unclear whether that previous rate was measured with similar methods used to assess prevalence today.
      Nonetheless, the current prevalence rate, exceeding 40%, is "extraordinary," Taylor said.
      "It's causing a problem of bronchiectasis. People are dying of bronchiectasis in association with HTLV-1 infection, and what is the response? If you can't see a response, then you might say it's neglected," he said. "The virus is neglected, and the diseases that it causes are neglected."
      The reason why HTLV-1 prevalence in an already endemic area is exceeding 40% remains something of a mystery, Gallo said.
      While musing on possible reasons, he questioned whether the HTLV-1 seen among indigenous communities in central Australia could be a variant that transmits more easily.
      "Nobody knows that either," he said. "That's possible."
      However, he added, there is no reason for the rest of the world to be concerned about the virus spreading more widely.
      Likely, "this virus, I don't care what the variation is, will not transmit casually," Gallo said.
      "In short, I would not be afraid to use towels, drink out of the same glass, be part of the family, et cetera," of an HTLV-1 positive person, he said. But he added that the virus certainly can transmit through breastfeeding, blood contact and sex.

      'We have to make up for what we didn't do before'

      On the other hand, why the HTLV-1 virus has been neglected in certain regions -- especially Australia's indigenous communities -- appears to be not as mysterious.
      Many regions around the world impacted by HTLV-1 are poorer communities that often go overlooked by the medical establishment and don't have as many health care resources, Gallo said.
      Around the world, there appear to be not many efforts to screen for HTLV-1, Taylor said. For instance, few countries have antenatal screening programs for it.
      "The only country which has a national antenatal screening program is Japan," he said. Screening and recommendations of formula feeding have been practiced in Nagasaki, Japan, since about 1987 and are being discussed in other parts of the world, including England and Jamaica.
      "Then, you have the situation where blood which is infected with HTLV-1 can be given to a recipient, an organ can be given to a recipient," he said. "So there are public health issues."
      In the United States, Australia and some other countries, donated tissues and donated bloodoften are tested for HTLV.
       
      Additionally, just a few years after HTLV-1 was discovered, HIV was identified for the first time. Between HTLV-1 and HIV, the latter got the most attention, Gallo said, partly because HIV is more efficient at transmitting.
      Now, "we have to make up for what we didn't do before," he said. "We have to get attention to HTLV-1 quick."
      In other words, the high prevalence of HTLV-1 in central Australia has become something of a wakeup call for the world to do more to prevent and reduce infections from the virus.
      "There's a lack of knowledge about HTLV-1," Taylor said.

       

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      Treatment

      In endemic areas, screening of candidate blood donors decreases the number of new infections in the population. Screening pregnant women and avoiding breastfeeding can reduce maternal transmission. Condom use offers protection against sexual transmission.

      Several drugs have been used in the treatment of HAM/TSP including Interferon, danazol, high dose vitamin C, azatioprine, antivirals employed in treatment of HIV infection (zidovudine and lamivudine), valproic acid among others, but results were disappointing. High dose steroids might provide transient improvement in early stages of disease.

      Although there is no specific treatment to date, relief of symptoms is a crucial aspect of the care of affected individuals. Spasticity (stiffness) can be treated with relaxant drugs (diazepam, baclofen), botulinic toxin injection and physical therapy. Anticholinergic drugs or urinary catheters are effective for urinary incontinence/urgency. Stool-softeners and laxants are commonly used for constipation.

      The treatment of pain and other sensory symptoms such as tingling sensation (paresthesias) is dictated by their quality and severity and may include anti- inflammatory, antidepressants and antiepileptic drugs. Coordinated efforts of a team of specialists consisted of neurologists, infectious disease specialists, urologists, physical therapists and other healthcare professionals are usually necessary for comprehensive care.

      Treatment of ATL includes the combination of interferon and zidovudine, intensive chemotherapy and allogenic haematopoietic stem cell transplantation. Prognosis depends on the ATL subtype. While chronic subtype has a relatively good prognosis, the median survival in acute subtype is less than one year in most series.

      Investigational Therapies

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      HTLV Type I and Type II

      NORD gratefully acknowledges Marco A. Lima, MD, PhD, Researcher, Instituto de e Pesquisa Clinica Evandro Chagas/FIOCRUZ, Rio de Janeiro, Brazil, for the preparation of this report.

      Synonyms of HTLV Type I and Type II

      • acute T-cell leukemia
      • acute T-cell lymphoma
      • ATL
      • HAM/TSP
      • HTLV-I associated myelopathy
      • tropical spastic paraparesis

      General Discussion

      HTLV-I was first isolated in 1980 from a patient originally thought to have a cutaneous lymphoma. It became clear that it was a distinct form of lymphoma, which was designated as acute T-cell leukemia/ lymphoma (ATL). Some years later, different groups in Martinique and Japan described an association between a chronic disease of the spinal cord and HTLV-I infection, which was later named HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Since then, several other conditions have been linked to HTLV infection.

      It is estimated that between 10 and 20 million people are infected by HTLV-I in the world. Only 0.25-2% of the infected individuals will develop a progressive neurologic disease named HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/TSP). Approximately 2-5% of HTLV-I carriers will develop ATL. More rarely, HTLV-I may lead to arthropathy, uveitis (inflammation of the eye), pneumonitis and thyroid problems. Areas of the world that are endemic to the HTLV-1 virus are the Caribbean, southern Japan, equatorial Africa, Middle East, South America, and Melanesia.

      Signs & Symptoms

      HAM/TSP usually has an insidious onset and chronic evolution. Initial symptoms are subtle and include gait problems, unexplained falls, low back pain, constipation, urinary urgency/incontinence and numbness or pain in the lower limbs. Over the years, progressive leg weakness ensues followed by the exacerbation of the urinary and sensory symptoms. The prognosis of the neurological disability is variable. While some patients are still ambulatory after one or two decades of disease, others may be confined to a wheelchair months after onset of disease.

      HTLV-I-induced ATL has four different subtypes: acute, lymphomatous, chronic and smoldering. Each of them has a distinct clinical picture and evolution. A combination of skin and bone lesions, pulmonary infiltrates, elevation of serum calcium, enlargement of the liver, spleen and lymph nodes, and opportunistic infections may be present.

      Causes

      The transmission of HIV (the virus responsible for AIDS) and HTLV-Type I infection are similar. Infection can occur by sexual contact with an infected individual, through sharing of contaminated needles and syringes by intravenous drug users, or as the result of a transfusion of contaminated blood. Mother to child transmission may happen through perinatal exposure or most often through breast-feeding. The intrauterine transmission is very rare.

      The cause of HAM/TSP has not been completely understood to date, since most infected individuals will never develop any symptoms or signs of disease. Theories include a direct effect of the virus on the central nervous system or an autoimmune process. In ATL, there is a disordered clonal expansion of blood cells called CD4+ T lymphocytes, which are infected by the virus.

      Affected Populations

      Populations in the endemic areas around the world, including the Caribbean, southern Japan, equatorial Africa, Middle East, South America and Melanesia, are at a higher risk as are immigrants from such areas. Women are infected at a 2:1 proportion.

      ATL is more common in patients who acquired HTLV-I infection during the perinatal period, with men having a threefold higher risk when compared to women. The latency between infection and development of symptoms is longer than 20 years in most ATL cases. HAM/TSP usually develops in the fourth or fifth decades but onset at extremes of age is observed. The latency period of HAM/TSP is shorter than in ATL, and women are more affected.

      Diagnosis

      The diagnosis of HTLV-I infection is usually made by detection of antibodies against the virus in the blood or cerebrospinal fluid. In some cases, techniques that detect HTLV-I genome in infected cells may be necessary.

      Concerning HAM/TSP, many HTLV-I infected individuals remain asymptomatic throughout their lives, beyond the positive laboratory findings of HTLV-I infection. Thus, it is necessary to rule out the presence of typical symptoms and exclusion of other disorders than can present in the same way (other infections, vitamin deficiencies, genetic disorders and compression of the spinal cord).

      ATL is diagnosed based on the clinical picture, evidence of HTLV-I integration into host cells, peripheral blood analysis and biopsy of affected sites. Atypical lymphocytes named flower cells may be present on examination of blood smears. Elevation of serum calcium (hypercalcemia) is common.

      Standard Therapies

      Treatment

      In endemic areas, screening of candidate blood donors decreases the number of new infections in the population. Screening pregnant women and avoiding breastfeeding can reduce maternal transmission. Condom use offers protection against sexual transmission.

      Several drugs have been used in the treatment of HAM/TSP including Interferon, danazol, high dose vitamin C, azatioprine, antivirals employed in treatment of HIV infection (zidovudine and lamivudine), valproic acid among others, but results were disappointing. High dose steroids might provide transient improvement in early stages of disease.

      Although there is no specific treatment to date, relief of symptoms is a crucial aspect of the care of affected individuals. Spasticity (stiffness) can be treated with relaxant drugs (diazepam, baclofen), botulinic toxin injection and physical therapy. Anticholinergic drugs or urinary catheters are effective for urinary incontinence/urgency. Stool-softeners and laxants are commonly used for constipation.

      The treatment of pain and other sensory symptoms such as tingling sensation (paresthesias) is dictated by their quality and severity and may include anti- inflammatory, antidepressants and antiepileptic drugs. Coordinated efforts of a team of specialists consisted of neurologists, infectious disease specialists, urologists, physical therapists and other healthcare professionals are usually necessary for comprehensive care.

      Treatment of ATL includes the combination of interferon and zidovudine, intensive chemotherapy and allogenic haematopoietic stem cell transplantation. Prognosis depends on the ATL subtype. While chronic subtype has a relatively good prognosis, the median survival in acute subtype is less than one year in most series.

      Investigational Therapies

      Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site

      For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

      Tollfree: (800) 411-1222

      TTY: (866) 411-1010

      Email: prpl@cc.nih.gov

      For information about clinical trials sponsored by private sources, contact:

      www.centerwatch.com

      Recent studies have examined the role of new approaches such as targeted therapy against surface molecule on ATLL cells, retinoid derivatives, and the proteasome inhibitor bortezomib but their efficacy remains to be established.

      Contact for additional information about research into and treatment for HTLV Type 1 and II:

      Marco A. Lima, MD, PhD

      Instituto de e Pesquisa Clinica Evandro Chagas-FIOCRUZ

      Rio de Janeiro, Brazil, 21040-900

      marco.lima@ipec.fiocruz.br

      Supporting Organizations

      References

      JOURNAL ARTICLES

      Ishitsuka K, Tamura K. Treatment of adult T-cell leukemia/lymphoma: past, present, and future. Eur J Haematol. 2008;80(3):185-96.

      Silva MT, Andrada-Serpa MJ, Leite AC, Lima MA, Araújo AQ. Intravenous methylprednisolone in tropical spastic paraparesis. Rev Neurol. 2008;46(3):185-6.

      Araújo A, Lima MA, Silva MT. Human T-lymphotropic virus 1 neurologic disease. Curr Treat Options Neurol. 2008;10(3):193-200.

      Lima MA, Harab RC, Schor D, Andrada-Serpa MJ, Araújo AQ. Subacute progression of human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. J Neurovirol. 2007;13 (5):468-73.

      Verdonck K, González E, Van Dooren S, Vandamme AM, Vanham G, Gotuzzo E. Human T-lymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infect Dis. 2007;7 (4):266-81.

      Carneiro-Proietti AB, Catalan-Soares BC, Castro-Costa CM, et al. HTLV in the Americas: challenges and perspectives. Rev Panam Salud Publica. 2006;19 (1):44-53.

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

      Proietti FA, Carneiro-Proietti AB, Catalan-Soares BC, Murphy EL. Global epidemiology of HTLV-I infection and associated diseases. Oncogene. 2005;24 (39):6058-68.

      Silva MT, Leite AC, Alamy AH, Chimelli L, Andrada-Serpa MJ, Araújo AQ. ALS syndrome in HTLV-I infection. Neurology. 2005;65(8):1332-3.

      Roucoux DF, Murphy EL. The epidemiology and disease outcomes of human T-lymphotropic virus type II. AIDS Rev. 2004;6(3):144-54.

      Years Published

      2008, 2012

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