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IntroductionHuman T-cell lymphotropic virus type 1 (HTLV-1) may cause spinal cord inflammation, leading to HTLV-1-associated myelopathy (HAM). HAM is a chronic and progressive neurological disorder that is associated with increased mortality and impaired quality of life. There are limited data on the incidence of HAM, with higher rates seen in Latin America and the Caribbean compared to Japan. We investigated the incidence of HAM in a cohort of initially asymptomatic people with HTLV-1 in the United Kingdom (UK).MethodsThis is a longitudinal retrospective observational study of people with confirmed HTLV-1 infection who first attended the National Centre for Human Retrovirology in London, UK, between 1st March 1991 and 31st March 2024. Clinical records were analysed to calculate the incidence rate and cumulative incidence of HAM. A secondary analysis was conducted to assess HAM incidence in people living with HTLV-1 and HIV coinfection. At the first visit, the HTLV-1 proviral load was compared between incident cases and those who remained asymptomatic during follow-up.ResultsIn a cohort with up to 33 years of follow-up of individuals living with HTLV-1 in the UK, the cumulative incidence of HTLV-1-associated myelopathy (HAM) was found to be 1.35% (4/297), with an incidence rate of 1.98 per 1,000 person-years. All people who developed HAM had a high proviral load at the first clinic visit. No cases of incident HAM were observed among individuals who had HIV-HTLV-1 coinfection during the study period.DiscussionThe incidence of HAM in the UK cohort is comparable to the rates reported in Latin America and the Caribbean and is higher than reported in other high-income countries. High proviral load of HTLV-1 predates the development of HAM.

The article focuses on evaluating chronic pain and its impact on functional capacity in individuals with HTLV-1. Topics include the prevalence and characteristics of chronic pain in these patients, the relationship between chronic pain and functional impairment, and the influence of sociodemographic and clinical factors on pain severity and functional outcomes.

Sweden is a country with a low prevalence of human lymphotropic T-cell virus (HTLV) infection, estimated at < 0.005%, but the infection rate is notably higher in specific risk groups such as HTLV-2 among intravenous drug users (IVDU) and people originating from HTLV-1 highly endemic areas. Thus, in the most recent study from 2012, the prevalence of HTLV-2 among IVDU in Stockholm was 3.2%. However, much of the epidemiological data on HTLV in Sweden stems from studies conducted primarily between the 1990s and 2007, and the impact of migration to Sweden during the past 15 years has not been evaluated. Despite Sweden's status as a country with generally low prevalence of HTLV, it is prudent to anticipate and prepare for several potential challenges associated with HTLV infection in the future. Proactive measures to enhance awareness, alongside strategies to curtail transmission and mitigate complications, are crucial for addressing this relatively rare, but significant health issue. In this work, we review the current epidemiological knowledge about HTLV in Sweden and discuss future Swedish perspectives. [ABSTRACT FROM AUTHOR]

Nearly 2–3% of those 10 to 20 million individuals infected with the Human T-cell lymphotropic virus type-1 (HTLV-1); are predisposed to developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). It is a neuro-inflammatory disease; differentiated from multiple sclerosis based on the presence of typical neurologic symptoms, confirmation of HTLV-1 infection, and other molecular biomarkers. A brief review of the epidemiology, host immune responses, and molecular pathogenesis of HAM/TSP is followed by detailed discussions about the host-related risk factors for developing HAM/TSP and success/failure stories of the attempted management strategies. Currently, there is no effective treatment for HAM/TSP. Anti-retroviral therapy, peculiar cytokines (IFN-α), some anti-oxidants, and allograft bone marrow transplantation have been used for treating these patients with limited success. Under current conditions, asymptomatic carriers should be examined periodically by a neurologist for early signs of spinal cord injury. Then it is crucial to determine the progress rate to adapt the best management plan for each patient. Corticosteroid therapy is most beneficial in those with acute myelitis. However, slow-progressing patients are best managed using a combination of symptomatic and physical therapy. Additionally, preventive measures should be taken to decrease further spread of HTLV-1 infection. [ABSTRACT FROM AUTHOR]

Background The peripartum period is both a highly vulnerable stage and a significant indicator of a population’s health status. Interest is increasing in human T-cell lymphotropic virus type-1 (HTLV-1) transmission due to its adverse health impacts. However, nationally representative data on HTLV-1 that are important for health planning are unavailable for this subpopulation. Purpose This study aimed to conduct a pooled estimate of HTLV-1 prevalence among pregnant women in Nigeria to quantify its clinical burden and public health implications. Methods This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 statement. Results After a systematic review of the Nigerian literature, 12 studies (2,821 pregnant or postnatal women) were included in the final evidence synthesis. The estimated HTLV-1 prevalence in Nigerian peripartum women following a positive screening test by enzyme-linked immunosorbent assay was 5.44% (95% confidence interval [CI], 3.16%–9.20%). A subgroup analysis of the 2 major regions showed a slightly higher prevalence in the Western versus Southern region (5.55% [95% CI, 2.49%–11.87%]; and 4.91% [95% CI, 2.11%–11.02%]; P=0.84). However, a subgroup analysis by geopolitical zone revealed that Southwestern and Northwestern Nigeria had the highest prevalence (9.23% [95% CI, 4.35%–18.55%; I2=93%] and 7.15% [95% CI, 1.54%–27.54%]; I2=92%). Our decade-old subgroup analysis found inconsistencies in the HTLV-1 prevalence. Furthermore, our literature review revealed a prevalence of HTLV infection among patients with various clinical types of lymphomas/leukemias and myelopathy of 2%–22%. Conclusion These findings have important implications in defining the epidemiological patterns of HTLV-1 infection in Nigeria. They also suggest the presence of HTLV-endemic clusters near low-endemic areas, even within the same geopolitical zones.

Background Flexibility is crucial to the harmonious execution of joint movements. While skeletal muscle dysfunction in patients with HTLV-1 can interfere with mobility, it is unclear whether these patients experience reduced flexibility.

Background: The peripartum period is both a highly vulnerable stage and a significant indicator of a population's health status. Interest is increasing in human T-cell lymphotropic virus type1 (HTLV1) transmission due to its adverse health impacts. However, nationally representative data on HTLV1 that are important for health planning are unavailable for this subpopulation. Purpose: This study aimed to conduct a pooled estimate of HTLV1 prevalence among pregnant women in Nigeria to quantify its clinical burden and public health implications. Methods: This systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis 2020 statement. Results: After a systematic review of the Nigerian literature, 12 studies (2,821 pregnant or postnatal women) were included in the final evidence synthesis. The estimated HTLV1 prevalence in Nigerian peripartum women following a positive screening test by enzyme-linked immunosorbent assay was 5.44% (95% confidence interval [CI], 3.16%-9.20%). A subgroup analysis of the 2 major regions showed a slightly higher prevalence in the Western versus Southern region (5.55% [95% CI, 2.49%-11.87%]; and 4.91% [95% CI, 2.11%-11.02%]; P=0.84). However, a subgroup analysis by geopolitical zone revealed that Southwestern and Northwestern Nigeria had the highest prevalence (9.23% [95% CI, 4.35%-18.55%; I²=93%] and 7.15% [95% CI, 1.54%-27.54%]; I²=92%). Our decade-old subgroup analysis found inconsistencies in the HTLV1 prevalence. Furthermore, our literature review revealed a prevalence of HTLV infection among patients with various clinical types of lymphomas/leukemias and myelopathy of 2%-22%. Conclusion: These findings have important implications in defining the epidemiological patterns of HTLV1 infection in Nigeria. They also suggest the presence of HTLV-endemic clusters near low-endemic areas, even within the same geopolitical zones. [ABSTRACT FROM AUTHOR]

Background and Objectives: HTLV-1 is responsible for two important diseases, HAM/TSP and ATLL. Approximately 10 to 20 million people are infected with HTLV-1 worldwide. Identifying altered genes in different cancers is crucial for finding potential treatment strategies. One of the proteins of the RAS/MAPK signaling pathway is MEK1, which is made from the MAP2K1 gene. The effects of the MAP2K1 gene on the MAPK signaling pathway are not yet fully elucidated. The current study aims to determine the MAP2K1 gene mutations and the level of MAP2K1 gene expression in ATLL patients compared to healthy individuals. Materials and Methods: Ten ATLL and 10 healthy control individuals were investigated in this study. We used ELISA test to screen anti-HTLV-I antibodies and PCR for confirmation of infection. Then, we extracted total RNA from fresh whole blood, and cDNA was synthesized. The expression levels of the MAP2K1 gene were examined by qRT-PCR, and to check possible mutations in the MAP2K1 gene; all samples were sequenced and analyzed by BioEdite Software. Results: MAP2K1 gene expression in the ATLL group was significantly higher than in the healthy control (P=0.001). The mutational sequencing analysis showed nucleotide 212 (SR) change and identification mutations at different nucleotides that were entirely different from the nucleotide mutations defined in the UniProt database. Conclusion: These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the MAP2K1 gene plays a vital role. [ABSTRACT FROM AUTHOR]

Objective: To determine the prevalence of signs and symptoms of HTLV‐1 and 2 infection in paediatric patients. Methods: We included cohort, case‐control and descriptive observational studies that reported the prevalence of signs and symptoms of HTLV‐1 and 2 infections in paediatric patients. Searches were performed in MEDLINE® (Ovid), EMBASE and LILACS from inception to the present, and we saturated information with other sources of published and unpublished literature. We decided not to perform meta‐analysis according to heterogeneity. Results: A total of eight studies met the inclusion criteria for qualitative analysis. No studies of HTLV‐2 were found. Females predominated and there was vertical transmission in nearly 100% of cases. Infective dermatitis was a common manifestation of HTLV in paediatric patients. In addition, persistent hyperreflexia, clonus and the Babinski sign were early neurological alterations observed in patients carrying the virus. Conclusion: HTLV screening is recommended in patients presenting infective dermatitis, persistent hyperreflexia, walking disturbances and in those who come from endemic zones. [ABSTRACT FROM AUTHOR]

Background and Objectives: HTLV-1 is responsible for two important diseases, HAM/TSP and ATLL. Approximately 10 to 20 million people are infected with HTLV-1 worldwide. Identifying altered genes in different cancers is crucial for finding potential treatment strategies. One of the proteins of the RAS/MAPK signaling pathway is MEK1, which is made from the MAP2K1 gene. The effects of the MAP2K1 gene on the MAPK signaling pathway are not yet fully elucidated. The current study aims to determine the MAP2K1 gene mutations and the level of MAP2K1 gene expression in ATLL patients compared to healthy individuals. Materials and Methods: Ten ATLL and 10 healthy control individuals were investigated in this study. We used ELISA test to screen anti-HTLV-I antibodies and PCR for confirmation of infection. Then, we extracted total RNA from fresh whole blood, and cDNA was synthesized. The expression levels of the MAP2K1 gene were examined by qRT-PCR, and to check possible mutations in the MAP2K1 gene; all samples were sequenced and analyzed by BioEdite Software. Results: MAP2K1 gene expression in the ATLL group was significantly higher than in the healthy control (P=0.001). The mutational sequencing analysis showed nucleotide 212 (S→R) change and identification mutations at different nucleotides that were entirely different from the nucleotide mutations defined in the UniProt database. Conclusion: These results could be a perspective in the prevention, prognosis, and targeted treatment of diseases in which the MAP2K1 gene plays a vital role.

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Human T cell lymphotropic virus (HTLV)-1-associated myelopathy is a chronic, disabling inflammatory disorder of the spinal cord caused by HTLV-1 infection. The diagnosis of HTLV-1-associated myelopathy (HAM) is based on clinical and laboratorial findings. The disease is characterized by the presence of spastic paraparesis associated with detection of anti-HTLV-1 antibodies or HTLV-1 genomes in blood and cerebrospinal fluid (CSF). New inflammatory markers have been proposed for the diagnosis and assessment of the prognosis of HAM. We reviewed the laboratory diagnostic and potential surrogate markers for HAM. The serological screening tests for detection of anti-HTLV-1/2 antibodies are highly sensitive and specific, but confirmation and typing of HTLV-1 or HTLV-2 infection by other serological or molecular methods are essential. Detection of intrathecal anti-HTLV-1 antibodies and quantification of the HTLV-1 provirus in CSF provide additional evidence for diagnosis especially in atypical cases or where alternative causes of neuroinflammation cannot be excluded. The CXC motif chemokine ligand 10 and neopterin in serum and CSF are now emerging as inflammatory markers with prognostic value and for HAM monitoring and management. In addition, measures of neurodegeneration, such as neurofilament light chain in the CSF and blood, may also contribute to the HAM prognosis. This review is useful for clinicians and researchers evaluating potential benefits and limitations of each biomarker in clinical practice. The advent of new markers makes it necessary to update the criteria for the best evidence-based approach and for worldwide consensus regarding the use of diagnostic and surrogate markers for HAM. [ABSTRACT FROM AUTHOR]

(1) Background: Tropical spastic paraparesis (TSP/HAM) associated with the T cell lymphotropic virus in type I humans (HTLV-1) is a slow, chronic, and progressive disease that causes balance changes. TSP/HAM diagnosis can be classified as probable, possible, and definite. We compared the static balance control of HTLV-1-infected patients with different TSP/HAM diagnosis. (2) Methods: Our sample consisted of 13 participants infected with HTLV-1 and 16 healthy participants. The center of pressure was recorded using a force platform with open and closed eyes. We divided the recordings into three intervals, period T1 (corresponds to the first 10 s); period T2 (from 10 to 45 s); period T3 (from 45 to 55 s). (3) Results: Eight participants infected with HTLV-1 were classified as probable TSP/HAM and five participants infected with HTLV-1 were classified as definite TSP/HAM. There was a significant increase in postural instability in patients with definite PET/MAH considering the structural and global variables of body sway compared to the control and the probable TSP/HAM. (4) Conclusions: We concluded that the severity of balance is directly related to the degree of signs and symptoms of TSP/HAM. [ABSTRACT FROM AUTHOR]

Introduction Neurogenic overactive bladder is a main feature of human T‐cell leukemia virus type 1‐associated myelopathy/tropical spastic paraparesis. We successfully performed intravesical onabotulinumtoxinA therapy for refractory neurogenic overactive bladder due to human T‐cell leukemia virus type 1‐associated myelopathy/tropical spastic paraparesis. Case presentation We retrospectively reviewed four neurogenic overactive bladder patients with human T‐cell leukemia virus type 1‐associated myelopathy/tropical spastic paraparesis who underwent bladder wall injections of onabotulinumtoxinA from April to October 2020. All patients were female. Their median age was 66 (range, 63–71) years. They were previously treated with β3‐adrenergic receptor agonists or anticholinergic drugs alone or in combination for ≥12 weeks. However, insufficient results were obtained. After 4 weeks of intravesical onabotulinumtoxinA therapy, overactive bladder symptoms improved and maximum cystometric capacity increased in all cases. Conclusion Intravesical onabotulinumtoxinA therapy may be useful for treating refractory overactive bladder due to human T‐cell leukemia virus type 1‐associated myelopathy/tropical spastic paraparesis.

BACKGROUND: The main symptoms of myelopathy associated with human T-cell lymphotropic virus type 1 or tropical spastic paraparesis (HAM / TSP) are the presence of high intensity pain in the lower back, spasticity and weakness in the lower limbs, loss of balance and difficulties in locomotion. Pulsed Transcranial Magnetic Stimulation (rTMS) has been able to influence cortical plasticity, decreasing spasticity, increasing motor performance and promoting analgesia in several similar conditions. OBJECTIVE: To analyze the effect of neuromodulation by pulsed transcranial magnetic stimulation (rTMS) on pain and functional mobility in individuals with HAM / TSP. METHODOLOGY: A randomized clinical trial will be conducted in a sample made up of 40 participants randomly allocated into two groups: Sham Group (SG) with 20 and Test Group (TG) with 20 patients. Individuals aged> 20 years, community walkers with or without orthosis, with chronic pain (? 6 months) in the lumbar region and / or lower limbs will be included. Individuals with epilepsy, cancer, pregnant women, patients with cardiac pacemakers, metallic implants in the brain or skull, users of illicit drugs and / or use of controlled medications in the last six months will be excluded. The protocol will be applied for 10 consecutive days with eight months of follow-up. Our hypothesis is that when using rTMs according to the proposed procedure, it will be possible to relieve pain and improve the functional mobility of these individuals with a long-lasting effect. CONCLUSION: We hope that rTMS is a promising treatment to reduce pain intensity and to improve functional mobility in individuals undergoing active modality. We declare this protocol a promising resource for the treatment of htlv-1 individuals in reducing pain and improving functional mobility. Yes, this protocol has already been applied to 6 patients. However, with the pandemic the study had to be discontinued. However, despite the small sample size and not being fully applied as suggested by the protocol, it was possible to notice a satisfactory result of the intervention. Thus, the application of this protocol can contribute to identify the result of this therapeutic modality in a safer way, as well as assist in the treatment of symptoms of this population, favoring a better quality of life.

Abstract Background Human T-cell lymphotropic virus type 1 (HTLV-1) spreads silently in the world’s population and causes several syndromes. Among these, HTLV-1 associated myelopathy, also called tropical spastic paraparesis (HAM/TSP), affects the nervous system. It causes sensorimotor losses, spasticity, muscle weakness, voiding and sexual dysfunction, pain, and balance disorders. There is limited knowledge of the feelings, experiences, and coping mechanisms associated with this neglected disease. The objective of the present qualitative study was to investigate the signs, meanings, and practices of people with HAM/TSP, through narratives obtained from focus groups and individual semi-structured face-to-face interviews. Results Thirty-eight individuals diagnosed with HAM/TSP participated in the study. The following categories and subcategories emerged from the participants: Signs—physical signs, symptoms, and discovery of the disease; Meanings—reaction to diagnosis and knowledge of disease, fears, and expectations; Practices—daily life, leisure, religious, and treatment activities. Conclusions People with HAM/TSP suffer from symptoms that limit their social participation, and they are affected by complex and multidimensional feelings. This awareness can contribute to the implementation of public policies—focused on the real perspective of these patients—that provide more directed, empathic, and harmonious care for these individuals.

Abstract Background: Physical therapy has positive results in people with tropical spastic paraparesis (TSP). However, mobility and distance from rehabilitation centers limit the participation in outpatient programs. Objective: To evaluate the impact of a home exercise program on the posture and functional mobility of people with TSP. Methods: A randomized controlled trial comparing three groups of people who performed guided exercises from a guidebook for six months: supervised (SG), unsupervised (WG), and control (CG). Primary outcomes: postural angles (SAPO®) and functional mobility (TUG). Secondary outcomes: gait parameters (CVMob®). Results: The protocol described in the guidebook improved postural angles and functional mobility. There were also positive gait parameter effects (p

Tropical spastic paraparesis (TSP) or human T-lymphotropic virus type 1 (HTLV-1) myelopathy is a chronic inflammatory disease of the spinal cord caused by HTLV-1. It usually presents as a disease of the lower extremities, characterized by paralysis and sensory loss. HTLV-1 is common. However, only a small fraction of those infected actually experience clinical symptoms. Respiratory complications are rare; this case discusses an uncommon presentation of acute respiratory failure in a patient with TSP. A bedridden 73-year-old female with HTLV-1-associated TSP, presenting with progressive deterioration of motor and sensory functions in the lower limbs for 10 years, was admitted with sepsis due to recurrent urinary tract infection. On admission, she had hypotension with leukocytosis. She had initial stabilization but showed hypoxia and hypotension on day 5 with a chest X-ray showing total left lung collapse due to an obstructive mucous plug. She has been given hypertonic saline nebulizers and chest physiotherapy, following which there was a partial recovery; however, she then suffered a cardiac arrest that was followed by a tracheostomy for airway protection. In this case, the potential respiratory risk factors associated with TSP, such as failure to clear secretions properly, are underlined. Further research is needed with respect to respiratory muscle involvement in TSP patients and proactive airway management strategies. The tracheostomy intervention performed here only proves the need for addressing respiratory complications in this vulnerable population., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Hamza et al.)

The origin of brain white matter lesion found in HTLV-1-associated myelopathy (HAM/TSP) remains undefined. We investigated the association between white matter lesions in HAM/TSP with cardiovascular risk factors. The group of 40 patients with HAM/TSP included 60% females and mean age of 58.6 ± 8 years old. The probability of 10-year cardiovascular disease was low in 53%, moderate in 38%, and high in 10% of the patients. There was no difference between the cardiovascular risk factors in HAM/TSP patients with and without brain lesions (p > 0.05). Our data suggest that the brain white matter abnormalities are not associated to increased cardiovascular risk in HAM/TSP. [ABSTRACT FROM AUTHOR]

To verify brain and spinal changes using magnetic resonance imaging in patients with HTLV-1–associated myelopathy/tropical spastic paraparesis. This was a systematic review. The descriptors used were tropical spastic paraparesis and magnetic resonance image. The keyword HTLV-1–associated myelopathy was also used. Twenty-three articles were included: 16 detected brain changes and 18 detected spinal changes. White matter lesions were the most frequent finding in the brain. Brain injuries were most frequently identified in the periventricular region, in the subcortical region, in the centrum semiovale, in the brain stem, and corpus callosum. Atrophy was the most frequent finding of the spinal cord, affecting the thoracic and cervical regions, and was associated with a longer evolution of myelopathy. White matter lesions in these regions were also observed. Cortical white matter lesions and thoracic spinal cord atrophy were the most frequently reported changes in patients with HTLV-1–associated myelopathy. [ABSTRACT FROM AUTHOR]

In the logic of integrality in health, one of the aspects less addressed by assistance services is the question of spirituality. This study utilized qualitative analysis from focus groups to identify whether spirituality can contribute to coping with problems arising from the HTLV-1 myelopathy associated or tropical spastic paraparesis (HAM/TSP). The testimonies were recorded and then transcribed. The information was then systematized by the analysis of thematic-categorical content. When giving voice to people who suffer from HAM/TSP, there is clear evidence that spirituality, understood broadly and not restricted to institutionalized religious practices, is expressed in narratives of feeling for others and trust in God. Through spiritual solutions, people with HAM/TSP find the strength to face their disability and pain. [ABSTRACT FROM AUTHOR]

BACKGROUND: The main symptoms of myelopathy associated with human T-cell lymphotropic virus type 1 or tropical spastic paraparesis (HAM / TSP) are the presence of high intensity pain in the lower back, spasticity and weakness in the lower limbs, loss of balance and difficulties in locomotion. Pulsed Transcranial Magnetic Stimulation (rTMS) has been able to influence cortical plasticity, decreasing spasticity, increasing motor performance and promoting analgesia in several similar conditions. OBJECTIVE: To analyze the effect of neuromodulation by pulsed transcranial magnetic stimulation (rTMS) on pain and functional mobility in individuals with HAM/TSP. METHODOLOGY: A randomized clinical trial will be conducted in a sample made up of 40 participants randomly divided into two groups: Sham Group (SG) with 20 and Test Group (TG) with 20 patients. Individuals aged > 20 years, community walkers with or without orthosis, with chronic pain (≥ 6 months) in the lumbar region and/or lower limbs will be included. Individuals with epilepsy, cancer, pregnant women, patients with cardiac pacemakers, metallic implants in the brain or skull, users of illicit drugs and/or use of controlled medications in the last six months will be excluded. The protocol will be applied for 10 consecutive days with a follow-up period of eight months. Our hypothesis is that when using rTMs according to the proposed procedure, it will be possible to relieve pain and improve the functional mobility of these individuals with a long-lasting effect. CONCLUSION: We hope that rTMS is a promising treatment to reduce pain intensity and improve functional mobility in individuals undergoing active modality. We declare this protocol to be a promising resource for the treatment of htlv-1 individuals to reduce pain and improve functional mobility. Yes, this protocol has already been used in 6 patients. However, due to the pandemic, the study had to be discontinued. However, despite the small sample size and not being fully applied as suggested by the protocol, it was possible to notice a satisfactory result of the intervention. Thus, the application of this protocol can contribute to identify the result of this therapeutic modality in a safer way, as well as assist in the treatment of symptoms in this population, leading to a better quality of life. [ABSTRACT FROM AUTHOR]

The association between high proviral load (PVL) in peripheral blood mononuclear cells (PBMC), cognitive disturbance and white matter brain lesions in HTLV-1-infected individuals is still undefined. A cross-sectional study included 62 participants: 22 asymptomatic carriers (mean age 43.4 ± 13.1 years old), 22 patients with HTLV-1-associated myelopathy (HAM/TSP) (mean age 51.5 ± 8.7 years old), and 18 uninfected controls (mean age 52.3 ± 11.1 years old). All individuals fulfilled the following criteria: between 18 and 65 years of age, more than 4 years of formal education, and completed neuropsychological evaluation and HTLV-1 serology. Infected individuals underwent brain conventional magnetic resonance imaging and PVL quantitative PCR (qPCR). Statistical analysis was adjusted in the models by age and education. Cognitive deficit was observed in all groups. Patients with HAM/TSP showed higher neurocognitive deviation in attention and motor skills, higher frequency (84%) of brain white matter lesions, and higher PVL median (range) 8.45 (0.5–71.4) copies/100 PBMC. Brain white matter lesion was associated with verbal memory deficit in HTLV-1-infected individuals (HAM/TSP and asymptomatic carriers) (p = 0.026). In addition, there was a correlation between higher PVL and neurocognitive dysfunction score (processing speed of visuomotor information and visuoconstructive praxis) in HTLV-1-infected patients. The study demonstrates an association between HTLV-1 infection, neurocognitive disorder, and white matter brain lesions on MRI as well as a correlation with higher HTLV-1 PVL, suggesting that the central nervous system involvement by HTLV-1 is not restricted to the spinal cord but involves the whole neuro-axis. HTLV-1-infected individuals should be tested for cognitive impairment. [ABSTRACT FROM AUTHOR]

In individuals with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP), spasticity is one of the main symptoms. The neurological signs of the disease are well defined, but details of how spasticity appears in these individuals have not been well explored. To describe spasticity location and severity of HAM/TSP individuals. Cross-sectional study with individuals older than 18 years, diagnosed with HAM/TSP and with lower limb spasticity. Pregnant women, individuals with other associated neurological diseases, and those using antispastic drugs were not included. Spasticity was assessed by the Modified Ashworth Scale (MAS), applied to the abductor, adductor, flexor, and extensor muscles of the hips, flexors, and extensors of the knees, dorsiflexors, plantiflexors, evertors, and inverters of the foot. Thirty participants were included. The plantiflexor muscles (90%), knee extensors (80%), knee flexors (63,3%), and adductors (50%) were most frequently affected by spasticity. Twenty-three (76.7%) individuals had mixed spasticity, 5 (16.7%) with distal spasticity and 2 (6.7%) with proximal spasticity. MAS was similar between the lower limbs in at least 6 of the 10 muscle groups of each individual. Spasticity was mostly mixed in the lower limbs, with more frequently mild severity. The individuals were partially symmetrical between the lower limbs. The most affected muscle groups were the plantiflexors, knee extensors and flexors and the hip adductors, consecutively, being predominantly symmetrical. [ABSTRACT FROM AUTHOR]

Background: Infection with the Human T-cell lymphotropic virus (HTLV) type 1 and 2 is endemic in South America. There are only a few clinical reports of this retrovirus in patients in Ecuador, without employing virus-isolation methods or viral DNA detection. The infection is usually neglected in health care settings and by public health authorities and no country wide prevalence data are available. Objectives: This study aims to detect the HTLV-1/2 infection in symptomatic individuals for tropical spastic paraparesis (TSP) using for the first time in Ecuador both immunological and molecular biology methodologies. Study Design: Blood samples of 9 symptomatic individuals with myelopathy were analyzed for the detection of the HTLV-1/2 virus with three methods: ELISA, an indirect immunofluorescence (IF) assay and a nested-PCR. Results: Five out of 9 (55.5%) myelopathy patients were positive for ELISA, IF and nested- HTLV-1/2 PCR. Conclusion. The high prevalence of HTLV-1/2 infection among myelopathy patients shows the endemicity of this retrovirus in Ecuador, the association of HTLV-1/2 infection with TSP and the need of the implementation of control and prevention interventions to overcome the further dissemination of this neglected infectious disease.

Abstract Background HTLV-1 infection is a neglected disease, despite infecting 10–15 million people worldwide and severe illnesses develop in 10% of carriers lifelong. Acknowledging a greater risk for developing HTLV-1 associated illnesses due to immunosuppression, screening is being widely considered in the transplantation setting. Herein, we report the experience with universal HTLV testing of donors and recipients of solid organ transplants in a survey conducted in Spain. Methods All hospitals belonging to the Spanish HTLV network were invited to participate in the study. Briefly, HTLV antibody screening was performed retrospectively in all specimens collected from solid organ donors and recipients attended since the year 2008. Results A total of 5751 individuals were tested for HTLV antibodies at 8 sites. Donors represented 2312 (42.2%), of whom 17 (0.3%) were living kidney donors. The remaining 3439 (59.8%) were recipients. Spaniards represented nearly 80%. Overall, 9 individuals (0.16%) were initially reactive for HTLV antibodies. Six were donors and 3 were recipients. Using confirmatory tests, HTLV-1 could be confirmed in only two donors, one Spaniard and another from Colombia. Both kidneys of the Spaniard were inadvertently transplanted. Subacute myelopathy developed within 1 year in one recipient. The second recipient seroconverted for HTLV-1 but the kidney had to be removed soon due to rejection. Immunosuppression was stopped and 3 years later the patient remains in dialysis but otherwise asymptomatic. Conclusion The rate of HTLV-1 is low but not negligible in donors/recipients of solid organ transplants in Spain. Universal HTLV screening should be recommended in all donor and recipients of solid organ transplantation in Spain. Evidence is overwhelming for very high virus transmission and increased risk along with the rapid development of subacute myelopathy.

Abstract Pregnancy was not associated with deterioration of HAM nor was HAM associated with adverse pregnancy outcome in this case. These findings suggest that women with HAM/TSP, even those who use a wheelchair, should not be discouraged from pregnancy.

We aimed to verify the influence of intrinsic and extrinsic cell apoptotic pathways on the inhibition of cellular apoptosis in patients with tropical spastic paralysis/myelopathy related to human T cell lymphotropic virus type 1. The databases accessed were PubMed, Scopus, Science Direct, and Web of Science. Neither the time of publishing nor the language of the articles was limited. The descriptors used for this systematic literature review were: Tropical Paraparesis, Proto-Oncogenic Protein C, Bcl-2, Bcl-X Protein, Bax protein, Fas ligand (FasL) protein, Fas receptor, TNF-related apoptosis-inducing ligand and Fas-associated protein with death domain (FADD)-like apoptosis regulating. The search resulted in 546 articles from which 9 articles were selected for analysis; ranging from serum levels of Bcl-2, Fas and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) measured by enzyme-linked immunosorbent assay and the levels of cellular expression of Bcl-2 and Bcl-xL the TCD4+ lymphocytes accessed by western blot. Most studies accessed either gene expression or polymorphism of Fas, FasL, and TRAIL in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), whereas one study used flow cytometry and fluorescence to determine Fas expression. Increased Bcl-xL expression inhibited T lymphocyte apoptosis, whereas Bcl-2, serum levels, and cellular expression did not influence T lymphocyte apoptosis and serum levels of Fas were significantly higher and associated with markers of leukocyte activation in patients with HAM/TSP. In addition, Fas polymorphism (FAS-670AA) was associated with higher proviral load. There is a need for additional research on this issue since the number of patients was small and the studies presented higher heterogeneity. [ABSTRACT FROM AUTHOR]

Pregnancy was not associated with deterioration of HAM nor was HAM associated with adverse pregnancy outcome in this case. These findings suggest that women with HAM/TSP, even those who use a wheelchair, should not be discouraged from pregnancy. [ABSTRACT FROM AUTHOR]

Abstract INTRODUCTION: Individuals with human T-cell lymphotropic virus 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) experience sensorimotor alterations, which can affect functional performance. Virtual reality (VR) videogaming is a therapeutic option, though there is scarce evidence for its use in this population. We aimed to investigate the therapeutic effects of a VR video game on functional mobility, balance, and gait speed in individuals with HAM/TSP. METHODS: We conducted a blinded, crossover clinical trial comprising 29 individuals with HAM/TSP and randomized them into two groups: (1) early therapy: rehabilitative protocol started immediately after the initial evaluation and (2) late therapy: rehabilitative protocol started 10 weeks later. We assessed all participants for balance using the Berg Balance Scale (BBS) scores, functional mobility using the Timed Up and Go (TUG) test, and gait speed using video camera and CvMob software. Differences were considered significant if p

Abstract INTRODUCTION: A good rating of the device in people with HTLV-1 in this population is essential for accuracy in prescribing data (walking). Thus, this study aimed to analyze the counterpart assessment methods that are best suited to patients with human T-cell lymphotropic virus (HTLV)-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP). METHODS: This cross-sectional study related stabilometric and kinematic variables of postural oscillations with Berg’s balance scale (BBS) and Timed Up and Go (TUG) in subjects with HAM/TSP compared to asymptomatic subjects. To assess the posterior and lateral postural projection, baropodometry and the Footwork® system was used, and the CVMob system was applied to kinematic parameters. The means comparison tests and correlations were applied with an alpha of 5%. RESULTS: Thirty-nine subjects (predominantly female) made up the sample. There was an increase in barodopometric oscillations, in the total oscillation area (p = 0.004), in the anteroposterior oscillation in the left (p = 0.015) and right views (p = 0.036), and in the lateral oscillation (p = 0.039) in the HAM/TSP group. Moderate correlations were found between oscillation baropodometry and the angular variation of the ankle, as well as with the BBS in the three angles and the TUG for lateral oscillation (p = 0.406). CONCLUSIONS: Each method has advantages and disadvantages, including cost accuracy. The best resources available at no additional cost for outpatient to use are the kinematic evaluation using a simple smartphone camera and free analysis software, and the TUG.

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Background: Human T-cell lymphotropic virus type 1 (HTLV-1) spreads silently in the world's population and causes several syndromes. Among these, HTLV-1 associated myelopathy, also called tropical spastic paraparesis (HAM/TSP), affects the nervous system. It causes sensorimotor losses, spasticity, muscle weakness, voiding and sexual dysfunction, pain, and balance disorders. There is limited knowledge of the feelings, experiences, and coping mechanisms associated with this neglected disease. The objective of the present qualitative study was to investigate the signs, meanings, and practices of people with HAM/TSP, through narratives obtained from focus groups and individual semi-structured face-to-face interviews. Results: Thirty-eight individuals diagnosed with HAM/TSP participated in the study. The following categories and subcategories emerged from the participants: Signs—physical signs, symptoms, and discovery of the disease; Meanings—reaction to diagnosis and knowledge of disease, fears, and expectations; Practices—daily life, leisure, religious, and treatment activities. Conclusions: People with HAM/TSP suffer from symptoms that limit their social participation, and they are affected by complex and multidimensional feelings. This awareness can contribute to the implementation of public policies—focused on the real perspective of these patients—that provide more directed, empathic, and harmonious care for these individuals. [ABSTRACT FROM AUTHOR]

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Human T-cell leukemia virus type 1 (HTLV-1) can cause HTLV-1 Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP). Current treatment options for HAM/TSP are limited. We present a woman with rapidly-progressive HAM/TSP with significant, sustained clinical improvement following initiation of mycophenolate mofetil (MMA). Peripheral blood mononuclear cells from the patient, her asymptomatic carrier husband and eight healthy controls were isolated. Frequencies of T-cell populations upon exposure to low and high MMA concentrations and differences in proliferation were analyzed using flow cytometry and a CSFE-proliferation assay. Characterization of T-cell function and proliferation showed higher levels of GranzymeB in HTLV-1+ donors. The improvement and stability of symptoms in this patient with HAM/TSP following MMA initiation requires further study as a potential treatment for HAM/TSP. [Display omitted] • HTLV-1 Associated Myelopathy/Tropical Spastic Paresis (HAM/TSP) leads to disability. • Current steroid-sparing treatment options for HAM/TSP are limited. • We present a patient with HAM/TSP who improved following treatment with steroids and Myocophenolate mofetil (MMA). • The potential mechanism of action of MMA in treating HAM/TSP requires further investigation. [ABSTRACT FROM AUTHOR]

Human T-lymphotropic virus type II (HTLV-II) is a human retrovirus which is endemic in Amerindian and pygmy tribes. Molecular subtypes show geographic segregation consistent with an ancient origin of this virus within humans in Africa or South America. More recently, injection drug users in the United States and Europe have become infected with HTLV-II, and secondary sexual transmission has introduced the virus at low levels into the general population and blood donors. HTLV-II has been linked with a spastic paraparesis called HTLV-associated myelopathy / tropical spastic paraparesis (HAM/TSP), and perhaps with other neurological syndromes. It is also associated with an increased incidence of pneumonia and bronchitis, inflammatory conditions such as arthritis, and perhaps with increased mortality. Except for a few cases of cutaneous lymphoma in patients coinfected with HIV, there is no evidence that HTLV-II causes lymphoproliferative disease. HTLV-II and HIV coinfection has not been proven to alter the course of HIV disease, but such patients may have altered levels of CD4+ and CD8+ lymphocytes, and antiretroviral therapy may paradoxically increase HTLV-II proviral load.

HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is an important cause of nontraumatic and noncompressive chronic myelopathy which generally has no improvement regardless of treatment. On the other hand, ossification of the ligamentum flavum (OLF) is also a cause of myelopathy; however, it can improve in some cases when surgical treatment is well applied. In this case report, we presented a case of a patient with HAM/TSP overlapping OLF which showed some improvement with surgical treatment.

• HTLV-1 infections are a health problem in many countries, and most of the time are a neglected disease. • There are few studies (seven manuscripts in Medline) about cognitive decline associated with HTLV-1. • This manuscript suggests cognitive impairment may be a long-time complication of HTLV-1 infection. • Cognitive impairment in HAM/TSP seems to be linked to persistent inflammatory activity. Myelopathy is a well-established long-term clinical manifestation of HTLV-1 infection. Besides motor dysfunction, cognitive impairment may be another consequence of HTLV-1 infection. Moreover, inflammatory markers may be associated with cognitive impairment in these patients. The present study compared the cognitive performance of HAM/TSP patients with healthy controls and investigated the associations between cognitive performance, proviral load and blood inflammatory markers. Eighty-three patients fulfilling diagnostic criteria for HAM/TSP were submitted to a comprehensive clinical, cognitive and functional evaluation, brain magnetic resonance imaging and determination of levels of IL-1β, IL-6, TNF-α, immunoglobulins and HTLV-1 proviral load in blood and cerebrospinal fluid. The control group was composed of 88 cognitively healthy subjects, matched for age, sex and educational level. Compared to healthy subjects, HAM/TSP patients displayed significant global cognitive impairment and executive function deficits. HAM/TSP cognitive impairment was significantly associated with altered levels of IgM, IgG, IL-6 and TNF-α in blood. There was no association between HAM/TSP cognitive impairment and HTLV-1 proviral load. This study suggests cognitive impairment may be a long-term clinical manifestation of HTLV-1 infection, which seems to be linked to the persistent inflammatory activity that is found in the disease. [ABSTRACT FROM AUTHOR]

Human retroviruses HIV and HTLV share transmission routes. HIV widely spread in Spain during the 80 s through injection drug use and sex, and nowadays HIV rates in Spain account for one of the largest in Europe. In contrast, HTLV-1 is not endemic in Spain, despite hosting huge numbers of migrants from highly endemic regions. Herein, we report the rate and main features of the HIV-HTLV co-infected population in Spain. A national registry exists in Spain for HTLV since year 1989. Data from standardized case report forms and one centralized lab repository were reviewed, especially for the subset with HTLV-HIV co-infection. Up to December 2018, a total of 369 individuals with HTLV-1 had been diagnosed in Spain. 64% of the population were females, and Latin American individuals accounted for 64.5%. Classical HTLV-associated illnesses were found in 12.7% (myelopathy) and 7.6% (leukemia). HIV coinfection was found in 12 (3.2%). Of those, 3 patients (25%) were female and 39 (75%) were of non-Spanish origin. All but two harbored HIV-1 subtype B, being non-B variants found in the two West Africans. Exposure had been sexual in most cases, being 4 homosexual men. Seven HTLV-HIV co-infected patients had developed AIDS and two had developed myelopathy. There was no evidence for increased HTLV-1 clinical pathogenicity due to HIV coinfection. HIV coinfection is infrequent (<5%) among HTLV-1 carriers in Spain. More than half of co-infected patients come from Latin America. Sexual contact is the most frequent risk behavior, being MSM one third of cases. Late diagnosis explains the high rate (9/12) of clinical manifestations in our HIV-HTLV co-infected population. [ABSTRACT FROM AUTHOR]