Review of dengue, zika and chikungunya infections in nervous system in endemic areas.

Dengue, zika, and chikungunya are arboviruses of great epidemiological relevance worldwide. The emergence and re-emergence of viral infections transmitted by mosquitoes constitute a serious human public health problem. The neurological manifestations caused by these viruses have a high potential for death or sequelae. The complications that occur in the nervous system associated with arboviruses can be a challenge for diagnosis and treatment. In endemic areas, suspected cases should include acute encephalitis, myelitis, encephalomyelitis, polyradiculoneuritis, and/or other syndromes of the central or peripheral nervous system, in the absence of a known explanation. The confirmation diagnosis is based on viral (isolation or RT-PCR) or antigens detection in tissues, blood, cerebrospinal fluid, or other body fluids, increase in IgG antibody titers between paired serum samples, specific IgM antibody in cerebrospinal fluid and serological conversion to IgM between paired serum samples (non-reactive in the acute phase and reactive in the convalescent). The cerebrospinal fluid examination can demonstrate: 1. etiological agent; 2. inflammatory reaction or protein-cytological dissociation depending on the neurological condition; 3. specific IgM, 4. intrathecal synthesis of specific IgG (dengue and chikungunya); 5. exclusion of other infectious agents. The treatment of neurological complications aims to improve the symptoms, while the vaccine represents the great hope for the control and prevention of neuroinvasive arboviruses. This narrative review summarizes the updated epidemiology, general features, neuropathogenesis, and neurological manifestations associated with dengue, zika, and chikungunya infection.

Dengue, zika e chikungunya são arboviroses de grande relevância epidemiológica em todo o mundo. A emergência e reemergência dessas infecções virais transmitidas por mosquitos constituem um grave problema de saúde pública humana. As manifestações neurológicas causadas por esses vírus têm alto potencial de morte ou sequelas. As complicações que ocorrem no sistema nervoso associadas às arboviroses podem representar um desafio diagnóstico e de tratamento. Em áreas endêmicas, casos suspeitos devem incluir encefalite, mielite, encefalomielite, polirradiculoneurite e/ou outras síndromes do sistema nervoso central ou periférico, na ausência de explicação conhecida. Caso confirmado de arbovirose neuroinvasivo é baseado na detecção viral (isolamento ou RT-PCR) ou de antígenos em tecidos, sangue, líquido cefalorraquidiano ou outros fluidos corporais, aumento dos títulos de anticorpos IgG entre amostras de soro pareadas, anticorpo IgM específico no líquido cefalorraquidiano e conversão sorológica para IgM entre amostras de soro pareadas. O exame do líquido cefalorraquidiano pode demonstrar: 1. agente etiológico; 2. reação inflamatória ou dissociação proteico-citológica, dependendo do quadro neurológico; 3. valor absoluto de IgM específica; 4. síntese intratecal de anticorpos IgG específicos (dengue e chikungunya); 5. exclusão de outros agentes infecciosos. O tratamento das complicações neurológicas visa melhorar os sintomas, enquanto a vacina representa a grande esperança para o controle e a prevenção das arboviroses neuroinvasivas. Esta revisão narrativa resume a atualização da epidemiologia, características gerais, neuropatogênese e manifestações neurológicas associadas à infecção pelos vírus da dengue, zika e chikungunya.

Review of dengue, zika and chikungunya infections in nervous system in endemic areas / Revisão da infecção por dengue, zika e chikungunya no sistema nervoso em áreas endêmicas

Abstract Dengue, zika, and chikungunya are arboviruses of great epidemiological relevance worldwide. The emergence and re-emergence of viral infections transmitted by mosquitoes constitute a serious human public health problem. The neurological manifestations caused by these viruses have a high potential for death or sequelae. The complications that occur in the nervous system associated with arboviruses can be a challenge for diagnosis and treatment. In endemic areas, suspected cases should include acute encephalitis, myelitis, encephalomyelitis, polyradiculoneuritis, and/or other syndromes of the central or peripheral nervous system, in the absence of a known explanation. The confirmation diagnosis is based on viral (isolation or RT-PCR) or antigens detection in tissues, blood, cerebrospinal fluid, or other body fluids, increase in IgG antibody titers between paired serum samples, specific IgM antibody in cerebrospinal fluid and serological conversion to IgM between paired serum samples (non-reactive in the acute phase and reactive in the convalescent). The cerebrospinal fluid examination can demonstrate: 1. etiological agent; 2. inflammatory reaction or protein-cytological dissociation depending on the neurological condition; 3. specific IgM, 4. intrathecal synthesis of specific IgG (dengue and chikungunya); 5. exclusion of other infectious agents. The treatment of neurological complications aims to improve the symptoms, while the vaccine represents the great hope for the control and prevention of neuroinvasive arboviruses. This narrative review summarizes the updated epidemiology, general features, neuropathogenesis, and neurological manifestations associated with dengue, zika, and chikungunya infection.

Resumo Dengue, zika e chikungunya são arboviroses de grande relevância epidemiológica em todo o mundo. A emergência e reemergência dessas infecções virais transmitidas por mosquitos constituem um grave problema de saúde pública humana. As manifestações neurológicas causadas por esses vírus têm alto potencial de morte ou sequelas. As complicações que ocorrem no sistema nervoso associadas às arboviroses podem representar um desafio diagnóstico e de tratamento. Em áreas endêmicas, casos suspeitos devem incluir encefalite, mielite, encefalomielite, polirradiculoneurite e/ou outras síndromes do sistema nervoso central ou periférico, na ausência de explicação conhecida. Caso confirmado de arbovirose neuroinvasivo é baseado na detecção viral (isolamento ou RT-PCR) ou de antígenos em tecidos, sangue, líquido cefalorraquidiano ou outros fluidos corporais, aumento dos títulos de anticorpos IgG entre amostras de soro pareadas, anticorpo IgM específico no líquido cefalorraquidiano e conversão sorológica para IgM entre amostras de soro pareadas. O exame do líquido cefalorraquidiano pode demonstrar: 1. agente etiológico; 2. reação inflamatória ou dissociação proteico-citológica, dependendo do quadro neurológico; 3. valor absoluto de IgM específica; 4. síntese intratecal de anticorpos IgG específicos (dengue e chikungunya); 5. exclusão de outros agentes infecciosos. O tratamento das complicações neurológicas visa melhorar os sintomas, enquanto a vacina representa a grande esperança para o controle e a prevenção das arboviroses neuroinvasivas. Esta revisão narrativa resume a atualização da epidemiologia, características gerais, neuropatogênese e manifestações neurológicas associadas à infecção pelos vírus da dengue, zika e chikungunya.

Economic analysis of antenatal screening for human T-cell lymphotropic virus type 1 in Brazil: an open access cost-utility model.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. METHODS: In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. FINDINGS: The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11 415 per quality-adjusted life-year (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian cost-effectiveness threshold ($18 107·74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. INTERPRETATION: HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide. FUNDING: None. TRANSLATIONS: For the Portuguese and Spanish translations of the abstract see Supplementary Materials section.

COVID-19 among People Living with HTLV-1 Infection in Rio de Janeiro, Brazil.

The impact of coronavirus disease 2019 (COVID-19) on people living with human T-cell leukemia virus type 1 (HTLV-1) is unknown. The aim of this study is to evaluate the COVID-19 risk factors and outcomes of HTLV-1-infected individuals. A retrospective study of seropositive HTLV-1 outpatients seen during the COVID-19 pandemic period (2020-2022) was conducted in a Tertiary Hospital in Rio de Janeiro, Brazil. We compared the demographic and comorbidity/risk factors in patients with COVID-19 and non-COVID-19 diagnoses. In addition, the clinical features of COVID-19 and vaccination status were also investigated in 51 HTLV-1-infected individuals. The majority (88.2%) had COVID-19 comorbidity/risk factors. Seven cases were vaccinated against COVID-19. Overall, 19 out of 51 (37.3%) individuals were diagnosed with COVID-19. We found differences only in the frequency of anxiety in both groups: 57.9% in the COVID-19 group vs. 15.6% in the non-COVID-19 (p < 0.05) group. Thirteen out of nineteen (68%) of the COVID-19 cases progressed to mild/moderate illness, one remained asymptomatic, and 26.3% progressed to severe illness. All of the individuals recovered at home, but the majority (57.9%) developed post-COVID-19 symptoms: anosmia and ageusia (31.6%), worsening anxiety (15.8%), and a feeling of pain in the legs (15.8%). The patients with post-COVID-19 conditions were unvaccinated. Our findings show that HTLV-1 did not increase the risk of lethal COVID-19 and underline the importance of promoting mental health in HTLV-1-infected individuals.

Economic analysis of antenatal screening for human T-cell lymphotropic virus type 1 in Brazil: an open access cost-utility model

Background Human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes severe diseases, such as aggressive cancer or progressive neurological disease. HTLV-1 affects mainly people in areas with low human development index and can be transmitted from mother to child, primarily through breastfeeding. Refraining from breastfeeding is an effective intervention to reduce the risk of infection in infants. However, HTLV-1 antenatal screening is not offered globally. According to WHO, the scarcity of cost-effectiveness studies is considered one of the major barriers to the implementation of policies to prevent HTLV-1 infection. Therefore, this study aimed to assess the cost-effectiveness of antenatal screening and postnatal interventions to prevent HTLV-1 mother-to-child transmission in Brazil and to develop an open-access, editable, mathematical model that can be used by other countries and regions to assess different scenarios. Methods In this cost-utility analysis, we constructed a decision tree and a Markov model to assess the cost-effectiveness of HTLV-1 antenatal screening and postnatal interventions (ie, avoidance of breastfeeding, by suppression of lactation with cabergoline, and provision of formula feed) to reduce transmission. For our model, we used data from Brazil and we took the perspective of the public health-care system to estimate costs. Findings The implementation of both screening and interventions would result in the prevention of 1039 infections in infants every year in Brazil with an incremental cost-effectiveness ratio (ICER) of US$11415 per quality-adjusted lifeyear (QALY). 88% of all probabilistic sensitivity analysis simulations had ICER values lower than the Brazilian costeffectiveness threshold ($18 107·74 per QALY). HTLV-1 prevalence in pregnant women, the risk of HTLV-1 transmission when breastfeeding lasts for 6 months or more, and the cost of screening tests were the variables with the largest effect on ICER. Interpretation HTLV-1 antenatal screening is cost-effective in Brazil. An open-access model was developed, and this tool could be used to assess the cost-effectiveness of such policy globally, favouring the implementation of interventions to prevent HTLV-1 mother-to-child transmission worldwide. (AU)

Emerging Monkeypox virus and neuroinflammatory disorders.

Alarming situation: Monkeypox is a zoonosis caused by a double-stranded DNA virus. The virus was isolated in monkeys in 1958. The first human case was detected in Africa in 1970. It is endemic in western and central Africa. The infection has worried public health authorities around the world since May 2022 with the emergence of thousands of cases in non-African countries. Objective: We discuss the neurological manifestations associated with monkeypox infection. Rare and Severe Complications: Although in the current outbreak, the disease appears to be self-limiting, with predominance of focal skin lesions, complications may occur, mainly in children and immunosuppressed patients. Neurological manifestations such as encephalitis, convulsion, dizziness, pain, fatigue, visual alteration, photophobia, headache and myalgia were previously reported. Encephalitis may be due to viral invasion of the central nervous system or an immune-mediated process. In both situations, rapid recognition is extremely important with the investigation of the cerebrospinal fluid exam, which can demonstrate the local inflammatory reaction, specific IgM and, possibly viral detection, in addition to the imaging study. Conclusions: We emphasize that health professionals should be alert to the emergence of neurological disorders associated with monkeypox infection in order to avoid sequelae and better characterize the current disease.

Human T Lymphotropic Virus 1-Associated Myelopathy: Overview of Human T Cell Lymphotropic Virus-1/2 Tests and Potential Biomarkers.

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.

Cardiovascular risk factors and brain white matter lesions in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP).

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.

Neopterin and CXCL-10 in Cerebrospinal Fluid as Potential Biomarkers of Neuroinvasive Dengue and Chikungunya.

Dengue (DENV) and chikungunya viruses (CHIKV) cause severe neurological complications, sometimes undiagnosed. Therefore, the use of more accessible neuroinflammatory biomarkers can be advantageous considering their diagnostic and prognostic potential for aggravated clinical outcomes. In this study, we aimed to evaluate neopterin and C-X-C motif chemokine ligand 10 (CXCL-10) in cerebrospinal fluid (CSF) for the diagnosis of neuroinvasive DENV and CHIKV. We analyzed the CSF of 66 patients with neurological disorders, comprising 12 neuroinvasive DENV/CHIKV, 20 inflammatory control (viral, bacterial, and fungal meningitis, and autoimmune disorders), and 24 noninflammatory control (cerebrovascular disease, dementia, neoplasm). There was no difference between the concentration of CSF neopterin in the neuroinvasive DENV/CHIKV and control groups. However, there was a significant difference in the CXCL-10 level when comparing the neuroinvasive DENV/CHIKV group and the non-inflammatory control (p < 0.05). Furthermore, we found a linear correlation between neopterin and CXCL-10 CSF levels in the three groups. For the DENV/CHIKV neuroinvasive diagnosis, the ROC curve showed the best cut-off values for CSF neopterin at 11.23 nmol/L (sensitivity of 67% and specificity of 63%), and for CSF CXCL-10 at 156.5 pg/mL (91.7% sensitivity and specificity). These results show that CXCL-10 in CSF represents an accurate neuroinflammatory biomarker that may contribute to neuroinvasive DENV/CHIKV diagnosis.

Management of HAM/TSP: Systematic Review and Consensus-based Recommendations 2019.

PURPOSE OF REVIEW: To provide an evidence-based approach to the use of therapies that are prescribed to improve the natural history of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP)-a rare disease. RECENT FINDINGS: All 41 articles on the clinical outcome of disease-modifying therapy for HAM/TSP were included in a systematic review by members of the International Retrovirology Association; we report here the consensus assessment and recommendations. The quality of available evidence is low, based for the most part on observational studies, with only 1 double-masked placebo-controlled randomized trial. SUMMARY: There is evidence to support the use of both high-dose pulsed methyl prednisolone for induction and low-dose (5 mg) oral prednisolone as maintenance therapy for progressive disease. There is no evidence to support the use of antiretroviral therapy. There is insufficient evidence to support the use of interferon-α as a first-line therapy.

Use of Cerebrospinal Fluid for the Diagnosis of Neuroinvasive Dengue, Zika, and Chikungunya: A 19-year systematic review.

INTRODUCTION: Cerebrospinal fluid analysis contributes to the diagnosis and neuropathogenesis of neuroinvasive arboviruses. Neurological complications caused by dengue, Zika, and chikungunya infections have high clinical relevance because of their high potential to cause death or neurological deficits. We aimed to evaluate the use of cerebrospinal fluid assays for diagnostic support in neurological disorders associated with dengue, chikungunya, and Zika infections. METHODS: A systematic review was carried out by searching the electronic databases LILACS, PubMed, Scopus, and Embase for articles written in English, Portuguese, or Spanish in the last 19 years. Published studies were reviewed using the terms "dengue," "Zika", "chikungunya", alone or in combination with "cerebrospinal fluid" in the period from 2000 to 2019. RESULTS: A total of 98,060 studies were identified; of these, 1.1% (1,041 studies, 58,478 cases) used cerebrospinal fluid assays for neurological investigations. The most frequent neurological disorders included encephalitis (41.4%), congenital syndromes (17%), and microcephaly associated with Zika virus infections (8.9%). Neuroinvasive disorders were confirmed in 8.03% of 58,478 cases by specific cerebrospinal fluid analyses. The main methods used were IgM-specific antibodies (66%) and reverse transcription-polymerase chain reaction (10%). The largest number of scientific papers (29%) originated from Brazil, followed by India (18.4%) and the United States (14.4%). CONCLUSIONS: Although cerebrospinal fluid analysis is of great importance for increasing neurological diagnostic accuracy and contributes to the early diagnosis of neuroinvasive dengue, chikungunya, and Zika infections, it is underused in routine laboratory investigations worldwide.

Association between high proviral load, cognitive impairment, and white matter brain lesions in HTLV-1-infected individuals.

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.

Use of Cerebrospinal Fluid for the Diagnosis of Neuroinvasive Dengue, Zika, and Chikungunya: A 19-year systematic review

Abstract INTRODUCTION: Cerebrospinal fluid analysis contributes to the diagnosis and neuropathogenesis of neuroinvasive arboviruses. Neurological complications caused by dengue, Zika, and chikungunya infections have high clinical relevance because of their high potential to cause death or neurological deficits. We aimed to evaluate the use of cerebrospinal fluid assays for diagnostic support in neurological disorders associated with dengue, chikungunya, and Zika infections. METHODS: A systematic review was carried out by searching the electronic databases LILACS, PubMed, Scopus, and Embase for articles written in English, Portuguese, or Spanish in the last 19 years. Published studies were reviewed using the terms "dengue," "Zika", "chikungunya", alone or in combination with "cerebrospinal fluid" in the period from 2000 to 2019. RESULTS: A total of 98,060 studies were identified; of these, 1.1% (1,041 studies, 58,478 cases) used cerebrospinal fluid assays for neurological investigations. The most frequent neurological disorders included encephalitis (41.4%), congenital syndromes (17%), and microcephaly associated with Zika virus infections (8.9%). Neuroinvasive disorders were confirmed in 8.03% of 58,478 cases by specific cerebrospinal fluid analyses. The main methods used were IgM-specific antibodies (66%) and reverse transcription-polymerase chain reaction (10%). The largest number of scientific papers (29%) originated from Brazil, followed by India (18.4%) and the United States (14.4%). CONCLUSIONS: Although cerebrospinal fluid analysis is of great importance for increasing neurological diagnostic accuracy and contributes to the early diagnosis of neuroinvasive dengue, chikungunya, and Zika infections, it is underused in routine laboratory investigations worldwide.

Current evidence of neurological features, diagnosis, and neuropathogenesis associated with COVID-19.

Recent reports indicate that besides respiratory and systemic symptoms among coronavirus disease (COVID-19) patients, the disease has a wide spectrum of neurological manifestations (encephalitis, meningitis, myelitis, acute disseminated encephalomyelitis, metabolic and acute hemorrhagic necrotizing encephalopathy, cerebrovascular diseases, Guillain-Barré syndrome, polyneuritis cranialis, dysautonomia, and myopathies). The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can spread from the respiratory system to the central nervous system, using transneuronal and hematogenous mechanisms. Although not every COVID-19 patient will test positive for the virus in the cerebrospinal fluid exam, the appearance of neurological symptoms associated with SARS-CoV-2 infection reveals the importance of understanding the neurologic manifestations and capacity for neural invasion associated with the pathogen. These aspects are relevant for correct diagnosis and treatment, and for the potential development of vaccines. This review highlights the latest evidence of SARS-CoV-2 infection with a focus on neurological involvement and potential neuropathogenesis mechanisms.

Health state utility values in people living with HTLV-1 and in patients with HAM/TSP: The impact of a neglected disease on the quality of life.

BACKGROUND: HTLV-1 is a neglected sexually transmitted infection despite being the cause of disabling neurological disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). There is no treatment for this infection and public health policies are essential to reduce its transmission. However, there are no data to support adequate cost-effective analysis in this field. The aim of this study was to obtain health state utility values for individuals with HAM/TSP and HTLV-1 asymptomatic carriers (AC). The impact of both states on quality of life (QoL) is described and compared to other diseases. METHODS: A cross-sectional observational study of 141 individuals infected with HTLV-1 (79 with HAM/TSP and 62 AC) from three Brazilian states (Rio de Janeiro, São Paulo and Alagoas) and from the United Kingdom. Participants completed a validated general health questionnaire (EQ-5D, Euroqol) from which country specific health state utility values are generated. Clinical and epidemiological data were collated. PRINCIPAL FINDINGS: Health state utility value for HAM/TSP was 0.2991. QoL for 130 reported clinical conditions ranges from 0.35 to 0.847. 12% reported their quality of life as worse as death. Low QoL was associated with severity rather than duration of disease with a moderate inverse correlation between QoL and Osame's Motor Disability Score (-0.4933) Patients who are wheelchair dependent had lowest QoL whilst those still walking unaided had the highest. AC also reported impaired QoL (0.7121) compared to general population. CONCLUSION: HTLV-1 and its associated neurological disease has a marked impact on QoL. This study provides robust data to support the development of cost-utility analysis of interventions for HTLV-1.

Creation and validation of a bladder dysfunction symptom score for HTLV-1-associated myelopathy/tropical spastic paraparesis.

BACKGROUND: Urinary dysfunction is one of the main features of human T-cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). However, a comprehensive assessment of the severity is difficult because a standardized assessment measure is unavailable. Therefore, this study aimed to develop a novel symptom score for the assessment of urinary dysfunction in HAM/TSP. We interviewed 449 patients with HAM/TSP using four internationally validated questionnaires for assessment of urinary symptoms (27 question items in total): the International Prostate Symptom Score; the International Consultation on Incontinence Questionnaire-Short Form; the Overactive Bladder Symptom Score; and the Nocturia Quality-of-Life questionnaire. We developed a symptom score based on the data of 322 patients who did not use urinary catheters by selecting question items from questionnaires focused on descriptive statistics, correlation analysis, and exploratory factor analysis. The score distribution, reliability, and validity of the developed score were evaluated. RESULTS: First, 16 questions related to quality of life, situations, or subjective assessment were omitted from the 27 questions. Exploratory factor analysis revealed that the remaining 11 questions pertained to three factors: frequent urination, urinary incontinence, and voiding symptoms. Three questions, which had similar questions with larger factor loading, were deleted. Finally, we selected eight question items for inclusion in the novel score. The score distribution exhibited no ceiling or floor effect. The Cronbach's alpha (0.737) demonstrated reliable internal consistency. The new score comprised two subscales with acceptable factorial validity (inter-factor correlation coefficient, 0.322): storage symptoms (frequent urination plus urinary incontinence) and voiding symptoms. The correlation between each item and the subscales suggested acceptable construct validity. CONCLUSIONS: We developed a novel score, the HAM/TSP-Bladder Dysfunction Symptom Score, and demonstrated its reliability and validity. The applicability of this score to patients using catheters should be examined in future research.