RESUMO

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.

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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.

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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.

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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.

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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)

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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.

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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.

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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.

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