Neurological Manifestations in Human T-Cell Lymphotropic Virus Type 1 (HTLV-1)–Infected Individuals Without HTLV-1–Associated Myelopathy/Tropical Spastic Paraparesis: A Longitudinal Cohort Study

Tanajura, Davi; Castro, Néviton; Oliveira, Paulo; Neto, Abraão; Muniz, André Luiz; Carvalho, Natália B.; Orge, Glória; Santos, Sara; Glesby, Marshall J.; Carvalho, Edgar M.

doi:10.1093/cid/civ229

Cited by 77 publications

(69 citation statements)

References 30 publications

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“…This family aggregation and its particular characteristics have been described recently by Nozuma et al [103]. Remarkably in a recent cohort study up to 30% of asymptomatic carriers presented mild neurological symptoms not fulfilling HAM/TSP criteria (sensory, motor, autonomic or urinary symptoms) [104]. The pathogenesis of these conditions is still obscure and currently two hypotheses are accepted, a direct viral effect over axon myelin and an inflammatory process driven by the cytotoxic T-lymphocyte response to the virus, as is suggested by the lymphocytic infiltrate present in biopsies.…”

Section: Pathogenesis and Clinical Featuressupporting

confidence: 60%

Infection with human retroviruses other than HIV-1: HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4

Nicolás

Ambrosioni

Paredes

et al. 2015

Expert Review of Anti-infective Therapy

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HIV-1 is the most prevalent retrovirus, with over 30 million people infected worldwide. Nevertheless, infection caused by other human retroviruses like HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4 is gaining importance. Initially confined to specific geographical areas, HIV-2, HTLV-1 and HTLV-2 are becoming a major concern in non-endemic countries due to international migration flows. Clinical manifestations of retroviruses range from asymptomatic carriers to life-threatening conditions, such as AIDS in HIV-2 infection or adult T-cell lymphoma/leukemia or tropical spastic paraparesis in HTLV-1 infection. HIV-2 is naturally resistant to some antiretrovirals frequently used to treat HIV-1 infection, but it does have effective antiretroviral therapy options. Unfortunately, HTLV still has limited therapeutic options. In this article, we will review the epidemiological, clinical, diagnostic, pathogenic and therapeutic aspects of infections caused by these human retroviruses.

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Section: Pathogenesis and Clinical Featuressupporting

confidence: 60%

Infection with human retroviruses other than HIV-1: HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4

Nicolás

Ambrosioni

Paredes

et al. 2015

Expert Review of Anti-infective Therapy

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“…The prevalence of HTLV-1 infection in other countries such as Turkmenistan, Brazil, Spain, Korea and Japan was found to be 0.007% [8] , 1.9% [9] , 0.001% [10] , 0.27% [11] , and 0.12% [12] , respectively. HTLV-1-and HTLV-2-infected carriers remain asymptomatic for a long time, serving as a potential source for the transmission of the disease [13] . The aim of this investigation was to determine the prevalence of HTLV-1 and HTLV-2 among healthy individuals in Neyshabur, North-Eastern Iran, during 2010-2014.…”

Section: Introductionmentioning

confidence: 99%

Seroepidemiology of HTLV-1 and HTLV-2 Infection in Neyshabur City, North-Eastern Iran, during 2010-2014

Salehi¹,

Mostafavi²,

Ghasemian³

et al. 2017

IBJ

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Background: Retroviruses of human T-lymphotropic viruses (HTLV-1 and HTLV-2) have been demonstrated to be endemic in the north-eastern region of Iran. This study was aimed to determine the HTLV-1 and HTLV-2 prevalence among healthy individuals in Neyshabur City during 2010-2014. Methods: A total of 8054 blood samples were collected from healthy participants in Neyshabur, North-Eastern Iran. The blood samples were screened for the presence of specific antibodies against HTLV-1 and HTLV-2 by using ELISA according to the manufacturer's instructions. Results: The overall seropositivity rate for HTLV-1 and HTLV-2 was found to be 6.55% (528 out of 8054) among participants. Conclusion: Both HTLV-1 and HTLV-2 were demonstrated to be at a high rate in healthy individuals. However, a smaller number of asymptomatic carriers were found in this study, as compared to those identified in previous investigations in the city.

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“…Arterial blood was sampled via the radial artery to enable generation of an arterial plasma input function. Blood samples taken at 5,10,20,30,50,70, and 90 min were also analyzed using highperformance liquid chromatography to determine the fraction of parent radioactivity in arterial plasma. The generation of the metabolite-corrected plasma input function has been detailed previously (15).…”

Section: Pet Imaging and Mr Imagingmentioning

confidence: 99%

“…HTLV-1 is the etiologic agent of a progressive neurologic disease, HTLV-1-associated myelopathy (HAM) (2). HAM overtly affects 2%-4% of HTLV-1-infected persons at some point during this life-long infection (3,4), while subclinical disease is also reported (5). HAM is characterized clinically by several or all of the following: progressive spastic paraparesis, lumbar pain frequently radiating to legs, urinary symptoms, constipation, and impotence (6).…”

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confidence: 99%

Evidence of Brain Inflammation in Patients with Human T-Lymphotropic Virus Type 1–Associated Myelopathy (HAM): A Pilot, Multimodal Imaging Study Using ¹¹C-PBR28 PET, MR T1-Weighted, and Diffusion-Weighted Imaging

Dimber¹,

Guo

Bishop³

et al. 2016

J Nucl Med

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HTLV-1-associated myelopathy (HAM; HTLV-1 is human T-lymphotropic virus type 1) is a chronic debilitating neuroinflammatory disease with a predilection for the thoracic cord. Tissue damage is attributed to the cellular immune response to HTLV-1-infected lymphocytes. The brains of HTLV-1-infected patients, with and without HAM but no clinical evidence of brain involvement, were examined using a specific 18-kDa translocator protein ligand, 11 C-PBR28, and T1-weighted and diffusion-weighted MRI. Methods: Five subjects with HAM and 2 HTLV-1 asymptomatic carriers were studied. All underwent clinical neurologic assessment including cognitive function and objective measures of gait, quantification of HTLV-1 proviral load in peripheral blood mononuclear cells, and human leukocyte antigenantigen D related expression on circulating CD81 lymphocytes. 11 C-PBR28 PET and MRI were performed on the same day. 11 C-PBR28 PET total volume of distribution and distribution volume ratio (DVR) were estimated using 2-tissue-compartment modeling. MRI data were processed using tools from the FMRIB Software Library to estimate mean diffusivity (MD) and gray matter (GM) fraction changes. The results were compared with data from age-matched healthy volunteers. Results: Across the whole brain, the total volume of distribution for the subjects with HAM (5.44 ± 0.84) was significantly greater than that of asymptomatic carriers (3.44 ± 0.80). The DVR of the thalamus in patients with severe and moderate HAM was higher than that in the healthy volunteers, suggesting increased translocator protein binding (z . 4.72). Subjects with more severe myelopathy and with high DR expression on CD81 lymphocytes had increased DVR and MD (near-significant correlation found for the right thalamus MD: P 5 0.06). On the T1-weighted MRI scans, the GM fraction of the brain stem was reduced in all HTLV-1-infected patients compared with controls (P , 0.001), whereas the thalamus GM fraction was decreased in patients with HAM and correlated with the disease severity. There was no correlation between neurocognitive function and these markers of central nervous system inflammation. Conclusion: This pilot study suggests that some patients with HAM have asymptomatic inflammation in the brain, which can be detected and monitored by 11 C-PBR28 PET together with structural and diffusion-weighted MRI.

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Neurological Manifestations in Human T-Cell Lymphotropic Virus Type 1 (HTLV-1)–Infected Individuals Without HTLV-1–Associated Myelopathy/Tropical Spastic Paraparesis: A Longitudinal Cohort Study

Abstract: Development of neurological symptoms or signs occurred in up to 30% of asymptomatic subjects during 8 years of follow-up.

Cited by 77 publications

References 30 publications

Infection with human retroviruses other than HIV-1: HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4

Infection with human retroviruses other than HIV-1: HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4

Seroepidemiology of HTLV-1 and HTLV-2 Infection in Neyshabur City, North-Eastern Iran, during 2010-2014

Evidence of Brain Inflammation in Patients with Human T-Lymphotropic Virus Type 1–Associated Myelopathy (HAM): A Pilot, Multimodal Imaging Study Using ¹¹C-PBR28 PET, MR T1-Weighted, and Diffusion-Weighted Imaging

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Neurological Manifestations in Human T-Cell Lymphotropic Virus Type 1 (HTLV-1)–Infected Individuals Without HTLV-1–Associated Myelopathy/Tropical Spastic Paraparesis: A Longitudinal Cohort Study

Abstract: Development of neurological symptoms or signs occurred in up to 30% of asymptomatic subjects during 8 years of follow-up.

Cited by 77 publications

References 30 publications

Infection with human retroviruses other than HIV-1: HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4

Infection with human retroviruses other than HIV-1: HIV-2, HTLV-1, HTLV-2, HTLV-3 and HTLV-4

Seroepidemiology of HTLV-1 and HTLV-2 Infection in Neyshabur City, North-Eastern Iran, during 2010-2014

Evidence of Brain Inflammation in Patients with Human T-Lymphotropic Virus Type 1–Associated Myelopathy (HAM): A Pilot, Multimodal Imaging Study Using 11C-PBR28 PET, MR T1-Weighted, and Diffusion-Weighted Imaging

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Evidence of Brain Inflammation in Patients with Human T-Lymphotropic Virus Type 1–Associated Myelopathy (HAM): A Pilot, Multimodal Imaging Study Using ¹¹C-PBR28 PET, MR T1-Weighted, and Diffusion-Weighted Imaging