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

Rosadas, Carolina; Assone, Tatiane; Yamashita, Marina Mayumi; Adonis, Adine; Puccioni-Sohler, Márzia; Santos, Marisa; Paiva, Afonso; Casseb, Jorge; Oliveira, Augusto César Penalva de; Taylor, Graham P.

doi:10.1371/journal.pntd.0008761

Cited by 31 publications

(33 citation statements)

References 47 publications

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“…It is the causative agent of a severe form of blood cancer called adult T-cell leukaemia/lymphoma (ATLL) 2 and a range of debilitating neuromuscular disorders—HTLV-associated myelopathy/tropical spastic paraparesis (HAM/TSP) 3 , which often lead to paralysis. Although only 5–10% of the estimated 10–20 million people 4 infected with HTLV-1 worldwide will develop ATLL 2 , a recent report showed that the vast majority of otherwise asymptomatic patients suffer from issues that severely impact their quality of life, including pain, discomfort and depression 5 . 12.7% of HAM/TSP patients reported their quality of life was worse than death 5 , based on the Euroqol five dimension questionnaire (EQ-5D).…”

Section: Introductionmentioning

confidence: 99%

“…Although only 5–10% of the estimated 10–20 million people 4 infected with HTLV-1 worldwide will develop ATLL 2 , a recent report showed that the vast majority of otherwise asymptomatic patients suffer from issues that severely impact their quality of life, including pain, discomfort and depression 5 . 12.7% of HAM/TSP patients reported their quality of life was worse than death 5 , based on the Euroqol five dimension questionnaire (EQ-5D).…”

Section: Introductionmentioning

confidence: 99%

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Structural basis for the inhibition of HTLV-1 integration inferred from cryo-EM deltaretroviral intasome structures

et al. 2021

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Between 10 and 20 million people worldwide are infected with the human T-cell lymphotropic virus type 1 (HTLV-1). Despite causing life-threatening pathologies there is no therapeutic regimen for this deltaretrovirus. Here, we screened a library of integrase strand transfer inhibitor (INSTI) candidates built around several chemical scaffolds to determine their effectiveness in limiting HTLV-1 infection. Naphthyridines with substituents in position 6 emerged as the most potent compounds against HTLV-1, with XZ450 having highest efficacy in vitro. Using single-particle cryo-electron microscopy we visualised XZ450 as well as the clinical HIV-1 INSTIs raltegravir and bictegravir bound to the active site of the deltaretroviral intasome. The structures reveal subtle differences in the coordination environment of the Mg2+ ion pair involved in the interaction with the INSTIs. Our results elucidate the binding of INSTIs to the HTLV-1 intasome and support their use for pre-exposure prophylaxis and possibly future treatment of HTLV-1 infection.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Structural basis for the inhibition of HTLV-1 integration inferred from cryo-EM deltaretroviral intasome structures

et al. 2021

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“…HTLV-1–associated myelopathy (HAM) is a debilitating condition that results from an inflammatory response mainly within the spinal cord, but with increasing evidence of widespread brain inflammation. HAM greatly impacts patient’s autonomy and quality of life, and, during follow-up, about 50% become wheelchair dependent [ 3 – 6 ]. In Brazil, the risk of HAM and other neurological diseases is reported to be higher than usual at 5% [ 7 – 9 ].…”

Section: Introductionmentioning

confidence: 99%

Blocking HTLV-1/2 silent transmission in Brazil: Current public health policies and proposal for additional strategies

et al. 2021

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Human T-cell lymphotropic viruses 1 and 2 (HTLV-1/2) are relatively common in Brazil but remain silent and neglected infections. HTLV-1 is associated with a range of diseases with high morbidity and mortality. There is no curative treatment for this lifelong infection, so measures to prevent transmission are essential. This narrative review discusses HTLV-1/2 transmission routes and measures to prevent its continuous dissemination. The public health policies that are currently implemented in Brazil to avoid HTLV-1/2 transmission are addressed, and further strategies are proposed.

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“… 2 The clinical course, although diverse, from mildly impaired mobility after decades to wheelchair dependency in weeks, greatly affects the patient's autonomy and quality of life. 3 Some asymptomatic individuals also have discreet neurologic signs suggesting limited CNS damage. 4 Cognitive dysfunction and encephalitis have also been reported with HTLV-1, indicating that the damage is not restricted to the spinal cord.…”

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confidence: 99%

Neurofilament Light in CSF and Plasma Is a Marker of Neuronal Damage in HTLV-1–Associated Myelopathy and Correlates With Neuroinflammation

Rosadas

Zetterberg

Heslegrave

et al. 2021

Neurol Neuroimmunol Neuroinflamm

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Background and ObjectivesTo evaluate the usefulness of CSF and plasma neurofilament light (Nf-L) as a biomarker for human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy (HAM).MethodsNf-L, CXCL10, and neopterin were measured by ELISA in 83 CSF samples obtained from 49 individuals living with HTLV-1/2. Plasma Nf-L was also measured by single molecule array. Results were correlated with duration of disease, age, mobility, CSF cell counts, CSF protein, and HTLV-1 proviral load.ResultsNf-L was detected in all CSF samples (median [range] = 575 [791.8–2,349] pg/mL) and positively correlated with markers of inflammation (CXCL10 (r = 0.733), neopterin (r = 0.499), cell count (r = 0.403), and protein levels (r = 0.693) in CSF; p < 0.0015). There was an inverse correlation between Nf-L and duration of disease (r = −0.584, p < 0.0001). Wheelchair-dependent patients had high concentrations of markers of inflammation and neuronal damage. Concentrations of CXCL10, neopterin, and Nf-L remained elevated in follow-up samples (mean follow-up 5.2 years). Nf-L in plasma correlated with concentration of Nf-L, neopterin, CXCL10, and protein in CSF.ConclusionsNf-L in plasma and CSF has potential to be used as a biomarker of disease activity in HAM. Neuronal damage seems to be more intense early in disease but persists long term. Wheelchair-dependent patients have ongoing neuroinflammation.

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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

Cited by 31 publications

References 47 publications

Structural basis for the inhibition of HTLV-1 integration inferred from cryo-EM deltaretroviral intasome structures

Structural basis for the inhibition of HTLV-1 integration inferred from cryo-EM deltaretroviral intasome structures

Blocking HTLV-1/2 silent transmission in Brazil: Current public health policies and proposal for additional strategies

Neurofilament Light in CSF and Plasma Is a Marker of Neuronal Damage in HTLV-1–Associated Myelopathy and Correlates With Neuroinflammation

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