Evaluation of the New Multi-HTLV Serological Assay: Improvement for HTLV-2 Detection.

Despite the accuracy of confirmatory tests for the diagnosis of human T cell lymphotropic virus (HTLV), inconclusive or false-negative results still occur when diagnosing human T cell lymphotropic virus type 2 (HTLV-2)-positive patients. The goal of this study was to evaluate the sensitivity and accuracy of a confirmatory immunoassay, the Multi-HTLV assay. A total of 246 plasma samples were tested by real-time polymerase chain reaction (qPCR) and used to calculate the sensitivity and typing accuracy of the Multi-HTLV assay. Of the 246 plasma samples, 127 were positive for human T cell lymphotropic virus type 1 (HTLV-1), 112 were positive for HTLV-2, and 7 were positive for both HTLV-1 and HTLV-2. Thereafter, the nonparametric Mann-Whitney U test was used to calculate the concordance between the qPCR test and Multi-HTLV assay in 12 samples with discrepant and inconclusive qPCR results. The Multi-HTLV assay showed high performance in identifying HTLV-1 and HTLV-2 with sensitivities of 97% [95% confidence interval (CI): 0.92-0.98] and 94% (0.87-0.96), respectively. However, due to typing performance (98% for HTLV-1 and 94% for HTLV-2), it had 95% agreement with positive HTLV-1 qPCR results (95% CI: 90.07-97.81) and 86% (78.04-91.01) of HTLV-2 qPCR results were positive. Moreover, this test was able to recognize 80% of indeterminate samples and all HTLV-2 positive samples that showed false-negative qPCR results. Our findings, derived from a substantial number of HTLV-positive samples, underscore the inherent reliability and feasibility of the Multi-HTLV assay, regardless of the molecular testing facilities. Furthermore, the distinctive multiparametric nature of this assay, combined with its straightforward procedural execution, introduces novel perspectives for analyzing specific serological profiles in each patient, as well as the potential for immunological monitoring of disease progression.

Could Cesarean Delivery Help Prevent Mother-to-Child Transmission of Human T-Lymphotropic Virus Type 1?

BACKGROUND: Mother-to-child transmission (MTCT) of human T-lymphotropic virus type 1 (HTLV-1) is an important route of transmission that can cause lifelong infection. There is high morbidity and mortality due to adult T-cell leukemia/lymphoma, HTLV-1-associated myelopathy (HAM), and other inflammatory disorders. These conditions develop in nearly 10% of people with HTLV-1 infection, with a higher risk if infection occurs early in life. Identification of risk factors can inform targeted measures to reduce HTLV-1 MTCT. This study aimed to investigate the potential of cesarean delivery to prevent HTLV-1 MTCT. METHODS: We performed a review of the cases of women and their offspring under regular follow-up at the HTLV-1 outpatient clinic at the Institute of Infectious Diseases Emilio Ribas. RESULTS: A total of 177 HTLV-1-infected women and 369 adult offspring were investigated. Overall, 15% of the children were positive for HTLV-1 and 85% were negative. Regarding vertical transmission, we found that a breastfeeding duration of >6 months was associated with MTCT. Moreover, maternal proviral load was not associated with transmission, but high educational level and cesarean delivery were identified as protective factors. CONCLUSIONS: HTLV-1 MTCT was associated with mother's age at delivery of >25 years, low educational level, prolonged breastfeeding, and vaginal delivery.

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.

High prevalence of skin disorders among HTLV-1 infected individuals independent of clinical status.

BACKGROUND: Human T-cell lymphotropic virus type 1 (HTLV-1) infection can increase the risk of developing skin disorders. This study evaluated the correlation between HTLV-1 proviral load and CD4(+) and CD8(+) T cells count among HTLV-1 infected individuals, with or without skin disorders (SD) associated with HTLV-1 infection [SD-HTLV-1: xerosis/ichthyosis, seborrheic dermatitis or infective dermatitis associated to HTLV-1 (IDH)]. METHODS: A total of 193 HTLV-1-infected subjects underwent an interview, dermatological examination, initial HTLV-1 proviral load assay, CD4(+) and CD8(+) T cells count, and lymphproliferation assay (LPA). RESULTS: A total of 147 patients had an abnormal skin condition; 116 (79%) of them also had SD-HTLV-1 and 21% had other dermatological diagnoses. The most prevalent SD-HTLV-1 was xerosis/acquired ichthyosis (48%), followed by seborrheic dermatitis (28%). Patients with SD-HTLV-1 were older (51 vs. 47 years), had a higher prevalence of myelopathy/tropical spastic paraparesis (HAM/TSP) (75%), and had an increased first HTLV-1 proviral load and basal LPA compared with patients without SD-HTLV-1. When excluding HAM/TSP patients, the first HTLV-1 proviral load of SD-HTLV-1 individuals remains higher than no SD-HTLV-1 patients. CONCLUSIONS: There was a high prevalence of skin disorders (76%) among HTLV-1-infected individuals, regardless of clinical status, and 60% of these diseases are considered skin disease associated with HTLV-1 infection.

Genomic analysis of ERVWE2 locus in patients with multiple sclerosis: absence of genetic association but potential role of human endogenous retrovirus type W elements in molecular mimicry with myelin antigen.

Human endogenous retroviruses (HERVs) arise from ancient infections of the host germline cells by exogenous retroviruses, constituting 8% of the human genome. Elevated level of envelope transcripts from HERVs-W has been detected in CSF, plasma and brain tissues from patients with Multiple Sclerosis (MS), most of them from Xq22.3, 15q21.3, and 6q21 chromosomes. However, since the locus Xq22.3 (ERVWE2) lack the 5' LTR promoter and the putative protein should be truncated due to a stop codon, we investigated the ERVWE2 genomic loci from 84 individuals, including MS patients with active HERV-W expression detected in PBMC. In addition, an automated search for promoter sequences in 20 kb nearby region of ERVWE2 reference sequence was performed. Several putative binding sites for cellular cofactors and enhancers were found, suggesting that transcription may occur via alternative promoters. However, ERVWE2 DNA sequencing of MS and healthy individuals revealed that all of them harbor a stop codon at site 39, undermining the expression of a full-length protein. Finally, since plaque formation in central nervous system (CNS) of MS patients is attributed to immunological mechanisms triggered by autoimmune attack against myelin, we also investigated the level of similarity between envelope protein and myelin oligodendrocyte glycoprotein (MOG). Comparison of the MOG to the envelope identified five retroviral regions similar to the Ig-like domain of MOG. Interestingly, one of them includes T and B cell epitopes, capable to induce T effector functions and circulating Abs in rats. In sum, although no DNA substitutions that would link ERVWE2 to the MS pathogeny was found, the similarity between the envelope protein to MOG extends the idea that ERVEW2 may be involved on the immunopathogenesis of MS, maybe facilitating the MOG recognizing by the immune system. Although awaiting experimental evidences, the data presented here may expand the scope of the endogenous retroviruses involvement on MS pathogenesis.

Meningoencephalitis and new onset of seizures in a patient with normal brain CT and multiple lesions on MRI.

Toxoplasmic encephalitis is the most common cerebral mass lesion in patients with AIDS. The definitive diagnosis requires direct demonstration of the tachyzoite form of Toxoplasma gondii in cerebral tissue. The presumptive diagnosis is based on serology, clinical and radiological features, and on response to anti-Toxoplasma therapy. Typically, patients have a subacute presentation of focal neurological signs, with multiple lesions in computed tomography (CT) or magnetic resonance imaging (MRI). However, the neurological and CT scan spectrum is broad. We report a case of toxoplasmic encephalitis in a heterosexual man without prior history of HIV infection. He was admitted with four days of headache, confusion, and new onset of seizures. His brain CT disclosed no alterations and MRI revealed multiple lesions. Empirical specific anti-Toxoplasma therapy was initiated and the patient experienced excellent clinical and radiological improvement. His HIV tests were positive and the CD4+ cell count was 74 cells/ml (8.5 %). On follow up, three months later, the general state of the patient was good, without neurological sequelae and with a normal MRI. We concluded that toxoplasmic encephalitis should be considered in the differential diagnosis of meningoencephalitis in sexually active individuals, including cases without prior history or suspicion of HIV infection, and no abnormalities on CT scan.

Meningoradiculitis due to Cryptococcus neofermans in an immunocompetent patient.

Meningoradiculitis refers to combined involvement of meninges and nerve roots. The most frequent location is the lumbosacral region. Etiology is diverse, including inflammatory, infectious and neoplastic disorders. Meningoradiculitis is a rare form of involvement in cryptococcal infection. We describe a case of subacute lower limbs flaccid paresis diagnosed as lumbosacral meningoradiculitis in view of cerebrospinal fluid (CSF) inflammatory changes and typical enhancement on MRI of lumbar spine. Cryptococcus neoformans was isolated from CSF. Extensive screening yielded no immunodeficiencies.

Meningoradiculitis due to Cryptococcus neofermans in an immunocompetent patient

Meningorradiculite refere-se ao envolvimento simultâneo das meninges e das raízes dos nervos. O local mais freqüentemente acometido é a região lombossacra. Patologias inflamatórias, infecciosas e neoplásicas são as causas mais freqüentes. Meningorradiculite é manifestação rara de infecção por Cryptococcus neoformans. Descrevemos um caso de paresia flácida dos membros inferiores, com diagnóstico de meningorradiculite lombossacra baseado nos achados clínicos, de ressonância magnética da coluna lombar e em alterações inflamatórias do líquido cefalorraqueano (LCR). Avaliação microbiológica do LCR revelou a presença de Cryptococcus neoformans e extensa investigação clínica e laboratorial excluiu imunodeficiências primárias e adquiridas.

Meningoencephalitis and new onset of seizures in a patient with normal brain CT and multiple lesions on MRI

Toxoplasmic encephalitis is the most common cerebral mass lesion in patients with AIDS. The definitive diagnosis requires direct demonstration of the tachyzoite form of Toxoplasma gondii in cerebral tissue. The presumptive diagnosis is based on serology, clinical and radiological features, and on response to anti-Toxoplasma therapy. Typically, patients have a subacute presentation of focal neurological signs, with multiple lesions in computed tomography (CT) or magnetic resonance imaging (MRI). However, the neurological and CT scan spectrum is broad. We report a case of toxoplasmic encephalitis in a heterosexual man without prior history of HIV infection. He was admitted with four days of headache, confusion, and new onset of seizures. His brain CT disclosed no alterations and MRI revealed multiple lesions. Empirical specific anti-Toxoplasma therapy was initiated and the patient experienced excellent clinical and radiological improvement. His HIV tests were positive and the CD4+ cell count was 74 cells/ml (8.5 percent). On follow up, three months later, the general state of the patient was good, without neurological sequelae and with a normal MRI. We concluded that toxoplasmic encephalitis should be considered in the differential diagnosis of meningoencephalitis in sexually active individuals, including cases without prior history or suspicion of HIV infection, and no abnormalities on CT scan.

Neurossífilis apresentaçäo como polirradiculopatia lombar: relato de caso / Neurosyphilis as a lumbar polyradiculopathy: case report

A neurossíphilis ocorre em 10 a 30 por cento dos pacientes com sífilis näo tratada, 5 a 35 anos após o início da infecçäo. As apresentaçöes clínicas säo bastante variáveis, podendo comprometer tanto o sistema nervoso central como o periférico. Nesse relato, um homem de 48 anos de idade com queixas de formigamento nas pernas há 3 meses, cursou com dor lombar e nos membros inferiores de forma progressiva, acarretando dificuldade para deambular. Procurou atendimento ortopédico em uma unidae de saúde de Diadema -SP, onde foi aventurada hipótese diagnóstica de hérnia de disco intervertebral, descartada após estudo tomográfico de coluna normal. A análise do líquor permitiu o diagnóstico de neurossífilis. Encaminhado para avaliaçäo e tratamento no Instituto de Infectologia Emílio Ribas. Tratado com penicilina cristalina por 21 dias, apresentou melhora clínica significativa, com diminuiçäo da dor e recuperaçäo da sensibilidade nos membros inferiores. Segue em acompanhamento ambulatorial sem recorrências até o momento