Changes in T cell phenotype and activated MAPKs are correlated to impaired cellular responses to antigens and glucocorticoids during HTLV-I infection.

Lymphocytes of human T-lymphotropic virus type-I (HTLV-I) infected patients were previously found tolerant to mitogenic stimuli as well as glucocorticoid treatment. These data suggest that common signaling events are impaired during this infection. The underlying mechanisms of these phenomena may include changes in cellular composition, cytokine milieu and the differential activation of mitogen-activated protein kinases (MAPKs). We investigated the role of (i) p38 and ERK MAPKs, (ii) lymphocyte subpopulations, (iii) and cytokines implicated in antigen or glucocorticoid-induced immunomodulation. Twenty-one asymptomatic carriers (AC), 19 patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and 21 healthy subjects took part in this study. Lymphocytes were isolated and cultured in vitro to assess lymphocyte proliferation and sensitivity to dexamethasone. The expression of phospho-MAPKs, lymphocyte subsets and cytokines were assessed by flow cytometry. Patients with HAM/TSP had a higher p38/ERK ratio (p<0.05) associated with a reduced response to mitogens (phytohaemagglutinin or PMA+ionomycin) (p<0.001) and higher sensitivity to dexamethasone (p<0.05). HAM/TSP patients presented increased frequency of activated T cells and CD8(+)CD28(-) regulatory T cells, being negatively related to the mitogenic response. These data suggest that multiple underlying mechanisms could be involved with HTLV-related changes in cellular response to mitogens and glucocorticoids.

Molecular evidence of HTLV-II subtype B among an urban population living in South Brazil.

Human T cell lymphotropic virus type II (HTLV-II) is a deltaretrovirus endemic in Indian populations living in Central and South America, among Pygmies tribes from Central Africa, and epidemic among injecting drug users (IDUs) in the United States, Europe, Southeast Asia, and South America. To date only the HTLV-IIa subtype has been demonstrated among Brazilians (Amazon basin Indians, blood donors, and IDUs). We analyzed HTLV-II isolates from 12 individuals living in the urban area of Porto Alegre, Southern Brazil, identified as seropositive for HTLVI/II in a blood donation. The HTLV-II long terminal repeat (LTR) region was sequenced and compared with nucleotide sequences of isolates HTLV-IIa (Mo), HTLV-IIb (NRA) prototypes. Phylogenetic analysis of the LTR region demonstrated that seven new isolates clustered together with American Indians HTLV-IIb isolates, and five new HTLV-IIa isolates clustered within the HTLV-IIa Brazilian subgroup, named the HTLV-IIc subtype. Both HTLV-IIa and IIb seem to be endemic in the urban area of Porto Alegre, South of Brazil, and could have reached this region via the Amazon basin and the Pacific Coast ancient human migratory pathways. To our knowledge this is the first study demonstrating the presence of HTLV-IIb among the urban population in Brazil.

Tuberculous meningoencephalomyelitis and coinfection with HTLV-I + HTLV-II: case report.

HTLV-I and HTLV-II are endemic in some areas of Brazil, where an associated disease, HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP) have been diagnosed in significant number of infected individuals. Tuberculosis has been demonstrated among those individuals, with higher prevalence than in the general population, suggesting that there is an increased risk for this comorbidity. We report the case of an individual coinfected with HTLV-I and HTLV-II, suffering from an insidious meningoencephalomyelitis caused by Mycobacterium tuberculosis. The patient was a 44 years old man successfully treated with steroids and antituberculous drugs, improving clinically and turning to a negative PCR and to a normal blood-cerebrospinal fluid barrier.

HTLV-II transmission to a health care worker.

Health care workers, mainly in emergency and forensic services, are at risk of exposure to bloodborne pathogens. Human T-cell lymphotropic virus type I and type II (HTLV-I and HTLV-II) are cosmopolitan human delta retroviruses causing endemic infection in Japan, the Caribbean basin, South America, and sub-Saharan Africa, and in clusters among intravenous drug users in Europe and the United States. The seroprevalence of HTLV-I and HTLV-II among Brazilian blood donors ranges from 0.08% to 1.35%. HTLV-I transmission to a Japanese researcher has already been reported. We describe the transmission of HTLV-II infection to a Brazilian laboratory worker caused by a needlestick injury when she was recapping a syringe after collecting material for arterial blood gas analysis. To our knowledge, this is the first report of an occupational transmission of HTLV-II to a health care worker.

Tuberculous meningoencephalomyelitis and coinfection with HTLV-I + HTLV-II: case report

Os vírus HTLV-I e HTLV-II são endêmicos em algumas regiões do Brasil, onde uma das doenças associadas, a paraparesia espástica tropical/mielopatia associada ao HTLV (PET/MAH), tem sido diagnosticada em significativo número de pacientes infectados. Nesses indivíduos, a prevalência de tuberculose é maior que na população geral, sugerindo que possa haver um maior risco para esta comorbidade. Relatamos o caso de um homem de 44 anos coinfectado HTLV-I + HTLV-II que desenvolveu meningoencefalomielite por Mycobacterium tuberculosis. O paciente apresentou recuperação clínica parcial, correção da disfunção de barreira hemato-liquórica e negativação no PCR, mediante o tratamento com corticoesteróides e tuberculostáticos.

Human T - cell lymphotropic virus type II in Guaraní Indians, Southern Brazil

O vírus linfotrópico de células T-humanas do tipo II (HTLV-II) é identificado em muitos grupos de ameríndios. No Brasil, tem sido encontrado em indivíduos da população urbana, bem como em índios oriundos da região Amazônica. Os Índios Guaraní, do Sul do país, foram investigados para infecção por HTLV-I/II. Três indivíduos, oriundos de uma amostra de 52 índios, demonstraram sororeatividade para HTLV-II (ensaio imunoenzimático e Western blot). Este estudo preliminar foi o primeiro a identificar a presença de infecção por HTLV-II em ameríndios do Sul do Brasil.

[Guide of clinical management of HTLV patient: neurological aspects]. / Guia de manejo clínico do paciente com HTLV: aspectos neurológicos.

The Brazilian Ministry of Health (STD and Aids Program) invited specialists to make up an informative guide to deal with HTLV patients. Among the different topics, the neurological aspects associated to HTLV were contemplated. A suspected case should include changes in force and reflexes, distal paresthesiae and autonomic dysfunction. The investigation of such case should be based on the syndrome shown by the patient. For patients with spinal cord syndrome, magnetic resonance imaging or myelography as well as spinal fluid studies should be carried out. For patients with neuropathic or myopathic syndrome, electroneuromyography and CPK dosing should be done, and for those with autonomic syndrome, a search for postural hypotension, ultrasonography of urinary tract and urodynamic studies should be requested. The treatment may be symptomatic (spasticity, neurogenic bladder, intestinal constipation and neuropathic pain) and specific to be carried out in specialized centers.

Guia de manejo clínico do paciente com HTLV: aspectos neurológicos / Guide of clinical management of HTLV patient: neurological aspects

O Ministério da Saúde (Programa DST e Aids) reuniu especialistas para elaborar um guia informativo de manejo do paciente com HTLV. Dentre os diferentes tópicos, foram contemplados os aspectos neurológicos associados à infecção pelo HTLV. Um caso suspeito de doença neurológica associada ao HTLV deve incluir alteração de força e reflexos, parestesias distais e disfunção autonômica. A investigação do caso suspeito deve ser baseada na síndrome exibida pelo paciente. Para o paciente com síndrome medular, deve-se solicitar ressonância magnética da medula ou mielografia, assim como, estudo do líquor. Para o paciente com síndrome neuropática ou miopática, deve-se solicitar eletroneuromiografia e dosagem de CPK, e para aquele com síndrome autonômica, pesquisa de hipotensão postural, ultrassonografia das vias urinárias e estudo urodinâmico. O tratamento pode ser sintomático (espasticidade, bexiga neurogênica, constipação intestinal e dor neuropática) e específico a ser feito em centros especializados.

Human T-cell lymphotropic virus type II in Guaraní Indians, Southern Brazil.

Human T-cell lymphotropic virus type II (HTLV-II) is found in many New World Indian groups on the American continent. In Brazil, HTLV-II has been found among urban residents and Indians in the Amazon region, in the North. Guaraní Indians in the South of Brazil were studied for HTLV-I/II infection. Among 52 individuals, three (5.76%) showed positive anti-HTLV-II antibodies (enzyme-linked immunosorbent assay and Western blot). This preliminary report is the first seroepidemiological study showing HTLV-II infection among Indians in the South of Brazil.

Quality assurance for cerebrospinal fluid protein analysis: international consensus by an Internet-based group discussion.

A group of neurologists and clinical neurochemists representing twelve countries worked towards a consensus on laboratory techniques to improve the quality of analysis and interpretation of cerebrospinal fluid (CSF) proteins. Consensus was approached via a virtual Lotus Notes-based TeamRoom. This new approach respecting multicultural differences, common views, and minority opinions, is available in http://www.teamspace.net/ CSF, presenting the implicit, complementary version of this explicit, printed consensus. Three key recommendations were made: CSF and (appropriately diluted) serum samples should be analyzed together in one analytical run, i.e., with reference to the same calibration curve. Results are evaluated as CSF/serum quotients, taking into account the non-linear, hyperbolic relation between immunoglobulin (Ig)- and albumin-quotients rather than using the linear IgG index or IgG synthesis rate. Controls should include materials with values within the reference ranges (IgM: 0.5-1.5 mg/l; IgA: 1-3 mg/l; IgG: 10-30 mg/l and albumin: 100-300 mg/l). The physiological, methodological and clinical significance of CSF/serum quotients is reviewed. We confirmed the previous consensus on oligoclonal IgG, in particular the usefulness of the five typical interpretation patterns. The group compared current external and internal quality assurance schemes and encouraged all members to maintain national or local traditions. Values for acceptable imprecision in the CSF quality assurance are proposed.

HTLV-I-associated myelopathy: are ferritin, S100beta protein, or guanine nucleotides CSF markers of disease?

In southern Brazil, there is an endemic high prevalence foci of HTLV-I and HTLV-II infection. HTLV-infected individuals may develop HAM/TSP. Little is known about HAM/TSP pathogenesis and there is a lack of disease progression markers. This study investigated ferritin, S-100beta protein, and guanine nucleotides (GN) concentrations in the CSF of 18 patients with HAM/TSP. In HAM/TSP patients, concentrations of ferritin and S100beta were increased, whereas GMP was reduced. CSF ferritin, S100beta, and GN are potential markers for HAM/TSP.

Urodynamic alterations in patients with HTLV-1 infection.

OBJECTIVES: The HTLV-1 is a retrovirus that causes several diseases, including tropical spastic paraparesis or HTLV-1 associated myelopathy (or TSP/HAM, as designated by the World Health Organization - WHO) described in 1985. In Brazil, the first cases were reported in 1989. In order to evaluate the urodynamic alterations of infected patients, 48 cases were studied: 26 TSP/HAM and 22 non-TSP/HAM. MATERIAL AND METHOD: Evaluation was performed by testing, cystometry, abdominal pressure, differential pressure, detrusor leak point pressure, maximum flow pressure, and electromyography. RESULTS: 80.76% TSP/HAM patients showed hyperreflexic bladder, and 34.16% had detrusor-sphincter dyssinergia; 82.6% of this group had abnormal uroflow tests. Non-TSP/HAM patients had hyperreflexic bladders in 22.72% of the cases, and detrusor-sphincter dyssinergia was not assessed. For these patients, uroflow rate was normal in 70% of the cases. CONCLUSIONS: Patients infected by the HTLV-1, with or without myelopathy, present significant urodynamic abnormalities and must have a complete urologic and urodynamic evaluation.

HTLV-I associated myelopathy in Porto Alegre (Southern Brazil)

Mielotapia associada ao HTLV-I/paraparesia espástica tropical (TSP/HAM) tem sido descrita de forma crescente em praticamente todas as regioes do Brasil. Relatam-se cinco casos confirmados e documentados de pacientes com TSP/HAM no Rio Grande do Sul, observando-se em todos paraparesia espática, bexiga neutrogênica e distúrbios sensitivos superficiais e/ou profundos de graus variáveis. Em um caso denotou-se padrao em surto e remissao, caracterizado por ataxia cerebelar (sugestivo de esclerose múltipla). Os cinco pacientes foram submetidos a investigaçao clínica, laboratorial, urodinâmica, neurofisiológica e de neuroimagem. O objetivo de presente trabalho foi apresentar a regiao sul do Brasil como uma área de significativa endemicidade de infecçao por HTLV-I/II (0,42 por cento de prevalência entre doadores de sangue), bem como evidenciar a existência de pacientes com doença neurológica associada a este retrovírus.