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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.

Human immunodeficiency virus type-1 (HIV-1), hepatitis B and C and other rapidly evolving viruses are characterized by extremely high levels of genetic diversity. To facilitate diagnosis and the development of prevention and treatment strategies that efficiently target the diversity of these viruses, and other pathogens such as human T-lymphotropic virus type-1 (HTLV-1), human herpes virus type-8 (HHV8) and human papillomavirus (HPV), we developed a rapid high-throughput-genotyping system. The method involves the alignment of a query sequence with a carefully selected set of pre-defined reference strains, followed by phylogenetic analysis of multiple overlapping segments of the alignment using a sliding window. Each segment of the query sequence is assigned the genotype and sub-genotype of the reference strain with the highest bootstrap (>70%) and bootscanning (>90%) scores. Results from all windows are combined and displayed graphically using color-coded genotypes. The new Virus-Genotyping Tools provide accurate classification of recombinant and non-recombinant viruses and are currently being assessed for their diagnostic utility. They have incorporated into several HIV drug resistance algorithms including the Stanford (http://hivdb.stanford.edu) and two European databases (http://www.umcutrecht.nl/subsite/spread-programme/ and http://www.hivrdb.org.uk/) and have been successfully used to genotype a large number of sequences in these and other databases. The tools are a PHP/JAVA web application and are freely accessible on a number of servers including: http://bioafrica.mrc.ac.za/rega-genotype/html/, http://lasp.cpqgm.fiocruz.br/virus-genotype/html/, http://jose.med.kuleuven.be/genotypetool/html/.

OBJECTIVE: The present study aims to describe ocular alterations in sickle cell disease patients in Bahia, a Northeast state, with the highest prevalence of the disease in Brazil. METHODS: We carried out a cross-sectional study in a group of 146 (292 eyes) sickle cell disease patients (90 HBSS and 56 HBSC). Ophthalmologic examination including indirect binocular ophthalmoscopy was performed. Examination was completed by fluorescein angiography to detect retinal lesions. RESULTS: The most frequent ocular lesions identified were "vascular tortuosity" and "black sunburst". Proliferative retinopathy was found in 22 (12.2%) eyes of HBSS patients and 25 (22.3%) eyes of HBSC patients (OR=2.06; CI95%: 1.5-4.06, p=0.022); Its frequency was higher among HBSS patients aged 20-39 years, while in HBSC patients, it peaked after 40 years (35.7% and 42.8%) and dropped sharply afterwards. CONCLUSION: Proliferative retinopathy was described as early as 10 years of age in both patients groups. Proliferative sickle retinopathy can result in blindness and the knowledge of the most prevalent ocular alterations and age risk will be important to establish a protocol of ophthalmologic follow-up, in order to prevent a severe visual loss and increase patient's life quality.OBJETIVO: O presente estudo teve como objetivo descrever as alterações oculares em pacientes portadores de doença falciforme, na Bahia, um estado do Nordeste, que tem a maior prevalência da doença no Brasil. MÉTODOS: Nós conduzimos um estudo de corte transversal em um grupo de 146 (292 olhos) pacientes com Doença Falciforme (90 HBSS e 56 HBSC). Para exame oftalmológico foi realizada oftalmoscopia binocular indireta complementada pela retinografia fluorescente para detecção de lesões retinianas decorrentes da Doença Falciforme. RESULTADOS: As lesões mais frequentemente encontradas foram o aumento da tortuosidade vascular e "black sumburst" Retinopatia proliferativa foi encontrada em 22 (12,2%) olhos de pacientes HBSS e 25 (22,3%) olhos de pacientes HBSC (OR=2.06; CI95%: 1.5-4.06, p=0. 022); essa frequência foi maior entre os pacientes HBSS com idade entre 20 - 39 anos, enquanto que nos pacientes HBSC foi maior nos acima de 40 anos (35.7% e 42.8%), decaindo abruptamente após essa idade. CONCLUSÃO: Retinopatia proliferativa foi descrita por volta dos dez anos de idade em ambos os grupos. A prevalência da retinopatia falciforme proliferativa pode resultar em cegueira e o conhecimento das alterações oculares mais prevalentes e idade de risco destas em pacientes com Doença Falciforme será importante para estabelecer um protocolo de acompanhamento oftalmológico, para prevenir um dano visual clinicamente grave, aumentando a qualidade de vida destes pacientes.

This study was carried out to evaluate the molecular pattern of all available Brazilian human T-cell lymphotropic virus type 1 Env (n = 15) and Pol (n = 43) nucleotide sequences via epitope prediction, physico-chemical analysis, and protein potential sites identification, giving support to the Brazilian AIDS vaccine program. In 12 previously described peptides of the Env sequences we found 12 epitopes, while in 4 peptides of the Pol sequences we found 4 epitopes. The total variation on the amino acid composition was 9 and 17% for human leukocyte antigen (HLA) class I and class II Env epitopes, respectively. After analyzing the Pol sequences, results revealed a total amino acid variation of 0.75% for HLA-I and HLA-II epitopes. In 5 of the 12 Env epitopes the physico-chemical analysis demonstrated that the mutations magnified the antigenicity profile. The potential protein domain analysis of Env sequences showed the loss of a CK-2 phosphorylation site caused by D197N mutation in one epitope, and a N-glycosylation site caused by S246Y and V247I mutations in another epitope. Besides, the analysis of selection pressure have found 8 positive selected sites (w = 9.59) using the codon-based substitution models and maximum-likelihood methods. These studies underscore the importance of this Env region for the virus fitness, for the host immune response and, therefore, for the development of vaccine candidates.

Trabalho completo: acesso restrito, p. 197-200 Submitted by Bruna Lessa (lessbruna@gmail.com) on 2012-05-17T19:58:59Z No. of bitstreams: 1 (25)v14n2a17.pdf: 733112 bytes, checksum: 52b7800ffff58770c219e97018e8e887 (MD5) Made available in DSpace on 2012-05-17T19:58:59Z (GMT). No. of bitstreams: 1 (25)v14n2a17.pdf: 733112 bytes, checksum: 52b7800ffff58770c219e97018e8e887 (MD5) Previous issue date: 2010-04 A mutation described as a G-to-A transition has been reported in SDF-1 gene (SDF1-3'A), being prevalent in all ethnic groups, except in Africans. This mutation is associated with the onset of AIDS progression. Our aim was to identify the frequency of this allele in different groups from Brazil: Tiriyó and Waiampi Amerindian tribes (Asian ancestry); selected blood donors from Joinville (German descendents); and from Salvador (predominance of African and Portuguese mixture). SDF1-3'A was screened by PCR/RFLP with MspI enzyme. Our results showed a high allelic frequency in Tiriyó tribe (0.24) and Joinville population (0.21), and a frequency of 0.17 and 0.05 in the Salvador population and in the Waiampi tribe, respectively. There was no statistical difference among the allelic frequencies in the studied ethnic groups, except in the Waiampi. Due to the great genetic diversity among Brazilian population and the lack of studies on SDF1-3'A allele, our study of this allelic frequency in these different Brazilian ethnic groups could be important to identification of biomarker for therapeutic support in progression to AIDS and a molecular marker for analysis of evolutionary relationships among human populations.

In order to evaluate if there is variation on the intensity of cerebral spinal fluid (CSF) response during HTLV-I associated tropical spastic paraparesis (TSP) evolution we retrospectively reviewed 128 cases.The results indicate that although CSF inflammatory alterations can persist over a 10-year period.they tend to become slight or even absent after the second year of TSP evolution. Com o objetivo de verificar se existe mudança na intensidade da resposta inflamatória do líquido cefalorraqueano (LCR) no curso da paraparesia espástica tropical (PET) associada ao HTLV-I foram estudados retrospectivamente os exames de LCR de 128 pacientes com PET. Os resultados indicam que embora as alterações inflamatórias possam persistir por período superior a 10 anos, existe tendência a diminuição de sua intensidade ou mesmo de normalização após o segundo ano de evolução da doença.

In order to evaluate the prevalence of HTLV-I infection and its association with tropical spastic paraparesis (TSP) in Bahia, a Northeastern State of Brazil, CSF and sera from TSP patients and CSF and/or sera from some selected groups of individuals were studied. The results seem to indicate a higher prevalence of HTLV-I infection in women than men with TSP and among individuals of HIV risk groups. Some alterations of routine analysis of CSF can suggest HTLV-I infection in TSP patients. Com o objetivo de avaliar a prevalência de infecção pelo HTLV-I e sua associação a paraparesia espática tropical na Bahia, foram estudadas amostras de líquido céfa-lorraqueano (LCR) e/ou soro de pacientes com esta doença e de outros grupos de indivíduos. Os resultados indicam que mulheres são mais afetadas pela doença associada à infecção pelo HTLV-I que os homens. Algumas alterações do exame do LCR podem sugerir infecção pelo HTLV-I em pacientes com paraparesia espática tropical.

An immunoradiometric assay, based on the precipitation of antigen-antibody complexes by polyethylene glycol (PEG) and on the subsequent binding of PEG-soluble radiolabelled staphylococcal protein A to the PEG-insoluble complexes, is described. The assay can be applied to the detection of naturally occurring, circulating immune complexes, and of complexes artificially created by mixing antigen and antibody solutions, which makes it of potential use for the detection of either antigen or antibody in several situations. Pre-treatment of the antibody-containing sera with 3% PEG greatly reduced the background values and increased the sensitivity of the assay. The assay was also applied to the detection and isolation of (1) Leishmania donovani antigens that did not cross-react with antigens of the related parasite Tryoanosoma cruzi (private antigens) and (2) private antigens of insect-derived metacyclic trypomastigotes of T. cruzi in relation to culture-derived metacyclic trypomastigotes of T. cruzi A simple and extremely effective procedure for washing precipitates with just one centrifugation is also described.

Antigenic differences between extracts prepared from insect- and axenic culture-derived T. cruzi were demonstrated by a protein A-binding immunoradiometric assay.

Immunoglobulin levels were measured in serum samples from 36 patients with different clinical forms of chronic Chagas' disease. Increased IgA levels were observed in 50% of the patients in the chronic digestive group and there was a significant correlation with the severity of the disease. IgG and IgM levels were within the normal range. Anti-ssDNA antibodies and EVI (endothelium, vessels and interstitium) antibodies were found in some patients with different clinical forms of the disease.

Soluble antigens from epimastigotes of Trypanosoma cruzi were analyzed by western blot in terms of their reactivity with sera from patients with Chagas' disease. In addition, sera from patients with visceral (AVL) and tegumentar leishmaniasis (ATL) were also tested in order to identify cross-reactivities with Trypanosoma cruzy antigens. Twenty eight polypeptides with molecular weights ranging from 14 kDa to 113 kDa were identified with sera from Chagas' disease patients. An extensive cross-reactivity was observed when sera from human visceral leishmaniasis were used, while only a slight cross-reaction was observed with sera from tegumentar leishmaniasis. On the other hand, 10 polypeptidesspecifically reacting with sera from Chagas' disease patients were identified. Among them, the antigens with molecular weights of 46 kDa and 25 kDa reacted with all sera teste and may be good candidates for specific immunodiagnosis of Chagas' disease. Antígenos solúveis de epimastigotas de Trypanosoma cruzi foram analisados por "imunoblot" a fim de verificar sua reatividade com soros de pacientes com doença de Chagas. Além disso, soro de pacientes com leishmaniose visceral (LVA) e tegumentar americana (LTA) foram também analisados com o objetivo de se identificar oa antígenos de reação cruzada com o Trypanosoma cruzi. Pelo menos 28 polipeptídeos, com pesos moleculares variando de 14 a 113 kDa foram identificados com soros de pacientes com doença de Chagas. Uma intensa reatividade cruzada foi observada quando foram utilizados soros de pacientes com leishmaniose visceral, enquanto que uma fraca reação cruzada foi observada com soros de pacientes portadores de leishmaniose tegumentar. Por outro lado, pelo menos 10 polipeptídeos puderam ser identificados apresentando reação específica com soros de pacientes chagásicos. Entre estes, os polipeptídeos de pesos moleculares de 46 kDa e 25 kDa que reagiram com todos esses soros e são potencialmente bons candidatos a antígenos específicos no diagnósticos sorológico da doença de Chagas.

A retrovirus infecting a Brazilian AIDS patient was isolated and characterized in terms of its reactivity with sera from individuals infected with human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2). The Western blot analysis revealed that the Brazilian isolate is very similar to the well characterized HIV-1 strain. The serum of the patient from whom the virus was isolated did not react with the 140 kDa envelope glycoprotein specific for HIV-2. Um retrovírus foi isolado de um paciente brasileiro com "Síndrome de Imunodeficiência Adquirida" (SIDA/AIDS) e caracterizado em termos de sua reatividade com soros de indivíduos infectados com vírus da imunodeficiência humana dos tipos 1 e 2 (HIV-1 e HIV-2). A análise antigênica por "Western blot" revelou que o isolado brasileiro é bastante similar a uma cepa de HIV-1 bem caracterizada. A identificação do retrovírus como HIV-1 e não HIV-2 é reforçada pelo fato dos anticorpos do paciente do qual foi isolado o vírus não terem reagido com a glicoproteínas de envelope de 140 kDa, específica para HIV-2.

We describe a sensitive radioassay for detecting erythrocyte-associated immunoglobulin employing the immunoglobulin-specific reagent Staphylococcus aureus protein A. The assay was used to determine the extent to which erythrocytes from patients with different connective tissue disease bind radiolabelled protein A. Increased amounts of protein A were bound by erythrocytes from patients with systemic lupus erythematosus or with progressive systemic sclerosis when compared to a control group, whereas there was no significant binding to erythrocytes from patients with rheumatoid arthritis or with polymyositis-dermatomyositis. The assay, because of its high sensitivity and of the availability of the reagent in pure form, should be useful for the investigation of cell-bound antibodies and for the differential diagnosis of connective tissue diseases.