Upregulation of hsa-miR-125b in HTLV-1 asymptomatic carriers and HTLV-1-associated myelopathy/tropical spastic paraparesis patients

The retrovirus human T lymphotropic virus type 1 (HTLV-1) promotes spastic paraparesis, adult T cell leukaemia and other diseases. Recently, some human microRNAs (miRNAs) have been described as important factors in host-virus interactions. This study compared miRNA expression in control individuals, asymptomatic HTLV-1 carriers and HTLV-1 associated myelopathy (HAM)/tropical spastic paraparesis patients. The proviral load and Tax protein expression were measured in order to characterize the patients. hsa-miR-125b expression was significantly higher in patients than in controls (p = 0.0285) or in the HAM group (p = 0.0312). Therefore, our findings suggest that miR-125b expression can be used to elucidate the mechanisms of viral replication and pathogenic processes.

Reduced muscle carnosine content in type 2, but not in type 1 diabetic patients

Carnosine is present in high concentrations in skeletal muscle where it contributes to acid buffering and functions also as a natural protector against oxidative and carbonyl stress. Animal studies have shown an anti-diabetic effect of carnosine supplementation. High carnosinase activity, the carnosine degrading enzyme in serum, is a risk factor for diabetic complications in humans. The aim of the present study was to compare the muscle carnosine concentration in diabetic subjects to the level in non-diabetics. Type 1 and 2 diabetic patients and matched healthy controls (total n = 58) were included in the study. Muscle carnosine content was evaluated by proton magnetic resonance spectroscopy (3 Tesla) in soleus and gastrocnemius. Significantly lower carnosine content (-45%) in gastrocnemius muscle, but not in soleus, was shown in type 2 diabetic patients compared with controls. No differences were observed in type 1 diabetic patients. Type II diabetic patients display a reduced muscular carnosine content. A reduction in muscle carnosine concentration may be partially associated with defective mechanisms against oxidative, glycative and carbonyl stress in muscle.

Equid herpesvirus type-1 exhibits neurotropism and neurovirulence in a mouse model

Intranasal inoculation of equid herpesvirus type-1 (EHV-1) Brazilian strains A4/72 and A9/92 induced an acute and lethal infection in four different inbred mouse strains. Clinical and neurological signs appeared between the 2nd and 3rd day post inoculation (dpi) and included weight loss, ruffled fur, a hunched posture, crouching in corners, nasal and ocular discharges, dyspnoea, dehydration and increased salivation. These signs were followed by increased reactivity to external stimulation, seizures, recumbency and death. The virus was recovered consistently from the brain and viscera of all mice with neurological signs. Histopathological changes consisted of leptomeningitis, focal haemorrhage, ventriculitis, neuronal degeneration and necrosis, neuronophagia, non-suppurative inflammation, multifocal gliosis and perivascular infiltration of polymorphonuclear and mononuclear cells. Immunohistochemical examination demonstrated that EHV-1 strains A4/72 and A9/92 replicated in neurons of the olfactory bulb, the cortex and the hippocampus. In contrast, mice inoculated with the EHV-1 Brazilian strain A3/97 showed neither weight loss nor apparent clinical or neurological signs; however, the virus was recovered consistently from their lungs at 3 dpi. These three EHV-1 strains showed distinct degrees of virulence and tissue tropism in mice. EHV-1 strains A4/72 and A9/92 exhibited a high degree of central nervous system tropism with neuroinvasion and neurovirulence. EHV-1 strain A3/97 was not neurovirulent despite being detected in the brains of infected BALB/c nude mice. These findings indicate that several inbred mouse strains are susceptible to neuropathogenic EHV-1 strains and should be useful models for studying the pathogenesis and mechanisms contributing to EHV-induced myeloencephalopathy in horses. (C) 2011 Elsevier Ltd. All rights reserved.

Immunogenicity of a meningococcal serogroup C conjugate vaccine in HIV-infected children, adolescents, and young adults

Children and adolescents infected with HIV typically have a lower response to immunization than do those in the general population. In most developed countries, meningococcal serogroup C conjugate vaccine is one of the recommended vaccines for such individuals. However, there have been no studies evaluating the antibody response to this vaccine in HIV-infected children, adolescents or young adults. In this study, we evaluated that response using serum bactericidal antibody (SBA) and enzyme-linked immunosorbent assay, comparing HIV-infected with non-HIV-infected patients, as well as analysing the occurrence of side effects. In non-responders, we assessed the antibody response to revaccination. This clinical trial involved 92 patients between 10 and 20 years of age: 43 HIV-infected patients (HIV+ group) and 49 non-HIV-infected patients (HIV- group). After one dose of the vaccine, 72.1% of the HIV+ group patients and 100% of the HIV- group patients were considered protected. Of the HIV+ group patients who received a second dose of the vaccine, only 40% acquired protection. Overall, 81.4% of the HIV+ group patients acquired protection (after one or two doses of the vaccine). Side effects occurred in 16.3% and 44% of the HIV+ group and HIV- group patients, respectively. Therefore, the meningococcal serogroup C conjugate vaccine proved to be safe and effective for use in HIV-infected children, adolescents, and young adults, although their antibody response was weaker than that shown by non-HIV-infected patients. This indicates the need to discuss changes to the immunization schedule for children, adolescents, and young adults infected with HIV, in order to ensure more effective protection against meningococcal disease. (c) 2012 Elsevier Ltd. All rights reserved.

Motor Neuron Disease and Acquired Axonal Neuropathy Association in HIV Infection: Case Report and Update

Background: A possible viral etiology has been documented in the genesis of motor neuron disorders and acquired peripheral neuropathies, mainly due to the vulnerability of peripheral nerves and the anterior horn to certain viruses. In recent years, several reports show association of HIV infection with Amyotrophic Lateral Sclerosis Syndrome, Motor Neuron Diseases and peripheral neuropathies. Objective: To report a case of an association between Motor Neuron Disease and Acquired Axonal neuropathy in HIV infection, and describe the findings of neurological examination, cerebrospinal fluid, neuroimaging and electrophysiology. Methods: The patient underwent neurological examination. General medical examinations were performed, including, specific neuromuscular tests, analysis of cerebrospinal fluid, muscle biopsy and imaging studies. Results and Discussion: The initial clinical presentation of our case was marked by cramps and fasciculations with posterior distal paresis and atrophy in the left arm. We found electromyography tracings with deficits in the anterior horn of the spinal cord and peripheral nerves. Dysphagia and release of primitive reflexes were also identified. At the same time, the patient was informed to be HIV positive with high viral load. He received antiretroviral therapy, with load control but with no clinical remission. Conclusion: Motor Neuron disorders and peripheral neuropathy may occur in association with HIV infection. However, a causal relationship remains uncertain. It is noteworthy that the antiretroviral regimen may be implicated in some cases.

Autoantibodies and High-Risk HLA Susceptibility Markers in First-Degree Relatives of Brazilian Patients with Type 1 Diabetes Mellitus: A Progression to Disease Based Study

The objective of this study was to determine the frequencies of autoantibodies to heterogeneous islet-cell cytoplasmic antigens (ICA), glutamic acid decarboxylase(65) (GAD(65)A), insulinoma-associated antigen-2 (IA-2A) and insulin (IAA)-and human leukocyte antigen (HLA) class II markers (HLA-DR and -DQ) in first degree relatives of heterogeneous Brazilian patients with type I diabetes(T1DM). A major focus of this study was to determine the influence of age, gender, proband characteristics and ancestry on the prevalence of autoantibodies and HLA-DR and -DQ alleles on disease progression and genetic predisposition to T1DM among the first-degree relatives. IAA, ICA, GAD(65)A, IA-2A and HLA- class II alleles were determined in 546 first-degree-relatives, 244 siblings, 55 offspring and 233 parents of 178 Brazilian patients with T1DM. Overall, 8.9% of the relatives were positive for one or more autoantibodies. IAA was the only antibody detected in parents. GAD(65) was the most prevalent antibody in offspring and siblings as compared to parents and it was the sole antibody detected in offspring. Five siblings were positive for the IA-2 antibody. A significant number (62.1%) of siblings had 1 or 2 high risk HLA haplotypes. During a 4-year follow-up study, 5 siblings (expressing HLA-DR3 or -DR4 alleles) and 1 offspring positive for GAD(65)A progressed to diabetes. The data indicated that the GAD(65) and IA-2 antibodies were the strongest predictors of T1DM in our study population. The high risk HLA haplotypes alone were not predictive of progression to overt diabetes.

Living Invisible: HTLV-1-Infected Persons and the Lack of Care in Public Health

Introduction: Human T-cell lymphotropic virus type 1 (HTLV-1) infection is intractable and endemic in many countries. Although a few individuals have severe symptoms, most patients remain asymptomatic throughout their lives and their infections may be unknown to many health professionals. HTLV-1 can be considered a neglected public health problem and there are not many studies specifically on patients' needs and emotional experiences. Objective: To better understand how women and men living with HTLV-1 experience the disease and what issues exist in their healthcare processes. Methods: A qualitative study using participant observation and life story interview methods was conducted with 13 symptomatic and asymptomatic patients, at the outpatient clinic of the Emilio Ribas Infectious Diseases Institute, in Sao Paulo, Brazil. Results and Discussion: The interviewees stated that HTLV-1 is a largely unknown infection to society and health professionals. Counseling is rare, but when it occurs, focuses on the low probability of developing HTLV-1 related diseases without adequately addressing the risk of infection transmission or reproductive decisions. The diagnosis of HTLV-1 can remain a stigmatized secret as patients deny their situations. As a consequence, the disease remains invisible and there are potentially negative implications for patient self-care and the identification of infected relatives. This perception seems to be shared by some health professionals who do not appear to understand the importance of preventing new infections. Conclusions: Patients and medical staff referred that the main focus was the illness risk, but not the identification of infected relatives to prevent new infections. This biomedical model of care makes prevention difficult, contributes to the lack of care in public health for HTLV-1, and further perpetuates the infection among populations. Thus, HTLV-1 patients experience an "invisibility" of their complex demands and feel that their rights as citizens are ignored.

Evaluation of inadequate anti-retroviral treatment in patients with HIV/AIDS

Introduction: Since the emergence of antiretroviral therapy, the survival of patients infected with human immunodeficiency virus has increased. Non-adherence to this therapy is directly related to treatment failure, which allows the emergence of resistant viral strains. Methods: A retrospective descriptive study of the antiretroviral dispensing records of 229 patients from the Center for Health Care, University Hospital, Federal University of Juiz de Fora, Brazil, was conducted between January and December 2009. Results: The study aimed to evaluate patient compliance and determine if there was an association between non-adherence and the therapy. Among these patients, 63.8% were men with an average age of 44.0 +/- 9.9 years. The most used treatment was a combination of 2 nucleoside reverse transcriptase inhibitors with 1 non-nucleoside reverse transcriptase inhibitor (55.5%) or with 2 protease inhibitors (28.8%). It was found that patients taking lopinavir/ritonavir with zidovudine and lamivudine had a greater frequency of inadequate treatment than those taking atazanavir with zidovudine and lamivudine (85% and 83.3%, respectively). Moreover, when the combination of zidovudine/lamivudine was used, the patients were less compliant (chi(2) = 4.468, 1 degree of freedom, p = 0.035). Conclusions: The majority of patients failed to correctly adhere to their treatment; therefore, it is necessary to implement strategies that lead to improved compliance, thus ensuring therapeutic efficacy and increased patient survival.

Oral health profile in patients infected with HTLV-1: Clinical findings, proviral load, and molecular analysis from HTLV-1 in saliva

Human T-lymphotropic virus type 1 (HTLV-1) is associated with adult T-cell leukemia (ATL) and HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) and has also been implicated in several disorders, including periodontal disease. The proviral load is an important biological marker for understanding HTLV-1 pathogenesis and elucidating whether or not the virus is related to the clinical manifestation of the disease. This study describes the oral health profile of HTLV-1 carriers and HAM/TSP patients in order to investigate the association between the proviral load in saliva and the severity of the periodontal disease and to examine virus intra-host variations from peripheral blood mononuclear cells and saliva cells. It is a cross-sectional analytical study of 90 individuals carried out from November 2006 to May 2008. Of the patients, 60 were HTLV-1 positive and 30 were negative. Individuals from the HTLV-1 positive and negative groups had similar mean age and social-economic status. Data were analyzed using two available statistical software packages, STATA 8.0 and SPSS 11.0 to conduct frequency analysis. Differences of P?<?0.05 were considered statistically significant. HTLV-1 patients had poorer oral health status when compared to seronegative individuals. A weak positive correlation between blood and saliva proviral loads was observed. The mean values of proviral load in blood and saliva in patients with HAM/TSP was greater than those in HTLV-1 carriers. The HTLV-1 molecular analysis from PBMC and saliva specimens suggests that HTLV-1 in saliva is due to lymphocyte infiltration from peripheral blood. A direct relationship between the proviral load in saliva and oral manifestations was observed. J. Med. Virol. 84:1428-1436, 2012. (c) 2012 Wiley Periodicals, Inc.

Manifestações orais em crianças HIV, em Moçambique

O objetivo foi comparar conhecimento de homens idosos ao de adultos jovens sobre Aids, considerando escolaridade. Estudo epidemiológico, descritivo e de corte transversal, em que foram analisadas informações de 30 idosos e 62 adultos jovens sobre conceito, transmissão, prevenção, diagnóstico e tratamento de Aids, investigadas por entrevista estruturada baseada em questionário validado padronizado. Para análise de contingência e de variância, empregaram-se distribuições de frequências e testes de Qui quadrado ou exato de Fisher e teste t de Student ou Mann-Whitney em nível de significância de 0,05. Foram empregados o teste de Mantel-Haenszel, em nível de significância de 0,05, e os Odds Ratio com intervalos de confiança a 95%, para influência da escolaridade. Constataram-se percepção individual de boa saúde maior em jovens (61,3% contra 43,3% dos idosos) e atividade sexual maior em idosos (80% contra 62,9% dos jovens). Apesar disso foi menos frequente idosos afirmarem conhecimento satisfatório sobre Aids (26,7% contra 80,6% dos jovens); história de teste de HIV (13,3% contra 24,2% dos jovens) e ter recebido orientação sobre Aids (36,7% dos idosos e 98,4% dos jovens). Os idosos tinham informação insuficiente sobre HIV/Aids comparados a adultos jovens, reforçando a necessidade de maior atenção à população idosa.

Can an immune-regulatory vaccine prevent HIV infection?

Developing vaccines to prevent the establishment of HIV infection has been fraught with difficulties. It might therefore be important to consider other new strategies. Since several studies suggest that anti-inflammatory stimuli can protect from HIV infection and because HIV replicates preferably in activated T cells, we suggest here that the reduction of immune activation through a HIV-specific regulatory T-cell vaccine might thwart early viral replication. Thus, because immune activation is a good predictor of disease progression and the immune activation set point has been shown to be an early event during HIV infection, vaccinating to achieve control of early virus-specific immune activation might be advantageous.

Human Endogenous Retrovirus K(HML-2) Gag and Env specific T-cell responses are not detected in HTLV-I-infected subjects using standard peptide screening methods

Abstract Background An estimated 10–20 million individuals are infected with the retrovirus human T-cell leukemia virus type 1 (HTLV-1). While the majority of these individuals remain asymptomatic, 0.3-4% develop a neurodegenerative inflammatory disease, termed HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP results in the progressive demyelination of the central nervous system and is a differential diagnosis of multiple sclerosis (MS). The etiology of HAM/TSP is unclear, but evidence points to a role for CNS-inflitrating T-cells in pathogenesis. Recently, the HTLV-1-Tax protein has been shown to induce transcription of the human endogenous retrovirus (HERV) families W, H and K. Intriguingly, numerous studies have implicated these same HERV families in MS, though this association remains controversial. Results Here, we explore the hypothesis that HTLV-1-infection results in the induction of HERV antigen expression and the elicitation of HERV-specific T-cells responses which, in turn, may be reactive against neurons and other tissues. PBMC from 15 HTLV-1-infected subjects, 5 of whom presented with HAM/TSP, were comprehensively screened for T-cell responses to overlapping peptides spanning HERV-K(HML-2) Gag and Env. In addition, we screened for responses to peptides derived from diverse HERV families, selected based on predicted binding to predicted optimal epitopes. We observed a lack of responses to each of these peptide sets. Conclusions Thus, although the limited scope of our screening prevents us from conclusively disproving our hypothesis, the current study does not provide data supporting a role for HERV-specific T-cell responses in HTLV-1 associated immunopathology.

Regional differences in clinical care among patients with type 1 diabetes in Brazil: Brazilian Type 1 Diabetes Study Group

Background To determine the characteristics of clinical care offered to type 1 diabetic patients across the four distinct regions of Brazil, with geographic and contrasting socioeconomic differences. Glycemic control, prevalence of cardiovascular risk factors, screening for chronic complications and the frequency that the recommended treatment goals were met using the American Diabetes Association guidelines were evaluated. Methods This was a cross-sectional, multicenter study conducted from December 2008 to December 2010 in 28 secondary and tertiary care public clinics in 20 Brazilian cities in north/northeast, mid-west, southeast and south regions. The data were obtained from 3,591 patients (56.0% females and 57.1% Caucasians) aged 21.2 ± 11.7 years with a disease duration of 9.6 ± 8.1 years (<1 to 50 years). Results Overall, 18.4% patients had HbA1c levels <7.0%, and 47.5% patients had HbA1c levels ≥ 9%. HbA1c levels were associated with lower economic status, female gender, age and the daily frequency of self-blood glucose monitoring (SBGM) but not with insulin regimen and geographic region. Hypertension was more frequent in the mid-west (32%) and north/northeast (25%) than in the southeast (19%) and south (17%) regions (p<0.001). More patients from the southeast region achieved LDL cholesterol goals and were treated with statins (p<0.001). Fewer patients from the north/northeast and mid-west regions were screened for retinopathy and nephropathy, compared with patients from the south and southeast. Patients from the south/southeast regions had more intensive insulin regimens than patients from the north/northeast and mid-west regions (p<0.001). The most common insulin therapy combination was intermediate-acting with regular human insulin, mainly in the north/northeast region (p<0.001). The combination of insulin glargine with lispro and glulisine was more frequently used in the mid-west region (p<0.001). Patients from the north/northeast region were younger, non-Caucasian, from lower economic status, used less continuous subcutaneous insulin infusion, performed less SBGM and were less overweight/obese (p<0.001). Conclusions A majority of patients, mainly in the north/northeast and mid-west regions, did not meet metabolic control goals and were not screened for diabetes-related chronic complications. These results should guide governmental health policy decisions, specific to each geographic region, to improve diabetes care and decrease the negative impact diabetes has on the public health system.

Aquaporin-4 Antibodies Are Not Related to HTLV-1 Associated Myelopathy

Introduction: The seroprevalence of human T-cell leukemia virus type 1 (HTLV-1) is very high among Brazilians (,1:200). HTLV-1 associated myelopathy or tropical spastic paraparesis (HAM/TSP) is the most common neurological complication of HTLV-1 infection. HAM/TSP can present with an acute/subacute form of longitudinally extensive myelitis, which can be confused with lesions seen in aquaporin-4 antibody (AQP4-Ab) positive neuromyelitis optica spectrum disorders (NMOSD) on MRI. Moreover, clinical attacks in patients with NMOSD have been shown to be preceded by viral infections in around 30% of cases. Objective: To evaluate the frequency of AQP4-Ab in patients with HAM/TSP. To evaluate the frequency of HTLV-1 infection in patients with NMOSD. Patients and Methods: 23 Brazilian patients with HAM/TSP, 20 asymptomatic HTLV-1+ serostatus patients, and 34 with NMOSD were tested for AQP4-Ab using a standardized recombinant cell based assay. In addition, all patients were tested for HTLV-1 by ELISA and Western blotting. Results: 20/34 NMOSD patients were positive for AQP4-Ab but none of the HAM/TSP patients and none of the asymptomatic HTLV-1 infected individuals. Conversely, all AQP4-Ab-positive NMOSD patients were negative for HTLV-1 antibodies. One patient with HAM/TSP developed optic neuritis in addition to subacute LETM; this patient was AQP4-Ab negative as well. Patients were found to be predominantly female and of African descent both in the NMOSD and in the HAM/TSP group; Osame scale and expanded disability status scale scores did not differ significantly between the two groups. Conclusions: Our results argue both against a role of antibodies to AQP4 in the pathogenesis of HAM/TSP and against an association between HTLV-1 infection and the development of AQP4-Ab. Moreover, the absence of HTLV-1 in all patients with NMOSD suggests that HTLV-1 is not a common trigger of acute attacks in patients with AQP4-Ab positive NMOSD in populations with high HTLV-1 seroprevalence.

Coinfecção de Tb/HIV em um distrito administrativo do município de São Paulo

OBJETIVO: caracterizar o perfil sóciodemográfico e epidemiológico de pessoas com co-infecção Tb/HIV, residentes no distrito administrativo Capão Redondo do Município de São Paulo no período de 2000 a 2009. MÉTODOS: Trata-se de um estudo retrospectivo. RESULTADOS: De um total de 1.612 casos de tuberculose, 162 casos foram positivos para o HIV. Houve predomínio da faixa etária de 30 a 39 anos (39,5%), sexo masculino (61,1%) e a forma pulmonar (68,5%). Apenas 47,5% dos casos evoluíram para a cura, 13% abandonaram o tratamento e 32,2% foram a óbito. RESULTADOS: Ressalta-se a necessidade do conhecimento da situação da co-infecção Tb/HIV no sentido de oferecer uma assistência adequada a esta clientela, considerando que ambas as enfermidades não podem ser discutidas isoladamente. CONCLUSÃO: Conclui-se que os casos de associação Tb/HIV contribuem para a não adesão ao tratamento e aumento da taxa de mortalidade.