Luiz Cláudio Arraes de Alencar

Multilevel analysis of hepatitis A infection in children and adolescents: a household survey in the Northeast and Central-west regions of Brazil

Background The objectives were to estimate the prevalence of hepatitis A among children and adolescents from the Northeast and Midwest regions and the Federal District of Brazil and to identify individual-, household- and area-levels factors associated with hepatitis A infection. Methods This population-based survey was conducted in 2004–2005 and covered individuals aged between 5 and 19 years. A stratified multistage cluster sampling technique with probability proportional to size was used to select 1937 individuals aged between 5 and 19 years living in the Federal capital and in the State capitals of 12 states in the study regions. The sample was stratified according to age (5–9 and 10- to 19-years-old) and capital within each region. Individual- and household-level data were collected by interview at the home of the individual. Variables related to the area were retrieved from census tract data. The outcome was total antibodies to hepatitis A virus detected using commercial EIA. The age distribution of the susceptible population was estimated using a simple catalytic model. The associations between HAV infection and independent variables were assessed using the odds ratio and corrected for the random design effect and sampling weight. Multilevel analysis was performed by GLLAMM using Stata 9.2. Results The prevalence of hepatitis A infection in the 5–9 and 10–19 age-group was 41.5 and 57.4%, respectively for the Northeast, 32.3 and 56.0%, respectively for the Midwest and 33.8 and 65.1% for the Federal District. A trend for the prevalence of HAV infection to increase according to age was detected in all sites. By the age of 5, 31.5% of the children had already been infected with HAV in the Northeast region compared with 20.0% in the other sites. By the age of 19 years, seropositivity was ∼70% in all areas. The curves of susceptible populations differed from one area to another. Multilevel modeling showed that variables relating to different levels of education were associated with HAV infection in all sites. Conclusion The study sites were classified as areas with intermediate endemicity area for hepatitis A infection. Differences in age trends of infection were detected among settings. This multilevel model allowed for quantification of contextual predictors of hepatitis A infection in urban areas.

ABCB1 and ABCC1 variants associated with virological failure of first‐line protease inhibitors antiretroviral regimens in Northeast Brazil patients

The present study aims at evaluating the association between seven single nucleotide polymorphisms (SNPs) in five genes involved on antiretroviral pharmacokinetic pathways and virological failure in first line highly active antiretroviral therapy. Seven candidate polymorphisms (rs3842 and rs1045642 in ABCB1, rs212091 and rs3743527 in ABCC1, rs3745274 in CYP2B6, rs628031 in SLC22A1 and rs1517618 in SLCO3A1) were evaluated if they were associated with virological failure through logistic regression analysis. The study design was a retrospective cohort, analyzing 187 patients from Recife metropolitan region (Pernambuco, Brazil): among these 160 obtained complete suppression of HIV‐1 replication (responders) and were compared to 27 non‐responders, which underwent virological failure. There was no association between CYP2B6, SLC22A1, and SLCO3A1 SNPs and virological failure. Using logistic regression analysis, a significant association was detected between rs1045642 (3435C>T, ABCB1) and rs212091 (198217T>C; 3′‐UTR, ABCC1) with virological failure of first‐line antiretroviral regimens containing protease inhibitors, when controlled by clinical factors, such as sex, age and race. The present results could contribute to unravel the influence of genetic background in anti‐HIV‐1 therapy outcome and help in treatment personalization of Northeast Brazil HIV infected patients.

Mannose binding lectin and mannose binding lectin-associated serine protease-2 genes polymorphisms in human T-lymphotropic virus infection

Variations in genes involved in the immune response pathways may influence the interaction between viruses (such as Human T‐lymphotropic virus, HTLV‐1) and the host. The mannose binding lectin (MBL) and its associated serine protease type 2 (MASP‐2) promote the activation of the lectin pathway of the complement system. As the interaction of complement system with HTLV‐1 is not well understood, the MBL2 promoter/exon 1 polymorphisms and a MASP2 missense polymorphism were examined in a Northeast Brazilian population, looking for a possible relationship between these variations and the susceptibility to HTLV‐1 infection. The present study describes an association between a polymorphism in the MASP2 gene and susceptibility to HTLV‐1 infection, and provides further evidence of an association between the MBL2 gene and HTLV‐1 infection. These findings suggest an important role of the complement system activation, via the lectin pathway, in the susceptibility to HTLV‐1 infection. J Med. Virol. 85:1829–1835, 2013.

Ausência de amebíase invasiva em aidéticos homossexuais masculinos, no Recife.

The purpose of this paper was to determine if among male homosexual SIDA patients, the Entamoeba histolytica was able to product invasive illness. From the 77 investigated patients only one (1.3%) has cysts of E. histolytica in his stools. Tide electroforesis of the only isolated strain has shown it was from zimodeme I, non pathogenic. Tloe research of antimebic antibodies was negative in the serum of the totality of patients. Those results showed that even in immunocompromissed patients with SIDA, E. histolytica strain found in Recife ivas not able to produce disease. The utilization of metronidazol is not indicated in amoebic cysts carriers.

Effectiveness of the First Dose of BCG against Tuberculosis among HIV-Infected, Predominantly Immunodeficient Children

The objective of this study was to estimate the protective effect of Bacille Calmette-Guérin (BCG) vaccine against tuberculosis among (predominantly immunodeficient) HIV-infected children in Angola. A hospital-based case-control study was conducted with 230 cases, children coinfected with tuberculosis, and 672 controls, HIV-infected children from the same hospital, aged 18 months to 13 years. The presence of a vaccination scar was taken as a proxy marker for BCG vaccination. The crude effectiveness was 8% (95% CI: −26 to 32) and the adjusted effectiveness was 30% (95% CI: −75 to 72). The present study suggests that BCG does not have a protective effect against tuberculosis among immunodeficient HIV-infected children. Since BCG is no longer given to HIV-infected children, the study may not be replicated. Accepting that these findings should be considered with caution, they are nonetheless likely to be the last estimate of BCG efficacy in a sufficiently powered study.

Dendritic Cell-Based Immunotherapies to Fight HIV: How Far from a Success Story? A Systematic Review and Meta-Analysis

The scientific community still faces the challenge of developing strategies to cure HIV-1. One of these pursued strategies is the development of immunotherapeutic vaccines based on dendritic cells (DCs), pulsed with the virus, that aim to boost HIV-1 specific immune response. We aimed to review DCs-based therapeutic vaccines reports and critically assess evidence to gain insights for the improvement of these strategies. We performed a systematic review, followed by meta-analysis and meta-regression, of clinical trial reports. Twelve studies were selected for meta-analysis. The experimental vaccines had low efficiency, with an overall success rate around 38% (95% confidence interval = 26.7%–51.3%). Protocols differed according to antigen choice, DC culture method, and doses, although multivariate analysis did not show an influence of any of them on overall success rate. The DC-based vaccines elicited at least some immunogenicity, that was sometimes associated with plasmatic viral load transient control. The protocols included both naïve and antiretroviral therapy (ART)-experienced individuals, and used different criteria for assessing vaccine efficacy. Although the vaccines did not work as expected, they are proof of concept that immune responses can be boosted against HIV-1. Protocol standardization and use of auxiliary approaches, such as latent HIV-1 reservoir activation and patient genomics are paramount for fine-tuning future HIV-1 cure strategies.

Sensitivity and specificity of BCG scar reading among HIV-infected children.

BCG scar has been used as an indicator of vaccination with BCG in the past, but the validity of scar among HIV-positive children is still unknown. The validity of BCG scar reading among such children was estimated, using three different gold standards. The sensitivity ranged from 81.3% (95%-CI: 78.0-84.2) to 91.6% (95%-CI: 88.4-94.0), when the gold standards were, respectively, information from the adult responsible for the child and the vaccination card. The specificity ranged from 90.5% (95% CI: 81.6-95.5) to 94.1% (95% CI: 87.7-97.4), when the gold standards were, respectively, the vaccination card and information from the adult responsible for the child. Reading of BCG scar was shown to be a good indicator for vaccination in the past, among HIV-infected children.

Prevalence of Guillain-Barré syndrome among Zika virus infected cases: a systematic review and meta-analysis

Zika virus (ZIKV) is an emergent flavivirus transmitted mainly through Aedes spp. mosquitoes that is posing challenge to healthcare services in countries experiencing an outbreak. Usually ZIKV infection is mild, but in some cases it has been reported to progress into neurological diseases such as microcephaly in infants and Guillain-Barré syndrome (GBS) in adults. GBS is a debilitating autoimmune disorder that affects peripheral nerves. Since ZIKV caused massive outbreaks in South America in the past few years, we aimed to systematically review the literature and perform a meta-analysis to estimate the prevalence of GBS among ZIKV-infected individuals. We searched PubMed and Cochrane databases and selected three studies for a meta-analysis. We estimated the prevalence of ZIKV-associated GBS to be 1.23% (95% CI=1.17-1.29%). Limitations include paucity of data regarding previous flavivirus infections and ZIKV-infection confirmation issues. Our estimate seems to be low, but cannot be ignored, since ZIKV outbreaks affects an overwhelming number of individuals and GBS is a life-threatening debilitating condition, especially in pregnant women. ZIKV infection cases must be closely followed to assure prompt care to reduce the impact of GBS associated-sequelae on the quality of life of those affected.