Viral diseases and human evolution

The interaction of man with viral agents was possibly a key factor shaping human evolution, culture and civilization from its outset. Evidence of the effect of disease, since the early stages of human speciation, through pre-historical times to the present suggest that the types of viruses associated with man changed in time. As human populations progressed technologically, they grew in numbers and density. As a consequence different viruses found suitable conditions to thrive and establish long-lasting associations with man. Although not all viral agents cause disease and some may in fact be considered beneficial, the present situation of overpopulation, poverty and ecological inbalance may have devastating effets on human progress. Recently emerged diseases causing massive pandemics (eg., HIV-1 and HCV, dengue, etc.) are becoming formidable challenges, which may have a direct impact on the fate of our species.

Hepatitis C prevalence and risk factors in hemodialysis patients in Central Brazil: a survey by polymerase chain reaction and serological methods

An hemodialysis population in Central Brazil was screened by polymerase chain reaction (PCR) and serological methods to assess the prevalence of hepatitis C virus (HCV) infection and to investigate associated risk factors. All hemodialysis patients (n=428) were interviewed in eight dialysis units in Goiânia city. Blood samples were collected and serum samples screened for anti-HCV antibodies by an enzyme-linked immunosorbent assay (ELISA). Positive samples were retested for confirmation with a line immunoassay (LIA). All samples were also tested for HCV RNA by the PCR. An overall prevalence of 46.7% (CI 95%: 42-51.5) was found, ranging from 20.7% (CI 95%: 8.8-38.1) to 90.4% (CI 95%: 79.9-96.4) depending on the dialysis unit. Of the 428 patients, 185 were found to be seropositive by ELISA, and 167 were confirmed positive by LIA, resulting in an anti-HCV prevalence of 39%. A total of 131 patients were HCV RNA-positive. HCV viremia was present in 63.5% of the anti-HCV-positive patients and in 10.3% of the anti-HCV-negative patients. Univariate analysis of risk factors showed that the number of previous blood transfusions, transfusion of blood before mandatory screening for anti-HCV, length of time on hemodialysis, and treatment in multiple units were associated with HCV positivity. However, multivariate analysis revealed that blood transfusion before screening for anti-HCV and length of time on hemodialysis were significantly associated with HCV infection in this population. These data suggest that nosocomial transmission may play a role in the spread of HCV in the dialysis units studied. In addition to anti-HCV screening, HCV RNA detection is necessary for the diagnosis of HCV infection in hemodialysis patients.

The distribution of Biomphalaria spp. in different habitats in relation to physical, biological, water contact and cognitive factors in a rural area in Minas Gerais, Brazil

A total of 256 sites in 11 habitats were surveyed for Biomphalaria in Melquiades rural area (State of Minas Gerais) in August and November 1999 and in March 2000. Of the 1,780 Biomphalaria collected, 1,721 (96.7%) were B. glabrata and 59 (3.3%) B. straminea. Snails were found in all habitats except in wells, with the largest mean numbers in tanks, seepage ponds and canals, and the smallest numbers in springs, rice fields and fishponds. People's knowledge of the occurrence of Biomphalaria at the collection sites and the presence of Biomphalaria ova were strongly correlated with the occurrence of snails, and distance between houses and collection sites, as well as water velocity were inversely correlated with Biomphalaria occurrence (p < 0.001). The strongest predictor o f Biomphalaria occurrence was the presence of tilapia fish in fishponds. Fourteen Biomphalaria (0.8% of all snails) found at 6 sites were infected with Schistosoma mansoni. Suggestions are made for the utilization of local people's knowledge in snail surveys and further studies are recommended on the possible use of tilapia for biological control of Biomphalaria in fishponds, as well as modeling of S. mansoni transmission and reinfection.

Intradermal vaccination of adults with three low doses (2 µg) of recombinant hepatitis B vaccine. I. Seroconversion rate and adverse effects

A total of 250 dentists (53.6% men and 46.4% women), with a mean age of 35.1 ± 9.8 years, were submitted to serological tests for the diagnosis of hepatitis B (HB) - HBsAg, anti-HBs, anti-HBc, HBeAg, and anti-HBe - using a radioimmunoassay. One or more of these markers were detected in 78 individuals (31.2%) who were excluded from the group to be vaccinated. Of the 172 HB-susceptible individuals, 135 (78.5%) responded to the call and were intradermally injected with three 2 µg doses of the Belgian HB recombinant vaccine, applied at an interval of one month between the 1st and 2nd dose and of five months between the 2nd and 3rd dose. A new determination of HB markers carried out 50 days after the 3rd dose showed that 110 (81.5%) individuals had become anti-HBs positive (65.5% good responders and 34.5% poor responders). Mean serum anti-HBs titer of these 110 dentists was 42.4 U S/N, similar in both sexes. The adverse effects analyzed in 106 dentists were: (a) local: pain (12.3%), burning sensation (14.1%), pruritus (25.5%), erythema (28.3%), local heat (18.9%), and a hypochromic spot (32.1%); (b) systemic (4.7%): discomfort in two patients, and fever, anorexia, and asthenia in one patient each. Intradermal administration of a fourth 2 µg vaccine dose to 39 dentists (poor or non-responders) increased the total number of anti-HBs-positive individuals from 110 (81.5%) to 114 (84.4%), with the number of good responders increasing from 72 (65.5%) to 85 (74.6%). We conclude that the Belgian recombinant vaccine applied in the scheme used here induces a high rate of seroconversion and causes only mild and transitory adverse effects.

Prevalence and risk factors of hepatitis C virus infection in hemodialysis patients from one center in Recife, Brazil

A hemodialysis population from a dialysis unit in the city of Recife, Northeastern Brazil, was screened to assess the prevalence of hepatitis C virus (HCV) infection and to investigate the associated risk factors. Hemodialysis patients (n = 250) were interviewed and serum samples tested for anti-HCV antibodies by enzyme-linked immunosorbent assay (ELISA). All samples were also tested for HCV RNA by reverse transcriptase nested polymerase chain reaction (RT-nested-PCR). Out of 250 patients, 21 (8.4%) were found to be seropositive by ELISA, and 19 (7.6%) patients were HCV RNA positive. HCV viraemia was present in 90.5% of the anti-HCV positive patients. The predominant genotype was HCV 1a (8/19), followed by 3a (7/19), and 1b (4/19). None of the anti-HCV negative patients were shown to be viraemic by the PCR. Univariate analysis of risk factors showed that time spent on hemodialysis, the number of blood transfusions and a blood transfusion before November 1993 were associated with HCV positivity. However, multivariate analysis revealed that blood transfusions before November 1993 were significantly associated with HCV infection in this population. Low prevalence levels were encountered in this center, however prospective studies are necessary to confirm these findings.

Clinical outcome and risk factors related to extended-spectrum beta-lactamase-producing Klebsiella spp. infection among hospitalized patients

Over the past two decades, nosocomial infections caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella spp. have become a major problem all around the world. This situation is of concern because there are limited antimicrobial options to treat patients infected with these pathogens, and also because this kind of resistance can spread to a wide variety of Gram-negative bacilli. Our objectives wereto evaluate among in-patients at a publicuniversity tertiary-care hospital with documented infection due to Klebsiella spp., which were the risk factors (cross-sectional analysis) and the clinical impact (prospective cohort) associated with an ESBL-producing strain. Study subjects were all patients admitted at the study hospital between April 2002 and October 2003, with a clinically and microbiologically confirmed infection caused by Klebsiella spp. at any body site, except infections restricted to the urinary tract. Of the 104 patients studied, 47 were infected with an ESBL-producing strain and 57 with a non-ESBL-producing strain. Independent risk factors associated with infection with an ESBL-producing strain were young age, exposure to mechanical ventilation, central venous catheter, use of any antimicrobial agent, and particularly use of a 4th generation cephalosporin or a quinolone. Length of stay was significant longer for patients infected with ESBL-producing strains than for those infected with non-ESBL-producing strains, although fatality rate was not significantly affected by ESBL-production in this cohort. In fact, mechanical ventilation and bacteremia were the only variables withindependent association withdeath detected in this investigation.

Prevalence, genotypes and risk factors associated with hepatitis C virus infection in hemodialysis patients in Campo Grande, MS, Brazil

A survey was conducted among the hemodialysis units of the city of Campo Grande, located in the state of Mato Grosso do Sul in the Mid-west region of Brazil, with the aim of investigating the prevalence, risk factors, and genotypes of hepatitis C virus (HCV) infection. A total of 163 patients were interviewed in five dialysis units. Serum samples were screened for anti-HCV. Positive samples were tested for HCV RNA and genotyped. The prevalence of anti-HCV was 11% (95% CI: 6.8-17.1). A history of transfusion with blood that was not screened for anti-HCV and length of time on hemodialysis were associated with HCV infection. HCV RNA was detected in 12 samples: ten were of genotype 1, subtypes 1a (75%) and 1b (8.3%), and two were of genotype 3, subtype 3a (16.7%).

Host genetic and epigenetic factors in toxoplasmosis

Analysing human genetic variation provides a powerful tool in understanding risk factors for disease. Toxoplasma gondii acquired by the mother can be transmitted to the fetus. Infants with the most severe clinical signs in brain and eye are those infected early in pregnancy when fetal immunity is least well developed. Genetic analysis could provide unique insight into events in utero that are otherwise difficult to determine. We tested the hypothesis that propensity for T. gondii to cause eye disease is associated with genes previously implicated in congenital or juvenile onset ocular disease. Using mother-child pairs from Europe (EMSCOT) and child/parent trios from North America (NCCCTS), we demonstrated that ocular and brain disease in congenital toxoplasmosis associate with polymorphisms in ABCA4 encoding ATP-binding cassette transporter, subfamily A, member 4 previously associated with juvenile onset retinal dystrophies including Stargardt's disease. Polymorphisms at COL2A1 encoding type II collagen, previously associated with Stickler syndrome, associated only with ocular disease in congenital toxoplasmosis. Experimental studies showed that both ABCA4 and COL2A1 show isoform-specific epigenetic modifications consistent with imprinting, which provided an explanation for the patterns of inheritance observed. These genetic and epigenetic risk factors provide unique insight into molecular pathways in the pathogenesis of disease.

Prevalence of hepatitis C virus infection and associated factors among male illicit drug users in Cuiabá, Mato Grosso, Brazil

Intravenous drug injection has been reported as the main risk factor for hepatitis C virus (HCV) infection. The aim of the present study was to describe the prevalence and the epidemiological profile of HCV infection among abusers of illegal injected and non-injected drugs in Cuiabá, state of Mato Grosso, Central Brazil. A cross-sectional study including 314 male drug users from eight detoxification centres was performed. Out of 314 subjects studied, 48 (15.2%) were intravenous drug users. Participants were interviewed and had blood samples taken and tested for the presence of anti-HCV antibodies. Positive samples were tested for the presence of HCV RNA. Genotyping was performed on HCV RNA-positive samples. The overall prevalence of anti-HCV antibodies was 6.4% (n = 20). Out of 20 anti-HCV antibody-positive subjects, 16 (80%) were also HCV RNA-positive. Genotype 1 predominated (75%), followed by 3a (25%). Subtype 1a was more common than 1b. HCV infection was more prevalent among intravenous drug users (33%) than non-injecting users (1.5%). Logistic regression analyses showed independent associations between HCV infection and intravenous drug use, imprisonment and increasing age. In the present study, injecting drug use was the factor most strongly associated to HCV infection and inhaling or sniffing did not represent an increased susceptibility to infection.

Morbidity and prognostic factors in chronic chagasic cardiopathy

Chagas disease is a pleomorphic clinical entity that has several unique features. The aim of this study is to summarise some of the recent contributions from our research group to knowledge of the morbidity and prognostic factors in Chagas heart disease. A retrospective study suggested that ischaemic stroke associated with left ventricular (LV) apical thrombi is the first clinical manifestation of Chagas disease observed in a large proportion of patients. LV function and left atrial volume (LAV) are independent risk factors for ischaemic cerebrovascular events during follow-up of Chagas heart disease patients. Pulmonary congestion in Chagas-related dilated cardiomyopathy is common but usually mild. Although early right ventricular (RV) involvement has been described, we have shown by Doppler echocardiography that RV dysfunction is evident almost exclusively when it is associated with left ventricle dilatation and functional impairment. In addition, RV dysfunction is a powerful predictor of survival in patients with heart failure secondary to Chagas disease. We have also demonstrated that LAV provides incremental prognostic information independent of clinical data and conventional echocardiographic parameters that predict survival.

Brazilian clinical trial of uniform multidrug therapy for leprosy patients: the correlation between clinical disease types and adverse effects

This study sought to verify the correlation between leprosy types and the adverse effects of treatment drugs. This quantitative, prospective, nested study was developed at the Dona Libânia Dermatology Centre in Fortaleza, Brazil. Data were collected from November 2007-November 2008. During this period, 818 leprosy patients were diagnosed and began treatment. Forty patients with tuberculoid leprosy (TT) were selected. Twenty patients followed a standard therapy of dapsone and rifampicin and 20 were administered dapsone, rifampicin and clofazimine (U-MDT). Twenty patients with borderline lepromatous (BL) and lepromatous leprosy (LL) were also selected and treated with U-MDT. All of the subjects received six doses. With the exception of haemolytic anaemia, there was a low incidence of adverse effects in all the groups. We did not observe any differences in the incidence of haemolytic anaemia or other side effects across groups of patients with TT, BL or LL treated with U-MDT.

Parasite load and risk factors for poor outcome among children with visceral leishmaniasis. A cohort study in Belo Horizonte, Brazil, 2010-2011

Clinical and laboratory risk factors for death from visceral leishmaniasis (VL) are relatively known, but quantitative real-time polymerase chain reaction (qPCR) might assess the role of parasite load in determining clinical outcome. The aim of this study was to identify risk factors, including parasite load in peripheral blood, for VL poor outcome among children. This prospective cohort study evaluated children aged ≤ 12 years old with VL diagnosis at three times: pre-treatment (T0), during treatment (T1) and post-treatment (T2). Forty-eight patients were included and 16 (33.3%) met the criteria for poor outcome. Age ≤ 12 months [relative risk (RR) 3.51; 95% confidence interval (CI) 1.89-6.52], tachydyspnoea (RR 3.46; 95% CI 2.19-5.47), bacterial infection (RR 3.08; 95% CI 1.27-7.48), liver enlargement (RR 3.00; 95% CI 1.44-6.23) and low serum albumin (RR 7.00; 95% CI 1.80-27.24) were identified as risk factors. qPCR was positive in all patients at T0 and the parasite DNA was undetectable in 76.1% of them at T1 and in 90.7% at T2. There was no statistical association between parasite load at T0 and poor outcome.

Prevalence of human papillomavirus infection, distribution of viral types and risk factors in cervical samples from human immunodeficiency virus-positive women attending three human immunodeficiency virus-acquired immune deficiency syndrome reference centres in northeastern Brazil

Human immunodeficiency virus (HIV)-positive patients have a greater prevalence of coinfection with human papillomavirus (HPV) is of high oncogenic risk. Indeed, the presence of the virus favours intraepithelial squamous cell lesion progression and may induce cancer. The aim of this study was to evaluate the prevalence of HPV infection, distribution of HPV types and risk factors among HIV-positive patients. Cervical samples from 450 HIV-positive patients were analysed with regard to oncotic cytology, colposcopy and HPV presence and type by means of polymerase chain reaction and sequencing. The results were analysed by comparing demographic data and data relating to HPV and HIV infection. The prevalence of HPV was 47.5%. Among the HPV-positive samples, 59% included viral types of high oncogenic risk. Multivariate analysis showed an association between HPV infection and the presence of cytological alterations (p = 0.003), age greater than or equal to 35 years (p = 0.002), number of partners greater than three (p = 0.002), CD4+ lymphocyte count < 200/mm3 (p = 0.041) and alcohol abuse (p = 0.004). Although high-risk HPV was present in the majority of the lesions studied, the low frequency of HPV 16 (3.3%), low occurrence of cervical lesions and preserved immunological state in most of the HIV-positive patients were factors that may explain the low occurrence of precancerous cervical lesions in this population.

Serial QuantiFERON-TB Gold In-Tube assay and tuberculin skin test to diagnose latent tuberculosis in household Mexican contacts: conversion and reversion rates and associated factors using conventional and borderline zone definitions

A cohort of 123 adult contacts was followed for 18‐24 months (86 completed the follow-up) to compare conversion and reversion rates based on two serial measures of QuantiFERON (QFT) and tuberculin skin test (TST) (PPD from TUBERSOL, Aventis Pasteur, Canada) for diagnosing latent tuberculosis (TB) in household contacts of TB patients using conventional (C) and borderline zone (BZ) definitions. Questionnaires were used to obtain information regarding TB exposure, TB risk factors and socio-demographic data. QFT (IU/mL) conversion was defined as <0.35 to ≥0.35 (C) or <0.35 to >0.70 (BZ) and reversion was defined as ≥0.35 to <0.35 (C) or ≥0.35 to <0.20 (BZ); TST (mm) conversion was defined as <5 to ≥5 (C) or <5 to >10 (BZ) and reversion was defined as ≥5 to <5 (C). The QFT conversion and reversion rates were 10.5% and 7% with C and 8.1% and 4.7% with the BZ definitions, respectively. The TST rates were higher compared with QFT, especially with the C definitions (conversion 23.3%, reversion 9.3%). The QFT conversion and reversion rates were higher for TST ≥5; for TST, both rates were lower for QFT <0.35. No risk factors were associated with the probability of converting or reverting. The inconsistency and apparent randomness of serial testing is confusing and adds to the limitations of these tests and definitions to follow-up close TB contacts.

Adherence to statin treatment and associated factors in female users from the Unified Health System (SUS)

Objective: To identify the adherence rate of a statin treatment and possible related factors in female users from the Unified Health System. Method: Seventy-one women were evaluated (64.2 ± 11.0 years) regarding the socio-economic level, comorbidities, current medications, level of physical activity, self-report of muscular pain, adherence to the medical prescription, body composition and biochemical profile. The data were analyzed as frequencies, Chi-Squared test, and Mann Whitney test (p<0.05). Results: 15.5% of women did not adhere to the medical prescription for the statin treatment, whose had less comorbidities (p=0.01), consumed less quantities of medications (p=0.00), and tended to be younger (p=0.06). Those patients also presented higher values of lipid profile (CT: p=0.01; LDL-c: p=0.02). Musculoskeletal complains were not associated to the adherence rate to the medication. Conclusion: The associated factors to adherence of dyslipidemic women to statin medical prescription were age, quantity of comorbidities and quantity of current medication.