George Tadeu Nunes Diniz

Is it better to be rich in a poor area or poor in a rich area? A multilevel analysis of a case–control study of social determinants of tuberculosis

BACKGROUND Tuberculosis is known to have socio-economic determinants at individual and at area levels, but it is not known whether they are independent, whether they interact and their relative contributions to the burden of tuberculosis. METHODS A case-control study was conducted in Recife, Brazil, to investigate individual and area social determinants of tuberculosis, to explore the relationship between determinants at the two levels and to calculate their relative contribution to the burden of tuberculosis. It included 1452 cases of tuberculosis diagnosed by the tuberculosis services and 5808 controls selected at random from questionnaires completed for the demographic census. Exhaustive information on social factors was collected from cases, using the questionnaire used in the census. Socio-economic information for areas was downloaded from the census. Multilevel logistic regression investigated individual and area effects. RESULTS There was a marked and independent influence of social variables on the risk of tuberculosis, both at individual and area levels. At individual level, being aged >or=20, being male, being illiterate, not working in the previous 7 days and possessing few goods, all increased the risk of tuberculosis. At area level, living in an area with many illiterate people and where few households own a computer also increased this risk; individual and area levels did not appear to interact. Twice as many cases were attributable to social variables at individual level than at area level. CONCLUSIONS Although individual characteristics are the main contributor to the risk of tuberculosis, contextual characteristics make a substantial independent contribution.

HLA-G 3' untranslated region polymorphisms are associated with systemic lupus erythematosus in 2 Brazilian populations.

Objective. HLA-G has well recognized tolerogenic properties in physiological and nonphysiological conditions. The 3′ untranslated region (3′UTR) of the HLA-G gene has at least 3 polymorphic sites (14-bpINS/DEL, +3142C/G, and +3196C/G) described as associated with posttranscriptional influence on messenger RNA production; however, only the 14-bpINS/DEL and +3142C/G sites have been studied in systemic lupus erythematosus (SLE). Methods. We investigated the HLA-G 3′UTR polymorphic sites (14-bpINS/DEL, +3003C/T, +3010C/G, +3027A/C, +3035C/T, +3142C/G, +3187A/G, and +3196C/G) in 190 Brazilian patients with SLE and 282 healthy individuals in allele, genotype, and haplotype analyses. A multiple logistic regression model was used to assess the association of the disease features with the HLA-G 3′UTR haplotypes. Results. Increased frequencies were observed of the 14-bpINS (p = 0.053), +3010C (p = 0.008), +3142G (p = 0.006), and +3187A (p = 0.013) alleles, and increased frequencies of the 14-bpINS-INS (p = 0.094), +3010 C-C (p = 0.033), +3142 G-G (p = 0.021), and +3187 A-A (p = 0.035) genotypes. After Bonferroni correction, only the +3142G (p = 0.05) and +3010C (p = 0.06) alleles were overrepresented in SLE patients. The UTR-1 haplotype (14-bpDEL/+3003T/+3010G/+3027C/+3035C/+3142C/+3187G/+3196C) was underrepresented in SLE (pcorr = 0.035). Conclusion. These results indicate that HLA-G 3′UTR polymorphic sites, particularly +3142G and +3010C alleles, were associated with SLE susceptibility, whereas UTR-1 was associated with protection against development of SLE.

Risk factors related to hypertension among patients in a cohort living with HIV/AIDS

INTRODUCTION Studies disagree as to whether there is a greater prevalence of hypertension among HIV/AIDS patients and the role of antiretroviral therapy. OBJECTIVE Evaluate the prevalence of hypertension and risk factors in a cohort of HIV-infected patients, with emphasis on antiretroviral therapy. METHOD Case-control study conducted at baseline of a cohort, between June/2007 and December/2008 in Pernambuco/Brazil. Blood pressure was classified as normal, prehypertension, and hypertension. RESULTS Of 958 patients, 245 (25.6%) had hypertension (cases), 325 (33.9%) had prehypertension, and 388 (40.5%) were normotensive (controls). Comparison between hypertensive and normotensive patients showed that traditional factors, such as age > 40 (OR = 3.06, CI = 1.91-4.97), male gender (OR = 1.85, CI = 1.15-3.01), BMI > 25 (OR = 5.51, CI = 3.36-9.17), and triglycerides > 150 mg/dL (OR = 1.69, CI = 1.05-2.71), were independently associated with hypertension. Duration of antiretroviral therapy and CD4 > 200 cells/mm³ were associated with hypertension in univariate analysis, but did not remain in final model. Type of antiretroviral schema and lipodystrophy showed no association with hypertension. CONCLUSION Hypertension in HIV/AIDS patients is partially linked to invariable factors, such as age and sex. Efforts should be directed toward controlling reversible factors, particularly excessive weight gain and unsuitable diet.

Risk Factors in Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome Patients Undergoing Antiretroviral Therapy in the State of Pernambuco, Brazil: A Case–Control Study

BACKGROUND Although human immunodeficiency virus (HIV)-associated lipodystrophy has been reported for more than a decade, there is still considerable uncertainty regarding the mechanisms involved in its pathogenesis. METHODS A case-control study was performed that aimed to identify the risk factors for lipodystrophy in HIV/acquired immunodeficiency syndrome (AIDS) patients undergoing antiretroviral therapy in Pernambuco, Brazil. RESULTS Between July and November, 2007, a total of 332 patients were enrolled in the study: 182 cases and 150 controls. The following factors were independently associated with lipodystrophy: Use of stavudine [odds ratio (OR), 4.0; 95% confidence interval (CI), 2.3-6.9], use of didanosine (OR, 1.8; 95% CI, 1.0-3.4), use of lopinavir/ritonavir for less than 3 years (OR, 0.5; 95% CI, 0.2-1.0) and use of nucleoside/nucleotide analogue reverse transcriptase inhibitors (NTRIs) for more than 3 years (OR, 2.9; 95% CI, 1.6-5.2). Other associated factors were: duration of antiretroviral therapy (OR, 4.3; 95% CI, 2.4-7.9) and duration of HIV infection (OR, 2.9; 95% CI, 1.8-4.7). There was no association with the use of protease inhibitor when it was adjusted for the use of NRTIs. CONCLUSION In this study, factors related to antiretroviral therapy were the main risk factors for lipodystrophy, corroborating the literature, but the findings also point to the need for further exploration into some of these associations, especially with the use of didanosine and lopinavir/ritonavir, which are less frequently reported. Future studies with a larger number of patients and a prospective design could provide valuable information for understanding this disorder.

Risk factors associated with death in patients who initiate treatment for tuberculosis after two different follow-up periods

INTRODUCTION: Mortality from tuberculosis, which should be a rare event, still affects a large portion of the population of developing countries. In this context, Recife, a city in the northeast of Brazil where this study was developed, has the highest tuberculosis mortality rates of the Brazilian capitals. OBJECTIVE: To analyze survival probability and identify risk factors for death from tuberculosis in a cohort of patients living in Recife who started treatment for tuberculosis. METHODOLOGY: A cohort of newly diagnosed TB cases was followed up from the beginning of treatment (in 2001-2003) until June 2007. Survival probability was estimated by Kaplan-Meier method; and Cox Regression analysis was used to identify risk factors. RESULTS: At the end of the follow-up period, the survival probability after beginning TB treatment was 95.9%. Older ages, positivity for HIV and late initial treatment were statistically associated with death from TB in one year follow-up. When the analysis was done considering the total period of follow-up, older ages, positivity serology for HIV, late initial treatment, weight loss, and history of previous treatment remained in the multivariate Cox regression model. CONCLUSION: A more comprehensive analysis, specifically for deaths from tuberculosis as the underlying and non-underlying cause, allowed identification of a greater number of predictive factors that would otherwise not be detected if follow-up had lasted only until the end of treatment. These results can guide feasible interventions for health services aiming to reduce case-fatality from tuberculosis.

Survival of HIV-infected patients after starting tuberculosis treatment: a prospective cohort study.

OBJECTIVES To estimate the probability of survival and to evaluate risk factors for death in a cohort of persons living with human immunodeficiency virus (PLHIV) who had started tuberculosis (TB) treatment. METHODS A prospective cohort study was conducted between June 2007 and December 2009 with HIV-infected patients who had started anti-tuberculosis treatment in the State of Pernambuco, Brazil. Survival data were analysed using the Kaplan-Meier estimator, the log-rank test and the Cox model. Hazard ratios and their respective 95%CIs were estimated. RESULTS Of a cohort of 2310 HIV-positive individuals, 333 patients who had commenced treatment for TB were analysed. The mortality rate was 5.25 per 10,000 person-years (95%CI 4.15-6.63). The probability of survival at 30 months was 74%. Risk factors for death in the study population were being female, age ≥30 years, having anaemia, not using highly active antiretroviral therapy (HAART) during treatment for TB and disseminated TB. Protective factors for death were a CD4 lymphocyte count >200 cells/mm(3) and treatment for TB having started in an out-patient clinic. CONCLUSIONS The use of HAART can prevent deaths among HIV-TB patients, corroborating the efficacy of starting HAART early in individuals with TB.

Correlation of biological serum markers with the degree of hepatic fibrosis and necroinflammatory activity in hepatitis C and schistosomiasis patients

Liver biopsy is the gold-standard method to stage fibrosis; however, it is an invasive procedure and is potentially dangerous. The main objective of this study was to evaluate biological markers, such as cytokines IL-13, IFN-gamma, TNF-alpha and TGF-beta, platelets, bilirubins (Bil), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total proteins, gamma-glutamil transferase (gamma-GT) and alkaline phosphatase (AP), that could be used to predict the severity of hepatic fibrosis in schistosomiasis and hepatitis C (HC) as isolated diseases or co-infections. The following patient groups were selected: HC (n = 39), HC/hepatosplenic schistosomiasis (HSS) (n = 19), HSS (n = 22) and a control group (n = 13). ANOVA and ROC curves were used for statistical analysis. P < 0.05 was considered significant. With HC patients we showed that TNF-alpha (p = 0.020) and AP (p = 0.005) could differentiate mild and severe fibrosis. With regard to necroinflammatory activity, AST (p = 0.002), gamma-GT (p = 0.034) and AP (p = 0.001) were the best markers to differentiate mild and severe activity. In HC + HSS patients, total Bil (p = 0.008) was capable of differentiating between mild and severe fibrosis. In conclusion, our study was able to suggest biological markers that are non-invasive candidates to evaluate fibrosis and necroinflammatory activity in HC and HC + HSS.

Profile of Patients with Hypertension Included in a Cohort with HIV/ AIDS in the State of Pernambuco, Brazil

BACKGROUND Hypertension (HBP) is modifiable risk factor, whose control may reduce cardiovascular disease in patients with human immunodeficiency virus (HIV). OBJECTIVE To estimate the prevalence of hypertension and describe the characteristics of patients with hypertension infected by HIV/AIDS. METHODS A cross-sectional study aligned to a cohort of patients with HIV/AIDS. The study considered hypertension at levels > 140/90 mmHg or use of antihypertensive drugs and pre-hypertension at levels > 120/80 mmHg. RESULTS Out of 958 patients, 388 (40.5%) were normotensive, 325 (33.9%) were pre-hypertensive, and 245 (25.6%) were hypertensive. Out of these 245 patients, 172 (70.2%) were aware of the fact there they were hypertensive, and 36 (14.8%) had blood pressure controlled. Sixty-two (62) patients (54.4%) were diagnosed with hypertension after HIV diagnosis. Lipodystrophy occurred in 95 (46.1%) patients; overweight/obesity in 129 (52.7%). Use of antiretrovirals occurred in 184 (85.9%), 89 (41.6%) with protease inhibitors (PI) and 95 (44.4%) without PI. Out of these patients, 74.7 used antivirals > 24 months. Age, family history of hypertension, waist circumference, body mass index and triglyceride levels were higher among hypertensive patients. Time of HIV infection, CD4 count, viral load, time and type of antiretroviral regimen were similar in hypertensive and prehypertensive patients. CONCLUSION The high frequency of uncontrolled hypertensive patients and cardiovascular risks in HIV-infected patients point out to the need for preventive and therapeutic measures against hypertension in this group.

Interleukin‐10 and tumour necrosis factor‐alpha serum levels in chronic Chagas disease patients

In Chagas disease, chronically infected individuals may be asymptomatic or may present cardiac or digestive complications, and it is well known that the human immune response is related to different clinical manifestations. Different patterns of cytokine levels have been previously described in different clinical forms of this disease, but contradictory results are reported. Our aim was to evaluate the serum levels of interleukin‐10 and tumour necrosis factor‐alpha in patients with asymptomatic and cardiac Chagas disease. The serum interleukin‐10 levels in patients with cardiomyopathy were higher than those in asymptomatic patients, mainly in those without heart enlargement. Although no significant difference was observed in serum tumour necrosis factor‐alpha levels among the patients, we found that cardiac patients also present high levels of this cytokine, largely those with heart dilatation. Therefore, these cytokines play an important role in chronic Chagas disease cardiomyopathy. Follow‐up investigations of these and other cytokines in patients with chronic Chagas disease need to be conducted to improve the understanding of the immunopathology of this disease.

The +3187A/G HLA-G polymorphic site is associated with polar forms and reactive reaction in leprosy.

Considering that variability in immune response genes has been associated with susceptibility to leprosy and with disease severity, leprosy presents clinicopathological variants that are highly associated with the immune response, HLA‐G has a well‐recognized role in the modulation of the immune response, and polymorphisms at the 3′ untranslated region (UTR) of the HLA‐G gene may influence HLA‐G production, we studied the polymorphic sites at the 3′ UTR of the HLA‐G gene in leprosy and their association with disease severity. We evaluated by sequencing analysis the allele, genotype, and haplotype frequencies of the 3′ UTR HLA‐G polymorphic sites (14‐bpINDEL/+3003C‐T/+3010C‐G/+3027A‐C/+3035C‐T/+3142C‐G/+3187A‐G/+3196C‐G) in 146 individuals presenting reactive leprosy from a highly endemic area, and associated with bacillary load and the type of reactive leprosy. A total of 128 healthy subjects were also studied. Allele, genotype, and haplotype frequencies for the 3′ UTR HLA‐G polymorphisms in leprosy patients did not differ from those observed in healthy donors. The +3187A allele was responsible for protection against the development of multibacillary leprosy in a dominant model (AA + AG)/GG, OR = 0.11, P = 0.018), and the +3187A allele and +3187A‐A genotype were overrepresented in type II reactive leprosy reaction. The effect of genetic factors on leprosy susceptibility may be hidden by environmental components in highly endemic areas. The HLA‐G + 3187A polymorphic site, which is related to unstable mRNA production, was associated with the development of polar forms of leprosy and reactive leprosy reaction.