Bioecological aspects of triatomines and marsupials as wild Trypanosoma cruzi reservoirs in urban, peri-urban and rural areas in the Western Brazilian Amazon.

In the Amazon region, Trypanosoma cruzi transmission cycles involve a great diversity of Triatominae vectors and mammal reservoirs. Some Rhodnius spp. mainly inhabit palm trees that act as microhabitats for hosts and vectors. The current study aimed to describe aspects of the bio-ecology of the vectors and reservoirs of T. cruzi in relation to human populations resident near areas with large quantities of palm trees, in rural, peri-urban and urban collection environments, located in the Western Brazilian Amazon. Rhodnius pictipes and Didelphis marsupialis were respectively the most predominant vector and reservoir, with rates of 71% for R. pictipes and 96.5% for D. marsupialis. The vast majority of T. cruzi isolates clustered with TcI. The most prevalent haplotype was TcI COII1 (69.7%). Mauritia flexuosa and Attalea phalerata were the main ecological indicators of infestation by triatomines. Birds were the most common food source (27,71%). T. cruzi isolated from R. robustus has the haplotype HUM-13, previously detected in a chronic Chagas patient living in the same area. Our results demonstrate the relevance of this study, with the occurrence of elevated infection rates in animals, and suggest the importance of the Amazon zones where there is a risk of infection in humans.

Multidrug-resistant tuberculosis in the Amazonas State, Brazil, 2000-2011.

SETTINGS: Amazonas is facing increasing challenges in tuberculosis (TB) control, with nearly 3000 cases per year, and multidrug-resistant TB (MDR-TB) may jeopardise the TB control programme. OBJECTIVE: To assess the number of MDR-TB cases in the Amazonas and to improve estimates of the burden of TB. DESIGNS: The Brazilian National Mandatory Disease Reporting System (SINAN) and the Brazilian Epidemiological Surveillance System of Multidrug Resistance (TBMR) were searched for MDR-TB cases in the State of Amazonas from 2000 to 2011. RESULTS: Eighty-one MDR-TB cases were notified. The rates of primary MDR-TB, initial MDR-TB during the first treatment regimen and acquired MDR-TB were respectively 3.8%, 13.7% and 82.7%; 26.9% of previously treated patients had ⩾ 4 treatment cycles. The MDR-TB cases reported 263 contacts, only 35.0% of whom were examined. The cure and death rates among the 81 patients with MDR-TB were respectively 45.7% and 25.9%. CONCLUSIONS: The number of MDR-TB cases seems incompatible with the high TB prevalence in the Amazonas. Most patients were unaware of contact with TB patients. TB is endemic in the Amazonas. This highlights the need for improving resistance investigation among all TB cases.

Functional variations in MBL2 gene are associated with cutaneous leishmaniasis in the Amazonas state of Brazil.

Functional variations in the mannose-binding lectin (MBL2) gene causing low levels of serum MBL are associated with susceptibility to numerous infectious diseases. We investigated whether there is genetic association of MBL2 variant alleles with cutaneous leishmaniasis (CL) caused by Leishmania guyanensis. We used PCR-restriction fragment length polymorphism to genotype six MBL2 variants, three in the promoter region and three in the exon 1. An association was noted between the single nucleotide polymorphism -221X/Y of the MBL2 gene and CL (P=2.9 × 10(-6); odds ratio (OR)=1.9 (1.4-2.5) consistent with the hypothesis that the -221X allele confers high risk to development of CL among L. guyanensis-infected individuals. Furthermore, L. guyanensis-infected individuals bearing the codon 57 allele C had a higher risk of developing CL (P=5 × 10(-5); OR=1.9 (1.4-2.6)). The low MBL expressor haplotype LXPB was also associated to CL (P=6 × 10(-4)). This study raises the possibility that functional polymorphisms in MBL2 gene play a role in clinical outcome of Leishmania infection.

Association of TNF -1031 C/C as a potential protection marker for leprosy development in Amazonas state patients, Brazil.

Polymorphisms present in the TNF promoter region has shown to influence the gene transcription. Leprosy displays different clinical manifestations according to the immune responses of the individual infected with Mycobacterium leprae. In this study, we evaluated the single nucleotide polymorphisms (SNPs) -238 G/A (rs361525), -308 G/A (rs1800629), -857 C/T (rs1799724), -863 A/C (rs1800630) and -1031 T/C (rs1799964) in the promoter region of the TNF to see whether these SNPs influence host-susceptibility to leprosy and the different clinical manifestation. Nucleotide sequencing was performed with DNA samples from 108 leprosy patients and 253 control subjects. An association between -1031 C/C genotype and protection from leprosy was observed when leprosy patients were compared to controls (OR 0.11; 95% CI=0.01-0.82; p=0.012). The -857 C/T genotype may be associated with susceptibility to leprosy (OR=1.81; 95% CI=1.09-3.00; p=0.028). Similar genotype and allele frequencies for the SNPs -308 G/A and -238 G/A were observed between leprosy patients and control subjects. Altogether, TNF polymorphisms in the promoter region may be predictive of leprosy outcome.

Primary drug resistance among pulmonary treatment-naïve tuberculosis patients in Amazonas State, Brazil.

BACKGROUND: Multidrug-resistant tuberculosis (MDR-TB) is the main indicator of previous treatment in tuberculosis (TB) patients. MDR-TB among treatment-naïve patients indicates infection with drug-resistant Mycobacterium tuberculosis strains, and such cases are considered primary drug-resistant cases. OBJECTIVE: To estimate the prevalence of drug resistance in pulmonary TB (PTB) treatment-naïve patients and to identify the socio-demographic and clinical characteristics of the resistant population. METHODS: A total of 205 treatment-naïve PTB patients from Manaus, Amazonas State, Brazil, were enrolled. Drug susceptibility testing (DST) was performed on all positive mycobacterial cultures using the 1% proportion method. RESULTS: Positive M. tuberculosis cultures were obtained from only 175 patients for DST. The prevalence of primary MDR-TB was 1.7% (3/175); 14.3% (25/175) of the cultures presented resistance to at least one of the drugs. Resistance to streptomycin, isoniazid, rifampicin and ethambutol was respectively 8.6%, 6.9%, 3.4% and 2.3%. An association between TB patients with resistance to more than one drug and known previous household contact with a TB patient was observed (P= 0.008, OR 6.7, 95%CI 1.2-67.3). CONCLUSIONS: Although the prevalence of primary MDR-TB currently is relatively low, it may become a major public health problem if tailored treatment is not provided, as resistance to more than one drug is significantly associated with household contact.

Polymorphisms assessment in the promoter region of IL12RB2 in Amazon leprosy patients.

Leprosy displays a wide clinical spectrum that is dependent of the type of immune response. We investigate here whether polymorphisms in the promoter region of the IL12RB2 gene are associated with susceptibility or resistance to clinical forms of leprosy. Nucleotide sequencing of the promoter region of IL12RB2 encompassing SNPs -1035 A/G, -1033 T/C, -1023 A/G, -650 del/G and -464 A/G was performed on DNA samples from 105 leprosy patients and 108 healthy controls. However, none of the SNPs were associated with susceptibility to the disease or any of its clinical forms. Similarly, haplotype analysis did not show any association. The haplotype -1035A/-1033T/-650G/-464A was prevalent, and homozygosity for this haplotype was associated to a lower distribution of CD4(+) T cells (p=0.041). Our data suggest that polymorphisms present in the promoter region of IL12RB2 may not be associated with susceptibility to leprosy or its clinical forms.

IL-17 and Regulatory Cytokines (IL-10 and IL-27) in L. braziliensis Infection.

Cutaneous leishmaniasis (CL) is characterized by high production of pro-inflammatory cytokines and development of pathology. Individuals with subclinical L. braziliensis infection (SC) have a positive skin test to leishmania, but do not develop disease. We evaluated whether the downregulation of inflammatory response in SC is mediated by IL-10 and IL-27 and whether IL-17 is associated with control of infection. Participants include SC individuals, patients with CL and healthy subjects. Cytokines protein and mRNA were detected by ELISA and real-time PCR. IFN-γ and TNF-α levels were higher in CL than in SC group. The IL-10 levels and mRNA for IL-10 were similar in both SC and CL. mRNA for IL-27 was increased in cells from SC after stimulation with L. braziliensis antigen. There was a tendency for increased levels of IL-17 in SC compared to CL. The weak type 1 immune response observed in SC L. braziliensis infection is not because of the regulatory effects of IL-10 and IL-27. The control of Leishmania infection may be mediated by innate immune response with participation of IL-17. The results from this pilot study warrant further larger studies to investigate the potential contributions of IL-17 and IL-27 to the control of L. braziliensis infection.

Influence of single-nucleotide polymorphisms on C-reactive protein levels in chronic kidney disease before and after kidney transplantation.

INTRODUCTION: We sought to evaluate 2 single-nucleotide polymorphisms (SNPs) in the C-reactive protein (CRP) gene promoter region for their effects on CRP levels in chronic kidney disease (CKD) patients before and after a successful kidney transplantation. METHODS: Fifty CKD patients were evaluated before and at the first and second years after the graft. Two SNPs were studied, a bi-allelic (G-->A) at the -409 and a tri-allelic (C-->T-->A) variation at the -390 position in the CRP gene. RESULTS: All patients presented the -409GG genotype. At the -390 position, the "A" allele was not found; there were 15 "CC" patients, 11 "TT" patients, and 24 "CT" patients. CRP levels were different among patients with various genotypes (P < .019). Also the presence of the allele "T" was sufficient to determine differences in CRP levels both in pretransplantation (P = .045) and at 1 year posttransplantation (P = .011), but not at the second year (P = .448). CONCLUSION: SNPs at the -390 position of the CRP gene promoter region influence CRP basal levels in such a way that the "C" allele correlated with the lowest and the "T" with the highest. We did not observe this influence in our patients at the second year posttransplantation.

Rheumatic fever and rheumatic heart disease: genetics and pathogenesis.

Molecular mimicry between streptococcal and human proteins is considered as the triggering factor leading to autoimmunity in rheumatic fever (RF) and rheumatic heart disease (RHD). Here, we present a review of the genetic susceptibility markers involved in the development of RF/RHD and the major immunopathological events underlying the pathogenesis of RF and RHD. Several human leucocyte antigen (HLA) class II alleles are associated with the disease. Among these alleles, HLA-DR7 is predominantly observed in different ethnicities and is associated with the development of valvular lesions in RHD patients. Cardiac myosin is one of the major autoantigens involved in rheumatic heart lesions and several peptides from the LMM (light meromyosin) region were recognized by peripheral and intralesional T-cell clones from RF and RHD patients. The production of TNF-alpha and IFN-gamma from heart-infiltrating mononuclear cells suggests that Th-1 type cytokines are the mediators of RHD heart lesions while the presence of few interleukin-4 producing cells in the valve tissue contributes to the maintenance and progression of the valvular lesions.

Autoimmune hepatitis in Brazil: an overview.

Autoimmune hepatitis is an immune cell-mediated chronic liver disease of unknown cause that leads, when untreated, to cirrhosis and liver failure. Importantly, this disease affects not only adults but children as well. Genetic susceptibility is clearly important and the major susceptibility factor identified up to now is the HLA-DRB1 locus, but other genes may play a role as well. HLA-DRB1 alleles present in South American patients differ from those found in patients in other parts of the world. In addition, we have recently identified two chromosomal regions where additional susceptibility factors may be found in Brazilian patients, namely, the class III MHC region and the 5q31 region where the IL-4 and IL-13 genes are located. This review discusses the current knowledge of the pathogenesis of this autoimmune disease occurring in the setting of an immune-privileged organ, the liver, and compares the data on gene polymorphisms studied in Brazil and in other parts of the world.