NINJURIN1 single nucleotide polymorphism and nerve damage in leprosy.

UNLABELLED: Leprosy, a chronic infectious disease caused by Mycobacterium leprae, can damage the peripheral nervous system and represents one of the leading causes of nontraumatic neuropathy in some developing countries. The NINJURIN1 is a cell adhesion molecule that provides suitable substrates for repair of Schwann cells after peripheral nerve injury. The single nucleotide polymorphism NINJ1, is the result of a transversion of an adenine to a nucleotide polymorphic cytokine (A→C), responsible for an amino acid exchange of asparagine to alanine at position 110 of the protein (asp110ala). OBJECTIVES: The aim of this study was to investigate the importance of the polymorphism in the NINJ1 gene for neural impairment during leprosy course. METHODS: A single nucleotide polymorphism (asp110ala) was searched in 218 leprosy patients and 244 non-leprosy subjects using a polymerase chain reaction/restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: No statistical differences were observed in the frequency of the asp110ala SNP between leprosy patients versus non-leprosy and multibacillary versus paucibacillary clinical forms. The C allele (ala110) is increased among patients exhibiting nerve impairment (p=0.0379). Also, leprosy patients with the CC genotype (ala/ala) had a higher risk (OR=4.21) of developing nerve disability when compared those carrying the AA genotype (asp/asp) (OR=0.69). CONCLUSION: Our results show an association between the studied C allele (ala110) and damage nerve in leprosy patients. SIGNIFICANCE: Ninjurin analysis showed that asp110ala could be a valuable prognostic marker, since C allele (ala110) have increased susceptibility to nerve damage.

Mycobacterium tuberculosis in a HIV-1-infected population from Southeastern Brazil in the HAART era.

OBJECTIVE: To evaluate retrospectively the microbiological profile of Mycobacterium species isolated from HIV-infected patients attending the HIV/TB reference health care units in São José do Rio Preto, Brazil. METHOD: Retrospective evaluation of all HIV-1 positive patients whose IAL-SJRP laboratorial analysis was positive for Mycobacterium sp. after diagnosis of HIV Infection, from January 2000 to December 2006. RESULTS: Of 198 patients, acid-fast staining detected mycobacteria early in 41%. Culture revealed 52.5% to be infected with Mycobacterium tuberculosis (MT). 42.4% had non-tuberculous mycobacteria (NTM) and 5.1% had MT/NTM positive cultures. Eleven per cent of MT strains were resistant to at least one of the antimycobacterial drugs and 3.1% were multidrug resistant. 39.4% of isolated mycobacteria were NTM species. CONCLUSION: Our data may serve as a starting point for further comparisons with other Brazilian regions and other developing countries. The data may provide important clues to the future understanding, prevention and control of such co-infections around the world.

Population genetics of GYPB and association study between GYPB*S/s polymorphism and susceptibility to P. falciparum infection in the Brazilian Amazon.

BACKGROUND: Merozoites of Plasmodium falciparum invade through several pathways using different RBC receptors. Field isolates appear to use a greater variability of these receptors than laboratory isolates. Brazilian field isolates were shown to mostly utilize glycophorin A-independent invasion pathways via glycophorin B (GPB) and/or other receptors. The Brazilian population exhibits extensive polymorphism in blood group antigens, however, no studies have been done to relate the prevalence of the antigens that function as receptors for P. falciparum and the ability of the parasite to invade. Our study aimed to establish whether variation in the GYPB*S/s alleles influences susceptibility to infection with P. falciparum in the admixed population of Brazil. METHODS: Two groups of Brazilian Amazonians from Porto Velho were studied: P. falciparum infected individuals (cases); and uninfected individuals who were born and/or have lived in the same endemic region for over ten years, were exposed to infection but have not had malaria over the study period (controls). The GPB Ss phenotype and GYPB*S/s alleles were determined by standard methods. Sixty two Ancestry Informative Markers were genotyped on each individual to estimate admixture and control its potential effect on the association between frequency of GYPB*S and malaria infection. RESULTS: GYPB*S is associated with host susceptibility to infection with P. falciparum; GYPB*S/GYPB*S and GYPB*S/GYPB*s were significantly more prevalent in the in the P. falciparum infected individuals than in the controls (69.87% vs. 49.75%; P<0.02). Moreover, population genetics tests applied on the GYPB exon sequencing data suggest that natural selection shaped the observed pattern of nucleotide diversity. CONCLUSION: Epidemiological and evolutionary approaches suggest an important role for the GPB receptor in RBC invasion by P. falciparum in Brazilian Amazons. Moreover, an increased susceptibility to infection by this parasite is associated with the GPB S+ variant in this population.

Evaluation of the naturally acquired antibody immune response to the Pv200L N-terminal fragment of Plasmodium vivax merozoite surface protein-1 in four areas of the Amazon Region of Brazil.

Frequency and levels of IgG antibodies to an N-terminal fragment of the Plasmodium vivax MSP-1 (Pv200L) protein, in individuals naturally exposed to malaria in four endemic areas of Brazil, were evaluated by enzyme-linked immunosorbent assay. Plasma samples of 261 P. vivax-infected individuals from communities of Macapá, Novo Repartimento, Porto Velho, and Plácido de Castro in the Amazonian region with different malaria transmission intensities. A high mean number of studied individuals (89.3%) presented with antibodies to the Pv200L that correlated with the number of previous malaria infections; there were significant differences in the frequency of the responders (71.9-98.7) and in the antibody levels (1:200-1:51,200) among the four study areas. Results of this study provide evidence that Pv200L is a naturally immunogenic fragment of the PvMSP-1 and is associated with the degree of exposure to parasites. The fine specificity of antibodies to Pv200L is currently being assessed.

Plasmodium vivax circumsporozoite genotypes: a limited variation or new subspecies with major biological consequences?

BACKGROUND: Plasmodium vivax circumsporozoite variants have been identified in several geographical areas. The real implication of the genetic variation in this region of the P. vivax genome has been questioned for a long time. Although previous studies have observed significant association between VK210 and the Duffy blood group, we present here that evidences of this variation are limited to the CSP central portion. METHODS: The phylogenetic analyses were accomplished starting from the amplification of conserved domains of 18 SSU RNAr and Cyt B. The antibodies responses against the CSP peptides, MSP-1, AMA-1 and DBP were detected by ELISA, in plasma samples of individuals infected with two P. vivax CS genotypes: VK210 and P. vivax-like. RESULTS: These analyses of the two markers demonstrate high similarity among the P. vivax CS genotypes and surprisingly showed diversity equal to zero between VK210 and P. vivax-like, positioning these CS genotypes in the same clade. A high frequency IgG antibody against the N- and C-terminal regions of the P. vivax CSP was found as compared to the immune response to the R- and V- repetitive regions (p = 0.0005, Fisher's Exact test). This difference was more pronounced when the P. vivax-like variant was present in the infection (p = 0.003, Fisher's Exact test). A high frequency of antibody response against MSP-1 and AMA-1 peptides was observed for all P. vivax CS genotypes in comparison to the same frequency for DBP. CONCLUSIONS: This results target that the differences among the P. vivax CS variants are restrict to the central repeated region of the protein, mostly nucleotide variation with important serological consequences.

Plasmodium vivax circumsporozoite variants and Duffy blood group genotypes in the Brazilian Amazon region.

The circumsporozoite protein (CSP) of the Plasmodium vivax infective sporozoite is considered to be a major target for the development of recombinant malaria vaccines. The Duffy blood group molecule acts as the red blood cell receptor for P. vivax. We review the frequency of P. vivax CSP variants and report their association with the Duffy blood group genotypes from Brazilian Amazon patients carrying P. vivax malaria. Peripheral blood samples were collected from 155 P. vivax-infected individuals from five Brazilian malaria-endemic areas. The P. vivax CSP variants and the Duffy blood group genotypes were assessed using PCR/RFLP. In single infections, the VK210 variant was the commonest followed by the P. vivax-like variant. The typing of P. vivax indicated that the frequency of variants among the study areas was significantly different from one to another. This is the first detection of the VK247 and P. vivax-like variant in single infections in endemic areas of Brazil. Association of the CSP P. vivax variants with the heterozygous Duffy blood group system genotype was significant for VK210 single infection. These observations provide additional data on the Plasmodium-host interactions concerning the Duffy blood group and P. vivax capability of causing human malaria.

Hanseníase: comparação entre a classificação operacional no sistema de informação de agravos de notificação e o resultado da baciloscopia / Leprosy: agreement between the operational classification data obtained from the SINAN and bacilloscopic examination

O estudo objetivou comparar a classificação operacional paucibacilar e multibacilar, descrita no Sistema de Informação de Agravos de Notificação-SINAN, com o resultado da baciloscopia (positivo/negativo) obtido pelo serviço de referência regional, Instituto Adolfo Lutz de São José do Rio Preto-SP. Trata-se de estudo descritivo e retrospectivo que utilizou como fonte de coleta, o livro de registros do Instituto Adolfo Lutz e a base de dados do SINAN dos casos notificados nos 32 municípios da microrregião de São José do Rio Preto, no período de 02/01/2004 a 31/12/2005. De 231 casos notificados, 1,7% (n=4) eram conhecidos apenas pelo Instituto Adolfo Lutz; 42% (n=97) apenas pelo SINAN e 56,3% (n=130) pelas duas fontes de informação. Destes, 19,2% (25/130) tinham baciloscopia positiva, sendo 0,8% (1/130) paucibacilar; 78,3% (105/130) tinham baciloscopia negativa, sendo 43,3% (58/130) multibacilar. Os casos conhecidos apenas pelo Instituto Adolfo Lutz (n=4) tinham baciloscopia positiva. Dos 42% (n=97) conhecidos apenas pelo SINAN, 54,2% foram classificados como multibacilar. Encontrou-se as seguintes discordâncias: um (0,8%) caso com baciloscopia positiva e classificado como paucibacilar; quatro casos (1,7%) com baciloscopia positiva que não foram notificados no SINAN e 42% (n=97) não realizaram baciloscopia no Instituto Adolfo Lutz. Conclui-se que o laboratório deveria estar integrado com a operacionalização das ações do programa de controle da hanseníase, em especial para que o exame de baciloscopia colabore efetivamente com o diagnóstico clínico primando assim para a consolidação de uma rede de assistência mais completa

Duffy blood group gene polymorphisms among malaria vivax patients in four areas of the Brazilian Amazon region.

BACKGROUND: Duffy blood group polymorphisms are important in areas where Plasmodium vivax predominates, because this molecule acts as a receptor for this protozoan. In the present study, Duffy blood group genotyping in P. vivax malaria patients from four different Brazilian endemic areas is reported, exploring significant associations between blood group variants and susceptibility or resistance to malaria. METHODS: The P. vivax identification was determined by non-genotypic and genotypic screening tests. The Duffy blood group was genotyped by PCR/RFLP in 330 blood donors and 312 malaria patients from four Brazilian Amazon areas. In order to assess the variables significance and to obtain independence among the proportions, the Fisher's exact test was used. RESULTS: The data show a high frequency of the FYA/FYB genotype, followed by FYB/FYB, FYA/FYA, FYA/FYB-33 and FYB/FYB-33. Low frequencies were detected for the FYA/FYX, FYB/FYX, FYX/FYX and FYB-33/FYB-33 genotypes. Negative Duffy genotype (FYB-33/FYB-33) was found in both groups: individuals infected and non-infected (blood donors). No individual carried the FYX/FYB-33 genotype. Some of the Duffy genotypes frequencies showed significant differences between donors and malaria patients. CONCLUSION: The obtained data suggest that individuals with the FYA/FYB genotype have higher susceptibility to malaria. The presence of the FYB-33 allele may be a selective advantage in the population, reducing the rate of infection by P. vivax in this region. Additional efforts may contribute to better elucidate the physiopathologic differences in this parasite/host relationship in regions endemic for P. vivax malaria, in particular the Brazilian Amazon region.

Differential antibody responses to Plasmodium falciparum invasion ligand proteins in individuals living in malaria-endemic areas in Brazil and Cameroon.

Antibody responses to malaria invasion ligands and proteins on the merozoite surface have been shown to interfere with red cell invasion and correlate with immunity to malaria. The current study is the first to characterize the antibody responses to EBA-140 and EBA-181, Plasmodium falciparum invasion ligands implicated in the alternative pathways of invasion, in age-matched populations of individuals living in endemic areas in both Brazil and Cameroon. Antibody responses to the proteins screened were different between populations. The African individuals reacted strongly with most fragments of these two EBAs, while the majority of the individuals from Mato Grosso, Brazil, reacted weakly and those from the Amazon had elevated responses to these EBA proteins. When compared with the responses against MSP-1(19) and EBA-175, it appeared that the Brazilian population has a variable ability to recognize P. falciparum invasion ligand proteins and that these responses are distinct from the African population.

Infecções Hospitalares por Stenotrophomonas maltophilia: aspectos clínico-epidemiológicos, microbiológicos e de resistência antimicrobiana / Hospital Infection by Stenotrophomonas maltophilia: clinical-epidemiological, microbiology aspects and antimicrobial resistance

A bactéria Stenotrophomonas maltophilia está ocupando papel importante no cenário das infecções hospitalares.É considerada patógeno emergente, sendo responsável por elevada morbi-letalidade, principalmente em pacientes sob terapia imunossupressora ou antibioticoterapia prolongada e de amplo espectro. Outros fatores de risco significativos incluem: longo tempo de internação, procedimentos invasivos, idade avançada e procedimento cirúrgico prévio. O tratamento dessas infecções tem sido objeto de preocupação, uma vez que a bactéria exibe resistência intrínseca à maioria dos antimicrobianos disponíveis, caracterizando-se assim como microrganismo multirresistente. Metodologias de tipagem fenotípica e genotípica têm sido utilizadas na tentativa de definir padrões de transmissão e disseminação intra- e inter-hospitalar, e na comunidade. Nesse contexto, a metodologia molecular é considerada o recurso técnico mais promissor no estabelecimento da epidemiologia desse importante patógeno

Genetic structure of Plasmodium falciparum populations in the Brazilian Amazon region.

After a major increase in incidence between the 1970s and the 1990s, the Brazilian Amazon region now accounts for the most cases of Plasmodium falciparum malaria in the Americas. Polymorphism of 10 microsatellite loci in the P. falciparum genome was studied in 196 isolates obtained from 5 populations in the region. There was significant multilocus linkage disequilibrium, particularly within populations with lower proportions of mixed-genotype infections. However, most multilocus genotypes in different isolates were distinct, and there was no evidence of any recent epidemic expansion of particular clones. Genetic divergence between populations was very substantial but did not fit a simple model of isolation by distance. Thus, different foci of P. falciparum in Brazil are quite independent, with distinct population structures and minimal gene flow, a finding that has implications for strategies to control infection and to contain the spread of drug resistance at a regional level.