BACKGROUND Leprosy is a chronic infectious disease caused by the obligate intracellular bacillus Mycobacterium leprae. Because leprosy diagnosis is complex and requires professional expertise, new tools and methodologies are needed to detect cases in early stages and prevent transmission. The M. leprae genome contains mce1A, which encodes a putative mammalian cell entry protein (Mce1A). We hypothesised that the presence of Mce1A on the cell surface could be detected by the host's immune system. OBJECTIVE The aim of this study was to evaluate antibody responses against the Mce1A protein in leprosy patients, household contacts of patients, and the general population to present an addition tool for leprosy diagnosis. METHODS A cross-sectional study involving 89 volunteers [55 leprosy cases, 12 household contacts (HHC) and 22 endemic controls (EC)] was conducted at Couto Maia Hospital, in Salvador, Bahia (BA), Brazil. RESULTS The median anti-Mce1A IgA was significantly higher in multibacillary (MB) and paucibacillary (PB) cases than in EC (p < 0.0001). A similar trend was observed in IgM levels, which were significantly higher in both MB (p < 0.0001) and PB (p = 0.0006) groups compared to in EC individuals. The greatest differences were observed for IgG class-specific antibodies against Mce1A. The median levels of MB and PB were significantly higher compared to both controls HHC and EC (MB or PB vs EC, MB vs HHC p < 0.0001; PB vs HHC, p = 0.0013). Among leprosy cases, IgG enzyme-linked immunosorbent assay sensitivity and specificity were 92.7% and 97.1%, respectively. IgG positivity was confirmed in 92.1% and 94.1% of MB and PB patients, respectively. CONCLUSION This novel diagnostic approach presents an easy, non-invasive, and inexpensive method for leprosy screening, which may be applicable in endemic areas.

Abstract Background: TB patients co-infected with HIV have worse treatment outcomes than non-coinfected patients. How clinical characteristics of TB and socioeconomic characteristics influence these outcomes is poorly understood. Here, we use polytomous regression analysis to identify clinical and epidemiological characteristics associated with unfavorable treatment outcomes among TB-HIV co-infected patients in Brazil. Methods: TB-HIV cases reported in the Brazilian information system (SINAN) between January 1, 2001 and December 31, 2011 were identified and categorized by TB treatment outcome (cure, default, death, and development of MDR TB). We modeled treatment outcome as a function of clinical characteristics of TB and patient socioeconomic characteristics by polytomous regression analysis. For each treatment outcome, we used cure as the reference outcome. Results: Between 2001 and 2011, 990,017 cases of TB were reported in SINAN, of which 93,147 (9.4%) were HIV co-infected. Patients aged 15–19 (OR = 2.86; 95% CI: 2.09–3.91) and 20–39 years old (OR = 2.30; 95% CI: 1.81–2.92) were more likely to default on TB treatment than those aged 0–14 years old. In contrast, patients aged ≥60 years were more likely to die from TB (OR = 2.22; 95% CI: 1.43–3.44) or other causes (OR = 2.86; 95% CI: 2.14–3.83). Black patients were more likely to default on TB treatment (OR = 1.33; 95% CI: 1.22–1.44) and die from TB (OR = 1.50; 95% CI: 1.29–1.74). Finally, alcoholism was associated with all unfavorable outcomes: default (OR = 1.94; 95% CI: 1.73–2.17), death due to TB (OR = 1.46; 95% CI: 1.25–1.71), death due to other causes (OR = 1.38; 95% CI: 1.21–1.57) and MDR-TB (OR = 2.29; 95% CI: 1.46–3.58). Conclusions: Socio-economic vulnerability has a significant effect on treatment outcomes among TB-HIV co-infected patients in Brazil. Enhancing social support, incorporation of alcohol abuse screening and counseling into current TB surveillance programs and targeting interventions to specific age groups are interventions that could improve treatment outcomes.

Abstract: The lipid-rich cell wall of Mycobacterium tuberculosis is a dynamic structure that is involved in the regulation of the transport of nutrients, toxic host-cell effector molecules, and anti-tuberculosis drugs. It is therefore postulated to contribute to the long-term bacterial survival in an infected human host. Accumulating evidence suggests that M. tuberculosis remodels the lipid composition of the cell wall as an adaptive mechanism against host-imposed stress. Some of these lipid species (trehalose dimycolate, diacylated sulphoglycolipid, and mannan-based lipoglycans) trigger an immunopathologic response, whereas others (phthiocerol dimycocerosate, mycolic acids, sulpholipid-1, and di-and polyacyltrehalose) appear to dampen the immune responses. These lipids appear to be coordinately expressed in the cell wall of M. tuberculosis during different phases of infection, ultimately determining the clinical fate of the infection. This review summarizes the current state of knowledge on the metabolism, transport, and homeostatic or immunostatic regulation of the cell wall lipids, and their orchestrated interaction with host immune responses that results in bacterial clearance, persistence, or tuberculosis.

Os profissionais de saúde apresentam risco aumentado de infecção latente da tuberculose (ILTB) em função da exposição ocupacional ao Mycobacterium tuberculosis. O estudo teve como objetivo estimar a prevalência da ILTB e fatores de risco entre profissionais de saúde na atenção primária em cinco cidades brasileiras. Realizamos um estudo transversal entre 2011 e 2013 entre profissionais de saúde na atenção primária, usando um questionário estruturado, e avaliamos a ILTB com o teste Quantiferon-TB Gold In-Tube. A magnitude das associações foi avaliada com o uso de modelos de regressão logística hierárquica. Entre 708 profissionais de saúde, a prevalência de ILTB era 27% (n = 196; IC95%: 24%-31%). Os seguintes fatores mostraram associação positiva com ILTB entre profissionais de saúde na atenção primária: idade > 50 anos (OR = 2,94; IC95%: 1,44-5,99), ausência de cicatriz de BCG (OR = 2,10; IC95%: 1,28-3,43), ex-tabagista (OR = 1,80; IC95%: 1,04-3,11), profissão enfermeiro (OR = 2,97; IC95%: 1,13-7,83), profissão técnico de enfermagem (OR = 3,10; IC95%: 1,26-7,60), profissão agente comunitário de saúde (OR = 2,60; IC95%: 1,06-6,40) e uso irregular de máscaras N95 (OR = 2,51; IC95%: 1,11-5,98). Enquanto isso, os profissionais de saúde que não trabalham em serviços de saúde que dispõem de programa de controle da TB tem menor probabilidade de apresentar ILTB (OR = 0,66; IC95%: 0,45-0,97). O estudo demonstrou risco ocupacional substancial de ILTB entre profissionais de saúde na atenção primária no Brasil. O programa brasileiro de controle da tuberculose, assim como os programas locais, devem focar esses profissionais de saúde, de risco elevado, através de atividades educativas, assim como, equipamento de proteção individual melhor para prevenir a aquisição de novos casos de infecção pela tuberculose.

Health care workers (HCW) are at increased risk of latent tuberculosis infection (LTBI) from occupational exposure to Mycobacterium tuberculosis. The objective was to determine the prevalence of and risk factors for LTBI among primary HCW in five Brazilian cities. We conducted a cross-sectional study, from 2011 to 2013, among primary HCW, using a structured questionnaire and an evaluated for LTBI using the Quantiferon-TB Gold in-tube test. The magnitude of the associations was assessed using hierarchical logistic regression models. Among 708 HCW, the LTBI prevalence was 27% (n = 196; 95%CI: 24%-31%). We found that the following factors were positively associated with LTBI in primary HCW: age > 50 years (OR = 2.94; 95%CI: 1.44-5.99), absence of a BCG scar (OR = 2.10; 95%CI: 1.28-3.43), self-reported ex-smoker status (OR = 1.80; 95%CI: 1.04-3.11), being a nurse (OR = 2.97; 95%CI: 1.13-7.83), being a nurse technician (OR = 3.10; 95%CI: 1.26-7.60), being a community health agent (OR = 2.60; 95%CI: 1.06-6.40), and irregular use of N95 masks (OR = 2.51; 95%CI: 1.11-5.98). In contrast, HCWs who do not work in health care facilities with a TB control program were less likely to have LTBI (OR = 0.66; 95%CI: 0.45-0.97). This study demonstrated a substantial occupational risk of LTBI among primary HCW in Brazil. The Brazilian TB control program, as well as local programs, need to target these high-risk HCW with education, as well as with better personal protective equipment to prevent acquisition of new TB infection.

Los profesionales de salud presentan un riesgo aumentado de infección latente de la tuberculosis (ILTB), en función de la exposición ocupacional al Mycobacterium tuberculosis. El objetivo del estudio fue estimar la prevalencia de la ILTB y sus factores de riesgo entre profesionales de salud en la atención primaria en cinco ciudades brasileñas. Realizamos un estudio transversal entre 2011 y 2013 entre profesionales de salud en la atención primaria, usando un cuestionario estructurado, y evaluamos la ILTB con el test Quantiferon-TB Gold In-Tube. La magnitud de las asociaciones fue evaluada con el uso de modelos de regresión logística jerárquica. Entre 708 profesionales de salud, la prevalencia de ILTB era 27% (n = 196; IC95%: 24%-31%). Los siguientes factores mostraron una asociación positiva con ILTB entre profesionales de salud en la atención primaria: edad > 50 años (OR = 2,94; IC95%: 1,44-5,99), ausencia de cicatriz de BCG (OR = 2,10; IC95%: 1,28-3,43), ex-fumador (OR = 1,80; IC95%: 1,04-3,11), profesión enfermero (OR = 2,97; IC95%: 1,13-7,83), profesión técnico de enfermería (OR = 3,10; IC95%: 1,26-7,60), profesión agente comunitario de salud (OR = 2,60; IC95%: 1,06-6,40) y uso irregular de máscaras N95 (OR = 2,51; IC95%: 1,11-5,98). Por otra parte, los profesionales de salud que no trabajan en servicios de salud que disponen de programa de control de la TB tienen una menor probabilidad de presentar ILTB (OR = 0,66; IC95%: 0,45-0,97). El estudio demostró riesgo ocupacional substancial de ILTB entre profesionales de salud en la atención primaria en Brasil. El programa brasileño de control de la tuberculosis, así como los programas locales, deben centrarse en esos profesionales de salud, de riesgo elevado, a través de actividades educativas, así como un mejor equipamiento de protección individual para prevenir el surgimiento de nuevos casos de infección por tuberculosis.

Os profissionais de saúde apresentam risco aumentado de infecção latente da tuberculose (ILTB) em função da exposição ocupacional ao Mycobacterium tuberculosis. O estudo teve como objetivo estimar a prevalência da ILTB e fatores de risco entre profissionais de saúde na atenção primária em cinco cidades brasileiras. Realizamos um estudo transversal entre 2011 e 2013 entre profissionais de saúde na atenção primária, usando um questionário estruturado, e avaliamos a ILTB com o teste Quantiferon-TB Gold In-Tube. A magnitude das associações foi avaliada com o uso de modelos de regressão logística hierárquica. Entre 708 profissionais de saúde, a prevalência de ILTB era 27% (n = 196; IC95%: 24%-31%). Os seguintes fatores mostraram associação positiva com ILTB entre profissionais de saúde na atenção primária: idade > 50 anos (OR = 2,94; IC95%: 1,44-5,99), ausência de cicatriz de BCG (OR = 2,10; IC95%: 1,28-3,43), ex-tabagista (OR = 1,80; IC95%: 1,04-3,11), profissão enfermeiro (OR = 2,97; IC95%: 1,13-7,83), profissão técnico de enfermagem (OR = 3,10; IC95%: 1,26-7,60), profissão agente comunitário de saúde (OR = 2,60; IC95%: 1,06-6,40) e uso irregular de máscaras N95 (OR = 2,51; IC95%: 1,11-5,98). Enquanto isso, os profissionais de saúde que não trabalham em serviços de saúde que dispõem de programa de controle da TB tem menor probabilidade de apresentar ILTB (OR = 0,66; IC95%: 0,45-0,97). O estudo demonstrou risco ocupacional substancial de ILTB entre profissionais de saúde na atenção primária no Brasil. O programa brasileiro de controle da tuberculose, assim como os programas locais, devem focar esses profissionais de saúde, de risco elevado, através de atividades educativas, assim como, equipamento de proteção individual melhor para prevenir a aquisição de novos casos de infecção pela tuberculose.

Health care workers (HCW) are at increased risk of latent tuberculosis infection (LTBI) from occupational exposure to Mycobacterium tuberculosis. The objective was to determine the prevalence of and risk factors for LTBI among primary HCW in five Brazilian cities. We conducted a cross-sectional study, from 2011 to 2013, among primary HCW, using a structured questionnaire and an evaluated for LTBI using the Quantiferon-TB Gold in-tube test. The magnitude of the associations was assessed using hierarchical logistic regression models. Among 708 HCW, the LTBI prevalence was 27% (n = 196; 95%CI: 24%-31%). We found that the following factors were positively associated with LTBI in primary HCW: age > 50 years (OR = 2.94; 95%CI: 1.44-5.99), absence of a BCG scar (OR = 2.10; 95%CI: 1.28-3.43), self-reported ex-smoker status (OR = 1.80; 95%CI: 1.04-3.11), being a nurse (OR = 2.97; 95%CI: 1.13-7.83), being a nurse technician (OR = 3.10; 95%CI: 1.26-7.60), being a community health agent (OR = 2.60; 95%CI: 1.06-6.40), and irregular use of N95 masks (OR = 2.51; 95%CI: 1.11-5.98). In contrast, HCWs who do not work in health care facilities with a TB control program were less likely to have LTBI (OR = 0.66; 95%CI: 0.45-0.97). This study demonstrated a substantial occupational risk of LTBI among primary HCW in Brazil. The Brazilian TB control program, as well as local programs, need to target these high-risk HCW with education, as well as with better personal protective equipment to prevent acquisition of new TB infection.

Los profesionales de salud presentan un riesgo aumentado de infección latente de la tuberculosis (ILTB), en función de la exposición ocupacional al Mycobacterium tuberculosis. El objetivo del estudio fue estimar la prevalencia de la ILTB y sus factores de riesgo entre profesionales de salud en la atención primaria en cinco ciudades brasileñas. Realizamos un estudio transversal entre 2011 y 2013 entre profesionales de salud en la atención primaria, usando un cuestionario estructurado, y evaluamos la ILTB con el test Quantiferon-TB Gold In-Tube. La magnitud de las asociaciones fue evaluada con el uso de modelos de regresión logística jerárquica. Entre 708 profesionales de salud, la prevalencia de ILTB era 27% (n = 196; IC95%: 24%-31%). Los siguientes factores mostraron una asociación positiva con ILTB entre profesionales de salud en la atención primaria: edad > 50 años (OR = 2,94; IC95%: 1,44-5,99), ausencia de cicatriz de BCG (OR = 2,10; IC95%: 1,28-3,43), ex-fumador (OR = 1,80; IC95%: 1,04-3,11), profesión enfermero (OR = 2,97; IC95%: 1,13-7,83), profesión técnico de enfermería (OR = 3,10; IC95%: 1,26-7,60), profesión agente comunitario de salud (OR = 2,60; IC95%: 1,06-6,40) y uso irregular de máscaras N95 (OR = 2,51; IC95%: 1,11-5,98). Por otra parte, los profesionales de salud que no trabajan en servicios de salud que disponen de programa de control de la TB tienen una menor probabilidad de presentar ILTB (OR = 0,66; IC95%: 0,45-0,97). El estudio demostró riesgo ocupacional substancial de ILTB entre profesionales de salud en la atención primaria en Brasil. El programa brasileño de control de la tuberculosis, así como los programas locales, deben centrarse en esos profesionales de salud, de riesgo elevado, a través de actividades educativas, así como un mejor equipamiento de protección individual para prevenir el surgimiento de nuevos casos de infección por tuberculosis.

Approximately 10% of the Brazilian indigenous population lives in the state of Mato Grosso do Sul (MS), where a large number of new cases of tuberculosis (TB) are reported. This study was conducted to assess TB occurrence, transmission and the utility of TB diagnosis based on the Ogawa-Kudoh (O-K) culture method in this remote population. The incidence of TB was estimated by a retrospective review of the surveillance data maintained by the Notifiable Diseases Surveillance System for the study region. The TB transmission pattern among indigenous people was assessed by genotyping Mycobacterium tuberculosis isolates using the IS 6110restriction fragment length polymorphism (RFLP) technique. Of the 3,093 cases identified from 1999-2001, 610 (~20%) were indigenous patients (average incidence: 377/100,000/year). The use of the O-K culture method increased the number of diagnosed cases by 34.1%. Of the genotyped isolates from 52 indigenous patients, 33 (63.5%) belonged to cluster RFLP patterns, indicating recently transmitted TB. These results demonstrate high, on-going TB transmission rates among the indigenous people of MS and indicate that new efforts are needed to disrupt these current transmissions.

The epidemiology of urinary tract infections (UTI) by Staphylococcus saprophyticus has not been fully characterised and strain typing methods have not been validated for this agent. To evaluate whether epidemiological relationships exist between clusters of pulsed field gel-electrophoresis (PFGE) genotypes of S. saprophyticus from community-acquired UTI, a cross-sectional surveillance study was conducted in the city of Rio de Janeiro, Brazil. In total, 32 (16%) female patients attending two walk-in clinics were culture-positive for S. saprophyticus. Five PFGE clusters were defined and evaluated against epidemiological data. The PFGE clusters were grouped in time, suggesting the existence of community point sources of S. saprophyticus. From these point sources, S. saprophyticus strains may spread among individuals.

This study provides the first description of healthcare-associated infections with Escherichia coli clonal group A (CgA) isolates in Latin America. Isolates were typed by enterobacterial repetitive intergenic consensus-PCR, pulsed-field gel electrophoresis, E. coli phylogenetic grouping, multilocus sequence typing and fimH single nucleotide polymorphism analysis. Out of 42 E. coli hospital isolates studied, three belonged to E. coli phylogenetic group D and ST69 and had fimH sequences identical to that of the CgA reference strain ATCC BAA-457. E. coli CgA is another potential source of resistant infections in hospitals.

Previous analysis of Pseudomonas aeruginosa class-1 integrons from Rio de Janeiro, Brazil, revealed the blaGES gene in one isolate. We screened isolates of two widespread PFGE genotypes, A and B, at a public hospital in Rio, for the presence of blaGES. The gene was detected in all seven P. aeruginosa isolates belonging to genotype B. Three of the seven genotype-B isolates were resistant to amikacin, aztreonam, ceftazidime, cefepime, ciprofloxacin, gentamicin, imipenem, meropenem, piperacillin-tazobactam and ticarcillin-clavulanic acid. The other four isolates were resistant to all these agents, except gentamicin, imipenem, meropenem and piperacillin-tazobactam. A synergistic effect between ceftazidime and imipenem or clavulanic acid suggested the production of GES-type ESBL.

A tipagem de cepas é uma ferramenta fundamental para a análise epidemiológica molecular e pode fornecer informações importantes sobre a dispersão dos vírus dengue. Neste trabalho, foi realizada a caracterização molecular de amostras de vírus DEN-2 isoladas no Brasil entre 1990-2000, de áreas geograficamente e temporalmente distintas, com o objetivo de investigar a distribuição genética deste sorotipo circulante no país. A reação em cadeia pela polimerase baseada em sítios de restrição específicos (RSS-PCR) apresentou o mesmo padrão para as 52 amostras Brasileiras, mostrando a circulação de apenas uma variante de vírus DEN-2. A análise filogenética utilizando alinhamento progressivo de sequências de 240 nucleotídeos da junção E/NS1 de 15 cepas mostrou que estas pertencem ao genotipo III (genotipo Jamaica).

Strain typing is a critical tool for molecular epidemiological analysis and can provide important information about the spread of dengue viruses. Here, we performed a molecular characterization of DEN-2 viruses isolated in Brazil during 1990-2000 from geographically and temporally distinct areas in order to investigate the genetic distribution of this serotype circulating in the country. Restriction site-specific polymerase chain reaction (RSS)-PCR presented the same pattern for all 52 Brazilian samples, showing the circulation of just one DEN-2 variant. Phylogenetic analysis using progressive pairwise alignments from 240-nucleotide sequences of the E/NS1 junction in 15 isolates showed that they belong to genotype III (Jamaica genotype).

In the last decade, dengue fever (DF) in Brazil has been recognized as an important public health problem, and an increasing number of dengue haemorrhagic fever (DHF) cases have been reported since the introduction of dengue virus type 2 (DEN-2) into the country in 1990. In order to analyze the complete genome sequence of a DEN-2 Brazilian strain (BR64022/98), we designed primers to amplify contiguous segments of approximately 500 base pairs across the entire sequence of the viral genome. Twenty fragments amplified by reverse transcriptase-PCR were cloned, and the complete nucleotide and the deduced amino acid sequences were determined. This constitutes the first complete genetic characterization of a DEN-2 strain from Brazil. All amino acid changes differentiating strains related to the Asian/American-Asian genotype were observed in BR64022/98, indicating the Asiatic origin of the strain.

Na região nordeste do Brasil a doença diarréica na infância continua sendo altamente endêmica. Com o objetivo de determinar a prevalência das diferentes categorias de E. coli diarreiogênica foi realizado um estudo prospectivo de dois anos em dois grandes centros urbanos dessa região. Entre maio de 1997 a junho de 1999, foram examinadas amostras de Escherichia coli isoladas de 237 fezes de crianças com diarréia (217 aguda e 20 persistente casos) e 231 de crianças sem diarréia (controles) atendidas em dois hospitais na região nordeste do Brasil quanto a adesão a células HEp-2 e hibridização com sondas genéticas especîficas para as seis categorias de E. coli diarreiogênica. E. coli que adere difusamente (DAEC) e E. coli enteroagregativa (EAEC) foram as categorias mais frequentemente isoladas tanto em casos como em controles. E. coli enteropatogênica atípica (EPEC) foi isolada tanto em casos (5.5%) como em controles (5.6%). Amostras de E. coli enteropatogênica (EPEC típica), caracterizadas pelo padrão de adesão localizada, hibridização positiva com a sonda EAF e pertencentes aos sorogrupos clássicos foram mais frequentes em casos do que em controles, significantemente relacionadas com diarréia (P = 0.03). Essas amostras constituíram o terceiro patógeno, depois de rotavirus e Shigella spp, com predomínio significantemente maior entre os casos. Concluindo, na região nordeste do Brasil as EPEC respondem por 9% dos casos de diarréia grave em crianças menores de dois anos.

Childhood diarrheal diseases remain highly endemic in northeastern Brazil. The attributable fraction of all diarrheal diseases among children less than 2 years of age due to Escherichia coli was examined in a 2-year prospective study in two large urban centers of Brazil. Between May 1997 and June 1999, fecal E. coli isolates from 237 children with diarrhea (217 acute and 20 persistent cases) and 231 children without diarrhea (controls) attending two hospitals in Northeast Brazil were tested for their pattern of adherence to HEp-2 cells and for colony hybridization with DNA probes specific for the six pathotypes of diarrheagenic E. coli. Enteroinvasive E. coli, enterotoxigenic E. coli and enterohemorrhagic E. coli were not isolated from any children. Diffusely adherent E. coli (DAEC) and enteroaggregative E. coli (EAEC) were the most frequent isolates with similar frequencies from children with or without diarrhea. Atypical EPEC (EAF-negative) strains were isolated with similiar frequency from both cases (5.5%) and controls (5.6%). Enteropathogenic E. coli (typical EPEC) strains, characterized by localized adherence pattern of adherence, hybridization with the EAF probe, and belonging to the classical O serogroups, were significantly associated with diarrhea (P = 0.03). These E. coli strains associated with diarrhea accounted for 9% of all children with diarrhea. Collectively, in Northeast Brazil, E. coli strains comprise a small proportion of severe diarrhea prevalence in children.

Twenty-one Mycobacterium avium multisolates, from ten human immunodeficiency virus-infected patients, were typed by restriction fragment length polymorphism using as marker the IS1245 and characterized by minimum inhibitory concentration for nine different antibiotics. Two out of four patients harboring multisolates with different fingerprint profile, were therefore considered as having a polyclonal infection, since their isolates were taken from sterile site. This result confirms that polyclonal infection caused by M. avium occurs with a nonnegligenciable frequency. Analyzing the multisolates susceptibility profile of each patient it was observed that most of them were infected with strains having appreciably different antimicrobial susceptibility patterns, no matter what the genotypic pattern of the strains was. These results have strong implication for the treatment of the patients.