The rheumatic heart disease healthcare paradox: disease persistence in slums despite universal healthcare coverage-a provider perspective qualitative study.

OBJECTIVES: Rheumatic heart disease (RHD) is a preventable disease frequently recognized in urban slums. Disease rates in Brazilian slums are incommensurate with the country's economic status and the existence of its universal healthcare system. Our study aimed to investigate what system issues may allow for disease persistence, focusing on issues surrounding access and utilization of primary and specialized healthcare services. STUDY DESIGN: This was a two-part (formative phase followed by implementation phase) qualitative study based on interviews and focus groups and analyzed via content analysis. METHODS: One focus group and 17 in-depth interviews with community health workers, primary care providers, and cardiologists who serve slum residents in Brazil and six interviews with key informants (community health researchers and cardiologists) were performed. Interviews with community health workers and primary care providers were from a single heath post in the neighborhood of Liberdade, a populous and previously unstudied slum in Salvador. Cardiologists were recruited from tertiary care referral hospitals in Salvador. RESULTS: Our findings revealed six major chronological categories/themes of issues and twenty subthemes that patients must overcome to avoid developing RHD or to have it successfully medically managed. Major themes include the effects of living in a slum (1), barriers to access and utilization of primary healthcare services (2), treatment in primary healthcare services (3), access/utilization of specialized healthcare services (4), treatment in specialized healthcare services (5), and certain systemic issues (6). CONCLUSION: Slums make residents sick in a manner of ways, and various bottlenecks impeding medical access to both primary care and specialty care exist, requiring multifaceted interventions. We detail major themes and finally suggest interventions that can allow for the health system to successfully eliminate RHD as a public health concern for slum residents.

A multiplexed, indirect enzyme-linked immunoassay for the detection and differentiation of E. coli from other Enterobacteriaceae and P. aeruginosa from other glucose non-fermenters.

Gram-negative bacteria (GNB) are important causes of community (CA) and hospital (HA)- associated infections. Here we describe the development of an indirect ELISA (I-ELISA), which can be used to detect and differentiate the Enterobacteriaceae Escherichia coli, and glucose non-fermenter Pseudomonas aeruginosa from other GNB species. The I-ELISA utilizes six antibodies for bacterial speciation, which were grouped according to their bacterial targets; Enterobacteriaceae (SL-EntA and CH1810 mAb), Escherichia coli (SL-EcA and 6103-46 mAb), Pseudomonas aeruginosa (SL-PaA and SL-PaB). The six, anti-GNB antibodies were first screened against a panel of well-characterized clinical GNB isolates to optimize assay conditions and to determine individual antibody sensitivity and specificity. When tested against a diverse, blinded panel of 94 GNB clinical isolates, the I-ELISA exhibited the following sensitivity/specificity for each target: Enterobacteriaceae (94.4%/95%), E. coli (82.6%/88.7%), P. aeruginosa (83.3%/96%). An I-ELISA to detect and differentiate the most common GNB pathogens offers advantage in terms of simplicity over diagnostic tests currently used in most clinical settings.

Serum antiphospholipid antibody levels as biomarkers for diagnosis of pulmonary tuberculosis patients.

SETTING: Salvador, Bahia, Brazil. OBJECTIVE: To evaluate the immunoglobulin (Ig)M and total IgG antibody response to cardiolipin (CL), phosphatidylcholine (PTC), phosphatidylethanolamine (PE), phosphatidylinositol (PI) and sulfatide (SL-I) as biosignatures that can be used to diagnose pulmonary tuberculosis (TB) and its applicability for monitoring the efficacy of anti-tuberculosis treatment. DESIGN: Serum samples from 37 adult pulmonary TB patients and 48 controls (16 healthy household contacts, 19 household contacts with latent tuberculous infection [LTBI] and 13 non-TB patients with lung disease) were screened using enzyme-linked immunosorbent assays (ELISAs) for IgM and total IgG against phospholipids. RESULTS: Levels of IgM response to CL, PE and PI, and IgG response to CL, PE, PI and PTC were significantly higher in TB patients than in control groups. Anti-CL IgG had the best performance characteristics, with a sensitivity and specificity of respectively 86.5% and 87.2%. This IgG anti-CL ELISA test detected 86.5% (32/37) of the TB patients, whereas the number detected using sputum smear was only 65.9% (24/37). After anti-tuberculosis treatment, the median value for all anti-phospholipid antibodies decreased significantly compared with baseline values (P < 0.05). CONCLUSION: Our results suggest that the total IgG anti-CL level could be useful to complement conventional bacteriological tests for the rapid diagnosis of adult pulmonary TB.

Diabetes increases the risk of recent-transmission tuberculosis in household contacts in São Paulo, Brazil.

SETTING: A cohort of household contacts of tuberculosis (TB) index cases from four public health clinics in São Paulo, Brazil. OBJECTIVE: To measure the association between diabetes mellitus (DM) among household contacts and recent-transmission TB (RT TB). DESIGN: Index TB cases (n = 263) identified from 2001 to 2002 in São Paulo, whose household contacts (n = 1383) were monitored for active TB until December 2010. RESULTS: From 2001 to 2010, there were 29 cases of RT TB among household contacts (cumulative incidence 2.1%, 95%CI 1.4-2.9). DM in household contacts was associated with RT TB (OR 3.96, 95%CI 1.33-11.79) even after adjustment for human immunodeficiency virus (HIV) status, smoking and alcohol use (adjusted OR [aOR] 3.21, 95%CI 1.01-10.19). HIV infection was also associated with RT TB (OR 6.40, 95%CI 1.40-29.40; aOR 4.81, 95%CI 0.96-24.18). Household contact DM was not associated with non-RT TB (OR 1.27, 95%CI 0.30-5.40). The time to diagnosis of TB was shorter in household contacts with and without DM (P = 0.035) and in household contacts with and without HIV (P = 0.0002). CONCLUSION: Household contact DM was associated with an increased risk of RT TB in a cohort in Brazil, lending support to the active screening of household contacts with DM for TB in Brazil.

Directly observed therapy of tuberculosis in Brazil: associated determinants and impact on treatment outcome.

SETTING: All Brazilian states. OBJECTIVES: To assess the determinants of tuberculosis (TB) in patients undergoing directly observed therapy (DOT) and the impact of DOT on treatment outcomes. DESIGN: This is a cross-sectional study among TB patients aged ⩾18 years conducted in 2011. The primary outcome was the status of DOT received, while the secondary was the outcome of anti-tuberculosis treatment. RESULTS: In 2011, 35 775 (38.3%) subjects received DOT. The odds of receiving DOT were higher in patients with the following characteristics: brown/mestizo patients (OR 1.18, 95%CI 1.14-1.22) and those of other ethnic groups (OR 2.01, 95%CI 1.79-2.27) compared to Whites, alcohol users (OR 1.37, 95%CI 1.28-1.47) and those with mental disorders (OR 1.88, 95%CI 1.54-2.29). The odds of receiving DOT were lower in human immunodeficiency virus positive patients (OR 0.64, 95%CI 0.60-0.68). Patients who did not receive DOT were more likely to default from anti-tuberculosis treatment (OR 0.62, 95%CI 0.57-0.66), die due to TB (OR 0.68, 95%CI 0.61-0.77) and to have unknown treatment outcomes (OR 0.71, 95%CI 0.66-0.76). The adjusted preventable fraction of DOT in the reduction of unfavorable outcomes was 25%. CONCLUSION: Sociodemographic and clinical characteristics are determinants of anti-tuberculosis treatment outcomes in patients undergoing DOT; DOT use led to a 25% reduction in unfavorable outcomes.

Pandemic lineages of extraintestinal pathogenic Escherichia coli.

Pathogenic Escherichia coli strains cause a wide variety of intestinal and extraintestinal infections. The widespread geographical clonal dissemination of intestinal pathogenic E. coli strains, such as E. coli O157:H7, is well recognized, and its spread is most often attributed to contaminated food products. On the other hand, the clonal dissemination of extraintestinal pathogenic E. coli (ExPEC) strains is also recognized, but the mechanism of their spread is not well explained. Here, I describe major pandemic clonal lineages of ExPEC based on multilocus sequence typing (MLST), and discuss possible reasons for their global dissemination. These lineages include sequence type (ST)131, ST393, ST69, ST95, and ST73, which are all associated with both community-onset and healthcare-associated infections, in particular urinary tract infections and bloodstream infections. As with many other types of drug-resistant Gram-negative and Gram-positive bacterial infections, drug-resistant ExPEC infections are recognized to be caused by a limited set of clonal lineages. However, reported observations on these major pandemic lineages suggest that the resistance phenotype is not necessarily the determinant of their clonal dissemination. Both epidemiological factors and their intrinsic biological 'fitness' are likely to contribute. An important public health and clinical concern is that pandemicity itself may be a determinant of progressive drug resistance acquisition by clonal lineages. New research is urgently needed to better understand the epidemiological and biological causes of ExPEC pandemicity.

Treatment outcomes of tuberculosis patients in Brazilian prisons: a polytomous regression analysis.

SETTING: Tuberculosis (TB) is a major public health problem and an important cause of infectious disease-related death in young adults. TB rates are higher in vulnerable populations, including prisoners. OBJECTIVE: To describe the clinical and epidemiological characteristics associated with anti-tuberculosis treatment outcomes in the Brazilian prison population. DESIGN: The study population consisted of prisoners diagnosed with TB identified through the Sistema de Informação de Agravos de Notificação (Information System for Notifiable Diseases) between January 2007 and December 2011. Pearson's χ(2) test was used to compare the proportions and covariates associated with the outcome of interest. These variables were further analysed using the polytomous regression model. RESULTS: Compared to those who completed anti-tuberculosis treatment, prisoners who defaulted from treatment were younger (P < 0.001), less educated (P < 0.001) and more likely to be alcoholic (P < 0.001); they were more likely to have recurrent or relapse TB (P < 0.001) and they were not under directly observed treatment (P < 0.001). Those who died from TB tended to be older (P < 0.001) and alcoholic (P < 0.001); they were also more likely to have received treatment of unknown type (P < 0.001) and to have both pulmonary and extra-pulmonary TB (EPTB). Prisoners who developed multidrug-resistant TB were more likely to experience TB recurrence, return to treatment after default, change treatment centres and have EPTB. CONCLUSION: Our results highlight the need to improve TB control and policies in correctional facilities. Improving treatment outcomes of prisoners will also prevent transmission to other prisoners, their family members, and health professionals.

Longitudinal surveillance for meningitis by Acinetobacter in a large urban setting in Brazil.

The study aim was to describe the emergence of carbapenem resistance and clonal complexes (CC), defined by multilocus sequence typing (MLST), in Acinetobacter baumannii in a surveillance system for meningitis. Starting in 1996 in an urban setting of Brazil, surveillance detected meningitis by Acinetobacter sp for the first time in 2002. Up to 2008, 35 isolates were saved. Carbapenem resistance emerged in 2006, reaching 70% of A. baumannii isolates in 2008, including one that was colistin resistant. A. baumannii belonged to CC113/79 (University of Oxford/Institute Pasteur schemes), CC235/162 and CC103/15. Dissemination of infections resistant to all antimicrobial agents may occur in the future.

Mycobacterium tuberculosis Mce1 protein complex initiates rapid induction of transcription of genes involved in substrate trafficking.

The mammalian cell entry (Mce)1 protein complex has an important role during the initial phase of a Mycobacterium tuberculosis (M. tuberculosis) infection. Murine macrophages were infected with M. tuberculosis H37Rv or Δ-mce1 H37Rv, and total RNA was isolated from the host cells at 15, 30 and 60 min, and 4 and 10 h post-infection. With the aim of studying the role for the Mce1 protein complex on host gene expression, the RNA was hybridized onto 44 K whole-genome microarrays. Selected genes were verified by reverse-transcriptase quantitative PCR (RT-QPCR). 'Transport' was the most overrepresented biological process during the first hour post H37Rv infection. Five genes (Abca1 (21.0-fold), Slc16a10 (3.1-fold), Slc6a12 (17.9-fold), Slc6a8 (2.3-fold) and Nr1h3, (5.5-fold)) involved in substrate trafficking were verified by RT-QPCR to be upregulated by >2-fold 1 h post H37Rv infection. By 1 h post Δ-mce1 H37Rv infection, only Abca1 and Slc6a12 were upregulated by >2-fold. A number of other genes, which may be directly involved in substrate trafficking or share the same transcription, were found to have expression profiles similar to the genes involved in substrate trafficking. The Mce1 protein complex has a significant role in the transcriptional activation of genes involved in substrate trafficking during the initial phase of an M. tuberculosis infection.

Globally dispersed mobile drug-resistance genes in gram-negative bacterial isolates from patients with bloodstream infections in a US urban general hospital.

Mobile drug-resistance genes with identical nucleic acid sequences carried by multidrug-resistant Escherichia coli strains that cause community-acquired infections are becomingly increasingly dispersed worldwide. Over a 2-year period, we analysed gram-negative bacterial (GNB) pathogens from the blood of inpatients at an urban public hospital to determine what proportion of these isolates carried such globally dispersed drug-resistance genes. Of 376 GNB isolates, 167 (44 %) were Escherichia coli, 50 (13 %) were Klebsiella pneumoniae, 25 (7 %) were Pseudomonas aeruginosa, 25 (7 %) were Proteus mirabilis and 20 (5 %) were Enterobacter cloacae; the remainder (24 %) comprised 26 different GNB species. Among E. coli isolates, class 1 integrons were detected in 64 (38 %). The most common integron gene cassette configuration was dfrA17-aadA5, found in 30 (25 %) of 119 drug-resistant E. coli isolates and in one isolate of Moraxella morganii. Extended-spectrum ß-lactamase (ESBL) genes were found in 16 E. coli isolates (10 %). These genes with identical sequences were found in nearly 40 % of bloodstream E. coli isolates in the study hospital, as well as in a variety of bacterial species from clinical and non-clinical sources worldwide. Thus, a substantial proportion of bloodstream infections among hospitalized patients were caused by E. coli strains carrying drug-resistance genes that are dispersed globally in a wide variety of bacterial species.

Severe infection in a lung transplant recipient caused by donor-transmitted carbapenem-resistant Acinetobacter baumannii.

We describe a case of proven donor transmission of carbapenem-resistant Acinetobacter baumannii, which resulted in severe infectious complications after lung transplantation. A single bla(OXA-23) positive strain, belonging to a new multilocus sequence type (ST231), was isolated from donor and recipient, who died 65 days after transplantation. This report highlights the current challenges associated with the potential transmission of multidrug-resistant infections through organ transplantation.

Risk factors for failure to complete a course of latent tuberculosis infection treatment in Salvador, Brazil.

BACKGROUND: Although treatment of latent tuberculosis infection (LTBI) is an essential component of tuberculosis (TB) control in countries such as the United States, it is not widely practiced in most TB-endemic countries. OBJECTIVE: To examine the practice of and adherence to LTBI treatment in a high-risk population in Brazil. DESIGN: We followed household contacts (HHCs) of patients hospitalized with pulmonary TB in Salvador, Brazil, for 6 months after they initiated LTBI treatment with isoniazid (INH). HHCs were asked to return to the hospital once a month for 6 months for follow-up visits and INH refills. RESULTS: Of 101 HHCs who initiated LTBI treatment, 54 (53.5%) completed the 6-month regimen. The risk of treatment non-completion was significantly higher in HHCs who reported side effects to INH (RR 2.69, 95%CI 1.3-5.8, P = 0.01), and in those who had to take two buses for a one-way trip to the hospital (RR 1.8, 95%CI 1.01-3.3, P = 0.04). Of the 101 HHCs, 29 (28.7%) did not return for any follow-up visits; these HHCs were significantly more likely to have a 2-bus commute to the hospital compared to HHCs who completed treatment (OR 20.69, 95%CI 2.1-208.4, P = 0.01). CONCLUSION: Nearly 50% of HHCs at high risk for developing TB completed a 6-month course of LTBI treatment. Completion of LTBI treatment was most affected by medication intolerance and commuting difficulties for follow-up visits.

Analysis of discordance between the tuberculin skin test and the interferon-gamma release assay.

OBJECTIVE: To analyze factors associated with discordance between tuberculin skin test (TST) and interferon-gamma release assay (IGRA) results among household contacts of pulmonary tuberculosis (PTB) patients. DESIGN: TST (purified protein derivative) and IGRA (QuantiFERON-TB Gold) were performed on household contacts of PTB patients diagnosed between 2006 and 2007 in Salvador, Brazil. Discordant test groups were compared with the TST-/IGRA- group. RESULTS: Of 261 household contacts satisfactorily tested by TST, 145 (55.6%) had positive TST results; of 298 satisfactorily tested by IGRA, 127 (43.1%) had positive results. The test agreement was 0.76 (kappa = 0.53, 95%CI 0.43-0.63). Sixty-one (24%) were discordant: 44 (72%) with TST+/IGRA- and 17 (28%) with TST-/IGRA+ results. Compared to the TST-/IGRA- group, the TST+/IGRA- and TST+/IGRA+ groups were significantly more likely to have a chest X-ray showing old lung scars (OR = 6.8, 95%CI 1.3-35.0; OR = 7.4, 95%CI 2.2-24.4, respectively). The TST-/IGRA+ group was exposed to their index cases for significantly longer than the TST-/IGRA- group (OR = 7.2, 95%CI 1.7-29.3). CONCLUSION: The TST+/IGRA- and TST+/IGRA+ groups shared more similar characteristics with each other than with the TST-/IGRA- group. In a setting endemic for TB, TST results appear to be more suitable in the decision to treat latent TB infection.

Reactive nitrogen intermediate susceptibility of Mycobacterium tuberculosis genotypes in an urban setting.

BACKGROUND: Mycobacterium tuberculosis genotypes resistant to reactive nitrogen intermediates (RNI) predominate in certain urban communities, suggesting that this phenotype influences disease transmission. OBJECTIVE: To compare different M. tuberculosis genotypes for resistance to RNI generated in vitro. DESIGN: We genotyped 420 M. tuberculosis isolates from a neighborhood in Sao Paulo, Brazil, and analyzed them for susceptibility to RNI generated in acidified sodium nitrite (ASN) solution. RESULTS: Seventy-one (43%) of 167 recent-infection strains and 68 (43%) of 158 endogenous infection strains showed moderate- to high-level ASN resistance. CONCLUSION: ASN resistance of M. tuberculosis is not necessarily a determining factor for enhanced transmission.

Epidemiology of meningococcal disease in southern Brazil from 1995 to 2003, and molecular characterization of Neisseria meningitidis using multilocus sequence typing.

OBJECTIVE: To describe the epidemiology of meningococcal disease (MD) in southern Brazil. METHODS: Retrospective cohort study among 2215 MD cases reported from 1995 to 2003 in Rio Grande do Sul (RS) State. RESULTS: The overall incidence fell by 50%; the case-fatality rate during this period was 22%. Even so, the incidence of MD remained high after the epidemic period ended in 1999. Together, the age groups of 1-4 years and infants accounted for 54.1% of reported cases with incidences of 11.3/100 000 and 31.3/100 000, respectively; 69.8% of cases were caused by Neisseria meningitidis serogroup B, which increased significantly. There was a significant decrease in serogroup C cases in the whole period. The phenotypes B:4,7:P1.19,15, B:15:P1.7,16 and B:NT:P1.3 caused almost 50% of all serotyped cases. Fifty-six isolates obtained from RS patients during the first non-epidemic year 2000 plus 20 isolates from other southern Brazilian states (Santa Catarina and Paraná), Denmark and France were typed by multilocus sequence typing. Twenty sequence types (STs) were identified, eight of them found only in RS. ST-33 (27%) and ST-259 (18%) were the most frequent; both belong to the ST-32/ET-5 complex. ST-259 cases showed a trend towards higher risk of fatal outcome. ST-259 isolates were not detected among geographic controls or in other studies in Brazil. CONCLUSION: Our data suggest that ST-33 and ST-259 clones and the emergence of the ST-103 isolates contributed to the continued high incidence of MD in RS.

A case of severe pancreatitis complicated by Raoultella planticola infection.

A 45-year-old-male presented with severe pancreatitis. Two bacterial isolates obtained from peritoneal fluid and abdominal purulent secretion were identified to the species level by 15 biochemical tests and four supplementary tests as Raoultella planticola. Identification was confirmed by rpoB gene sequencing. R. planticola is difficult to identify in the clinical laboratory, and the clinical significance of this isolation remains uncharacterized. This is the first report of pancreatitis with a primary infection by R. planticola.

Pseudomonas aeruginosa epidemic strain carrying bla(SPM) metallo-beta-lactamase detected in Rio de Janeiro, Brazil.

The present study was designed to characterize beta-lactamase genes and evaluate polymerase chain reaction (PCR) typing for multidrug-resistant Pseudomonas aeruginosa pulsed-field gel electrophoresis (PFGE) genotype A isolates from Rio de Janeiro, Brazil, collected between April 1999 and March 2000 and one additional isolate collected in June 2002. As reported previously, all of the genotype A isolates produced non-characterized metallo-beta-lactamase. These isolates (22) were screened for the bla(SPM) gene by PCR and dot-blotting. Isolates were typed by PCR fingerprinting with primers RAPD-1, 272, 208, 1290, ERIC-1 and ERIC-2. The bla(SPM) gene was detected in 18 (82%) of the 22 isolates. PCR fingerprinting gave results that correlated with PFGE, except with primer 1290. In Rio de Janeiro and other Brazilian states, nearly all SPM-producing P. aeruginosa isolates belong to a single PFGE type accounting for a large proportion of drug-resistant P. aeruginosa hospital infections. RAPD PCR fingerprinting may be a useful technique to screen for an epidemic multidrug-resistant strain in Brazil.

Survival characteristics of Salmonella enterica serovar Enteritidis in chicken egg albumen.

Salmonella enterica serovar Enteritidis (SE) is a major foodborne pathogen primarily causing human infection through contaminated chicken eggs. To understand how SE survives in chicken egg albumen, we systematically and quantitatively analysed the survival properties of SE in egg albumen and identified factors affecting its survival. Survival assays of SE in egg indicate that egg albumen restricted the growth of SE. A major factor that controlled SE's growth in egg albumen was iron restriction, since egg albumen supplemented with iron allowed SE to grow, and iron acquisition mutants of SE showed decreased survival in egg albumen. In addition, low pH of albumen, high concentrations of bacteria and low incubation temperatures of bacteria with albumen facilitates the survival of SE. Our results suggest that egg albumen uses multiple mechanisms to control SE including iron limitation, surface interaction and possible enzymatic activities.

The changing prevalence of drug-resistant Escherichia coli clonal groups in a community: evidence for community outbreaks of urinary tract infections.

A multidrug-resistant clonal group (CgA) of Escherichia coli was shown to cause half of all trimethoprim-sulphamethoxazole (TMP-SMZ)-resistant urinary tract infections (UTIs) in a college community between October 1999 and January 2000. This second study was conducted to determine the fate of CgA. Urine E. coli isolates from women with UTI, collected between October 2000 and January 2001, were tested for antibiotic susceptibility, O serogroup, ERIC2 PCR and DNA macrorestriction patterns using pulsed-field gel electrophoresis. The proportion of UTIs caused by CgA declined by 38% (P<0.001) but the prevalence of resistance to TMP-SMZ did not change. Six additional clonal groups were identified and these were responsible for 32% of TMP-SMZ-resistant UTIs. The temporal decline in the proportion of UTIs caused by CgA provides evidence that CgA caused a community outbreak of UTI. The fluctuation and occurrence of other E. coli clonal groups in this community suggest that a proportion of community-acquired UTIs may be caused by E. coli disseminated from one or more point sources.