Association of Upper Respiratory Streptococcus pneumoniae Colonization With Severe Acute Respiratory Syndrome Coronavirus 2 Infection Among Adults.

BACKGROUND: Streptococcus pneumoniae interacts with numerous viral respiratory pathogens in the upper airway. It is unclear whether similar interactions occur with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We collected saliva specimens from working-age adults undergoing SARS-CoV-2 molecular testing at outpatient clinics and via mobile community-outreach testing between July and November 2020 in Monterey County, California. After bacterial culture enrichment, we tested for pneumococci by means of quantitative polymerase chain reaction targeting the lytA and piaB genes, and we measured associations with SARS-CoV-2 infection using conditional logistic regression. RESULTS: Analyses included 1278 participants, with 564 enrolled in clinics and 714 enrolled through outreach-based testing. The prevalence of pneumococcal carriage was 9.2% (117 of 1278) among all participants (11.2% [63 of 564] in clinic-based testing and 7.6% [54 of 714] in outreach-based testing). The prevalence of SARS-CoV-2 infection was 27.4% (32 of 117) among pneumococcal carriers and 9.6% (112 of 1161) among noncarriers (adjusted odds ratio [aOR], 2.73 [95% confidence interval (CI): 1.58-4.69). Associations between SARS-CoV-2 infection and pneumococcal carriage were enhanced in the clinic-based sample (aOR, 4.01 [95% CI: 2.08-7.75]) and among symptomatic participants (3.38 [1.35-8.40]), compared with findings within the outreach-based sample and among asymptomatic participants. The adjusted odds of SARS-CoV-2 coinfection increased 1.24-fold (95% CI: 1.00-1.55-fold) for each 1-unit decrease in piaB quantitative polymerase chain reaction cycle threshold value among pneumococcal carriers. Finally, pneumococcal carriage modified the association of SARS-CoV-2 infection with recent exposure to a suspected coronavirus disease 2019 case (aOR, 7.64 [95% CI: 1.91-30.7] and 3.29 [1.94-5.59]) among pneumococcal carriers and noncarriers, respectively). CONCLUSIONS: Associations of pneumococcal carriage detection and density with SARS-CoV-2 suggest a synergistic relationship in the upper airway. Longitudinal studies are needed to determine interaction mechanisms between pneumococci and SARS-CoV-2.

Risk factors for extended-spectrum beta-lactamase (ESBL)-producing E. coli carriage among children in a food animal-producing region of Ecuador: A repeated measures observational study.

BACKGROUND: The spread of antibiotic-resistant bacteria may be driven by human-animal-environment interactions, especially in regions with limited restrictions on antibiotic use, widespread food animal production, and free-roaming domestic animals. In this study, we aimed to identify risk factors related to commercial food animal production, small-scale or "backyard" food animal production, domestic animal ownership, and practices related to animal handling, waste disposal, and antibiotic use in Ecuadorian communities. METHODS AND FINDINGS: We conducted a repeated measures study from 2018 to 2021 in 7 semirural parishes of Quito, Ecuador to identify determinants of third-generation cephalosporin-resistant E. coli (3GCR-EC) and extended-spectrum beta-lactamase E. coli (ESBL-EC) in children. We collected 1,699 fecal samples from 600 children and 1,871 domestic animal fecal samples from 376 of the same households at up to 5 time points per household over the 3-year study period. We used multivariable log-binomial regression models to estimate relative risks (RR) of 3GCR-EC and ESBL-EC carriage, adjusting for child sex and age, caregiver education, household wealth, and recent child antibiotic use. Risk factors for 3GCR-EC included living within 5 km of more than 5 commercial food animal operations (RR: 1.26; 95% confidence interval (CI): 1.10, 1.45; p-value: 0.001), household pig ownership (RR: 1.23; 95% CI: 1.02, 1.48; p-value: 0.030) and child pet contact (RR: 1.23; 95% CI: 1.09, 1.39; p-value: 0.001). Risk factors for ESBL-EC were dog ownership (RR: 1.35; 95% CI: 1.00, 1.83; p-value: 0.053), child pet contact (RR: 1.54; 95% CI: 1.10, 2.16; p-value: 0.012), and placing animal feces on household land/crops (RR: 1.63; 95% CI: 1.09, 2.46; p-value: 0.019). The primary limitations of this study are the use of proxy and self-reported exposure measures and the use of a single beta-lactamase drug (ceftazidime with clavulanic acid) in combination disk diffusion tests for ESBL confirmation, potentially underestimating phenotypic ESBL production among cephalosporin-resistant E. coli isolates. To improve ESBL determination, it is recommended to use 2 combination disk diffusion tests (ceftazidime with clavulanic acid and cefotaxime with clavulanic acid) for ESBL confirmatory testing. Future studies should also characterize transmission pathways by assessing antibiotic resistance in commercial food animals and environmental reservoirs. CONCLUSIONS: In this study, we observed an increase in enteric colonization of antibiotic-resistant bacteria among children with exposures to domestic animals and their waste in the household environment and children living in areas with a higher density of commercial food animal production operations.

Viral hepatitis C pandemic: Challenges and threats to its elimination.

Under the WHO plan, the global elimination of the HCV pandemic is scheduled for 2030. The burden of HCV infection in developed countries is largely borne by people who inject drugs (PWID): new infections and reinfections are related to their risky behaviour. Although safe and sensitive hepatitis C diagnostic tools and directly acting antiviral medication are widely used, major challenges to disease elimination still remain in developed countries, where the WHO plan is in progress. The challenge is in the involvement and engagement of infected PWID. There is a strong need to change our uptake and treatment strategies to address all patients from the risk groups, connect them with the healthcare system and cure them with the vision to eliminate this HCV pandemic.

A novel plasmid-encoded mcr-4.3 gene in a colistin-resistant Acinetobacter baumannii clinical strain.

OBJECTIVES: To identify the molecular mechanism of colistin resistance in an MDR Acinetobacter baumannii clinical strain isolated in 2008 from a meningitis case in Brazil. METHODS: Long- and short-read WGS was used to identify colistin resistance genes in A. baumannii strain 597A with a colistin MIC of 64 mg/L. MS was used to analyse lipid A content. mcr was cloned into pET-26b (+) and transformed into Escherichia coli BL21(λDE3)pLysS for analysis. RESULTS: A novel plasmid (pAb-MCR4.3) harbouring mcr-4.3 within a Tn3-like transposon was identified. The A. baumannii 597A lipid A MS spectra showed a main molecular ion peak at m/z=2034, which indicated the addition of phosphoethanolamine to the lipid A structure. E. coli BL21 transformed with pET-26b-mcr-4.3 gained colistin resistance with a colistin MIC of 8 mg/L. CONCLUSIONS: Colistin resistance in A. baumannii 597A was correlated with the presence of a novel plasmid-encoded mcr-4.3 gene.

Prevalence of ß-Lactam Drug-Resistance Genes in Escherichia coli Contaminating Ready-to-Eat Lettuce.

Thirty-four Escherichia coli isolates from 91 ready-to-eat lettuce packages, obtained from local supermarkets in Northern California, were genotyped by multilocus sequence typing, tested for susceptibility to antimicrobial agents, and screened for ß-lactamase genes. We found 15 distinct sequence types (STs). Six of these genotypes (ST1198, ST2625, ST2432, ST2819, ST4600, and ST5143) have been reported as pathogens found in human samples. Twenty-six (76%) E. coli isolates were resistant to ampicillin, 17 (50%) to ampicillin/sulbactam, 8 (23%) to cefoxitin, and 7 (20%) to cefuroxime. blaCTX-M was the most prevalent ß-lactamase gene, identified in eight (23%) isolates. We identified a class A broad-spectrum ß-lactamase SED-1 gene, blaSED, reported by others in Citrobacter sedlakii isolated from bile of a patient. This study found that fresh lettuce carries ß-lactam drug-resistant E. coli, which might serve as a reservoir for drug-resistance genes that could potentially be transmitted to pathogens that cause human infections.

In utero cytomegalovirus infection and development of childhood acute lymphoblastic leukemia.

It is widely suspected, yet controversial, that infection plays an etiologic role in the development of acute lymphoblastic leukemia (ALL), the most common childhood cancer and a disease with a confirmed prenatal origin in most cases. We investigated infections at diagnosis and then assessed the timing of infection at birth in children with ALL and age, gender, and ethnicity matched controls to identify potential causal initiating infections. Comprehensive untargeted virome and bacterial analyses of pretreatment bone marrow specimens (n = 127 ALL in comparison with 38 acute myeloid leukemia cases in a comparison group) revealed prevalent cytomegalovirus (CMV) infection at diagnosis in childhood ALL, demonstrating active viral transcription in leukemia blasts as well as intact virions in serum. Screening of newborn blood samples revealed a significantly higher prevalence of in utero CMV infection in ALL cases (n = 268) than healthy controls (n = 270) (odds ratio [OR], 3.71, confidence interval [CI], 1.56-7.92, P = .0016). Risk was more pronounced in Hispanics (OR=5.90, CI=1.89-25.96) than in non-Hispanic whites (OR=2.10 CI= 0.69-7.13). This is the first study to suggest that congenital CMV infection is a risk factor for childhood ALL and is more prominent in Hispanic children. Further investigation of CMV as an etiologic agent for ALL is warranted.

Escherichia coli from Commercial Broiler and Backyard Chickens Share Sequence Types, Antimicrobial Resistance Profiles, and Resistance Genes with Human Extraintestinal Pathogenic Escherichia coli.

Escherichia coli recovered from poultry, and extraintestinal pathogenic E. coli (ExPEC), responsible for most cases of urinary tract infection (UTI) and bloodstream infection (BSI) in humans, may share genetic characteristics, suggesting that poultry are a potential source of ExPEC. Here, we compared E. coli isolated from commercial broiler and backyard chickens (n = 111) with ExPEC isolated from patients with community- or hospital-acquired UTI or BSI (n = 149) from Southeast Brazil. Isolates were genotyped by multilocus sequence typing, tested for susceptibility to antimicrobial agents, and screened for ß-lactamase genes. We found that 10 genotypes were shared among poultry and human isolates: sequence type (ST) 10, ST48, ST58, ST88, ST90, ST93, ST131, ST602, ST617, and ST1018. Thirty-five (23%) ExPEC and 35 (31%) poultry E. coli isolates belonged to the shared STs. ST58 and ST88 isolates from human and poultry sources shared identical antimicrobial resistance profiles. blaTEM-1 was the most prevalent ß-lactamase gene, identified in 65 (92%) of 71 ExPEC and 29 (67%) of 43 poultry E. coli that tested positive for ß-lactamase genes. Commercial broiler chicken isolates shared the extended-spectrum ß-lactamase (ESBL) genes blaCTX-M-2,blaCTX-M-8, and blaSHV-2 with human isolates; backyard chicken isolates lacked ESBL genes. In conclusion, several genotypic and phenotypic characteristics were shared between human and poultry E. coli; this suggests that there is potential for transmission of E. coli and antimicrobial resistance genes from poultry to humans, perhaps through environmental contamination, direct contact, or consumption. Additional research is needed to understand the potential direction and pathways of transmission.

[Variations in the detection of congenital Zika syndrome associated with changes in protocolsVariación de la detección del síndrome congénito por el virus del Zika en función de los cambios de los protocolos]. / Variação na detecção da síndrome congênita do Zika em função de alterações em protocolos.

In 2015, Brazil faced a Zika virus epidemic that spread to other countries in the world. As a result, recommendations regarding reporting criteria for congenital Zika syndrome (CZS) were issued in the form of protocols. The frequent changes in these recommendations may have affected clinical management and the access to post-diagnostic support by children who were affected by CZS, but who ended up not being identified. In the present study, 39 cases of CZS reported in the state of Espírito Santo, Brazil, from 2015 to 2016 were re-classified in terms of diagnosis using the current protocol, which is different from the protocol used in 2015. According to this re-classification, only eight out of 36 cases would be confirmed, based on the criterion of two or more signs or symptoms of CZS with or without microcephaly plus positive serologic results. Also, considering the decrease in the head circumference cut-off point defining microcephaly, 17 cases would no longer meet the definition for this condition. Even though the current protocol does not rely on head circumference alone for CZS reporting and confirmation, it should be noted that this is still the main sign considered by health care teams, and therefore the decrease in the cut-off point might have compromised early CZS detection. A review of "ruled out" cases would be advisable in moments of protocol transition to determine whether these cases have been correctly classified.

En el 2015, Brasil enfrentó una epidemia de infección por el virus del Zika que se propagó por varios países del mundo. Posteriormente, se divulgaron recomendaciones acerca de los criterios de notificación de casos del síndrome congénito por el virus del Zika (SCZ) por medio de protocolos. Los cambios frecuentes de esas recomendaciones podrían haber afectado el manejo clínico y el acceso al apoyo posterior al diagnóstico de los niños afectados, pero no identificados. En el presente estudio, se reclasificó el diagnóstico de 39 casos del SCZ notificados en el estado de Espírito Santo en el período 2015-2016, de acuerdo con el protocolo vigente en la actualidad, que es distinto del que regía en el 2015. Por causa de la reclasificación, se confirmaron únicamente ocho de los 36 casos, con observancia del criterio de dos o más signos o síntomas del SCZ acompañados o no de microcefalia y con confirmación serológica. Además, por la disminución del perímetro cefálico que define la microcefalia, 17 casos no correspondieron a esa afección. A pesar de que en el protocolo vigente no se utiliza solamente el perímetro cefálico como criterio para la notificación y confirmación del SCZ, cabe resaltar que este hallazgo es, con todo, la mayor señal para los equipos de salud, puesto que indica un riesgo de falta de detección temprana del SCZ. Convendría examinar los casos "descartados" en el momento de la transición entre protocolos, con el fin de determinar si se clasificaron correctamente.

Persistent Pandemic Lineages of Uropathogenic Escherichia coli in a College Community from 1999 to 2017.

The incidence of drug-resistant community-acquired urinary tract infections (CA-UTI) continues to increase worldwide. In 1999 to 2000, a single lineage of uropathogenic Escherichia coli (UPEC) sequence type 69 (ST69) caused 51% of trimethoprim-sulfamethoxazole-resistant UTI in a Northern California university community. We compared the clonal distributions of UPEC and its impact on antimicrobial resistance prevalence in the same community during two periods separated by 17 years. We analyzed E. coli isolates from urine samples from patients with symptoms of UTI who visited a health service between September 2016 and May 2017 and compared them to UPEC isolates collected similarly between October 1999 and March 2000. Isolates were tested for antimicrobial drug susceptibility and genotyped by multilocus sequence typing. In 1999 to 2000, strains belonging to ST95, ST127, ST73, ST69, ST131, and ST10 caused 125 (56%) of 225 UTI cases, while the same STs caused 148 (64%) of 233 UTI cases in 2016 to 2017. The frequencies of ampicillin resistance and ciprofloxacin resistance rose from 24.4% to 41.6% (P < 0.001) and from 0.9% to 5.1% (P < 0.003), respectively. The six STs accounted for 78.6% and 72.7% of these increases, respectively. Prevalence of drug-resistant UTI in this community appears to be largely influenced by a small set of dominant UPEC STs circulating in the same community 17 years apart. Further research to determine the origin and reasons for persistence of these dominant genotypes is necessary to combat antimicrobial-resistant CA-UTI.

An Enzyme-Mediated Amplification Strategy Enables Detection of ß-Lactamase Activity Directly in Unprocessed Clinical Samples for Phenotypic Detection of ß-Lactam Resistance.

Biochemical assays that can identify ß-lactamase activity directly from patient samples have the potential to significantly improve the treatment of bacterial infections. However, current ß-lactamase probes do not have the sensitivity needed to measure ß-lactam resistance directly from patient samples. Here, we report the development of an instrument-free signal amplification technology, DETECT, that connects the activity of two enzymes in series to effectively amplify the activity of ß-lactamase 40 000-fold, compared to the standard ß-lactamase probe nitrocefin.

Population structure of Streptococcus pneumoniae colonizing children before and after universal use of pneumococcal conjugate vaccines in Brazil: emergence and expansion of the MDR serotype 6C-CC386 lineage.

Objectives: To determine the population structure and change in drug resistance of pneumococci colonizing children before and after the introduction of the 10-valent and 13-valent pneumococcal conjugate vaccines (PCV10/13) in Brazil. Methods: We used MLST to analyse 256 pneumococcal isolates obtained from children aged <6 years before (2009-10; n = 125) and after (2014; n = 131) the introduction of the PCV10 and PCV13. Antimicrobial susceptibility and capsular types were previously determined. Results: We identified 97 different STs. Ninety (35.2%) isolates were related to international clones. The most frequent lineages were serogroup 6-CC724 (where CC stands for clonal complex) and the MDR serotype 6C-CC386 in the pre- and post-PCV10/13 periods, respectively. Penicillin-non-susceptible pneumococci (PNSP) formed 24% and 38.9% of the pre- and post-PCV10/13 isolates, respectively (P = 0.01). In the pre-PCV10/13 period, serotype 14-ST156 was the predominant penicillin-non-susceptible lineage, but it was not detected in the post-PCV10/13 period. Serotype 14-ST156 and serotype 19A-ST320 complex isolates had the highest penicillin and ceftriaxone MICs in the pre- and post-PCV10/13 periods, respectively. In turn, serotype 6C-CC386 comprised almost 30% of the PNSP and over 40% of the erythromycin-resistant isolates (MIC >256 mg/L) in the post-PCV10/13 period. Conclusions: Although PNSP strains were polyclonal, most resistant isolates belonged to a single genotype from each period. Higher erythromycin resistance prevalence (42%) in the post-PCV10/13 period was mainly attributed to MDR serotype 6C-CC386. Ongoing surveillance of pneumococcal clonal composition is important to evaluate PCV use outcomes and to identify factors other than PCVs that drive pneumococcal drug resistance evolution.

The association between community-associated Staphylococcus aureus colonization and disease: a meta-analysis.

BACKGROUND: Colonization with Staphylococcus aureus is a well-defined risk factor for disease in hospitals, which can range from minor skin infections to severe, systemic diseases. However, the generalizability of this finding has not been thoroughly investigated outside of the hospital environment. We aimed to assess the role of S. aureus colonization as a risk factor for disease in the community. METHODS: We performed a meta-analysis of observational studies and searched PubMed for articles published between December 1979 and May 23, 2016. We included cohort, cross-sectional, and case-control studies that reported quantitative estimates of both S. aureus colonization and disease statuses of all study subjects. We excluded studies on recently hospitalized subjects, long-term care facilities, surgery patients, dialysis patients, hospital staff, S. aureus outbreaks, and livestock-associated infections. Our meta-analysis was performed using random-effects analysis to obtain pooled odds ratios (ORs) to compare the odds of S. aureus disease with respect to S. aureus colonization status. RESULTS: We identified 3477 citations, of which 12 articles on 6998 subjects met the eligibility criteria. Overall, subjects colonized with S. aureus were more likely to progress to disease than those who were non-colonized: (OR 1.87, 95% CI 1.21-2.88, n = 7 studies). We observed a larger effect with methicillin-resistant S. aureus colonization (7.06, 4.60-10.84, n = 7 studies). However, the methicillin-sensitive S. aureus colonization was not associated with greater odds of disease (1.20, 0.69-2.06, n = 4 studies). Heterogeneity was present across studies in all of the subgroups: S. aureus (I2 = 95.0%, χ2 = 120.3, p < 0.001), MRSA (I2 = 92.8%, χ2 = 82.8, p = p < 0.001), and MSSA (I2 = 86.3%, χ2 = 21.8, p < 0.001). CONCLUSIONS: While the majority of papers individually support the assumption that colonization is a risk factor for S. aureus disease in the general population, there is marked heterogeneity between studies and further investigation is needed to identify the major sources of this variance. There is a shortage of literature addressing this topic in the community setting and a need for further research on colonization as a focus for disease prevention.

Risk factors associated with cluster size of Mycobacterium tuberculosis (Mtb) of different RFLP lineages in Brazil.

BACKGROUND: Tuberculosis (TB) transmission is influenced by patient-related risk, environment and bacteriological factors. We determined the risk factors associated with cluster size of IS6110 RFLP based genotypes of Mycobacterium tuberculosis (Mtb) isolates from Vitoria, Espirito Santo, Brazil. METHODS: Cross-sectional study of new TB cases identified in the metropolitan area of Vitoria, Brazil between 2000 and 2010. Mtb isolates were genotyped by the IS6110 RFLP, spoligotyping and RDRio. The isolates were classified according to genotype cluster sizes by three genotyping methods and associated patient epidemiologic characteristics. Regression Model was performed to identify factors associated with cluster size. RESULTS: Among 959 Mtb isolates, 461 (48%) cases had an isolate that belonged to an RFLP cluster, and six clusters with ten or more isolates were identified. Of the isolates spoligotyped, 448 (52%) were classified as LAM and 412 (48%) as non-LAM. Our regression model found that 6-9 isolates/RFLP cluster were more likely belong to the LAM family, having the RDRio genotype and to be smear-positive (adjusted OR = 1.17, 95% CI 1.08-1.26; adjusted OR = 1.25, 95% CI 1.14-1.37; crude OR = 2.68, 95% IC 1.13-6.34; respectively) and living in a Serra city neighborhood decrease the risk of being in the 6-9 isolates/RFLP cluster (adjusted OR = 0.29, 95% CI, 0.10-0.84), than in the others groups. Individuals aged 21 to 30, 31 to 40 and > 50 years were less likely of belonging the 2-5 isolates/RFLP cluster than unique patterns compared to individuals < 20 years of age (adjusted OR = 0.49, 95% CI 0.28-0.85, OR = 0.43 95% CI 0.24-0.77and OR = 0. 49, 95% CI 0.26-0.91), respectively. The extrapulmonary disease was less likely to occur in those infected with strains in the 2-5 isolates/cluster group (adjustment OR = 0.45, 95% CI 0.24-0.85) than unique patterns. CONCLUSIONS: We found that a large proportion of new TB infections in Vitoria is caused by prevalent Mtb genotypes belonging to the LAM family and RDRio genotypes. Such information demonstrates that some genotypes are more likely to cause recent transmission. Targeting interventions such as screening in specific areas and social risk groups, should be a priority for reducing transmission.

Subcellular Partitioning and Intramacrophage Selectivity of Antimicrobial Compounds against Mycobacterium tuberculosis.

The efficacy of antimicrobial drugs against Mycobacterium tuberculosis, an intracellular bacterial pathogen, is generally first established by testing compounds against bacteria in axenic culture. However, inside infected macrophages, bacteria encounter an environment which differs substantially from broth culture and are subject to important host-dependent pharmacokinetic phenomena which modulate drug activity. Here, we describe how pH-dependent partitioning drives asymmetric antimicrobial drug distribution in M. tuberculosis-infected macrophages. Specifically, weak bases with moderate activity against M. tuberculosis (fluoxetine, sertraline, and dibucaine) were shown to accumulate intracellularly due to differential permeability and relative abundance of their ionized and nonionized forms. Nonprotonatable analogs of the test compounds did not show this effect. Neutralization of acidic organelles directly with ammonium chloride or indirectly with bafilomycin A1 partially abrogated the growth restriction of these drugs. Using high-performance liquid chromatography, we quantified the degree of accumulation and reversibility upon acidic compartment neutralization in macrophages and observed that accumulation was greater in infected than in uninfected macrophages. We further demonstrate that the efficacy of a clinically used compound, clofazimine, is augmented by pH-based partitioning in a macrophage infection model. Because the parameters which govern this effect are well understood and are amenable to chemical modification, this knowledge may enable the rational development of more effective antibiotics against tuberculosis.

ELISA-based assay of immunoglobulin G antibodies against mammalian cell entry 1A (Mce1A) protein: a novel diagnostic approach for leprosy.

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.

Risk factors for differential outcome following directly observed treatment (DOT) of slum and non-slum tuberculosis patients: a retrospective cohort study.

BACKGROUND: Brazil's National Tuberculosis Control Program seeks to improve tuberculosis (TB) treatment in vulnerable populations. Slum residents are more vulnerable to TB due to a variety of factors, including their overcrowded living conditions, substandard infrastructure, and limited access to healthcare compared to their non-slum dwelling counterparts. Directly observed treatment (DOT) has been suggested to improve TB treatment outcomes among vulnerable populations, but the program's differential effectiveness among urban slum and non-slum residents is not known. METHODS: We retrospectively compared the impact of DOT on TB treatment outcome in residents of slum and non-slum census tracts in Rio de Janeiro reported to the Brazilian Notifiable Disease Database in 2010. Patient residential addresses were geocoded to census tracts from the 2010 Brazilian Census, which were identified as slum (aglomerados subnormais -AGSN) and non-slum (non-AGSN) by the Census Bureau. Homeless and incarcerated cases as well as those geocoded outside the city's limits were excluded from analysis. RESULTS: In 2010, 6,601 TB cases were geocoded within Rio de Janeiro; 1,874 (27.4 %) were residents of AGSN, and 4,794 (72.6 %) did not reside in an AGSN area. DOT coverage among AGSN cases was 35.2 % (n = 638), while the coverage in non-AGSN cases was 26.2 % (n = 1,234). Clinical characteristics, treatment, follow-up, cure, death and abandonment were similar in both AGSN and non-AGSN TB patients. After adjusting for covariates, AGSN TB cases on DOT had 1.67 (95 % CI: 1.17, 2.4) times the risk of cure, 0.61 (95 % CI: 0.41, 0.90) times the risk of abandonment, and 0.1 (95 % CI: 0.01, 0.77) times the risk of death from TB compared to non-AGSN TB cases not on DOT. CONCLUSION: While DOT coverage was low among TB cases in both AGSN and non-AGSN communities, it had a greater impact on TB cure rate in AGSN than in non-AGSN populations in the city of Rio de Janeiro.

Understanding the barriers to successful adoption and use of a mobile health information system in a community health center in São Paulo, Brazil: a cohort study.

BACKGROUND: Mobile technology to support community health has surged in popularity, yet few studies have systematically examined usability of mobile platforms for this setting. METHODS: We conducted a mixed-methods study of 14 community healthcare workers at a public healthcare clinic in São Paulo, Brazil. We held focus groups with community healthcare workers to elicit their ideas about a mobile health application and used this input to build a prototype app. A pre-use test survey was administered to all participants, who subsequently use-tested the app on three different devices (iPhone, iPad mini, iPad Air). Usability was assessed by objectively scored data entry errors and through a post-use focus group held to gather open-ended feedback on end-user satisfaction. RESULTS: All of the participants were women, ranging from 18-64 years old. A large percentage (85.7%) of participants had at least a high school education. Internet (92.8%), computer (85.7%) and cell phone (71.4%) use rates were high. Data entry error rates were also high, particularly in free text fields, ranging from 92.3 to 100%. Error rates were comparable across device type. In a post-use focus group, participants reported that they found the app easy to use and felt that its design was consistent with their vision. The participants raised several concerns, including that they did not find filling out the forms in the app to be a useful task. They also were concerned about an app potentially creating more work for them and personal security issues related to carrying a mobile device in low-income areas. CONCLUSION: In a cohort of formally educated community healthcare workers with high levels of personal computer and cell phone use, we identified no technological barriers to adapting their existing work to a mobile device based system. Transferring current data entry work into a mobile platform, however, uncovered underlying dissatisfaction with some data entry tasks. This dissatisfaction may be a more significant barrier than the data entry errors our testing revealed. Our results highlight the fact that without a deep understanding of local process to optimize usability, technology-based solutions in health may fail. Developing such an understanding must be a central component in the design of any mHealth solution in global health.

Association of class 1 and 2 integrons with multidrug-resistant Acinetobacter baumannii international clones and Acinetobacter nosocomialis isolates.

The Acinetobacter baumannii clonal complex 113/79 (CC113/79) and class 2 integrons predominate in Latin America; a relationship between these characteristics was explored. The presence of integrases was determined in successive hospital Acinetobacter isolates (163 A. baumannii isolates and 72 Acinetobacter nosocomialis isolates). Most isolates had integrons, but class 1 and 2 integrons were present significantly more often in CC109/1 and CC113/79, respectively. The high prevalence of CC113/79 in Latin America may account for the predominance of class 2 integrons.

Rapid induction of high-level carbapenem resistance in heteroresistant KPC-producing Klebsiella pneumoniae.

Enterobacteriaceae strains producing the Klebsiella pneumoniae carbapenemase (KPC) have disseminated worldwide, causing an urgent threat to public health. KPC-producing strains often exhibit low-level carbapenem resistance, which may be missed by automated clinical detection systems. In this study, eight Klebsiella pneumoniae strains with heterogeneous resistance to imipenem were used to elucidate the factors leading from imipenem susceptibility to high-level resistance as defined by clinical laboratory testing standards. Time-kill analysis with an inoculum as low as 3 × 10(6) CFU/ml and concentrations of imipenem 8- and 16-fold higher than the MIC resulted in the initial killing of 99.9% of the population. However, full recovery of the population occurred by 20 h of incubation in the same drug concentrations. Population profiles showed that recovery was mediated by a heteroresistant subpopulation at a frequency of 2 × 10(-7) to 3 × 10(-6). Samples selected 2 h after exposure to imipenem were as susceptible as the unexposed parental strain and produced the major outer membrane porin OmpK36. However, between 4 to 8 h after exposure, OmpK36 became absent, and the imipenem MIC increased at least 32-fold. Individual colonies isolated from cultures after 20 h of exposure revealed both susceptible and resistant subpopulations. Once induced, however, the high-level imipenem resistance was maintained, and OmpK36 remained unexpressed even without continued carbapenem exposure. This study demonstrates the essential coordination between blaKPC and ompK36 expression mediating high-level imipenem resistance from a population of bacteria that initially exhibits a carbapenem-susceptibility phenotype.

Molecular epidemiological characterization of uropathogenic escherichia coli from an outpatient urology clinic in rural Japan.

In the remote Japanese community of Saku, a rural town in the Nagano Prefecture, a large proportion of outpatient urinary tract infections was caused by well-recognized globally dispersed clonal lineages of uropathogenic Escherichia coli (UPEC). However, most of these strains were drug susceptible, suggesting that factors other than selection pressure account for the clonal spread of drug-susceptible UPEC.