CTX-M-15–producing Enteroaggregative Escherichia coli as Cause of Travelers’ Diarrhea

Travelers’ diarrhea is a major public health problem. From patients in whom diarrhea developed after travel to India, 5 enteroaggregative Escherichia coli strains carrying β-lactamase CTX-M-15 were identified; 3 belonged to clonal complex sequence type 38. This β-lactamase contributes to the multidrug resistance of enteroaggregative E. coli, thereby limiting therapeutic alternatives

Surgery for Valvular Heart Disease: A Population-Based Study in a Brazilian Urban Center

BACKGROUND: In middle income countries, the burden of rheumatic heart disease (RHD) remains high, but the prevalence of other heart valve diseases may rise as the population life expectancy increases. Here, we compared population-based data on surgical procedures to assess the relative importance of causes of heart valve disease in Salvador, Brazil. METHODOLOGY/PRINCIPAL FINDINGS: Medical charts of patients who underwent surgery for valvular heart disease from January 2002-December 2005 were reviewed. Incidence of surgery for valvular heart disease was calculated. Logistic regression was used to identify factors associated with in-hospital death following surgery. The most common etiologies for valvular dysfunction in 491 valvular heart surgery patients were RHD (60.3%), degenerative valve disease (15.3%), and endocarditis (4.5%). Mean annual incidence for surgeries due to any valvular heart diseases, RHD, and degenerative valvular disease were 5.02, 3.03, and 0.77 per 100,000 population, respectively. Incidence of surgery due to RHD was highest in young adults; procedures were predominantly paid by the public health sector. In contrast, the incidence of surgery due to degenerative valvular disease was highest among those older than 60 years of age; procedures were mostly paid by the private sector. The overall in-hospital case-fatality ratio was 11.9%. Independent factors associated with death included increase in age (odds ratio: 1.04 per year of age; 95% confidence interval: 1.02-1.06), endocarditis (6.35; 1.92-21.04), multiple valve operative procedures (4.35; 2.12-8.95), and prior heart valve surgery (2.49; 1.05-5.87). CONCLUSIONS/SIGNIFICANCE: RHD remains the main cause for valvular heart surgery in Salvador, which primarily affects young adults without private health insurance. In contrast, surgery due to degenerative valvular disease primarily impacts the elderly with private health insurance. Strategies to reduce the burden of valvular heart disease will need to address the disparate factors that contribute to RHD as well as degenerative valve disease

Rheumatic Heart Disease and Beta-hemolytic Streptococci in Salvador, Brazil: A Study of Slum Health

Despite the near disappearance of rheumatic heart disease (RHD) in wealthier nations ofthe world, this disease continues to cause substantial morbidity and mortality in poorcountries worldwide. The burden is projected to be particularly important amongresidents of urban slums in poor countries. However, the epidemiologic features of RHDin developing countries are poorly understood. RHD is characterized by damage tocardiac valves that is the long-term consequence of an immune process initiated byinfection with Streptococcus pyogenes (Group A Streptococcus; GAS). Progression toRHD often takes decades; it would require decades-long prospective studies to observeassociations between GAS infections and the outcome of RHD in the same subjects.Therefore, in this dissertation we first attempted to assess the current burden of RHD inSalvador (Chapter 2), a city where more than half of the population is living in slums, byconducting a population-based study of operations performed for cardiac valve disease.We found that a large proportion of valvular surgeries performed in Salvador from 2002-2005 was for RHD. We then wished to investigate possible reasons for the large burdenof this disease. It is known that RHD is influenced by biological factors of beta-hemolyticStreptococcus as well as health-care seeking behavior and treatment of streptococcalinfections. Therefore, in the third and fourth chapters of this dissertation we focused onthe biological factors of Streptococcus, focusing our work to address current hypothesesregarding RHD pathogenesis as found in the literature, such as: 1) the association ofinfection or colonization with certain streptococcal strain types and clinical outcome; 2)the increased risk of RHD with repeated infections with a diverse set of GAS strains, and3) the possible association of RHD with Streptococcus spp. other than GAS.In Chapter 3, we compared the genotypes of GAS strains recovered from children aged 3-15 years of age who live in slum versus non-slum communities. This was done todetermine if there are differences in the strain genotype distributions (as measured bygenotype diversity) in these two populations. Detection of differences in genotypedistributions by community (estimating slum communities to have higher diversity ofgenotypes circulating in the population compared to non-slum populations), wouldprovide preliminary data to support the hypothesis that high GAS genotype diversity inslums may be associated with the observation of high prevalence of RHD in slumpopulations compared to the low prevalence of RHD among non-slum populations.Furthermore, we investigated two additional species of beta-hemolytic streptococci fromslum and non-slum communities as well, and found an unexpected finding thatcolonization with Streptococcus dysgalactiae equisimilis was associated with lower oddsof sore throat in children (Chapter 4). We discuss possible explanations for this finding,including biological plausibility as well as alternate explanations. While ourobservational studies can not define causal associations between epidemiologic featuresof beta-hemolytic Streptococcus and the outcome of RHD, they provide preliminary datathat the epidemiologic features of GAS and non-GAS infections in urban slums ofSalvador may be distinct from that in non-slum populations

Distribution of superantigens in group A streptococcal isolates from Salvador, Brazil.

BackgroundGroup A streptococcus (GAS) causes invasive disease, superficial disease, and can asymptomatically colonize humans. Superantigens are one virulence factor found in GAS. Previous studies found associations between the genes that encode superantigens and emm type of GAS. It is unknown if these associations are due to underlying biological factors that limit the distribution of superantigens or, alternatively, if these associations are due to the expansion of local GAS linages where these studies took place. To further address this question we screened GAS isolates collected from Salvador, Brazil for 11 known superantigen genes.MethodsSeventy-seven GAS isolates were screened by PCR for superantigen genes. These superantigen genes were speA, speC, speG, speH, speI, speJ, speK, speL, speM, ssa, and smeZ. We used Fisher's two-sided exact test to identify associations between superantigens and GAS emm type. We then compared our results to previous reports of superantigen prevalence and superantigen association with emm type.ResultsIn our collection we found several emm type and superantigen genotype combinations that have previously been reported in isolates from Europe and Australia. We also found that speA was significantly associated with emm type 1, and that speC was significantly associated with emm type 12.ConclusionsOur study reports superantigen genotypes of GAS from a region of the world that is lacking this information. We found evidence of common GAS superantigen genotypes that are spread worldwide as well as novel superantigen genotypes that, so far, are unique to Brazil

Clinical outcomes associated with SARS-CoV-2 Omicron (B.1.1.529) variant and BA.1/BA.1.1 or BA.2 subvariant infection in Southern California

Epidemiologic surveillance has revealed decoupling of Coronavirus Disease 2019 (COVID-19) hospitalizations and deaths from case counts after emergence of the Omicron (B.1.1.529) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant globally. However, assessment of the relative severity of Omicron variant infections presents challenges because of differential acquired immune protection against Omicron and prior variants and because longer-term changes have occurred in testing and healthcare practices. Here we show that Omicron variant infections were associated with substantially reduced risk of progression to severe clinical outcomes relative to time-matched Delta (B.1.617.2) variant infections within a large, integrated healthcare system in Southern California. Adjusted hazard ratios (aHRs) for any hospital admission, symptomatic hospital admission, intensive care unit admission, mechanical ventilation and death comparing individuals with Omicron versus Delta variant infection were 0.59 (95% confidence interval: 0.51-0.69), 0.59 (0.51-0.68), 0.50 (0.29-0.87), 0.36 (0.18-0.72) and 0.21 (0.10-0.44), respectively. This reduced severity could not be explained by differential history of prior infection among individuals with Omicron or Delta variant infection and was starkest among individuals not previously vaccinated against COVID-19 (aHR = 0.40 (0.33-0.49) for any hospital admission and 0.14 (0.07-0.28) for death). Infections with the Omicron BA.2 subvariant were not associated with differential risk of severe outcomes in comparison to BA.1/BA.1.1 subvariant infections. Lower risk of severe clinical outcomes among individuals with Omicron variant infection should inform public health response amid establishment of the Omicron variant as the dominant SARS-CoV-2 lineage globally

Distribution of superantigens in group A streptococcal isolates from Salvador, Brazil

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-02-27T16:26:25Z No. of bitstreams: 1 Berman HF Distribution of superantigens....pdf: 197957 bytes, checksum: fe310ef26181ee406383d2386dcb5b96 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-02-27T16:37:13Z (GMT) No. of bitstreams: 1 Berman HF Distribution of superantigens....pdf: 197957 bytes, checksum: fe310ef26181ee406383d2386dcb5b96 (MD5)Made available in DSpace on 2018-02-27T16:37:14Z (GMT). No. of bitstreams: 1 Berman HF Distribution of superantigens....pdf: 197957 bytes, checksum: fe310ef26181ee406383d2386dcb5b96 (MD5) Previous issue date: 2014Fogarty International Center, NIH, Grant number TW006563.University of California. School of Public Health. Division of Infectious Disease and Vaccinology. Berkeley, CA, USAUniversity of California. School of Public Health. Division of Infectious Disease and Vaccinology. Berkeley, CA, USA / Kaiser Permanente Southern California Research and Evaluation. Pasadena, CA, USAFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, BrasilUniversity of California. School of Public Health. Division of Infectious Disease and Vaccinology. Berkeley, CA, USAGroup A streptococcus (GAS) causes invasive disease, superficial disease, and can asymptomatically colonize humans. Superantigens are one virulence factor found in GAS. Previous studies found associations between the genes that encode superantigens and emm type of GAS. It is unknown if these associations are due to underlying biological factors that limit the distribution of superantigens or, alternatively, if these associations are due to the expansion of local GAS linages where these studies took place. To further address this question we screened GAS isolates collected from Salvador, Brazil for 11 known superantigen genes. Methods: Seventy-seven GAS isolates were screened by PCR for superantigen genes. These superantigen genes were speA, speC, speG, speH, speI, speJ, speK, speL, speM, ssa, and smeZ. We used Fisher’s two-sided exact test to identify associations between superantigens and GAS emm type. We then compared our results to previous reports of superantigen prevalence and superantigen association with emm type. Results: In our collection we found several emm type and superantigen genotype combinations that have previously been reported in isolates from Europe and Australia. We also found that speA was significantly associated with emm type 1, and that speC was significantly associated with emm type 12. Conclusions: Our study reports superantigen genotypes of GAS from a region of the world that is lacking this information. We found evidence of common GAS superantigen genotypes that are spread worldwide as well as novel superantigen genotypes that, so far, are unique to Brazil

Association of SARS-CoV-2 BA.4/BA.5 Omicron lineages with immune escape and clinical outcome.

Expansion of the SARS-CoV-2 BA.4 and BA.5 Omicron subvariants in populations with prevalent immunity from prior infection and vaccination, and associated burden of severe COVID-19, has raised concerns about epidemiologic characteristics of these lineages including their association with immune escape or severe clinical outcomes. Here we show that BA.4/BA.5 cases in a large US healthcare system had at least 55% (95% confidence interval: 43-69%) higher adjusted odds of prior documented infection than time-matched BA.2 cases, as well as 15% (9-21%) and 38% (27-49%) higher adjusted odds of having received 3 and ≥4 COVID-19 vaccine doses, respectively. However, after adjusting for differences in epidemiologic characteristics among cases with each lineage, BA.4/BA.5 infection was not associated with differential risk of emergency department presentation, hospital admission, or intensive care unit admission following an initial outpatient diagnosis. This finding held in sensitivity analyses correcting for potential exposure misclassification resulting from unascertained prior infections. Our results demonstrate that the reduced severity associated with prior (BA.1 and BA.2) Omicron lineages, relative to the Delta variant, has persisted with BA.4/BA.5, despite the association of BA.4/BA.5 with increased risk of breakthrough infection among previously vaccinated or infected individuals

Factors associated with Group A <it>Streptococcus emm </it>type diversification in a large urban setting in Brazil: a cross-sectional study

Abstract Background Group A Streptococcus (GAS) strain diversity varies across different regions of the world, according to low versus high-income countries. These differences may be related to geographic, environmental, socioeconomic, or host-related factors. However, local factors may also affect strain diversity. We compared the emm types of GAS isolates from children with and without sore throat in one large urban setting in Brazil. Methods Children 3-15 years of age were consecutively recruited from slum and non-slum pediatric outpatient clinics between April-October, 2008. Throat cultures were performed and data intake forms were completed. GAS isolates were typed by emm sequencing. Results From 2194 children, 254 (12%) GAS isolates were obtained. Of 238 GAS isolates that were emm-typed, 61 unique emm types were identified. Simpson's diversity index of the emm types was higher among isolates from slum children [97% (96%-98%)] than those of non-slum children [92% (89%-96%)]. Two emm types (66.0, 12.0) were more frequently isolated from children with sore throat (p emm type (27G.0) demonstrated a protective effect. Conclusions The emm type diversity from children attending slum clinics resembled the emm diversity of low income countries rather than that of children attending a non-slum clinic in the same city. Local factors, such as crowding, may enhance the frequency of GAS transmission and horizontal gene transfers that contribute to increased strain diversity in the slums. GAS vaccine coverage and control of GAS infections will need to take these local factors and strain differences into consideration.</p

Factors associated with Group A Streptococcus emm type diversification in a large urban setting in Brazil: a cross-sectional study

Abstract Background Group A Streptococcus (GAS) strain diversity varies across different regions of the world, according to low versus high-income countries. These differences may be related to geographic, environmental, socioeconomic, or host-related factors. However, local factors may also affect strain diversity. We compared the emm types of GAS isolates from children with and without sore throat in one large urban setting in Brazil. Methods Children 3-15 years of age were consecutively recruited from slum and non-slum pediatric outpatient clinics between April-October, 2008. Throat cultures were performed and data intake forms were completed. GAS isolates were typed by emm sequencing. Results From 2194 children, 254 (12%) GAS isolates were obtained. Of 238 GAS isolates that were emm-typed, 61 unique emm types were identified. Simpson's diversity index of the emm types was higher among isolates from slum children [97% (96%-98%)] than those of non-slum children [92% (89%-96%)]. Two emm types (66.0, 12.0) were more frequently isolated from children with sore throat (p &lt; 0.05), and one emm type (27G.0) demonstrated a protective effect. Conclusions The emm type diversity from children attending slum clinics resembled the emm diversity of low income countries rather than that of children attending a non-slum clinic in the same city. Local factors, such as crowding, may enhance the frequency of GAS transmission and horizontal gene transfers that contribute to increased strain diversity in the slums. GAS vaccine coverage and control of GAS infections will need to take these local factors and strain differences into consideration

Increased vaccine sensitivity of an emerging SARS-CoV-2 variant

Host immune responses are a key source of selective pressure driving pathogen evolution. Emergence of many SARS-CoV-2 lineages has been associated with enhancements in their ability to evade population immunity resulting from both vaccination and infection. Here we show diverging trends of escape from vaccine-derived and infection-derived immunity for the emerging XBB/XBB.1.5 Omicron lineage. Among 31,739 patients tested in ambulatory settings in Southern California from December, 2022 to February, 2023, adjusted odds of prior receipt of 2, 3, 4, and ≥5 COVID-19 vaccine doses were 10% (95% confidence interval: 1-18%), 11% (3-19%), 13% (3-21%), and 25% (15-34%) lower, respectively, among cases infected with XBB/XBB.1.5 than among cases infected with other co-circulating lineages. Similarly, prior vaccination was associated with greater point estimates of protection against progression to hospitalization among cases with XBB/XBB.1.5 than among non-XBB/XBB.1.5 cases (70% [30-87%] and 48% [7-71%], respectively, for recipients of ≥4 doses). In contrast, cases infected with XBB/XBB.1.5 had 17% (11-24%) and 40% (19-65%) higher adjusted odds of having experienced 1 and ≥2 prior documented infections, respectively, including with pre-Omicron variants. As immunity acquired from SARS-CoV-2 infection becomes increasingly widespread, fitness costs associated with enhanced vaccine sensitivity in XBB/XBB.1.5 may be offset by increased ability to evade infection-derived host responses