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

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

Inverse Association between Lancefield Group G Streptococcus Colonization and Sore Throat in Slum and Nonslum Settings in Brazil▿

Group G Streptococcus has been implicated as a causative agent of pharyngitis in outbreak situations, but its role in endemic disease remains elusive. We found an unexpected inverse association of Streptococcus dysgalactiae subsp. equisimilis colonization and sore throat in a study of 2,194 children of 3 to 15 years of age in Salvador, Brazil