Dynamics and determinants of SARS-CoV-2 RT-PCR testing on symptomatic individuals attending healthcare centers during 2020 in Bahia, Brazil

RT-PCR testing data provides opportunities to explore regional and individual determinants of test positivity and surveillance infrastructure. Using Generalized Additive Models, we explored 222,515 tests of a random sample of individuals with COVID-19 compatible symptoms in the Brazilian state of Bahia during 2020. We found that age and male gender were the most significant determinants of test positivity. There was evidence of an unequal impact among socio-demographic strata, with higher positivity among those living in areas with low education levels during the first epidemic wave, followed by those living in areas with higher education levels in the second wave. Our estimated probability of testing positive after symptom onset corroborates previous reports that the probability decreases with time, more than halving by about two weeks and converging to zero by three weeks. Test positivity rates generally followed state-level reported cases, and while a single laboratory performed ~90% of tests covering ~99% of the state's area, test turn-around time generally remained below four days. This testing effort is a testimony to the Bahian surveillance capacity during public health emergencies, as previously witnessed during the recent Zika and Yellow Fever outbreaks

Avaliação de marcadores associados à sintese de hemoglobina fetal em indivíduos com anemia falciforme e persistência hereditária da hemoglobina fetal

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2012-11-19T18:11:37Z No. of bitstreams: 1 Nadja de Jesus G. dos Santos. Hemoglobina fetal...pdf: 2812470 bytes, checksum: 55476e9f2f10311274d9f1a3382fda56 (MD5)Made available in DSpace on 2012-11-19T18:11:37Z (GMT). No. of bitstreams: 1 Nadja de Jesus G. dos Santos. Hemoglobina fetal...pdf: 2812470 bytes, checksum: 55476e9f2f10311274d9f1a3382fda56 (MD5) Previous issue date: 2012Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.O estudo de marcadores associados à síntese de hemoglobina fetal (HbF) é de grande interesse científico, pois contribui para o entendimento dos mecanismos regulatórios dos genes envolvidos na síntese das cadeias globínicas gama, uma vez que esta Hb é importante na modulação genética da anemia falciforme (HbSS). O objetivo desse estudo foi investigar a influência de alterações em genes envolvidos na síntese de HbF e suas associações com marcadores laboratoriais e clínicos na HbSS e caracterizar o fenótipo e o genótipo de indivíduos com o perfil sugestivo de persistência hereditária de hemoglobina fetal (PHHF). Dessa forma, foi realizado um estudo de corte transversal, seguido de caso-controle com a casuística de 43 indivíduos HbSS com HbF> 3,0% e 3 indivíduos com perfil sugestivo de PHHF. O presente estudo foi aprovado pelo CEP-CpGM-Fiocruz. Os polimorfismos HBG2 -396/-391del, HBG2 SNP -369 C>G, HBG2 -309 A>G, HBG2 -157 T>C, HBG1 -499 T>A, HBG1 -369 C>G, HBG1 -271 C>T e HBG1-225/-222del foram investigados por sequenciamento automático de DNA; os haplótipos ligados ao gene da globina beta foram investigados por PCR-RFLP; os polimorfismos BCL11Ars766432, BCL11Ars6732518, OR51B5/6rs4910756, OR51B5/6rs7483122, HMIPrs11759553, HMIPrs35959442 foram investigados por PCR em tempo real; a talassemia alfa 23.7 Kb e as deleções PHHF-1, PHHF-2 e PHHF-4 por PCR. As análises hematológicas foram realizadas em contador automático de células, o perfil de hemoglobina foi confirmado por cromatografia líquida de alto desempenho e as dosagens bioquímicas foram investigadas por quimiluminescência. As concentrações de HbF foram associadas com HbS (pT foi associado com a concentração de HbF (p=0,027; RP=4,45; IC95%= 1,14 – 17,41) e ferro (p=0,0076); o HBG1 -499 T>A com as concentrações de glicose (p=0,007) e de alfa-1 antitripsina (p=0,008); o HBG1 -225/-222del com as concentrações de colesterol LDL (p=0,017); o HBG2 -396/-391del com as concentrações de HbS (p=0,017), creatinina (p=0,042) e bilirrubina p=0,030), sendo associado também ao quadro clínico mais grave da doença, com ocorrência frequente de crises vaso-oclusivas (p=0,046), litíase biliar (p=0,021) e o uso de hemoterápicos (p=0,009); o BCL11A rs766432 com a contagem de reticulócitos (p 3.0% and 3 individuals with a suggestive profile of HPFH. Polymorphisms HBG2 -396/-391del, the HBG2 SNP -369 C> G, HBG2 -309 A> G, HBG2 -157 T> C, HBG1 -499 T> A, HBG1 -369 C> G HBG1 the -271 C> T and HBG1-225/-222del were investigated by automated DNA sequencing; haplotypes linked to the beta globin gene were investigated by PCR-RFLP; single nucleotide polymorphisms of BCL11Ars766432, BCL11Ars6732518, OR51B5/6rs4910756, OR51B5/6rs7483122 , HMIPrs11759553, HMIPrs35959442 were investigated by real-time PCR, alpha thalassemia 2 with 3.7 Kb deletion and HPFH-1 , HPFH-2 and HPFH-4 deletions by PCR Hematological tests were performed in automatic cell counter, the profile of hemoglobin was confirmed by high performance liquid chromatography and biochemical analysis were investigated by immunochemistry assay method. Levels of HbF were associated with HbS (p T was associated with the concentration of HbF (p = 0.027, PR = 4.45, 95% CI 1.14 - 17.41) and iron (p= 0.0076); the HBG1 - 499 T> A was associated with the level of glucose (p= 0.007) and alpha-1 antitrypsin (p= 0.008); the HBG1 -225/-222del with LDL cholesterol concentrations (p= 0.017); the HBG2 - 396/-391del with Hb concentrations (p= 0.017), creatinine (p= 0.042) and bilirubin (p= 0.030), and also with a more severe clinical disease, with frequent occurrence of vaso-occlusive crises (p= 0.046), gallstones (p= 0.021) and the use of haemotherapic (p= 0.009); the BCL11A rs766432 with the reticulocyte count (p<0.0001) and the concentration of total cholesterol (p= 0.033) and BCL11Ars6736518 with the level of glucose (p= 0.049) and eosinophil count (p= 0.012); the HMIPrs35959442 with ferritin concentrations (p= 0.035), creatinina (p= 0.008 ) and MCV (p= 0.022), the HMIPrs11759553 with concentrations of uric acid (p= 0.033) and ferritin (p= 0.020); and the polymorphisms OR51B5/6rs7483122 and the OR51B5/6rs4910756 with creatinine concentrations (p= 0.001 ). Multivariate analysis pointed for the association of the genotype CAR / CAR with a decrease in HbF concentration with the use of blood therapy. The alpha thalassemia 2 with 3.7 Kb deletion showed a protective effect, being associated with concentrations of ALT (p= 0.044), AST (p= 0.039) and lymphocyte count (p= 0.050). The three cases associated with HPFH phenotype did not show significant association with clinical and laboratory data, including the case 3, that showed the genotype HbSF. It is noteworthy that these individuals were not classified in any described HPFH type investigated. Further studies should be conducted in order to validate results found in this work and to clarify the possible mechanisms by which those investigated molecular markers can interfere with the modulation of the HbF synthesis and if they have mechanisms differentiate from the ones commonly investigated, once that the present study described association with important biomarkers that have been used for monitoring individuals with HbSS

Association between the haptoglobin and heme oxygenase 1 genetic profiles and soluble CD163 in susceptibility to and severity of human malaria

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-07-14T12:34:54Z No. of bitstreams: 1 Mendonça VRR and Association between....pdf: 1483842 bytes, checksum: 789494313a7e9e5c126a3356d3e09691 (MD5)Made available in DSpace on 2014-07-14T12:34:54Z (GMT). No. of bitstreams: 1 Mendonça VRR and Association between....pdf: 1483842 bytes, checksum: 789494313a7e9e5c126a3356d3e09691 (MD5) Previous issue date: 2012Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). São Paulo, SP, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, BrasilNational Institute of Allergy and Infectious Diseases. National Institutes of Health. Immunobiology Section. Laboratory of Parasitic Diseases. Bethesda, Maryland, USAeFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Medicina da Bahia. Salvador, BA, Brasil / Instituto Nacional de Ciência e Tecnologia de Investigação em Imunologia (iii-INCT). São Paulo, SP, BrasilIntravascular hemolysis is a hallmark event in the immunopathology of malaria that results in increased systemic concentrations of free hemoglobin (Hb). The oxidation of Hb by free radicals causes the release of heme, which amplifies inflammation. To circumvent the detrimental effects of free heme, hosts have developed several homeostatic mechanisms, including the enzyme haptoglobin (Hp), which scavenges cell-free Hb, the monocyte receptor CD163, which binds to Hb-Hp complexes, and heme oxygenase-1 (HO-1), which degrades intracellular free heme. We tested the association between these three main components of the host response to hemolysis and susceptibility to malaria in a Brazilian population. The genetic profiles of the HMOX1 and Hp genes and the plasma levels of a serum inflammatory marker, the soluble form of the CD163 receptor (sCD163), were studied in 264 subjects, including 78 individuals with symptomatic malaria, 106 individuals with asymptomatic malaria, and 80 uninfected individuals. We found that long (GT)n repeats in the microsatellite polymorphism region of the HMOX1 gene, the Hp2 allele, and the Hp2.2 genotype were associated with symptomatic malaria. Moreover, increased plasma concentrations of heme, Hp, HO-1, and sCD163 were associated with susceptibility to malaria. The validation of these results could support the development of targeted therapies and aid in reducing the severity of malari

Promoter region sequence differences in the A and G gamma globin genes of Brazilian sickle cell anemia patients.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-07-14T17:15:00Z No. of bitstreams: 1 Barbosa CG Promoter region sequence....pdf: 483623 bytes, checksum: fbf61b3b309bc1783260895e8c38e953 (MD5)Made available in DSpace on 2014-07-14T17:15:00Z (GMT). No. of bitstreams: 1 Barbosa CG Promoter region sequence....pdf: 483623 bytes, checksum: fbf61b3b309bc1783260895e8c38e953 (MD5) Previous issue date: 2010Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Brasília, DF, BrasilUniversidade do Estado do Amazonas. Manaus, AM, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, Brasil / Universidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, BrasilFetal hemoglobin (HbF), encoded by the HBG2 and HBG1 genes, is the best-known genetic modulator of sickle cell anemia, varying dramatically in concentration in the blood of these patients. This variation is partially associated with polymorphisms located in the promoter region of the HBG2 and HBG1 genes. In order to explore known and unknown polymorphisms in these genes, the sequences of their promoter regions were screened in sickle cell anemia patients and correlated with both their HbF levels and their βS-globin haplotypes. Additionally, the sequences were compared with genes from 2 healthy groups, a reference one (N = 104) and an Afro-descendant one (N = 98), to identify polymorphisms linked to the ethnic background.The reference group was composed by healthy individuals from the general population. Four polymorphisms were identified in the promoter region of HBG2 and 8 in the promoter region of HBG1 among the studied groups. Four novel single nucleotide polymorphisms (SNP) located at positions -324, -317, -309 and -307 were identified in the reference group. A deletion located between -396 and -391 in the HBG2 promoter region and the SNP -271 C→T in the HBG1 promoter region were associated with the Central African Republic βS-globin haplotype. In contrast, the -369 C→G and 309 A→G SNPs in the HBG2 promoter region were correlated to the Benin haplotype. The polymorphisms -396_-391 del HBG2, -369 SNP HBG2 and -271 SNP HBG1 correlated with HbF levels. Hence, we suggest an important role of HBG2 and HBG1 gene polymorphisms on the HbF synthesis

The leftward deletion 4.2 KB alpha-thalassemia in two sickle cell anemia siblings

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2014-07-15T13:09:20Z No. of bitstreams: 1 Takahashi D The leftward....pdf: 91839 bytes, checksum: 163e2ec27a7eccbee29867ff6178021d (MD5)Made available in DSpace on 2014-07-15T13:09:21Z (GMT). No. of bitstreams: 1 Takahashi D The leftward....pdf: 91839 bytes, checksum: 163e2ec27a7eccbee29867ff6178021d (MD5) Previous issue date: 2010Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, BrasilFundação de Hematologia e Hemoterapia da Bahia. HEMOBA. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação de Hematologia e Hemoterapia da Bahia. HEMOBA. Salvador, BA, BrasilUniversidade Federal da Bahia. Faculdade de Farmácia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Salvador, BA, BrasilA presença da deleção –α thal 3.7Kb está associada com melhor prognóstico de pacientes que possuem anemia falciforme (AF), contudo não existem estudos na literatura a respeito da associação da –α thal 4.2Kb com a evolução clínica desses pacientes. No presente relato são descritos achados laboratoriais e perfil de hemoglobina de dois irmãos que possuem AF em associação com a –α thal 4.2Kb. Ambos os pacientes apresentam anemia acentuada, baixos índices de Volume Corpuscular Médio (VCM) e contagem de leucócitos elevada. Estudos adicionais são necessários para elucidar uma possível associação entre a –α thal 4.2Kb e a gravidade da AF.The presence of –αthal 3.7Kb deletion is associated with better prognosis of Sickle Cell Anemia (SCA) patients, but here are not reports in the literature regarding association of –α thal 4.2Kb and its importance among SCA clinical outcome. In this report, we describe Hemoglobin profile and laboratory findings of two siblings who have SCA and are silent carriers of –α thal 4.2Kb. Both described patients have severe anemia, lower rates of Mean Corpuscular Volume (MCV) and a high leukocytes count. Further studies are required to establish a possible association between –α thal 4.2Kb and SCA severity