Thesis (M.P.H.)--University of Michigan, 1946.

Thesis (M.P.H.)--University of Michigan, 1946.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / O Streptococcus (S.) pneumoniae à considerado como o principal agente causador de morbidade e mortalidade em crianÃas menores de cinco anos de idade. Todas as doenÃas pneumocÃcicas comeÃam com o estabelecimento da colonizaÃÃo do S. pneumoniae na nasofaringe, podendo progredir para doenÃa invasiva se as barreiras naturais forem cruzadas. Nas Ãltimas dÃcadas, o aumento do nÃmero de cepas de S. pneumoniae resistentes à antibiÃticos β-lactÃmicos e a outras classes de antimicrobianos tem dificultado o tratamento da infecÃÃo pneumocÃcica. Atualmente cerca de 13 sorotipos de S. pneumoniae respondem por mais de 85% dos isolados invasivos. A vacina pneumocÃcica polissacarÃdica conjugada 7-valente tem sido amplamente recomendada para crianÃas menores de cinco anos. Os objetivos desse estudo foram determinar a prevalÃncia de S. pneumoniae em crianÃas portadoras, a frequÃncia de isolados de S. pneumoniae de indivÃduos com infecÃÃo sistÃmica, o perfil de sensibilidade a antimicrobianos e os sorotipos mais comuns, em Fortaleza, Brasil. Os isolados de portadores foram recuperados a partir de swabs de nasofaringe de crianÃas usuÃrias de creches, enquanto que os isolados de infecÃÃo sistÃmica foram cedidos pelo LACEN-CE. Foram realizadas as ConcentraÃÃes InibitÃrias MÃnimas (CIM) para penicilina e ceftriaxona para todos os isolados, e levofloxacina apenas para os isolados de nasofaringe. Os pontos de corte das CIM foram determinados de acordo com o CLSI (2007). As sorotipagens dos isolados sistÃmicos foram realizadas pela reaÃÃo de Quellung, enquanto que a genotipagem capsular dos isolados de portadores foi realizada pela tÃcnica de multiplex PCR. De 215 crianÃas usuÃrias de creches, foram isolados S. pneumoniae em 152 (71%). As CIM de 137 isolados de portadores mostraram uma taxa resistÃncia de 71% para penicilina e de 21% para ceftriaxona. NÃo houve resistÃncia nos testes com levofloxacina. Comparado a um estudo similar, realizado hà 10 anos, em Fortaleza, nossos resultados apresentaram um aumento significativo nas taxas de resistÃncia à penicilina e ceftriaxona. De 26 isolados de nasofaringe que apresentaram resistÃncia plena, apenas, seis isolados (23%) tiveram a genotipagem capsular identificada por multiplex PCR. A incidÃncia de isolados invasivos neste estudo por ano, foi de, aproximadamente, 1 caso/100.000 hab. Dos 52 isolados, 42% apresentaram resistÃncia à penicilina e 13,5% à ceftriaxona. Os sorotipos mais comuns dos isolados sistÃmicos foram 19F (12%), 14, 3, 6A (8% cada), 4, 18C e 9V (6% cada), com cobertura estimada, tanto para vacina pneumocÃcica conjugada 7-valente quanto para a 10-valente, de 31,8%. / Streptococcus (S.) pneumoniae is considered the principal causative agent of morbidity and mortality in children younger than five years of age. All pneumococcal diseases are initiated by establishing a S. pneumoniae colonization in nasopharynx, the disease progressing to systemic disease if natural barrier are crossed. During the last decades, the increasing amount of resistant S. pneumoniae strains to beta-lactams and other classes of antimicrobials has modified the treatment of pneumococcal infection. At present, nearly 13 serotypes respond for more than 85% of invasive isolates. The 7-valent polysaccharide-conjugated pneumococcal vaccine has been widely recommended for use in children younger than five years. The aims of this study were to determine the S. pneumoniae carrier in children, the frequence of serotypes from systemic infection patients, the susceptibility profile to antimicrobials in Fortaleza, Brazil. Carrier state isolates were recovered from nasopharyngeal swabs from children attending day-care center facilities, while the isolates from systemic infection fournished by LACEN-CE. Minimal Inhibitory Concentrations (MIC) to penicillin and ceftriaxone were assessed for all isolates, and levofloxacin MIC only from nasopharyngeal isolates. MIC cut-offs were determined according to CLSI standards (2007). Serotyping of systemic isolates was performed by Quellung reaction, while capsular genotyping of carrier isolates was performed by multiplex PCR assay. OF 215 children attending day-care centers, 152 S. pneumoniae isolates were identified (71%). Penicillin MIC showed 71% of resistance, and for ceftriaxone, 21% of resistance. No resistance was found for levofloxacin MIC testing. When compared to a 10-year old similar study in Fortaleza, our results have shown a significant increase of penicillin and ceftriaxone resistance rates. Of 26 isolates tested, only six nasopharyngeal isolates (23%) were positively genotyped by multiplex PCR. The incidence of invasive isolates was 1/100,000 inhab. per year. Of 52 systemic isolates serotyped, 42% were penicillin-resistant, and 13.5% were ceftriaxone-resistant. Systemic serotypes identified were 19F, 3, 6A, 4, 18C and 9V, with a estimated coverage by the 7-valent and 10-v pneumococcal polysaccharide conjugated vaccines of 31.8%.

Includes bibliographical references / Asymptomatic children can be a major reservoir of pharyngeal Group A Streptococcus (GAS) with reported figures ranging from <10% to >20% in developing countries. There is a need to document GAS carriage in school children, which, together with the molecular characterisation (M-typing) of strains harboured in the pharynx of carriers, will help to ascertain the extent to which disease strains are prevalent amongst carriers. This background information would serve to assist healthcare providers in diagnosing symptomatic GAS pharyngitis, as well as could potentially contribute to the development of a GAS vaccine. Currently, data on GAS carriage prevalence and M-type distribution in African countries are largely scant. We therefore undertook to perform a systematic review to determine the prevalence and type distribution of asymptomatic streptococcus carriage in children aged 5 -15years, residing in African countries. Methods: We conducted a comprehensive literature search among a number of databases, using an African search filter to identify GAS prevalence studies that report on children between the ages of 5 - 15 years who reside in African countries. Electronic searches were complemented by a hand search performed on reference lists of potentially included studies. The search was not limited by year of publication and language. Two evaluators independently reviewed, rated, and abstracted data from each article. Prevalence estimates were pooled in a meta-analysis and stratified according to region and study design using Stata®. Specifically, we applied the random effects metaprop routine to aggregate prevalence estimates and account for between study variability in calculating the overall pooled estimates and 95% CI for GAS carriage prevalence.

Foot-and-mouth disease (FMD) is an economically devastating picornaviral disease affecting over 40 species of cloven-hoofed animals. The virus occurs as seven immunologically distinct serotypes which are characterized by high levels of intra- and intertypic variation. The three South African Territories (SAT) serotypes 1-3 are endemic to sub-Saharan Africa, a region where the epidemiology of the disease is particularly complex due to the presence of six of the seven serotypes, the role of wildlife in virus maintenance and the apparently higher levels of variation in the endemic serotypes. These factors make it imperative to establish methods suited to elucidating the regional epidemiology. One of the integral parts of this process is the genetic characterization of regionally representative viruses in order to assess the variation in the field and to clarify the role of wildlife. Nucleotide sequence data and methods suited to studying the SAT-types are however limited. A first priority was therefore to establish a PCR-based nucleotide sequencing technique targeting the highly immunogenic and phylogenetically informative 1D genome region encoding the VP1 protein. The screening of multiple serotypes and subtypes prevalent on the African continent confirmed that this method was robust and well-suited to molecular epidemiological studies in the southern Africa region. The method was first applied in the characterization of FMD virus recovered from the reproductive tract of free-living African buffalo in the Kruger National Park. Nucleotide sequencing assisted in authentication of the results and indicated that carrier status was likely, but it was not possible to unequivocally demonstrate persistent infection of FMDV. In a separate study, the role of impala antelope (Aepyceros melampus) in the epidemiology of the disease in South Africa was assessed. Genetic characterization of impala and African buffalo (Syncerus caffer) viruses collected over an eleven year period confirmed that inter-species transmission occurred on several occasions and that virus can persist in impala populations for more than 12 months. Inter-species transmission and investigation of the possible mechanisms facilitating virus transmission from persistently infected buffalo focussed on the Kruger National Park in South Africa. In order to ensure regional relevance the study was broadened to incorporate buffalo populations throughout southern Africa. Viruses of the three SAT-types recovered from diverse African buffalo populations were therefore characterized. The results reveal that independently evolving viral lineages occur in distinct geographical regions for each of the SAT-types examined and that the levels of intratypic variation are in the order of 52 - 55 % on nucleotide level across the genome region characterized. Given the strict locality-specific grouping of buffalo viruses the likely usefulness of this database for tracing the origin and course of contemporary and historical SAT-type outbreaks was investigated. Molecular epidemiological studies conclusively show that buffalo are indeed the ultimate source of infection for susceptible cloven-hoofed animals occurring in close proximity, that interspecies transmission occurs between cattle and antelope and that trans-boundary transmission of virus remains a threat to disease security in southern African countries. / Thesis (PhD (Microbiology))--University of Pretoria, 2007. / Microbiology and Plant Pathology / unrestricted

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2005. / Härtill 5 uppsatser.

Introdução - O estado de portador assintomático ocorre quando o hospedeiro alberga o agente etiológico sem apresentar doença. Os fatores associados ao estado de portador de Neisseria não patogênica (NNP) e Neisseria meningitidis (Nm) diferem entre si, no entanto, as características epidemiológicas de ambas ainda são pouco exploradas. Objetivos - Estimar a prevalência, analisar possíveis diferenças em distintos estratos sociais, identificar o genótipo das cepas isoladas, assim como, investigar fatores associados ao estado de portador de Nm e de NNP em núcleos familiares residentes em Cuiabá-MT. Método - Estudo transversal de base populacional, desenvolvido de 07/2016 a 07/2017, incluindo todos os moradores de uma amostra probabilística estratificada composta de 243 núcleos familiares (domicílios) de área urbana, em bairros de alta e baixa renda do município de Cuiabá. Foram incluídos os domicílios com ao menos uma criança de 12 e 60 meses de idade. Todos os residentes nos domicílios selecionados foram submetidos a coleta de swab de orofaringe para o isolamento de Neisseria spp. Para a comparação de proporções utilizou-se o teste do qui-quadrado. Foram estimadas as razões de prevalências (RP) com seus respectivos intervalos de confiança 95% (IC95%) e para a investigação de fatores associados ao estado de portador de Nm e de NNP foram utilizados modelos de regressão de Poisson. O ajuste das variáveis no modelo final foi avaliado pelo teste de Hosmer e Lemeshow. Resultados: Foram estudados 1.050 indivíduos residentes em 233 núcleos familiares. A prevalência de portadores de Neisseria spp. foi de 10,6% (111/1.050), a de Nm de 2,4% (25/1.050) e de NNP de 8,2% (86/1.050). Dentre 111 portadores, 62 (56,0%) foram por N. lactamica, 25 (22,0%) por Nm, 21 (19,0%) por N. subflava., duas (2,0%) por N. mucosa e uma (1,0%) por N. polysaccharea. Das Nm, 76% (19/25) eram não grupáveis, 16% (4/25) eram do sorogrupo B, 4% (1/25) do sorogrupo C e 4% (1/25) do sorogrupo W. A prevalência de Nm em bairros de baixa renda foi de 2,8% (23/816) e nos de alta renda de 0,8% (2/234) (p=0,058), com uma razão de prevalência (RP) de 3,3 (IC95%:0,8-13,9). A prevalência de NNP em bairros de baixa renda foi de 8,2% (67/816) e em bairros de alta renda de 8,1% (19/234), com uma RP de 1,0 (IC95%:0,6-1,6). Permaneceram independentemente associados ao estado de portador de Nm após ajuste para conviver com tabagista no domicílio e por número de pessoas por dormitório: i) residir em bairro de baixa renda (RPajustada=2,6); ii) faixa etária de 5 a 14 anos (RPajustada=2,7); iii) faixa etária de 15 a 29 anos (RPajustada=2,4) e faixa etária de 30 e anos e mais (RPajustada=1,4). Após o ajuste para a infecção respiratória nos últimos cinco dias, apresentar asma, três ou mais pessoas por dormitório e sexo masculino, mostraram-se independentemente associados ao estado de portador de NNP: i) pertencer a faixa etária de cinco a 14 anos de idade (RPajustada=2,8) e de menores de cinco anos de idade (RPajustada=7,2); ii) residir em casa precária/quitinete (RPajustada=2,1). Conclusões - O contexto social influencia o estado de portador de Nm e NNP. As vacinas conjugadas meningocócicas podem prevenir doenças direta e indiretamente e tais resultados podem subsidiar a elaboração de estratégias de intervenção, especialmente para a identificação de grupos alvo de programas de vacinação. / Introduction - The asymptomatic carrier state occurs when the host harbors the etiologic agent without presenting disease. The associated factors with the carrier state of non-pathogenic Neisseria (NNP) and Neisseria meningitidis (Nm) differ among them, however, the epidemiological characteristics of both are still poorly explored. Objectives - To estimate the prevalence, to analyze possible differences in different social strata, to identify the genotype of the isolated strains, as well as to investigate associated factors with the Nm and NNP carrier state in family\'s households living in Cuiabá-MT. Methods - A cross-sectional study was conducted in 07/2016 a 07/2017, in the city of Cuiabá, including all residents of a stratified probabilistic sample which was composed by 243 urban households (families nucleus) with high and low income neighborhoods of the city of Cuiabá. Households with at least one child between 12 and 60 months age were included. All residents in the selected households were submitted to oropharynx swab collection for the isolation of Neisseria spp. To compare proportions the chi-square test was used. For the estimates of prevalence ratios (PR) and the respective 95% confidence intervals (95% CIs), for the analysis of the associated factors with Nm and NNP carrier state Poisson regression models were used. The adjustment of the variables in the final model was evaluated by the Hosmer e Lemeshow test. Results - A total of 1,050 individuals residing in 233 families nucleus were studied. The prevalence of Neisseria spp. was of 10.6% (111/1,050), Nm of 2.4% (25/1,050) and NNP of 8.2% (86/1,050). Among 111 carriers, 62 (56.0%) were by N. lactamica, 25 (22.0%) by Nm, 21 (19.0%) by N. subflava, two (2.0%) by N. mucosa and one (1.0%) by N. polysaccharea. Of the Nm, 76% (19/25) were non-grouping, 16% (4/25) were serogroup B, 4% (1/25) serogroup C and 4% (1/25) serogroup W. Prevalence of Nm in low-income neighborhoods was 2.8% (23/816) and high-income (0.8%) (2/234) (p=0.058), with a prevalence ratio of 3.3 (95% CI:0.8-13.9). The prevalence of NNP in low-income neighborhoods was 8.2% (67/816) and in high-income neighborhoods of 8.1% (19/234), with a PR of 1.0 (95% CI:0,6-1,6). They remained independently associated with Nm state after adjusting to live with a smoker at home and by number of people per dormitory: i) living in a low-income neighborhood (PRadjusted=2.6); ii) age group of 5 to 14 years (PRadjusted=2.7); iii) age range of 15 to 29 years (PRadjusted=2.4) and age group of 30 years and over (PRadjusted=1.4). After adjusting for respiratory infection in the last five days, presenting asthma, three or more people per dormitory and male sex, were independently associated with NNP status: i) belonging to the age group of five to 14 years of age (PRadjusted=2.8) and of children under five years of age (RPadjusted=7.2); ii) residing in a precarious home/kitchenette (PRadjusted= 2.1). Conclusions - The social context influences the carrier state of Nm and NNP. Meningococcal conjugate vaccines can prevent diseases directly and indirectly and such results may support the development of intervention strategies, especially for the identification of target groups of vaccination programs.

INTRODUÇÃO: Neisseria meningitidis é uma das principais causas de meningite bacteriana em todo o mundo. No Brasil, a vacina meningocócica conjugada C foi introduzida no calendário básico do Programa Nacional de Imunizações em 2010 para a população abaixo de 2 anos de idade. Este estudo teve como objetivos avaliar a taxa de portadores sadios de meningococo em nasofaringe entre estudantes de medicina através de métodos fenotípicos e genotípicos. Além disso, foram analisados os fatores de risco associados ao estado de portador sadio. MÉTODOS: Trezentos e setenta e cinco (375) estudantes da Faculdade de Medicina da Universidade de São Paulo foram submetidos à coleta de swabs de nasofaringe, de outubro a novembro de 2010: desta casuística, 190 estudantes foram submetidos à coleta de dois swabs. Os swabs foram encaminhados ao Laboratório de Investigação Médica (LIM) de Bacteriologia para isolamento e caracterização das cepas: o primeiro swab foi submetido a cultivo em meio seletivo, testes bioquímicos e reação em cadeia da polimerase com primers específicos para dois genes de Neisseria meningitidis, ctrA e crgA. O segundo swab foi submetido à extração direta de DNA, sem cultivo prévio. Todas as cepas isoladas foram genogrupadas com primers específicos direcionados aos genogrupos A, B, C, Y e W. RESULTADOS: A prevalência geral de portadores sadios foi 45,6%. A taxa de portadores obtida após cultivo em meio seletivo e testes bioquímicos foi 6,1%. A taxa de colonização resultante da PCR dos produtos de cultivo em meio seletivo foi 15.4%. Destas cepas, a maioria pertencia ao genogrupo B. A partir da extração direta de DNA de 190 amostras clínicas, obtivemos 69,5% de positividade de portadores sadios, sendo o genogrupo C predominante nestas amostras. A PFGE mostrou que todas as cepas isoladas eram policlonais. Não houve relação estatisticamente significativa entre os fatores de risco avaliados e o estado de portador sadio. CONCLUSÕES: Este estudo avaliou a prevalência de portadores sadios em adultos jovens no Brasil antes da introdução da vacina meningocócica C conjugada no calendário vacinal de rotina. A prevalência variou de 6,1% a 69,5% dentre os diferentes métodos utilizados, com uma prevalência geral de 45,6%. Comparando-se os diferentes métodos, os métodos genotípicos mostraram-se superiores na detecção de portadores sadios, especialmente quando o DNA é extraído diretamente da amostra clínica / BACKGROUND: Neisseria meningitidis is one of the leading causes of bacterial meningitis worldwide. In Brazil, the meningococcal C conjugate vaccine was introduced as a part of basic vaccination schedule in the public health system in 2010 to the population under 2 years old. The objectives of this study were to evaluate the rate of asymptomatic carriers of meningococci in the nasopharynx among medical students by phenotypic and genotypic methods. Furthermore, the risk factors for carriage were also analyzed. METHODS: Three hundred seventy-five (375) students from University of São Paulo Medical School underwent nasopharyngeal swab collection from October to November, 2010. From those students, 190 of them underwent collection of two swabs; they were sent to the laboratory for isolation and characterization of strains: the first one were submitted to culture on solid plates with selective medium, biochemical tests, and Polymerase Chain Reaction (PCR) with specific primers for two genes of Neisseria meningitidis, ctrA and crgA. From the second swab, direct DNA extraction to PCR reactions were performed, with no previous culture. All strains isolated were genogrouped with specific primers targeting A, B, C, Y and W groups. RESULTS: The overall carriage rate was 45,6%. Carriage rate by culture on solid plates and biochemical tests was 6.1%. The rate obtained from PCR targeting genes ctrA and crgA of colony growth on selective medium was 15.4%. From those strains, the majority belongs to genogroup B. With direct extraction of DNA from 190 clinical samples, we obtained a positivity of 69.5% of meningococcal carriage, and the genogroup C was the main genogroup from those samples. The PFGE showed that the samples were polyclonal. CONCLUSIONS: This study has evaluated the rate of asymptomatic carriers in young people in Brazil before the vaccine introduction in the vaccine routine schedule of infants. The prevalence of nasopharyngeal carriage by meningoccoci among medical students was 6.1% for the phenotypic method, 15.4% by PCR after growth in selective medium and 69.5% by PCR from DNA extracted from clinical samples. In the comparison of the phenotypic and genotypic methods, it was observed that genotypic are superior to phenotypic methods, especially when direct DNA extraction from clinical specimen is performed