A research report submitted to the School of Public Health, Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment of the requirements of the degree of Masters in Science in Epidemiology and Biostatistics Johannesburg, April 2013 / Haemophilus influenzae type b disease (Hib) was a major cause of childhood disease but has nearly been eliminated in developed countries after the introduction of Hib conjugate vaccine. An increase in non-typeable H. influenzae (NTHi) disease was observed in some countries post-Hib vaccination which prompted concerns about possible serotype replacement. Hib disease in children <5 years of age decreased by a minimum estimate of 71% in South Africa after the Hib vaccine introduction in 1999. The epidemiology of Hib disease among persons >5 year olds and NTHi disease in all ages has not been described in South Africa before. The aim of this study is therefore to describe the trends and factors associated with invasive Hib and NTHi disease in South Africa, 2003-2009 among persons of all ages.

Thesis (M.S.)--University of Missouri, School of Mines and Metallurgy, 1921. / The entire thesis text is included in file. Typescript. Illustrated by author. Title from title screen of thesis/dissertation PDF file (viewed May 29, 2009) Includes bibliographical references (p. 25).

Thesis (doctoral)--Lund University, 1995. / Added t.p. with thesis statement inserted.

Thesis (doctoral)--Lund University, 1995. / Added t.p. with thesis statement inserted.

Made available in DSpace on 2012-05-07T15:02:16Z (GMT). No. of bitstreams: 2 license.txt: 1748 bytes, checksum: 8a4605be74aa9ea9d79846c1fba20a33 (MD5) 000004.pdf: 872019 bytes, checksum: b8e894b7b58911018e4a590c0266cbe1 (MD5) Previous issue date: 2010 / Fundação Oswaldo Cruz. Instituto Nacional de Controle de Qualidade em Saúde / A bactéria Haemophilus da espécie influenzae, pode causar no homem diversas infecções, invasivas ou não. O H. influenzae do tipo b (Hib), antes da introdução da vacina conjugada contra Hib, associava-se a infecções como epiglotite, artrite séptica, bacteriemia, pneumonia septicemia e meningite, principalmente em crianças. As outras espécies tipáveis (a,c,d,e,f) e não tipáveis estavam associadas a infecções do trato respiratório adquiridas na comunidade. Após a introdução dessa vacina, houve redução expressiva das doenças causadas pelo Hib em diversas partes do mundo, inclusive no Brasil. Atualmente, outros tipos da espécie H. influenzae (Hi) que não o Hib estão sendo isoladas não somente em crianças, causando infecções graves. O ressurgimento de casos por Hib, em crianças vacinadas, tem sido reportado como possível falha vacinal. Esses fatos preocupam a Saúde Pública no mundo, demonstrando que mudanças epidemiológicas podem estar ocorrendo devido à seleção de cepas após a introdução da vacina. Neste estudo, mudanças genéticas na região capsular do Hi foram encontradas em cepas isoladas nos períodos pré e pós-vacinal de três estados brasileiros. Através do estudo de susceptibilidade foram encontradas cepas produtoras de β-lactamase (BLA+) e não produtoras resistentes a ampicilina (BLNAR). A análise de redução da susceptibilidade às quinolonas foi avaliada utilizando-se o ácido nalidíxico como marcador, confrontando-se a resistência deste antibiótico com os marcadores moleculares das regiões determinantes de resistência a quinolonas (QRDRs) através do sequenciamento dos genes gyrA e parC que codificam a síntese das proteínas GyrA e ParC. Os resultados obtidos demonstraram que o ácido nalidíxico é o antibiótico mais indicado desse grupo para detectar a redução da sensibilidade. / The bacteria specie Haemophilus influenzae can cause several infections on men, either invasive or not. Before the introduction of conjugated vaccine against type b H. influenzae (Hib), it was associated to infections like epiglottitis, septic arthritis, bacteremia, pneumonia, septicemia and meningitis, occurring mostly in children. The other typeable species (a,c,d,e,f) and not typeable (NT) were associated to infections of respiratory trait acquired in the community. After introducing this vaccine, expressive reduction of diseases caused by Hib has been observed worldwide, including Brazil. Recently, different types of H. influenzae species other than Hib have been isolated in children and adults, causing severe infections. The reemergence of Hib cases in vaccinated children has been reported as a possible vaccine failure. These facts are a concern to public health departments around the world showing that epidemiologic changes may happen due to the selection of strains after vaccine introduction. In this study, genetic changes in the capsular region of Hi were found in isolated strains in the pre and post vaccinal periods in three Brazilian states. Through susceptibility studies, β-lactamase producer strains were found as well as non producer resistant to ampicilin (BLNAR). Analysis of susceptibility reduction to quilonones was evaluated by using nalidixic acid as a marker, and comparing the resistance to this antibiotic to molecular markers of the determining regions of resistance to quilonones (QRDRs) through sequencing of gyrA and parC genes that codify the synthesis of GyrA and ParC proteins. The results show that nalidixic acid is the most suitable antibiotic of this group able to detect sensibility reduction to quinolones. This study shows that there is a need for routine and research laboratories to evaluate and develop simple and quick methods to indicate possible capsule changes and emergence of resistant strains, to help epidemiological and sanitary surveillance.

Las infecciones respiratorias agudas (IRAs) constituyen una de las cinco primeras causas de morbilidad y mortalidad a nivel mundial. Una bacteria causante de infecciones respiratorias agudas, principalmente en niños menores de 5 años es Haemophilus influenzae tipo b. “Se estima que provoca por lo menos tres millones de casos de enfermedad grave al año y alrededor de 86.000 de funciones, la mayor parte se registra en países en desarrollo”.El objetivo fue identificar Haemophilus influenzae tipo b en lactantes menores de 1año hospitalizados con diagnóstico de infección respiratoria aguda y presencia de tos coqueluchoide.

Proefschrift Universiteit van Amsterdam. / Rugtitel: Pathogenesis of Haemophilus influenzae infection in COPD patients. Met lit. opg. - Met samenvatting in het Nederlands.

Diss. (sammanfattning) Stockholm : Karol. inst. / Härtill 4 uppsatser.

Thesis (Ph. D.)--University of Chicago, 1906. / Also issued in print.

Universiẗat, Diss., 2005--Würzburg.