Thesis (M.Sc.). / Written for the Dept. of Biology. Title from title page of PDF (viewed 2008/05/14). Includes bibliographical references.

MSc (Med), Faculty of Health Sciences, University of the Witwatersrand, 2011 / Despite being a fulminant pathogen, Neisseria meningitidis (meningococcus) is part of the commensal flora of the human nasopharynx. Globally, five meningococcal serogroups (A, B, C, Y and W135) cause the majority of invasive disease. Most serogroup B cases occur sporadically but may be endemic or epidemic within a geographic region. In South Africa, there are limited data on invasive serogroup B clones and the antigenic diversity of certain meningococcal outer membrane proteins. This study examined the molecular epidemiology of serogroup B meningococci in South Africa from 2002 through 2006. Invasive meningococcal isolates were submitted to a national laboratory-based surveillance system. For this study, serogroup B isolates were characterised by pulsed-field gel electrophoresis (PFGE), PorA, FetA and multilocus sequence (MLST) typing. PorA, FetA and multilocus sequence (MLST) typing were performed on all 2005 isolates (n=58) and randomly selected isolates from other years (n=25). A total of 2144 invasive cases were reported over the study period. Of these, 76% (1627/2144) had viable isolates available for serogrouping and 307 (19%) were serogroup B. Serogroup B cases were reported from across the country however the majority were from the Western Cape province. The highest incidence of serogroup B was in children less than 5 years of age. Isolates displayed a high level of diversity by PFGE. Despite this diversity the majority of serogroup B meningococci collected over the 5-year period could be grouped into several clonal clusters representative of global invasive MLST clonal complexes. Overall, the most predominant MLST clones in South Africa were ST-32/ET-5 and ST-41/44/lineage 3. In addition, at least 19 PorA types and 16 FetA types were determined among selected isolates. Globally invasive serogroup B disease is caused by heterogeneous strains however, prolonged outbreaks in several countries have been due to strains of the ST-32/ET-5 and ST-41/44/lineage 3 clonal complexes. At present, serogroup B disease in South Africa is not dominated by an epidemic clone, however, global clonal complexes ST-32/ET-5 and ST-41/44/lineage 3 are circulating in Western Cape and Gauteng, respectively.

This dissertation reports the findings of a study which was carried out in the Cape Town City Council area, in order to establish whether the offering of rifampicin to household contacts, of patients with meningococcal disease, resulted in protection of those contacts against developing the disease during a 32 week follow up period. The study took the form of a retrospective follow up of 3 350 household contacts of 412 cases notified over a 4-year period (mid 1988-mid 1992). It was found that the offering of rifampicin to the household contacts resulted in an odds ratio of not developing meningococcal disease over the 32-week follow up period of 14, 17 (SD = 12, 34). Although there was a tendency for contacts who were not offered rifampicin to have been younger, and of male gender, when compared to those who were offered prophylaxis, these demographic differences were not statistically significant at the 0,05 level. Furthermore, three out of the four male second cases, all in the younger age group, were in fact offered prophylaxis. It seems desirable that prophylaxis should be given as soon as possible. It is concluded, therefore, that the offering of rifampicin to household contacts of patients with meningococcal disease, living under the prevailing social circumstances in the Western Cape, has protective benefit for those contacts. It is likely that the chemoprophylaxis programme prevented up to 88 cases of meningococcal disease over the study period of four years, as well as preventing 8 deaths from this disease, in the CCC population.

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

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

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 4 uppsatser.

Submitted by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-28T11:44:16Z No. of bitstreams: 2 Dissertação - Lísia Gomes Martins de Moura Tomich - 2016.pdf: 2901743 bytes, checksum: 22cd41bfc4499cfd4754d856635357af (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2016-09-28T11:44:45Z (GMT) No. of bitstreams: 2 Dissertação - Lísia Gomes Martins de Moura Tomich - 2016.pdf: 2901743 bytes, checksum: 22cd41bfc4499cfd4754d856635357af (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2016-09-28T11:44:45Z (GMT). No. of bitstreams: 2 Dissertação - Lísia Gomes Martins de Moura Tomich - 2016.pdf: 2901743 bytes, checksum: 22cd41bfc4499cfd4754d856635357af (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2016-08-15 / Conselho Nacional de Pesquisa e Desenvolvimento Científico e Tecnológico - CNPq / INTRODUCTION: Routine infant immunization with meningococcal C conjugate vaccine (MenC-V) started in Brazil in November 2010, administered at three, five and 12 months of age with no catch-up for older age-groups. However, by March 2010, a vaccination campaign with MenC-V was performed in Salvador in individuals under five years-old, and from 10 to 24 yearsold. In São Paulo state, the outbreaks occurred in teenagers and young adults prompting one-time vaccination campaign from 2010 to 2014 targeting these age-groups. OBJECTIVE: To assess the direct and indirect impact (herd effect) of vaccination on invasive meningococcal disease (MD) for capsular group C (MenC) four years after the introduction of MenC-V in three scenarios: i) Brazil as a whole (routine vaccination in childhood only); ii) Brazil except for Salvador (vaccination campaign with teenagers during the year of MenC-V introduction); and iii) São Paulo state (vaccination campaign for adolescents and young adults during 2010-2014 to control outbreaks). METHODS: We performed an ecological quasi-experimental design from 2008 to 2014 using data from the National Reference Laboratory for Meningitis, and data from the National Information System for Notifiable Diseases. A deterministic linkage was performed between the two databases to improve the accuracy of the detection of MD, especially in capsular groups. An interrupted time-series analysis was conducted using the Holt-Winters technique to control for pre-existing trends and seasonal variations. The MenC vaccination impact was evaluated as the percentage of reduction in the incidence rates of MenC in the post-vaccination period (2012 to 2014), using the pre-vaccination period (2008 to 2010) to estimate what would be expected on the post-vaccination period, whether the vaccination had not been introduced. For Salvador, we analyzed the effect of the vaccination on the number of MenC cases. RESULTS: A total of 18,136 invasive MD cases were analyzed. For Brazil as a whole, the vaccination reduced 67.4% (lower 95%CI 42.5%) the rates for MenC for infants under 12 months, 92.3% (lower 95%CI 77.7%) for the age-group 12-23 months, and 65.7% (lower 95%CI 28%) for children aged 2-4 years. Indirect impact (20-24.7%) was observed in the age-group 5-19 years. When excluding Salvador from the analysis of Brazil, the indirect impact was observed only for children in the age-group 5-9 years. In the scenario of São Paulo state, similarly to Brazil, significant impact was observed in the target age-groups, in addition to indirect impact in the age group 5-9 years. In Salvador, in addition to the effect on the vaccinated population a sharp and sustainable decline of MenC cases was observed in all age-groups not target for vaccination. Overall, 1,170 cases of MenC were averted in Brazil after the introduced of Men-C vaccination. CONCLUSION: The strategy of catch-up for adolescents and young adults, especially during the year of MenC-V introduction may lead to rapid and sustainable herd effect. / A vacina meningocócica conjugada contra o grupo capsular C (MenC-V) foi introduzida no calendário de imunização infantil brasileiro em novembro de 2010, sendo administrada aos três, cinco e 12 meses de idade sem catch-up para os demais grupos etários. Entretanto, em março de 2010, uma campanha de vacinação com MenC-V foi realizada em Salvador para indivíduos menores de cinco anos de idade e de 10 a 24 anos. No estado de São Paulo os surtos ocorreram em adolescentes e adultos jovens, determinando campanhas de vacinações de bloqueio nessa faixa etária nos anos de 2010 a 2014. OBJETIVO: Avaliar o impacto direto e indireto (rebanho) da vacinação nas taxas de incidência de doença meningocócica (DM) invasiva pelo grupo capsular C (MenC) após quatro anos da introdução da MenC-V em três cenários: i) Brasil como um todo (imunização de rotina somente de crianças); ii) Brasil exceto Salvador (campanha de vacinação em adolescentes no ano de introdução da MenCV); e iii) estado de São Paulo (vacina de rotina na infância e vacinações de bloqueio em adolescentes e adultos jovens para controlar surtos). MÉTODOS: Foi realizado um estudo ecológico quasi-experimental para avaliar o impacto da vacinação em série histórica de 2008 a 2014 usando os bancos de dados do Laboratório Nacional de Referência para Meningites Bacterianas, Instituto Adolfo Lutz (IAL) e o Sistema de Informação de Agravos de Notificação (Sinan). Um processo de vinculação (linkage) determinístico entre as duas bases foi realizado para melhorar a acurácia da detecção de casos de DM, especialmente de grupo capsulares. Uma análise de série temporal interrompida foi conduzida utilizando a técnica de Holt-Winters para controlar por tendência pré-existente e variações sazonais. O desfecho foi taxa de MenC. O impacto da vacinação foi avaliado pelo percentual de redução da incidência de MenC no período pós-vacinal (2012 a 2014), utilizando o período pré-vacinal (2008 a 2010) para estimar o que seria esperado no período pós-vacinal, caso a vacinação não tivesse sido introduzida. Para Salvador foi analisado o efeito da MenC-V no número de casos de MenC. RESULTADOS: Um total de 18.136 casos de DM invasiva foram analisados. Para o Brasil como um todo, a vacinação reduziu significativamente a DM por MenC na faixa etária alvo, com redução de 67,4% (limite inferior do IC95% 42,5%) em menores de 12 meses, 92,3% (limite inferior do IC95% 77,7%) para faixa etária de 12-23 meses e 65,7% (limite inferior do IC95% 28%) em crianças de 2-4 anos, e efeito rebanho foi observado na faixa etária de 5 a 19 anos com 20-24,7%. Quando se exclui Salvador na análise do Brasil, impacto indireto significativo foi observado somente em crianças de 5-9 anos. No cenário São Paulo, semelhante ao Brasil, observou-se impacto estatisticamente significante nas faixas etárias alvo do PNI, além do efeito rebanho na faixa etária de 5-9 anos de idade. Para Salvador, o impacto da vacinação apresentou um declínio acentuado e sustentável em todas as faixas etárias fora do alvo da vacinação. Ao todo, 1.170 casos de MenC foram evitados no período estudado. CONCLUSÃO: A estratégia de vacinação de catch-up em adolescentes e adultos jovens, especialmente no ano de introdução da MenC-V, promoveu um rápido e sustentável rebanho.