This document describes an evaluation of acute (meningitis)-encephalitis syndrome (AES/AMES) surveillance established in India, Bangladesh and China. The key objectives of the project included 1) building on existing networks for syndromic surveillance and laboratory confirmation, 2) establishing laboratory-based surveillance for vaccine-preventable causes of encephalitis and meningitis, 3) enhancing capacity to use data to guide disease control and prevention programs, and 4) improving capacity to recognize new or emerging diseases. The syndromes encompass several diseases, including Japanese encephalitis (JE), pneumococcal meningitis, Haemophilus influenzae type b (Hib), and meningococcal meningitis. The purpose of the evaluation is to assess the extent to which the key objectives were met in the three project countries, compare and contrast the experiences among the countries, document the strengths and weaknesses, and make recommendations. The indicators used in the evaluation include feasibility of integration, availability of country protocols, appropriate training, data quality, sensitivity, specificity, positive predictive value, negative predictive value, representativeness, timeliness, integration with AFP surveillance, simplicity and efficiency, acceptability, usefulness, flexibility, stability, and sustainability. The criteria and standards are based on WHO recommendations. Data sources include AES/AMES epidemiologic and laboratory data sets, trip reports, country reports, field observations, and published bulletins. All countries made substantial progress in a relatively short period of time using the infrastructure and technical tools of existing surveillance and laboratory networks for acute flaccid paralysis. After one year, India and Bangladesh collects and maintains high quality epidemiologic data, exceeds targets for timeliness of reporting, and has quality-assured capacity for laboratory confirmation of Japanese encephalitis (JE) virus infection. India now has regional laboratory capacity for reference testing on virology and bacteriology. After two years of operations, China has population-based surveillance data for JE that meets targets for timeliness. Several levels have well-established capacity for laboratory confirmation of JE virus infection. The national level has the technical ability to provide proficiency testing for virology and to provide reference testing for bacteriology. In all countries, challenges in building capacity for basic bacteriology, quality control and quality assurance for all laboratory testing, and management of laboratory data.

Mortality and morbidity rates associated with tuberculous meningitis (TBM) are substantial. The average duration of the untreated disease from onset to death is about 17 days. The prognosis of TBM is known to correlate with the stage of the disease at the time of diagnosis and commencement of chemotherapy. Early diagnosis improves the chances of recovery without neurological sequelae. Early diagnosis is a problem because the presenting symptoms are non-specific and the onset of the disease is typically insidious. To date no single test is available that is totally reliable and specific for TBM. I have attempted to develop a reliable and easily applicable test for the diagnosis of TBM. In fulfilling this objective, the work undertaken may be divided into three major sections:- 1. Detection of soluble Mycobacterium tuberculosis antigens in the cerebrospinal fluid (CSF) of patients with TBM and in control groups by using Mycobacterium bovis BCG antigens. The technique used was that of inhibition enzyme-linked immunosorbent assay (ELISA). The principle of this technique is illustrated in Fig. 5. 2. Detection of soluble M. tuberculosis antigens in the CSF of tuberculous and control groups of patients by using antibodies raised against M.bovis BCG. The technique used was that of the double antibody sandwich ELISA. An outline of this ELISA is given in Fig. 6. 3. Correlation of chloride levels in the blood and CSF of patients with tuberculous and other forms of meningitis. It has been established that the SERUM/CSF ratio of bromide tends towards unity in patients with TBM because the permeability of the blood-brain barrier is impaired. Since both bromide and chloride are chemically similar (both being halides), it was thought that a similar pattern may exist for BLOOD/CSF chloride ratios; and this was investigated. The method used for the INHIBITION ELISA had to be standardized before the samples could be tested. This involved investigating the acceptability of various microtitre plates; determination of the optimal working dilutions for the coating solution and conjugate; and determination of optimal conditions for the various incubation periods, both in terms of time and temperature. A total of 70 specimens was tested. These consisted of 25 normal CSF controls; 25 pleural and ascitic fluid samples; 10 TBM samples, and 10 bacterial meningitis CSF samples. It was found that a distinction existed between the absorbance values obtained from positive TBM CSF samples (Mean 0,658 + 0,043) and that from normal CSF samples (Mean 1,089 + 0,224). The mean absorbance of the culture-positive bacterial CSF's also differed significantly from the other 2 groups (Tables VII; IX). Some overlap occurred amongst the absorbance values of bacterial culture positive CSF's (Range 0,975-0,879) and normal CSF's (Range 1,486-0,934). The mean absorbance value for bacterial positive CSF samples (0,920 _+ 0,029) differed significantly (p <0,01) from those of normal CSF (1,089 + 0,224) and TBM CSF's (0,658 + 0,043). The difference between the mean values obtained with tuberculous and non-tuberculous groups of pleural and ascitic fluid was also significant (p < 0,01). The method used for the DOUBLE ANTIBODY SANDWICH ELISA was that of Sada et al. (1983). Before the samples could be tested, the method had to be standardized and similar investigations to those for the INHIBITION ELISA were performed. In addition, antibodies raised against M.bovis BCG were conjugated to alkaline phosphatase since no commercial preparation was available. Unfortunately no distinction was recorded between negative and positive test specimens, even on repetition of the entire procedure. Measurement of chloride was done by a fully automated procedure using the BECKMAN ASTRA-8. A total of 149 samples were tested. Of these 10 were tuberculous, 34 were viral, and the remainder were bacterial meningitis. No pattern was established that could differentiate TBM from viral or bacterial meningitis. The results obtained are tabulated in Table III and illustrated in Figures 9, 10, and 11. In summarizing, the use of the INHIBITION ELISA technique for the accurate diagnosis of TBM seems promising. However, its validity in the clinical situation will have to be assessed further and with greater numbers of specimens before it can be adopted as a diagnostic procedure for TBM. OBJECTIVE. To determine 1. The ability and reliability of the INHIBITION ELISA1 technique to detect mycobacterial antigens in pleural, ascitic, and cerebrospinal fluids. 2. The accuracy and reproducibility of the double antibody sandwich ELISA in the detection of mycobacterial antigens in CSF of patients with tuberculous meningitis (TBM). 3. Whether a correlation exists between blood and CSF chloride levels in patients with tuberculous and other forms of meningitis. / Thesis (M.Med.Sc.)-University of Natal, Durban, 1985.

University, Diss., 2004--Ulm. / Literaturverz.

Tierärztl. Hochsch., Diss., 2004--Hannover.

Stellenbosch University. Faculty of Medicine and Health Sciences. Interdisciplinary Health Sciences. Family Medicine and Primary Care. / Thesis (MFamMed) -- Stellenbosch University, 2010. / Bibliography / ENGLISH ABSTRACT: Introduction: This thesis summarises the findings of a medical audit on the management of Cryptococcal Meningitis (CM). The study population of HIV positive adults (N = twenty five) were admitted during November 2009 – June 2010 to five hospitals of the Cape Winelands (East) District, Western Cape, South Africa. In the context of the HIV pandemic, CM has become the most common cause of community-acquired meningitis, and has poor outcomes if left untreated. The South African HIV Clinician Society has published treatment guidelines in 2007. These guidelines have been used by the audit team to compile a list of measurable criteria (with set targets) to evaluate the structure, process and outcome of CM management. A pilot audit (2008) at the regional hospital has demonstrated that certain target standards were not met. Aims and Objectives: The aim was to improve the quality of the clinical care of HIV-patients diagnosed with CM in the Cape Winelands (East) district. The objectives included the review of the audit criteria and target standards, demonstrating improvement in quality of CM care at the Level 1 and 2 hospitals, identifying new interventions based on the findings and providing recommendations to the health facilities. Methods In 2009, the researcher formed a new audit team, reviewed the audit criteria and held teaching interventions based on the national treatment guidelines. An intervention, based on the findings of the pilot audit, aimed at improving the clinical team’s adherence to the treatment guidelines. Results The audit identified the following areas that did not meet the target standards: the availability of Amphotericin B (Ampho B) and spinal manometers; the use of manometry in all initial lumbar punctures (LPs); completing fourteen days of the required Ampho B treatment; renal monitoring in patients on Ampho B; commencement of antiretroviral treatment (ART) by week four; and, the two-month survival figures post-diagnosis. The re-audit at the Level 2 hospital highlighted the need for improved medical record keeping to aid the audit process. Arrangement of inpatient ART counselling happened more consistently at the Level 1 hospitals. Adherence to the ART target and measures to prevent Ampho B related morbidity is comparable to that of the Level 2 hospital. The audit has also provided insight to the researcher and audit team on the practical challenges of conducting a prospective data collection technique across different care settings. Recommendations Level 1 hospitals should continue to manage CM patients. The availability of spinal manometers and closer adherence to renal monitoring require attention. Formal feedback to the audit team and clinical teams is planned. A multimodal interdisciplinary Quality Improvement approach (such as an integrated care pathway) is recommended and a future re-audit is encouraged to assess improved adherence to the CM management guidelines. The buy-in of stakeholders (management, health care workers and patients), the ongoing support of an audit team and a committed Quality Improvement environment will allow the medical audit process to become ingrained in the South African public healthcare setting. / AFRIKAANSE OPSOMMING: Inleiding Hierdie tesis bied ‘n opsomming van die sleutelbevindinge van ‘n mediese oudit van Cryptokokkale Menigitis (CM) sorg. Die studie groep van MIV-positiewe volwassenes (N = vyf-en-twintig) het binne-pasiënt behandeling ontvang gedurende November 2009 tot Junie 2010 in vyf hospitale van die Kaapse Wynland (Oos) distrik. In die konteks van die MIV pandemie het CM die mees algemene oorsaak van gemeenskapsverworwe meningitis geword, en het swak uitkomste indien onbehandeld. Die Suid-Afrikaanse HIV Clinici Vereniging het in 2007 behandelingsriglyne gepubliseer. Hierdie riglyne het die oudit span gebruik om ‘n lys van meetbare kriteria (met teiken standaarde) saam te stel om die struktuur, proses en uitkoms fasette van CM sorg te evalueer. ‘n Proef oudit (2008) by die streekshospitaal het getoon dat sekere teiken standaarde nie behaal was nie. Doelstelling Die doelstelling was om die kwaliteit van kliniese sorg van MIV-pasiënte met CM (in die Kaapse Wynland (Oos) distrik) te verbeter. Die doelstelling sluit in die hersiening van die oudit kriteria, die bevesting van verbetering in kwaliteit CM sorg by vlak 1 en 2 hospitale, identifisering van nuwe ingreep-moontlikhede gebaseer op die bevindinge en die verskaffing van toepaslike aanbevelings aan die gesondheidsorg fasiliteite. Metodes Die navorser het in 2009 ‘n nuwe oudit span gevorm, die oudit kriteria hersien en opleidingsingrepe geskoei op die nasionale riglyne gefasiliteer. Opleidingsingrepe, gebaseer op bevindinge van die proef oudit, het ten doel gehad dat die kliniese span die nasionale riglyne nakom. Resultate Die oudit het die volgende areas uitgelig waar daar nie aan die teikenstandaarde voldoen was nie: the beskikbaarheid van Amphotericin B (Ampho B) en spinale manometers; die gebruik van manometrie in alle aanvanklike lumbaal punksies (LPs); voltooi van die veertien dae Ampho B behandelingsteiken; nierfunksie monitoring van pasiënte op Ampho B; aanvang van anti-retovirale behandeling teen week vier; en, die twee maande oorlewing post-diagnose syfers. Die opvolg oudit by die vlak 2 hospitaal bevestig die belang van verbeterde kliniese notas om die oudit proses te vergemaklik. Die reël van binne-pasiënt ART berading gebeur meer bestendig in Vlak 1 hospitale. Bereiking van die ART teiken en maatreëls om Ampho B verwante morbiditeit te voorkom, is vergelykbaar met die bevindinge by die vlak 2 hospitaal. Die oudit het die navorser en die oudit span ingelig rakende die praktiese uitdagings om ‘n prospektiewe data insamelingsmetode te poog in verskillende kliniese kontekste. Aanbevelings Vlak 1 hospitale kan steeds CM pasiënte versorg. Die beskikbaarheid van spinale manometers en deeglike nierfunksie monitering sal die behaling van teiken standaarde vergemaklik. Formele terugvoer aan die oudit span en kliniese span word beoog. ‘n Multimodale interdissiplinêre Kwaliteitsverbeterings benadering (soos ‘n geïntegreerde sorgplan) word aanbeveel en ‘n toekomstige oudit word aangemoedig om verbetering in toepassing van die CM riglyne te evalueer. Dit is belangrik om die sleutelspelers (bestuur, gesondheidswerkers en pasiënte) te betrek. Verder word voortgesette ondersteuning van die oudit span en ‘n toegewyde omgewing van kwaliteitsverbetering aanbeveel. Sodoende sal die oudit proses in Suid-Afrikaanse publieke sorg geintegreer word.

Submitted by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2016-05-11T14:07:03Z No. of bitstreams: 1 Jailton_Azevedo Silva Junior. Impacto da vacina...2015.pdf: 2256825 bytes, checksum: 6da623ba97a2d68604f3b4a098585b07 (MD5) / Approved for entry into archive by Ana Maria Fiscina Sampaio (fiscina@bahia.fiocruz.br) on 2016-05-11T14:07:15Z (GMT) No. of bitstreams: 1 Jailton_Azevedo Silva Junior. Impacto da vacina...2015.pdf: 2256825 bytes, checksum: 6da623ba97a2d68604f3b4a098585b07 (MD5) / Made available in DSpace on 2016-05-11T14:07:15Z (GMT). No. of bitstreams: 1 Jailton_Azevedo Silva Junior. Impacto da vacina...2015.pdf: 2256825 bytes, checksum: 6da623ba97a2d68604f3b4a098585b07 (MD5) Previous issue date: 2015 / Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / INTRODUÇÃO: Em 2010, a vacina conjugada 10-valente (PCV10) foi incorporada ao programa nacional de imunizações (PNI) brasileiro. Este imunobiológico confere imunização contra os dez principais tipos capsulares de Streptococcus pneumoniae, patógeno responsável por diversas manifestações clínicas e com elevada contribuição nas taxas de incidência e mortalidade por meningite, que é a condição clínica mais grave. OBJETIVO: O presente estudo teve como objetivo avaliar o impacto da PCV10 na epidemiologia da meningite pneumocócica na região metropolitana de Salvador (RMS) Bahia, comparando o período anterior (2008-2010) e posterior (2011-2013) a sua utilização, bem como realizar uma caracterização molecular minuciosa a partir de uma série histórica (1996-2012) entre os isolados resistentes a penicilina (PNSSP com CIM≥ 0,125 μg/mL) e para os sorotipos não-vacinais (2008-2012). MATERIAL E MÉTODOS: Foram incluídos todos casos de meningite pneumocócica confirmados laboratorialmente no período entre 1996 a 2013. Taxas de incidência para a Salvador e RMS foram calculadas com base nos dados populacionais do IBGE/2010. A determinação do tipo capsular foi realizada através da técnica de Multiplex-PCR e/ou reação de Quellung. A sensibilidade a nove antimicrobianos foi testada através das técnicas disco-difusão, microdiluição e E-test. Para caracterizar o perfil molecular foram aplicadas as técnicas de genotipagem de PFGE e MLST. RESULTADOS: Um total de 939 casos de meningite pneumocócica foram identificados no período de 1996- 2013, sendo que 70 casos ocorrem entre 2011 a 2013 (período pós-vacinal). A incidência de meningite pneumocócica em todas as faixas etárias na RMS reduziu de 0,70 casos/100.000 habitantes para 0,59 casos/100.000 habitantes considerando o período de três anos antes e após a vacinação com PCV10 [p< 0,05; RR IC 95%: 1,46 (1,03-2,05)]. Esta redução foi significativa na faixa etária de 0-2 anos e nos casos por sorotipos relacionados à PCV10. Não houve aumento significativo de casos por sorotipos não vacinais nesta casuística, apesar do surgimento de casos por sorotipos não-vacinais não detectados anteriormente na série histórica de MP (10F, 21, 22F, 15A e 24F). Os isolados resistentes à penicilina analisados na série histórica se restringiram a 13 sorotipos, entre os quais: 14 (45,1 %; 78/173), 23F (19,1%; 33/173), 6B (14,4 %; 25/173), 19F (9,2 %; 16/173) e 19A (5,2 %; 9/173). 94% dos casos nãosusceptíveis à penicilina (PNSSP) foram de sorotipos vacinais. Os grupos clonais caracterizados pelo PFGE/MLST predominantes ao longo dos anos foram representados pelo sorotipo 14, denominado grupo A/ST 66 [35,3 % (61/173)] e grupo GK/ST 156 [4.6 % (8/173)], este último associado com níveis elevados de resistência a penicilina e ceftriaxona. Não foram detectados grupos clonais emergentes associados a tipos capsulares não-vacinais. CONCLUSÕES: Estes achados sugerem que a introdução da PCV10 modificou a epidemiologia da meningite pneumocócica na população estudada. / INTRODUCTION: In 2010, the 10-valent pneumococcal conjugate vaccine (PCV10) was introduced into the Brazilian national immunization program (NIP). This immunobiological provides immunization against the main ten capsular types of Streptococcus pneumoniae, the pathogen responsible for different clinical manifestations and high contribution in the incidence and mortality from meningitis, which is the most severe clinical condition. OBJECTIVE: This study aimed to evaluate the impact of PCV10 in the epidemiology of pneumococcal meningitis in the metropolitan area of Salvador (RMS) Bahia, comparing the previous (2008-2010) and after (2011-2013) periods its use, as well as conduct a thorough molecular characterization from a historical series (1996-2012) among isolates resistant to penicillin (PNSSP with CIM≥ 0.125 g / ml) and nonvaccine serotypes (2008-2012). MATERIAL AND METHODS: We included all cases of pneumococcal meningitis laboratory confirmed for the period 1996 to 2013. Incidence rates for Salvador and RMS were calculated based on population data from IBGE/2010. The capsular type determination was performed by multiplex PCR and/or Quellung reaction. Isolates Nine antibiotics were tested by disk-diffusion test, broth micro-dilution and E-test. To characterize the molecular profiling techniques were applied genotyping PFGE and MLST. RESULTS: A total of 939 cases of pneumococcal meningitis were identified during 1996-2013 period, with 70 cases occurring between 2011-2013 (post-vaccination period). The incidence of pneumococcal meningitis in all age groups in the RMS decreased from 0.70 cases / 100,000 inhabitants to 0.59 cases / 100,000 inhabitants considering the three-year period before and after vaccination with PCV10 [p <0.05; RR 95% CI: 1.46 (1.03 to 2.05)]. This reduction was significant in the age group 0-2 years and in cases by serotypes related to PCV10. There was no significant increase in cases by serotypes not vaccine in this series, despite the emergence of cases by serotypes not-vaccine previously undetected in the historical series of MP (10F, 21, 22F, 15A and 24F). The penicillin resistant isolates analyzed the historical series were restricted to 13 serotypes, including: 14 (45.1%; 78/173), 23F (19.1%; 33/173), 6B (14.4%; 25/173), 19F (9.2%, 16/173) and 19A (5.2%, 9/173). 94% of nonsusceptible to penicillin cases (PNSSP) were vaccine serotypes. Clonal groups characterized by PFGE / MLST predominant over the years have been represented by serotype 14, group called A / ST 66 [35.3% (61/173)] and Group GK / TS 156 [4.6% (8/173) ], the latter associated with elevated levels of penicillin and ceftriaxone resistance. Not were detected emerging clonal groups associated with capsular types non-vaccination. CONCLUSIONS: These findings suggest that the introduction of PCV10 changed the epidemiology of pneumococcal meningitis in the population studied.

Thesis (Master's Diploma(Technology (Medical Technology))-- Cape Technikon, 1997 / Meningitis in children is a common and serious disease. Bacterial and tuberculous meningitis often lead to neurological complications. A sensitive marker to predict brain damage in children with meningitis could be of great importance. Frithz F et aI, 1982 suggested that increased adenylate kinase values could indeed be used as a marker for brain damage. Adenylate kinase (AK) is an enzyme present in brain tissue. Low concentrations are present in normal cerebrospinal fluid (CSF) « 1 uti). Increased concentrations were found in cases of ischemic brain damage (Frithz et aI, 1982), malignant brain tumours (Ronquist G et aI, 1977) and bacterial meningitis. As AK has a low molecular weight (22,00 Daltons), in comparison to other kinases (40,000 Daltons) it is one of the first enzymes that can be detected in the CSF after brain damage and it can thus be used as a reliable marker for brain cell damage. The aim of this study was to quantify the AK values in CSF of children with bacterial and tuberculous meningitis and to evaluate their use to predict the neurological outcome in children with bacterial and tuberculous meningitis. Eighty eight children with tuberculous meningitis (TBM) and thirty three children with bacterial meningitis were included in the study. Sixty children with suspected meningitis but who were later diagnosed with urinary tract infections, gasto-enteritis, bronchitis, febrile convulsions or other non-neurological infections were used as controls. The results showed raised AK values in the CSF of children with bacterial- and TB meningitis. There was a statistically significant difference of AK values between stage III and II TBM AK values in patients at week 1 after diagnosis (p=0,03). There was also a statistically significant correlation between CSF AK values and lactate concentrations (P=0,001) which reflected hypoxic brain metabolism. Although AK values did not always correlate directly with the patients’ clinical outcome, there is proof that increased AK values in CSF can be used to predict neurological outcome.

Os aspectos epidemiolÃgicos da DoenÃa MeningocÃcica no tempo (ano e mÃs) e espaÃo (fatores ambientais) foram investigados de 1986 a 1998 em FortalezaâCearÃ-Brasil. As informaÃÃes foram obtidas de bancos de dados do Estado e MunicÃpio e de prontuÃrios mÃdicos. Na construÃÃo do diagrama de controle, o mÃtodo dos quartis foi comparado ao do desvio padrÃo, o primeiro detectou o inÃcio de uma epidemia mais precocemente. Os meses de marÃo, abril e maio registraram os maiores nÃmeros de casos, como tambÃm, as maiores mÃdias mensais de precipitaÃÃo, umidade relativa do ar e as menores mÃdias mensais de evaporaÃÃo. Observou-se que os casos da doenÃa meningocÃcica ocorreram semanas apÃs o aumento da precipitaÃÃo (500mm/mÃs); da umidade relativa do ar (>80%); da reduÃÃo da insolaÃÃo (<200horas/mÃs); e da evaporaÃÃo (<50mm/mÃs), sugerindo que essas variÃveis poderiam influenciar no comportamento da DoenÃa MeningocÃccica em Fortaleza. / The epidemiological aspects of the Meningococcal Disease in Fortaleza, State do CearÃ, Brazil, from 1986 to 1998, related to time and environmental factors were studied. The information was obtained from the Municipal and State Secretaries of Health data bank and also from patient records. The quartile method detected an epidemic sooner than the standard deviation. The months of March, April and May registered the largest number of cases, as well as the highest monthly averages of rain precipitation and relative humidity and the smallest monthly averages of evaporation. In Fortaleza, the cases of Meningococcal Disease occurred weeks after the increase in precipitation (500mm/mo) in relative humidity (>80%), the reduction of insulation (<200horas/mo) and evaporation (<50mm/mo); suggesting that those variables can influence the behavior of MD in Fortaleza.

Infecções por Neisseria meningitidis estão associadas a altos índices de morbimortalidade no mundo. Na Região da Grande São Paulo a Doença Meningocócica (DM) causada por Neisseria meningitidis sorogrupo C começou a se tornar prevalente em 2001 , representando, em 2003, 62,7% de todos os casos de DM sorogrupados sendo que aproximadamente 88,5% dessas cepas eram não sorotipados e não sorosubtipados (C:NST:NSST). Estes dados sugeriam que um fenótipo, C: NST:NSST, tinha emergido na Grande São Paulo e, considerando-se a importância histórica da doença na região, iniciamos o presente estudo com o objetivo de esclarecer a mudança na dinâmica da DM pela determinação das características fenotípicas e genotípicas destas cepas. Para tanto, analisamos por sorotipagem, tipagem das regiões Variáveis da PorA e PorB e do gene 16S RNA ribossomal, 753 cepas de N. meningitidis C isoladas de casos de DM provenientes da Grande São Paulo, no período de 1990 a 2003. Dado a impossibilidade de caracterização do novo fenótipo pelos anticorpos monoclonais disponíveis mundialmente, objetivamos também a produção de hibridomas produtores desses anticorpos para caracterização do fenótipo C:NST:NSST. Foram selecionadas duas linhagens celulares híbridas, produtoras de anticorpos monoclonais que reconhecem as proteínas PorA e PorB deste novo fenótipo. Entre as 255 cepas de N. meningitidis C inicialmente caracterizadas como NST:NSST, 75% (n=191) tomaram-se completamente sorotipadas como 23:P1.14-6. A análise da similaridade do gene 16S RNA ribossomal das cepas analisadas demonstrou um único padrão genético, sugerindo a clonalidade deste novo fenótipo. Os dados obtidos neste trabalho, demonstram a introdução, na Região da Grande São Paulo, de um novo clone de Neisseria meningitidis C apresentando o fenótipo C:23:P1.14-6 e que está sendo responsável pelo aumento dos casos de DM causada por este sorogrupo. / Neisseria meningitidis (Men) is an important cause of morbidity and mortality and is a leading cause of bacterial meningitis and septicemia in children and young adults in Brazil. Meningococcal disease caused by MenC started becoming the most prevalent serogroup in 2001, representing 62.7% of all MD cases serogrouped in 2003 in Greater Sao Paulo and approximately 88.5% of MenC isolates were nonserotypeable and non-serosubtypeable (NST:NSST). This data suggested that a novel invasive isolate (C:NT:NSST) had emerged in GSP, and considering the historical importance of MenC disease in the region, we initiated this study to better understand the dynamics of MD looking at the phenotypic and molecular characteristics of these isolates. To accomplish this goal, we characterized 753 MenC isolates recovered during the period of 1990 to 2003 by serotyping, PorS and PorA VR typing, 16S rRNA gene typing and produced new serotyping monoclonal antibodies (MAbs) to characterize the C:NST:NSST isolates. We were able to select two hybridoma cells that recognizes PorB and PorA proteins. Among the 255 strains initially characterized as NST:NSST, 75% (n=191) of them became completely serotyped as 23:P1 .14-6. Sy 16S RNA ribossomal typing, these strains showed the same pattern suggesting strain clonality. Our data demonstrate the introduction of a new clone of Neisseria rneningitidis C presenting the phenotype C:23:P1.14-6 and that is being responsible for the increase of the cases of DM caused by this serogroup in Great Sao Paulo.

Meningitis remains a frightening disease with a high morbidity and mortality in spite of optimal treatment. In South Africa in particular, the incidence of HIV-infected patents with meningitis has risen considerably during the past decade. The first part of this meningitis study evaluated prognostic indicators in meningitis. In 100 adult patients with meningitis it was found that the Glasgow Coma Scale (GCS) at admission was a good indicator of the ultimate prognosis of the patient, with a GCS value of > 12 associated with a good outcome in 88% of patients. A GCS value of < 8 predicted an unfortunate outcome in 88% of patients. A high CSF protein level was also associated with an unfortunate outcome but the statistical significance was not as marked as with the GCS value. Age, CSF-neutrophil count, and glucose levels were also evaluated as possible prognostic indicators but were not found to be statistically significant. The electroencephalograms of 12 patients with pneumococcal meningitis showed that a grade 4 dysfunction within 48 hours of admission indicated a poor outcome; CT brain scans of 26 patients with TB meningitis showed that an adverse outcome was seen particularly in patients with TB meningitis and infarcts while in 33 patients with bacterial meningitis no specific sign was found to indicate a bad prognosis - probably due to the small number of patients evaluated. Prognostic factors in cryptococcal meningitis were lastly evaluated retrospectively in 44 patients; age, CSF white cell count and CD 4 counts were not found to be associated with outcome, while a GCS value of ≤ 14 at admission was found in almost three quarters of patients with an eventual adverse outcome. The second part of the study evaluated the impact of HIV-infection on meningitis. Between 1994 and 1998, the HIV-epidemic caused a marked shift in the spectrum of meningitis towards chronic infections such as TB and cryptococcal meningitis, while the incidence of HIV-related cases with meningitis rose from 14% in 1994 to 5% in 1998. A comparison of clinical, CSF and pathological findings and outcomes in 20 HIV-positive and 17 HIV-negative patients with tuberculous meningitis showed that HIV-infection does not significantly alter clinical and CSF findings in TB meningitis in South Africa, but ventricular dilatation and infarcts occur more frequently in HIV-positive patients. Diagnostic aids in meningitis were assessed in the final part of this study. The polymerase chain reaction for TB was measured in the CSF of 10 patients with suspected tuberculous meningitis and disappointingly only positive in two patients in spite of positive CSF cultures for TB in an additional four patients. Lymphnode biopsies were performed on seven patients with intracranial tuberculosis. Excision biopsy of an enlarged Iymphnode showing caseating granulomas and/or acid-fast bacilli confirmed the diagnosis of TB within 48 hours of admission. Thus, Iymphnode biopsies may be an effective and practical aid in diagnosing intracranial TB. Adenosine deaminase (ADA) levels are often elevated in both tuberculous and bacterial meningitis. ADA iso-enzymes analysis in 26 patients however, showed that the ADA2 iso-enzyme was the major contributor to increased ADA activity in the CSF of patients with tuberculous meningitis and not with bacterial meningitis. The EEG was evaluated as diagnostic aid in 55 patients with meningitis to discriminate between viral and non-viral meningitis. Sensitivities of 70% and 80% of VEEG and QEEG's respectively were attained for the prediction of patients with non-viral meningitis, while the VEEG had a specificity of 100% for the prediction of viral meningitis. / Thesis (MD (Neurology))--University of Pretoria, 2005. / Neurology / unrestricted