Centro de Imunologia do Instituto Adolfo Lutz ao longo dos anos / Immunology Center of Instituto Adolfo Lutz over the years

O Instituto Adolfo Lutz (IAL) foi criado em 1940 como resultado da unificação dos Institutos Bacteriológico e Bromatológico, um moderno laboratório voltado ao controle de doenças, inaugurando uma nova fase de laboratórios de saúde pública no estado de São Paulo. Os primeiros testes sorológicos oferecidos à população foram executados pelas "antigas" Seções de Sorologia e de Imunologia. Essas seções destacam-se no desenvolvimento científico do IAL pela realização de pesquisas, produção científica e inovação tecnológica, seguramente, fundamentais para a saúde pública no decorrer dos anos. O Centro de Imunologia do IAL (CIM-IAL) foi criado em 2010, com a unificação das Seções de Sorologia e Imunologia, quando ocorreu a reorganização institucional. O CIM-IAL contribuiu para importantes avanços científicos na área da saúde, reforçando sua capacidade de desenvolver pesquisas, executar e monitorar o diagnóstico e a vigilância de diferentes agravos. Este manuscrito tem como objetivo apresentar os principais acontecimentos que ressaltam o papel fundamental na busca de soluções para os problemas de saúde pública, desde a época das Seções de Sorologia e Imunologia até tornar-se o Centro de Imunologia. Na elaboração deste trabalho foram utilizadas bibliografias contendo dados históricos, científicos e relatos de profissionais da área.

A new phase of Public Health Laboratories in the state of São Paulo occurred in 1940, with the unification of Instituto Bacteriológico and Bromatológico, creating the Instituto Adolfo Lutz (IAL), a modern laboratory focused on solving problems in this area. The first diagnostic tests offered to the population were carried out by the "old" Serology and Immunology Sections. It's worth highlighting the importance of these sections in the scientific development of the IAL by carrying out research, scientific production and technological innovation, which have certainly been fundamental to public health over the years. The Immunology Center (CIM) of IAL was created in 2010, when organizational adaptation took place with the junction of the Serology and Immunology Sections. The CIM-IAL has undergone important advances in the health area, reinforcing its capacity to develop research, carry out and monitor the diagnosis and surveillance of different diseases. This manuscript aims to present the main events that highlight the fundamental role in the search for solutions to public health problems, from the time of the Serology and Immunology Sections until it became the CIM. In the preparation, bibliographies were used based on historical and scientific data and reports from professionals in the field.

Genomic characterization of invasive meningococcal X isolates from Brazil, 1992–2022 / Caracterización genómica de aislamientos invasivos de meningococo X de Brasil, 1992–2022

Introduction: Invasive meningococcal disease (IMD) is a major health problem. Given the post-COVID-19 pandemic scenario with the loosening of the non-pharmacological measures to control the virus transmission and considering the observed global reduction of meningococcal vaccination coverage, an increase in IMD cases can be expected. Methodology: Using whole-genome sequencing, we characterized six Neisseria meningitidis serogroup X (MenX) isolates recovered from IMD cases in Brazil in the last 30 years. Results: The predominance (66.6%, 4/6) of ST2888 presenting fHbp 160, NHBA 129, NadA 21, and PorA 19,15 was found on isolates. Two novel STs, 15458 and 15477, were described. Conclusion: This study describes the circulation of MenX lineage ST2888 in Brazil, previously reported only in Europe. Continuous universal surveillance is crucial to implement prompt public health measures aiming to prevent and control non-vaccine preventable serogroup X IMD cases.(AU)

Genomic characterization of invasive meningococcal X isolates from Brazil, 1992-2022.

INTRODUCTION: Invasive meningococcal disease (IMD) is a major health problem. Given the post-COVID-19 pandemic scenario with the loosening of the non-pharmacological measures to control the virus transmission and considering the observed global reduction of meningococcal vaccination coverage, an increase in IMD cases can be expected. METHODOLOGY: Using whole-genome sequencing, we characterized six Neisseria meningitidis serogroup X (MenX) isolates recovered from IMD cases in Brazil in the last 30 years. RESULTS: The predominance (66.6%, 4/6) of ST2888 presenting fHbp 160, NHBA 129, NadA 21, and PorA 19,15 was found on isolates. Two novel STs, 15458 and 15477, were described. CONCLUSION: This study describes the circulation of MenX lineage ST2888 in Brazil, previously reported only in Europe. Continuous universal surveillance is crucial to implement prompt public health measures aiming to prevent and control non-vaccine preventable serogroup X IMD cases.

Invasive Meningococcal X Disease during the COVID-19 Pandemic, Brazil.

Invasive meningococcal disease persists as a fulminant disorder worldwide. Although cases caused by Neisseria meningitidis serogroup X (MenX) occur infrequently, outbreaks have been reported in countries in Africa in recent decades. We report 2 cases of MenX invasive meningococcal disease in São Paulo, Brazil, in 2021 and 2022, during the COVID-19 pandemic.

Development and Validation of Multiplex Quantitative Real-Time PCR Assays for Simultaneous Detection and Differentiation of HTLV-1 and HTLV-2, Using Different PCR Platforms and Reagent Brands.

Brazil currently has the highest number of individuals infected with human T-lymphotropic virus 1- and 2- (HTLV-1 and HTLV-2) globally. At present, neither molecular protocols nor commercial assays are available for HTLV-1/-2 diagnosis or validated by the Brazilian Ministry of Health regulatory agency (ANVISA). We developed and validated two in-house multiplex quantitative real-time PCR for HTLV-1/-2 (mqPCR_HTLV) assays, targeting the pol and tax genes, for the simultaneous identification of HTLV-1, HTLV-2, and the albumin reference gene. The robustness of the assays was evaluated on two platforms using seven commercial master mix formulations. The reactions employed double plasmids (pHTLV1-Alb and pHTLV2-Alb) for the standard curve's construction and for expressing the detection limit of the assays. They were able to detect 10 and 10 copies of HTLV-1 and 10 and 70 copies of HTLV-2 for the tax and pol targets, respectively. High efficiency was obtained using both the platforms and all the reagents evaluated and were successfully reproduced by other analysts. DNA samples from HTLV-1/-2-infected and non-infected patients and from HIV/HTLV-coinfected patients were evaluated to determine the feasibility of their use in routine diagnosis. The mqPCR_HTLV (pol and tax) assays demonstrated an overall specificity of 100% and a sensitivity of 97.4% when testing samples from patients without HIV infection, and sensitivities of 77.1% (pol) and 74.6% (tax) in samples from HIV/HTLV-coinfected patients. In addition, they resolved the issue of HTLV western blotting (WB) indeterminate and WB-untyped results in 45.5 and 66.7% of cases, respectively. The developed mqPCR_HTLV (pol and tax) assays indicated their feasibility for efficient and reliable HTLV diagnosis in various core facility laboratories under different conditions and supplies.

Development and Validation of Multiplex Quantitative Real-Time PCR Assays for Simultaneous Detection and Differentiation of HTLV-1 and HTLV-2, Using Different PCR Platforms and Reagent Brands

Brazil currently has the highest number of individuals infected with human T-lymphotropic virus 1- and 2- (HTLV-1 and HTLV-2) globally. At present, neither molecular protocols nor commercial assays are available for HTLV-1/-2 diagnosis or validated by the Brazilian Ministry of Health regulatory agency (ANVISA). We developed and validated two in-house multiplex quantitative real-time PCR for HTLV1/-2 (mqPCR_HTLV) assays, targeting the pol and tax genes, for the simultaneous identification of HTLV-1, HTLV-2, and the albumin reference gene. The robustness of the assays was evaluated on two platforms using seven commercial master mix formulations. The reactions employed double plasmids (pHTLV1-Alb and pHTLV2-Alb) for the standard curve's construction and for expressing the detection limit of the assays. They were able to detect 10 and 10 copies of HTLV-1 and 10 and 70 copies of HTLV-2 for the tax and pol targets, respectively. High efficiency was obtained using both the platforms and all the reagents evaluated and were successfully reproduced by other analysts. DNA samples from HTLV-1/-2-infected and non-infected patients and from HIV/HTLV-coinfected patients were evaluated to determine the feasibility of their use in routine diagnosis. The mqPCR_HTLV (pol and tax) assays demonstrated an overall specificity of 100% and a sensitivity of 97.4% when testing samples from patients without HIV infection, and sensitivities of 77.1% (pol) and 74.6% (tax) in samples from HIV/HTLV-coinfected patients. In addition, they resolved the issue of HTLV western blotting (WB) indeterminate and WB-untyped results in 45.5 and 66.7% of cases, respectively. The developed mqPCR_HTLV (pol and tax) assays indicated their feasibility for efficient and reliable HTLV diagnosis in various core facility laboratories under different conditions and supplies. (AU)

Emergence of Neisseria meningitidis W South American sublineage strain variant in Brazil: disease and carriage.

Introduction. Invasive meningococcal disease is a major health problem, impacting morbidity and mortality worldwide. Exploratory genomics has revealed insights into adaptation, transmissibility and virulence to elucidate endemic, outbreaks or epidemics caused by Neisseria meningitidis serogroup W (MenW) strains.Gap Statement. Limited information on the genomics of Neisseria meningitis serogroup W ST11/cc11 is available from emerging countries, especially in contemporary isolates.Aim. To (i) describe the antigenic diversity and distribution of genetic lineages of N. meningitidis serogroup W circulating in Brazil; (ii) study the carriage prevalence of hypervirulent clones in adolescents students and (iii) analyse the potential risk factors for meningococcal carriage.Methodology. Using whole-genome sequencing, we analysed the genomic diversity of 92 invasive N. meningitidis serogroup W isolates circulating in Brazil from 2016 to 2019. A cross-sectional survey of meningococcal carriage was conducted in 2019, in the city of Florianópolis, Brazil, among a representative sample of 538 students.Results. A predominance (58.5 %, 41/82) of ST11/cc11 presenting PorB2-144, PorA VR1-5, VR2-2, FetA 1-1, and a novel fHbp peptide 1241 was found on invasive N. meningitidis W isolates, on the other hand, a high diversity of clonal complexes was found among carriage isolates. The overall carriage rate was 7.5 % (40/538). A total of 28 of 538 swab samples collected were culture positive for N. meningitidis, including four serogroup/genogroup B isolates (14.8 %;4/27), 1 serogroup/genogroup Y isolate (3.7 %;1/27), 22 (81.5 %; 22/27) non-groupable isolates. No MenW isolate was identified among carriages isolates.Conclusion. This report describes the emergence of the new MenW ST11/cc11 South America sublineage variant, named here, 2016 strain, carrying a novel fHbp peptide 1241, but its emergence, was not associated with an increased MenW carriage prevalence. Continuous surveillance is necessary to ascertain the role of this sublineage diversification and how its emergence can impact transmission.

Emergence of Neisseria meningitidis W South American sublineage strain variant in Brazil: disease and carriage

Introduction. Invasive meningococcal disease is a major health problem, impacting morbidity and mortality worldwide. Exploratory genomics has revealed insights into adaptation, transmissibility and virulence to elucidate endemic, outbreaks or epidemics caused by Neisseria meningitidis serogroup W (MenW) strains.Gap Statement. Limited information on the genomics of Neisseria meningitis serogroup W ST11/cc11 is available from emerging countries, especially in contemporary isolates.Aim. To (i) describe the antigenic diversity and distribution of genetic lineages of N. meningitidis serogroup W circulating in Brazil; (ii) study the carriage prevalence of hypervirulent clones in adolescents students and (iii) analyse the potential risk factors for meningococcal carriage.Methodology. Using whole-genome sequencing, we analysed the genomic diversity of 92 invasive N. meningitidis serogroup W isolates circulating in Brazil from 2016 to 2019. A cross-sectional survey of meningococcal carriage was conducted in 2019, in the city of Florianópolis, Brazil, among a representative sample of 538 students.Results. A predominance (58.5 %, 41/82) of ST11/cc11 presenting PorB2-144, PorA VR1-5, VR2-2, FetA 1-1, and a novel fHbp peptide 1241 was found on invasive N. meningitidis W isolates, on the other hand, a high diversity of clonal complexes was found among carriage isolates. The overall carriage rate was 7.5 % (40/538). A total of 28 of 538 swab samples collected were culture positive for N. meningitidis, including four serogroup/genogroup B isolates (14.8 %;4/27), 1 serogroup/genogroup Y isolate (3.7 %;1/27), 22 (81.5 %; 22/27) non-groupable isolates. No MenW isolate was identified among carriages isolates.Conclusion. This report describes the emergence of the new MenW ST11/cc11 South America sublineage variant, named here, 2016 strain, carrying a novel fHbp peptide 1241, but its emergence, was not associated with an increased MenW carriage prevalence. Continuous surveillance is necessary to ascertain the role of this sublineage diversification and how its emergence can impact transmission.

Evolução na vigilância laboratorial do Haemophilus influenzae nas meningites e pneumonias bacterianas, por PCR em tempo real, no Estado de São Paulo (2010-2019) / Evolução na vigilância laboratorial do Haemophilus influenzae nas meningites e pneumonias bacterianas, por PCR em tempo real, no Estado de São Paulo (2010-2019)

Haemophilus influenzae (Hi) é um importante patógeno causador de meningites (MB) e pneumonias bacterianas (PB), principalmente em países onde a imunoprevenção é precária ou inexistente. O Hi é classificado em tipáveis (sorotipos a, b, c, d, e, f) e não tipáveis (HiNt), de acordo com a presença ou ausência da cápsula polissacarídica, respectivamente. A cápsula é o principal fator de virulência dos Hi e o gene bexA, responsável pela sua expressão, é comumente empregado na detecção molecular e vigilância das MB e PB causadas por Hi. Em 2010, o Instituto Adolfo Lutz (IAL) implantou a PCR em tempo real (qPCR) empregando esse alvo genético para a detecção de Hi. Entretanto, relatos de falha na detecção de alguns Hi encapsulados e HiNt motivaram a substituição do gene alvo para essa bactéria. Desta forma, em agosto de 2012, o IAL fez a substituição do bexA pelo alvo genético hpd no ensaio de qPCR, permitindo a detecção de Hi tipáveis e não tipáveis. Neste estudo, avaliamos o impacto da substituição do alvo genético na vigilância das MB e PB analisando o emprego do alvo genético bexA, no período de 2010 a julho de 2012, em comparação com o emprego do hpd, de agosto de 2012 a 2019. Esta substituição promoveu a melhoria na detecção de variantes não vacinais de Hi nas MB e PB em 37% e 23%, respectivamente, com predomínio de Hia e HiNt, contribuindo para o aprimoramento da vigilância laboratorial das doenças invasivas causadas por Hi. (AU)

Haemophilus influenzae (Hi) is an important pathogen pathogen causing bacterial Meningitis (BM) and bacterial pneumonia (BP), especially in countries where immunoprevention is poor or absent. Hi is differentiated into encapsulated (serotypes a, b, c, d, e, f), and unencapsulated (HiNt), according to the presence or lack of the polysaccharide capsule, respectively. The capsule is the main Hi virulence factor; the bexA gene, responsible for its expression, has been largely used for molecular detection and surveillance of BM and BP. In 2010, the Adolfo Lutz Institute (ALI) implemented real-time PCR (qPCR) using the bexA gene for detecting Hi; but reports on its failing to detect some encapsulated Hi and HiNt caused IAL to replace bexA with hpd as the target gene in the qPCR assay, extending Hi detection to both encapsulated and unencapsulated Hi. In this study, we assessed the impact of replacing the target gene on BM and BP surveillance, by analyzing the use of bexA target gene, within the period from 2010 to July 2012, compared with the use of hpd, from August 2012 to 2019. Adopting the hpd target gene in BM and BP surveillance improved the detection of non-vaccine Hi variants by 37% and 23%, respectively, predominantly Hia and HiNt; and it has contributed to improve laboratory surveillance of invasive Hi diseases. (AU)

Long-term effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae in children in Brazil.

Brazil introduced the 10-valent pneumococcal vaccine (PCV10) to the routine national immunization program (NIP) in March 2010. In 2017, we investigated the effects of PCV10 on nasopharyngeal carriage of vaccine-types (VT) and non-vaccine-types (NVT) of Streptococcus pneumoniae (Spn) among children living in São Paulo city. We also compared the prevalence of VT and NVT with previous carriage surveys performed in 2010 (baseline) and 2013. METHOD: The carriage survey was conducted among 531 children, aged 12 months to <24 months, recruited from public Primary Health Units during the immunization campaign, using previous surveys methodology, except for qPCR, which was performed in the 2017 survey only. RESULTS: No statistical difference was found in the prevalence of Spn either by culture (59.7%) or by qPCR (61.2%). Spn carriage increased from 40.3% (baseline) to 59.7% (2017 survey) (p < 0.001). Colonization by VT isolates significantly decreased by 90.9% (19.8-1.8%) and 95.5% (19.8-0.9%) in the 2013 and 2017 surveys, respectively, compared to that at baseline. NVT isolates increased significantly by 128% (19.6-44.8%) and 185% (19.6-55.9%) in the respective post-PCV10 surveys, most led to high prevalence of serotypes 6C (27%), 15B (9.8%), 19A (9.2%), 15A (6.0%), and 16F (5.7%). In 2017, reduction in serotype 6A (4.2-0.6%, p < 0.001) and increase in serotype 19A (1.8-6.0%, p = 0.001) were found; serotype 3 isolate was not detected in the present survey. We identified the emergence of 19A isolates CC320, associated with high penicillin (MIC ≥ 2.0 mg/L) and cefotaxime (MIC ≥ 1.0 mg/L) values. CONCLUSION: After 7 years of PCV10 introduction in the NIP, colonization by VT among toddlers decreased substantially to a residual level, along with substantial serotype replacement by novel serotypes not present in any current conjugated pneumococcal vaccine and serotype 19A. The present findings can assist policy decisions in Brazil.

Long-term effect of 10-valent pneumococcal conjugate vaccine on nasopharyngeal carriage of Streptococcus pneumoniae in children in Brazil

Brazil introduced the 10-valent pneumococcal vaccine (PCV10) to the routine national immunization program (NIP) in March 2010. In 2017, we investigated the effects of PCV10 on nasopharyngeal carriage of vaccine-types (VT) and non-vaccine-types (NVT) of Streptococcus pneumoniae (Spn) among children living in São Paulo city. We also compared the prevalence of VT and NVT with previous carriage surveys performed in 2010 (baseline) and 2013. Method: The carriage survey was conducted among 531 children, aged 12 months to <24 months, recruited from public Primary Health Units during the immunization campaign, using previous surveys methodology, except for qPCR, which was performed in the 2017 survey only. Results: No statistical difference was found in the prevalence of Spn either by culture (59.7%) or by qPCR (61.2%). Spn carriage increased from 40.3% (baseline) to 59.7% (2017 survey) (p < 0.001). Colonization by VT isolates significantly decreased by 90.9% (19.8­1.8%) and 95.5% (19.8­0.9%) in the 2013 and 2017 surveys, respectively, compared to that at baseline. NVT isolates increased significantly by 128% (19.6­44.8%) and 185% (19.6­55.9%) in the respective post-PCV10 surveys, most led to high prevalence of serotypes 6C (27%), 15B (9.8%), 19A (9.2%), 15A (6.0%), and 16F (5.7%). In 2017, reduction in serotype 6A (4.2­0.6%, p < 0.001) and increase in serotype 19A (1.8­6.0%, p = 0.001) were found; serotype 3 isolate was not detected in the present survey. We identified the emergence of 19A isolates CC320, associated with high penicillin (MIC 2.0 mg/L) and cefotaxime (MIC 1.0 mg/L) values. Conclusion: After 7 years of PCV10 introduction in the NIP, colonization by VT among toddlers decreased substantially to a residual level, along with substantial serotype replacement by novel serotypes not present in any current conjugated pneumococcal vaccine and serotype 19A. The present findings can assist policy decisions in Brazil

Use of cerebrospinal fluid and serum samples impregnated on FTATM Elute filter paper for the diagnosis of infections caused by Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae.

BACKGROUND: The lack of information regarding the burden of acute bacterial meningitis in Latin America leads to a reduction in the estimated incidence rates of the disease, and impairs public health decisions on the use and follow-up of preventive interventions, particularly, the evaluation of existing vaccination policies. The use of the real-time PCR in diagnostic routine procedures has resulted in a substantial increase in confirmed bacterial meningitis cases. However, in resource-poor countries, these assays are only available in reference laboratories. Sample transportation to these laboratories is a critical constraint, as it requires specialized, high cost courier services. To overcome this barrier we evaluated the use of FTATM Elute filter paper cards for the conservation and processing of samples under normal environmental conditions, as they would be when transported from remote and under-equipped healthcare facilities to the reference centers. A total of 401 samples received in 2015 as part of Sao Paulo's national surveillance for routine diagnosis were selected for this study. METHODS: The sensitivity and specificity of real-time PCR were evaluated using fresh serum and cerebrospinal fluid (CSF) samples processed using our laboratory's standard DNA extraction, and processing the same samples after being dried and stored on FTATM card, and DNA extracted following the manufacturer's instructions. RESULTS: The sensitivities for detection of Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae from CSF dried and stored on FTATM cards were 98%, 92%, and 100%, respectively, and with serum samples were 73%, 88%, and 100%, respectively. When compared to our laboratory's standard methodology, results showed high concordance, with Kappa index ranges of 0.9877-1.00 for CSF, and 0.8004-1.00 for serum samples. CONCLUSION: The use of FTATM cards for CSF and serum conservation and transport represents a rapid, reliable, and cost-effective alternative that will allow obtaining valuable epidemiological information that would otherwise be lost.

Use of cerebrospinal fluid and serum samples impregnated on FTATM Elute filter paper for the diagnosis of infections caused by Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae

Background The lack of information regarding the burden of acute bacterial meningitis in Latin America leads to a reduction in the estimated incidence rates of the disease, and impairs public health decisions on the use and follow-up of preventive interventions, particularly, the evaluation of existing vaccination policies. The use of the real-time PCR in diagnostic routine procedures has resulted in a substantial increase in confirmed bacterial meningitis cases. However, in resource-poor countries, these assays are only available in reference laboratories. Sample transportation to these laboratories is a critical constraint, as it requires specialized, high cost courier services. To overcome this barrier we evaluated the use of FTATM Elute filter paper cards for the conservation and processing of samples under normal environmental conditions, as they would be when transported from remote and under-equipped healthcare facilities to the reference centers. A total of 401 samples received in 2015 as part of Sao Paulo's national surveillance for routine diagnosis were selected for this study. Methods The sensitivity and specificity of real-time PCR were evaluated using fresh serum and cerebrospinal fluid (CSF) samples processed using our laboratory's standard DNA extraction, and processing the same samples after being dried and stored on FTATM card, and DNA extracted following the manufacturer's instructions. Results The sensitivities for detection of Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae from CSF dried and stored on FTATM cards were 98%, 92%, and 100%, respectively, and with serum samples were 73%, 88%, and 100%, respectively.

Prevalence, risk factors and molecular characteristics of meningococcal carriage among brazilian adolescents

BACKGROUND: In 2010, introduction of the meningococcal C conjugate vaccine in Brazil for children <2 years provided an immediate reduction in the incidence rates of disease among the age groups targeted for the vaccine, but no early impact was observed in unvaccinated age groups. Knowledge about meningococcal carriage is crucial for improving our understanding of the disease epidemiology and for designing effective vaccination programs. Taking in account the very limited published data currently available describing meningococcal carriage in Brazil, we performed a study to evaluate the prevalence of Neisseria meningitidis carriage among adolescent students. METHODS: A cross-sectional study was conducted in 2012 to assess the prevalence of meningococcal carriage among a representative sample of 1208 students 11­19 years of age in Campinas, Brazil. Genotypic and phenotypic characterization of isolated carriage strains and the effect of potential risk factors for carriage were also analyzed. Results: The overall carriage prevalence was 9.9% (95% confidence interval, 8.3­11.8%), with dominance of serogroup C (1.32%), followed by serogroups B (0.99%), E (0.74%), Y (0.49%) and W (0.25%). A lower level of education of the parents was independently associated with a higher risk of carriage. A high diversity of genotypes was found among carriage strains. CONCLUSIONS: The evidence gathered during this study provides estimates of carriage prevalence in Brazilian adolescents, showing an unusually high dominance of serogroup C. These results have important implications in future strategies to optimize the impact of the current meningococcal C vaccination program in Brazil

Prevalence, Risk Factors and Molecular Characteristics of Meningococcal Carriage Among Brazilian Adolescents.

BACKGROUND: In 2010, introduction of the meningococcal C conjugate vaccine in Brazil for children <2 years provided an immediate reduction in the incidence rates of disease among the age groups targeted for the vaccine, but no early impact was observed in unvaccinated age groups. Knowledge about meningococcal carriage is crucial for improving our understanding of the disease epidemiology and for designing effective vaccination programs. Taking in account the very limited published data currently available describing meningococcal carriage in Brazil, we performed a study to evaluate the prevalence of Neisseria meningitidis carriage among adolescent students. METHODS: A cross-sectional study was conducted in 2012 to assess the prevalence of meningococcal carriage among a representative sample of 1208 students 11-19 years of age in Campinas, Brazil. Genotypic and phenotypic characterization of isolated carriage strains and the effect of potential risk factors for carriage were also analyzed. RESULTS: The overall carriage prevalence was 9.9% (95% confidence interval, 8.3-11.8%), with dominance of serogroup C (1.32%), followed by serogroups B (0.99%), E (0.74%), Y (0.49%) and W (0.25%). A lower level of education of the parents was independently associated with a higher risk of carriage. A high diversity of genotypes was found among carriage strains. CONCLUSIONS: The evidence gathered during this study provides estimates of carriage prevalence in Brazilian adolescents, showing an unusually high dominance of serogroup C. These results have important implications in future strategies to optimize the impact of the current meningococcal C vaccination program in Brazil.

Prevalência de infecção por HTLV-1 e HTLV-2 em pacientes infectados pelo HIV em serviço especializado de São Paulo / Prevalence of HTLV-1 and HTLV-2 in patients infected with HIV from a Reference Center of São Paulo

Os HTLV-1, HTLV-2 e HIV compartilham as mesmas vias de transmissão e as prevalências de coinfecção HIV/HTLV-1 e HIV-HTLV-2 variam de acordo com a região geográfica, a população de estudo e a época em que foi realizada a pesquisa. Altas taxas de coinfecção foram detectadas em pacientes com Aids em São Paulo na década de 1990 e foram associadas ao uso de drogas injetáveis (UDI). Neste estudo foi determinada a prevalência e os fatores de risco para a coinfecção HIV/HTLV em pacientes do CRT-DST/Aids de São Paulo. Amostras de sangue de 1.608 pacientes que aceitaram participar do estudo foram encaminhadas ao Instituto Adolfo Lutz para pesquisa de anticorpos anti-HTLV-1/2 por ensaio imunoenzimático e Western Blot (WB) e para pesquisa de DNA proviral pela PCR em tempo real pol. Na triagem sorológica, 51 soros resultaram reagentes para HTLV. Destes, pelo WB, 23 (1,43%) confirmaram infecção HTLV-1, 12 (0,75%) HTLV-2 e 6 (0,37%) HTLV não tipado. Pela PCR houve detecção de mais um caso de HTLV-1 (total 1,49%) e cinco casos de HTLV-2 (total 1,06%). Houve associação entre infecção HTLV-1/2 e gênero feminino (p=0.0027), cor negro/pardo (p=0.0332), infecção pelo HBV (p=0.0019), HCV e UDI (p<0.0000). A PCR em tempo real foi útil para confirmar casos com resultado HTLV não tipado e Indeterminado pelo WB e pode ser usada como primeiro teste confirmatório seguido do WB. A baixa prevalência de coinfecção HIV/HTLV no presente estudo parece estar relacionada a mudanças na população exposta ao HIV e na troca de cocaína injetável por crack no momento atual...

Carriage rate and effects of vaccination after outbreaks of serogroup C meningococcal disease, Brazil, 2010.

During 2010, outbreaks of serogroup C meningococcal (MenC) disease occurred in 2 oil refineries in São Paulo State, Brazil, leading to mass vaccination of employees at 1 refinery with a meningococcal polysaccharide A/C vaccine. A cross-sectional study was conducted to assess the prevalence of meningococci carriage among workers at both refineries and to investigate the effect of vaccination on and the risk factors for pharyngeal carriage of meningococci. Among the vaccinated and nonvaccinated workers, rates of overall meningococci carriage (21.4% and 21.6%, respectively) and of MenC carriage (6.3% and 4.9%, respectively) were similar. However, a MenC strain belonging to the sequence type103 complex predominated and was responsible for the increased incidence of meningococcal disease in Brazil. A low education level was associated with higher risk of meningococci carriage. Polysaccharide vaccination did not affect carriage or interrupt transmission of the epidemic strain. These findings will help inform future vaccination strategies.

Evolution of bacterial meningitis diagnosis in São Paulo State-Brazil and future challenges.

Bacterial meningitis (BM) is a severe disease and still represents a serious public health problem with high rates of morbidity and mortality. The most common cases of BM around the world, mainly in Brazil, have been caused by Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type b. Bacterial culture is the gold-standard technique for BM confirmation, but approximately 50% of suspected cases are not culture-confirmed, due to problems related to improper transportation and seeding or previous antibiotic treatment. Immunological methods present low sensitivity and have possibility of cross-reactions. Real time PCR (qPCR) is a molecular technique and has been successful used for BM diagnosis at Instituto Adolfo Lutz in São Paulo State, Brazil, since 2007. The incorporation of qPCR in the Public Health surveillance routine in our state resulted in diminishing 50% of undetermined BM cases. Our efforts are focused on qPCR implementation in the BM diagnostic routine throughout Brazil.