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.

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...

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.

Evolution of bacterial meningitis diagnosis in Sao Paulo State-Brazil and future challenges / Evolucao do diagnostico das meningites bacterianas no Estado de Sao Paulo-Brasil e os futuros desafios

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.

A meningite bacteriana (MB) é uma doença grave e ainda representa um sério problema de saúde pública, com altas taxas de morbidade e mortalidade. Os casos mais comuns de MB em todo o mundo, principalmente no Brasil, tem sido causados por Neisseria meningitidis, Streptococcus pneumoniae e Haemophilus influenzae tipo b. Cultura bacteriana é a técnica padrão-ouro para a confirmação de MB, mas cerca de 50% dos casos suspeitos não são confirmados por cultura, devido a problemas relacionados ao transporte inadequado e semeadura ou antibioticoterapia prévia. Métodos imunológicos apresentam baixa sensibilidade e têm possibilidade de reações cruzadas. PCR em tempo real (qPCR) é uma técnica molecular e tem sido utilizada com êxito para o diagnóstico de MB no Instituto Adolfo Lutz, em São Paulo, Brasil, desde 2007. A incorporação da qPCR na rotina de vigilância em Saúde Pública em nosso estado resultou na diminuição de 50% dos casos de MB indeterminadas. Nossos esforços estão focados na implementação da qPCR na rotina diagnóstica de MB em todo o Brasil.

Use of sodC versus ctrA for real-time polymerase chain reaction-based detection of Neisseria meningitidis in sterile body fluids.

We evaluated the use of a newly described sodC-based real-time-polymerase chain reaction (RT-PCR) assay for detecting Neisseria meningitidis in normally sterile sites, such as cerebrospinal fluid and serum. The sodC-based RT-PCR assay has an advantage over ctrA for detecting nongroupable N. meningitidis isolates, which are commonly present in asymptomatic pharyngeal carriage. However, in our study, sodC-based RT-PCR was 7.5% less sensitive than ctrA. Given the public health impact of possible false-negative results due to the use of the sodC target gene alone, sodC-based RT-PCR for the diagnosis of meningococcal meningitis should be used with caution.

Ocorrência de resultados falso-negativos na reação de PCR em Tempo Real (PCR-TR) no diagnóstico da doença meningocócica / False-negative results in Real-Time PCR (RT-PCR) formeningococcal disease diagnosis

Factors responsible for false-negative results (F-N) in RT-PCR assay for detecting N. meningitidis in serumand CSF samples were investigated. As the meningococcal disease should be rapidly treated because ofits high mortality and epidemic potential, the F-N in diagnostic testing may cause treatment failuresand/or on disease restraint in community. Thus, it is crucial to learn the factors which cause F-N in RTPCRassays. The F-N were induced by inhibition, low quantity of target DNA in extracted samples, andinadequate temperature employed at PCR annealing procedure. As bacterial DNA concentration in samplesmight be highly variable, the ideal sample volume to be extracted could not be defined. As previouslyrecommended for N. meningitidis gene-grouping by RT-PCR assay, the annealing temperature at 60 °Cwas not suitable for B and W135 genogroups. Altogether, these factors induced F-N in 31 samples; therefore,30 % of N. meningitidis detected by RT-PCR were classified as non-genogrouped. The inhibitors and/orthe low amount of target DNA induced F-N on RT-PCR, independently of the specimen volume used forextracting DNA. However, adjustments on the PCR annealing temperature and amount of extracted DNAadded into the reaction might avoid the occurrence of the majority of F-N.

Avaliação de resultados discrepantes obtidos na execução de PCR em tempo real em amostras de pacientes com suspeita clínica de meningite bacteriana / Inconsistent results in real-time PCR in analyzing samples from patients with suspected bacterial meningitis

O princípio básico para obter resultado confiável é a compatibilidade entre as réplicas e suareprodutibilidade. Na rotina diagnóstica por PCR em tempo real (PCR-TR), em que centenas de amostrassão processadas, a obtenção de resultados com Cts tardios ou réplicas que diferem entre si por mais de trêsunidades, são inevitáveis. Das 3.000 amostras processadas em 2010, em duplicata, na rotina diagnósticadas meningites bacterianas por PCR-TR na pesquisa de N. meningitidis, S. pneumoniae e H. influenzae,157 (5,2 %), apresentaram inconsistência entre as réplicas (diferença entre Cts maior do que 3) e/ou altosvalores de Cts; e os ensaios foram retestados. O presente trabalho investigou estes resultados obtidos, osbenefícios destas repetições e as possíveis razões da ocorrência dos resultados discrepantes. Verificouseque, apenas 18 (11 %) das amostras submetidas à repetição, apresentaram resultados positivos. Erroshumanos inerentes à pipetagem, como o uso de pipetas não calibradas, a baixa concentração de DNAalvo nas amostras, a degradação da sonda ou mesmo a possível contaminação aleatória são fatores quecontribuem para induzir resultados discrepantes. A realização do ensaio de PCR-TR com amostras emduplicata e a repetição de ensaios com resultados discordantes é um artifício eficiente para avaliar e definirestes resultados.

Fast test for assessing the susceptibility of Mycobacterium tuberculosis to isoniazid and rifampin by real-time PCR.

Mycobacterium tuberculosis is the bacterium that causes tuberculosis (TB), a leading cause of death from infectious disease worldwide. Rapid diagnosis of resistant strains is important for the control of TB. Real-time polymerase chain reaction (RT-PCR) assays may detect all of the mutations that occur in the M. tuberculosis 81-bp core region of the rpoB gene, which is responsible for resistance to rifampin (RIF) and codon 315 of the katG gene and the inhA ribosomal binding site, which are responsible for isoniazid (INH). The goal of this study was to assess the performance of RT-PCR compared to traditional culture-based methods for determining the drug susceptibility of M. tuberculosis. BACTEC TM MGIT TM 960 was used as the gold standard method for phenotypic drug susceptibility testing. Susceptibilities to INH and RIF were also determined by genotyping of katG, inhA and rpoB genes. RT-PCR based on molecular beacons probes was used to detect specific point mutations associated with resistance. The sensitivities of RT-PCR in detecting INH resistance using katG and inhA targets individually were 55% and 25%, respectively and 73% when combined. The sensitivity of the RT-PCR assay in detecting RIF resistance was 99%. The median time to complete the RT-PCR assay was three-four hours. The specificities for tests were both 100%. Our results confirm that RT-PCR can detect INH and RIF resistance in less than four hours with high sensitivity.

Fast test for assessing the susceptibility of Mycobacterium tuberculosis to isoniazid and rifampin by real-time PCR

Mycobacterium tuberculosis is the bacterium that causes tuberculosis (TB), a leading cause of death from infectious disease worldwide. Rapid diagnosis of resistant strains is important for the control of TB. Real-time polymerase chain reaction (RT-PCR) assays may detect all of the mutations that occur in the M. tuberculosis 81-bp core region of the rpoB gene, which is responsible for resistance to rifampin (RIF) and codon 315 of the katG gene and the inhA ribosomal binding site, which are responsible for isoniazid (INH). The goal of this study was to assess the performance of RT-PCR compared to traditional culture-based methods for determining the drug susceptibility of M. tuberculosis. BACTEC TM MGIT TM 960 was used as the gold standard method for phenotypic drug susceptibility testing. Susceptibilities to INH and RIF were also determined by genotyping of katG, inhA and rpoB genes. RT-PCR based on molecular beacons probes was used to detect specific point mutations associated with resistance. The sensitivities of RT-PCR in detecting INH resistance using katG and inhA targets individually were 55% and 25%, respectively and 73% when combined. The sensitivity of the RT-PCR assay in detecting RIF resistance was 99%. The median time to complete the RT-PCR assay was three-four hours. The specificities for tests were both 100%. Our results confirm that RT-PCR can detect INH and RIF resistance in less than four hours with high sensitivity.

Nova versão do ensaio da PCR em tempo real para o diagnóstico laboratorial e vigilância epidemiológica das meningites bacterianas / Impreved real time PCR assay for diagnostic and epidemiological surveillance of bacterial meningitis

A incorporação do ensaio “triplex” de PCR em tempo-real (PCR-TR) àvigilância das meningites bacterianas a partir de 2007 aumentou a detecção de S. pneumoniae em 52%, de N. meningitidis em 85% e de H. influenzae em 20%. Entretanto, a detecção do H. influenzae se limitou às cepas capsuladas de 4 sorotipos (“a”, “b”, “c”, “d”). Em 2011, um novo ensaio para detectar todos os sorotipos de H. influenzae, inclusive os H. influenzae não tipáveis, foi proposto,com a substituição do gene bexA pelo gene hpd no ensaio triplex (“triplexmodificado”) responsável pela proteína D de H. influenzae. Foram analisadas1619 amostras clínicas de líquido cefalorraquidiano e/ou sangue de pacientes com suspeita de meningite bacteriana do município de São Paulo no período de junho a dezembro de 2011, nos dois formatos de PCR-TR “triplex”. O novo ensaio “triplex modificado” (com o gene hpd) detectou 13 casos adicionais de H. influenzae, não registrados pelo outro formato (com o gene bexA). Destes 13 casos adicionais, 12 foram Hi-nt e um do sorotipo “f”. Não houve modificação na sensibilidade em detectar amostras positivas para N. meningitidis ou S. pneumoniae. O emprego deste novo formato “triplex modificado” irá aprimorar o diagnóstico e a vigilância epidemiológica das meningites bacterianas, contribuindo com a redução dos casos de meningite sem etiologia definida

Validação da técnica de contraimunoeletroforese (CIE) para o diagnóstico laboratorial das meningites por Neisseria meningitidis sorogrupos A, B, C e W135 / Validation of the counterimmunoelectrophoresis assay for laboratory diagnosis of meningitis caused by Neisseria meningitidis serogroups A, B, C and W135

A contraimunoeletroforese (CIE) é uma técnica amplamente empregada no Brasil para o diagnóstico laboratorial indireto das meningites causadas por Neisseria meningitidis (Men) dossorogrupos A, B, C e W135 ou Haemophilus influenzae sorotipo b (Hib). O objetivo deste trabalho foi validar a CIE empregando-se 301 amostras de líquido cefalorraquidiano (LCR) e 236amostras de soro de pacientes com suspeita de meningite bacteriana dos municípios de São Paulo e Campinas no período de 4 de junho de 2007 a 30 de maio de 2009. Em amostras de LCR, a CIE apresentou sensibilidade de 62,7% (42/67) (IC 95%, 50%-74,2%) e especificidade de 88,9% (208/234) (IC 95%, 84,1%-92,6%) para a detecção de Men. Em soro, a sensibilidade foi de35,3% (6/17) (IC 95%, 14,2%-61,7%) e a especificidade de 90,9% (199/219) (IC 95%, 86,3%-94,4%) Estes mesmos parâmetros não foram calculados para o componente Hib, devido à indisponibilidade de número significativo de amostras com cultura positiva para esta bactéria. Osresultados demonstraram que a técnica de CIE, embora tenha apresentado alta especificidade, apresentou baixa sensibilidade, especialmente em amostras de soro; assim, o uso da CIE não é recomendado como teste único para o diagnóstico das meningites bacterianas. Portanto, ressaltasea necessidade do emprego de outros testes indiretos com alta sensibilidade e especificidade, como a PCR em tempo real, para a melhoria do diagnóstico e do sistema de vigilância da doença

Uso da técnica de PCR em tempo real no diagnóstico etiológico das meningites baterianas assocadas ao Staphyloccoccus aureus / Real-time PCR for etiological dianosis of bacterial meningitis associated in Staphylococus aureus

Dados do Sistema de Informação de Agravos de Notificação (SINAN) mostram que, no município de São Paulo, em 2010 o gênero Staphylococcus esteve associado a 15 casos de meningite bacteriana confirmados por cultura. O objetivo deste trabalho foi analisar a frequência das meningites associadas à espécie Staphylococcus aureus no município de São Paulo no ano de 2010 por meio da técnica de PCR em tempo real (PCR-TR). Foram analisadas amostras de líquido cefalorraquidiano (LCR) e soro de 1.214 pacientes com suspeita de meningite bacteriana. Para a extração de DNA das amostras foi utilizado o kit comercial Nucleospin Blood® (Macherey-Nagel). A reação de PCR-TR utilizou o sistema TaqMan®, empregando-se o gene nuc, específico do S. aureus, como alvo. A espécie S. aureus esteve associada à meningite bacteriana em 16 (1,3%)dos 1.214 casos analisados. Todos estes casos tinham pelo menos um examecomplementar (bacterioscopia, cultura, contraimunoeletroforese e/ou teste deaglutinação pelo látex) realizado e PCR-TR em formato multiplex para Neisseriameningitidis, Streptococcus pneumoniae e Haemophilus influenzae negativo.Nenhum destes casos foi confirmado no SINAN como associado ao gêneroStaphylococcus. A técnica de PCR-TR pode representar ferramenta adicional àcultura para o diagnóstico etiológico das meningites associadas ao S. aureus,contribuindo para o aumento do número de casos de meningite bacteriana cometiologia determinada no município de São Paulo

Implantação e otimização da PCR em tempo real para o diagnóstico da influenza A (H1N1) pandêmica no Instituto Adolfo Lutz e perspectivas para 2010 / Implementation and optimization of real time PCR for diagnosis of pandemic influenza A (H1N1) at Instituto Adolfo Lutz and perspectives for 2010

Os autores apresentam sua experiência no diagnóstico laboratorial de InfluenzaA (H1N1) em 37.240 amostras clínicas obtidas de pacientes com suspeita de gripe, encaminhadas ao Instituto Adolfo Lutz para análise. Eles apresentam os algoritmos de testes moleculares empregados, comparam a eficiência dos mesmos quanto à sensibilidade, especificidade e custo e, finalmente sugerem um novo algoritmo para ser usado em caso de nova epidemia de Influenza A (H1N1) em 2010.

The authors present their experience with the molecular diagnosis of Influenza A (H1N1) with 37.240 clinicalsamples obtained from individuals suspected of flu, sent to Instituto Adolfo Lutz for analysis. They show the used algorithms, compare their efficiency in terms of sensitivity, specificity and cost, and suggest a new algorithm to be employed in case of an outbreak of Influenza A (H1N1) in 2010.

Severe myalgia of the lower extremities as the first clinical feature of meningococcal purpura fulminans.

In patients with meningococcal infection, devastating presentations, such as purpura fulminans, which can progress to extensive tissue necrosis of the limbs and digits, have a significant social impact. The case presented herein illustrates such a phenomenon in a patient who developed bilateral necrosis of the lower extremities as a result of infection with Neisseria meningitis. We emphasize that severe myalgia was the first clinical manifestation of meningococcal purpura fulminans in our case. However, myalgia has typically been overlooked and undervalued as an early clinical feature of meningococcal sepsis. Early recognition and prompt initial antibiotic therapy continue to be the cornerstones of the successful management of this dramatic disease, reducing morbidity and mortality.