Phenotypic and molecular characterization of serogroup C Neisseria meningitidis associated with an outbreak in Bahia, Brazil.

OBJECTIVE: To characterize meningococcal strains isolated from five cases of meningococcal disease (MD) associated with an outbreak in Trancoso - BA, occurred in October 2009. All cases, with the exception of a 39-year-old male, attended a dance party with approximately 1000 youngsters in a rural site. MATERIALS AND METHODS: The epidemiological investigation was conducted by the Epidemiological Surveillance Service of Bahia State. Meningococcal strains were characterized at Adolfo Lutz Institute, the Brazilian National Reference Laboratory for Bacterial Meningitis by conventional techniques (serotype, serosubtype and antimicrobial susceptibility test) and by molecular methods (Pulsed-field gel electrophoresis - PFGE and Multilocus Sequence Typing - MLST). RESULTS: The PFGE showed 2 closely related restriction profiles, designated as PFGE types A and A1, having 92% relatedness to each other. MLST characterization showed both A and A1 clones were ST-3780, which belongs to the ST-103 complex. All isolates displayed the phenotype C:23:P1.5 and were susceptible to all antibiotics tested. CONCLUSIONS: This is the first reported MD outbreak associated with serogroup C ST-103 complex in Brazil, as well as the party and illicit drug-use associated outbreak.

[Detection of rifampicin-resistant strains of Neisseria meningitidis in Uruguay]. / Detección de cepas de Neisseria meningitidis resistentes a rifampicina en el Uruguay.

The objective of this study was to characterize the phenotype and genotype of two isolates of rifampicin-resistant Neisseria meningitidis associated with two independent events involving transmission of severe meningococcal meningitis that occurred in September and October 2010 in Montevideo, Uruguay. The most recent 10 years of data from the national antimicrobial resistance surveillance system were reviewed to estimate the frequency of the particular meningococcal features that were characterized. Rifampicin resistance was studied using the epsilometer test. The serotype and serosubtype of the isolates were determined by ELISA, and the genotype was characterized using DNA digestion with Nhel and pulse field gel electrophoresis. The two isolates were identical: B:2a:P1.5. In the collection of 408 strains of N. meningitidis isolated in Uruguay in the past 10 years, the phenotype only appeared in two isolates, which were sensitive to rifampicin. The two isolates studied also shared a single pulse type, which was different from that of two other rifampicin-resistant isolates obtained in 2003 and 2007. Consequently, it was concluded that both cases of transmission were caused by a single rifampicin-resistant strain, which could have been an import from another country or else the result of a drift from serogroup C to B due to selective pressure exerted by vaccines administered to the population. It is essential to maintain and maximize surveillance. However, since this type of finding has been sporadic so far, unless a secondary case is identified, there is no justification for changing the antimicrobial drug currently being administered to contacts as prophylaxis.

[Meningococcal disease caused by Neisseria meningitidis: epidemiological, clinical, and preventive perspectives]. / Enfermedad por meningococo, Neisseria meningitidis: perspectiva epidemiológica, clínica y preventiva.

Bacterial meningitis constitutes a significant global public health problem. In particular, Neisseria meningitidis continues to be a public health problem among human populations in both developed and developing countries. Meningococcal infection is present as an endemic and an epidemic disease. Meningococcal disease is manifested not only as meningitis, but also as meningococcemia. The latter is usually fulminant. The global persistence of N. meningitidis is due to the significant number of carriers and the dynamics of transmission and disease. Approximately 500 million people worldwide are carriers of the bacterium in their nasopharynx. Multiple factors have been identified that predispose to the transmissibility of N. meningitidis, including active or passive inhalation tobacco smoking, upper viral respiratory tract infections, drought seasons, and overcrowding. These factors explain the frequent occurrence of outbreaks in military barracks, schools, prisons, and dormitories. Some of the determinants of invasiveness of the bacteria include nasopharyngeal mucosal damage in colonized individuals, virulence of the strains, absence of bactericidal antibodies, and deficiencies of the complement system. During both endemic and epidemic scenarios of meningococcal disease, control measures should include treating the cases with appropriate antimicrobial therapy (penicillin, ceftriaxone, or chloramphenicol); providing chemoprophylactic drugs to contacts (rifampin or ciprofloxacin), and close observation of contacts. Nevertheless, the key to effective control and prevention of meningococcal disease is immunoprophylaxis. Available vaccines include the polysaccharide monovalent, bivalent (serogroups A, C), or tetravalent (A, C, Y, W-135 serogroups) vaccines; conjugate vaccine (serogroup C); and the combined vaccine with outer membrane proteins and polysaccharide (serogroups B, C). Due to a recent increase in case reporting of serogroup C N. meningitidis in Mexico, we have developed a national response strategy that includes availability of vaccines and medications for chemoprophylaxis. This review aims at providing health care workers with updated information regarding the epidemiological, clinical, and preventive aspects of meningococcal disease. The English version of this paper is available at: http://www.insp.mx/salud/index.html.

Enfermedad por meningococo, Neisseria meningitidis: perspectiva epidemiológica, clínica y preventiva / Meningococcal disease caused by Neisseria meningitidis: epidemiological, clinical, and preventive perspectives

La meningitis bacteriana continúa siendo uno de los grandes problemas de la salud pública mundial. En particular, la infección por Neisseria meningitidis afecta tanto a países desarrollados como subdesarrollados, y se presenta en formas endémicas y epidémicas. La enfermedad meningocóccica se puede manifestar clínicamente no sólo como meningitis, sino con cuadros fulminantes de meningococcemia. La persistencia de N. meningitidis se debe al gran porcentaje de portadores y a la dinámica de transmisión de la bacteria. Aproximadamente 500 millones de personas en el mundo son portadoras de N. meningitidis en la nasofaringe. Los factores de transmisiblidad identificados han sido el tabaquismo activo o pasivo, la presencia de infecciones virales del tracto respiratorio superior, épocas de sequía, y el hacinamiento. Por lo anterior, se han descrito brotes de enfermedad meningocóccica en cuarteles militares, escuelas, cárceles y dormitorios. Algunos determinantes que permiten la invasión sistémica incluyen daños en la mucosa nasofaríngea de portadores, cepas virulentas con formación de cápsula, ausencia de anticuerpos bactericidas y deficiencias del sistema del complemento. El control de la enfermedad meningocóccica en circunstancias endémicas y epidémicas se logra por el tratamiento de casos con antibióticos adecuados (penicilina, ceftriaxona o cloranfenicol), la quimioprofilaxis de contactos cercanos (ciprofloxacina, rifampicina o ceftriaxona), y la vigilancia clínica de éstos. Sin embargo, es fundamental subrayar que la clave para el control efectivo de la enfermedad meningocóccica es la inmunoprofilaxis. Las vacunas disponibles incluyen las de polisacáridos monovalentes o bivalentes (serogrupos A y C), tetravalentes (A, C, Y, W-135), la conjugada (C) o la combinada de proteínas de membrana celular y polisacárido (B y C). Recientemente nos hemos visto forzados a establecer planes nacionales de respuesta que incluyen la disponibilidad de vacuna y de medicamentos para quimioprofilaxis, debido a que se ha documentado un incremento de casos de enfermedad por N. meningitidis, serogrupo C, en el país. Es por lo anterior que esta revisión está dirigida a proporcionar al personal de salud un recordatorio de los aspectos relevantes de la epidemiología, y de los clínicos y preventivos de la enfermedad meningocóccica.

[Approximation to the dynamics of meningococcal meningitis through dynamic systems and time series]. / Una aproximación a la dinámica de la meningitis meningocócica mediante sistemas dinámicos y series de tiempo.

Meningococcal meningitis is subjected to epidemiological surveillance due to its severity and the occasional presentation of epidemic outbreaks. This work analyses previous disease models, generate new ones and analyses monthly cases using ARIMA time series models. The results show that disease dynamics for closed populations is epidemic and the epidemic size is related to the proportion of carriers and the transmissiveness of the agent. In open populations, disease dynamics depends on the admission rate of susceptible and the relative admission of infected individuals. Our model considers a logistic populational growth and carrier admission proportional to populational size, generating an endemic dynamics. Considering a non-instantaneous system response, a greater realism is obtained establishing that the endemic situation may present a dynamics highly sensitive to initial conditions, depending on the transmissiveness and proportion of susceptible individuals in the population. Time series model showed an adequate predictive capacity in terms no longer than 10 months. The lack of long term predictability was attributed to local changes in the proportion of carriers or on transmissiveness that lead to chaotic dynamics over a seasonal pattern. Predictions for 1995 and 1996 were obtained.

Intercontinental spread of Neisseria meningitidis clones of the ET-5 complex.

The genetic structure of populations of Neisseria meningitidis was examined by an analysis of electrophoretically demonstrable allelic variation at 15 structural genes encoding enzymes in 688 isolates. Variation among strains in serogroup and serotype has little relationship to the complex structure of populations revealed by enzyme electrophoresis, which involves 14 major lineages of clones diverging from one another at more than half their genetic loci. Clones of one of these lineages, the ET-5 complex, have been identified as the causative agent of recent outbreaks and epidemics of meningococcal disease in Europe, South Africa, Latin America, and the United States. There is evidence that organisms of the ET-5 complex reached Florida via human immigrants from Cuba.

Meningococcal disease: still with us.

In spite of considerable success in the development of drugs and vaccines, the problem of disease due to Neisseria meningitidis is far from solved. As late as the 1970s, epidemics of meningococcal disease occurred in at least 30 countries in all parts of the world. Most of the epidemics were caused by group A organisms, but epidemics due to groups B and C also took place occasionally. The case/fatality rate was usually less than 10% among patients with true meningitis; among those with "pure" septicemia, it was as high as 70%. Children less than five years old are most prone to meningococcal disease, but mortality is often highest among young adults. Because close contacts of the index case are at considerable risk--at least several hundred times higher than in the rest of the population--they should be protected immediately with an appropriate antibiotic and, if possible, with a vaccine as well. At the present time, however, no vaccine is available for use against group B organisms, which in nonepidemic conditions are the most prevalent of all meningococci.

The risk of meningitis among classroom contacts during an epidemic of meningococcal disease.

During an epidemic of meningococcal disease in Belo Horizonte, Brazil, a retrospective survey was carried out to assess the risk of meningitis associated with exposure in a schoolroom. Forty-seven of 17,012 students reportedly had meningitis in August-November 1974, an incidence of 276 per 100,000. Four of 1356 students with classroom exposure to a case contracted meningitis (secondary attack rate, 295 per 100,000). The results indicate that in the population surveyed, 95% of whom were from 7 to 14 years of age, there is no significantly increased risk associated with classroom exposure to a student with meningitis. Antibiotic prophylaxis of classroom contacts is therefore not indicated and should be reserved for contacts known to be at increased risk, such as members of the patient's household or those having direct contact with the patient's oral secretions.