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Scientific knowledge of meningococcal infection has increased greatly since the epidemic nature of the illness was first described by Vieusseux at the dawn of the nineteenth century. In fact, revolutionary advances have been made in public-health measures, antimicrobial therapy, diagnostic procedures, anti-inflammatory drugs and supportive care facilities. Based on the knowledge accumulated to date, it is generally accepted that the pathogenesis of meningococcal infection involves multiple links that interconnect in a complex web of phenomena fromNeisseria meningitidisattachment to meningococcal sepsis or meningitis. In fact, a myriad of strongly interacting inflammatory molecules and cells have been implicated in neisserial infection, illustrating the complexity of meningococcal pathogenesis. In addition, many of these signallers are critically involved in outcomes in the human host. Deciphering the pathogenesis of meningococcal infection could expand our knowledge and provide important clues to the host–pathogen interaction, as well as leading to the development of new therapeutic tools. Herein, we review the history of the discovery and characterization of meningococcal disease, epidemiological features of the disease with an emphasis on recent developments in Brazil, the cellular and molecular basis of disease, and discuss diagnosis and therapy.

O conhecimento científico da doença meningocócica cresceu significativamente desde que a natureza epidêmica da enfermidade foi pioneiramente descrita por Vieusseux no começo do século dezenove. De fato, dois séculos depois, houve avanços revolucionários nas esferas de saúde pública, técnicas diagnósticas, antibioticoterapia, assim como nas terapias adjuvantes envolvendo modulação das cascatas de coagulação e inflamação. Além disso, terapia de suporte para manter a homeostase via monitorização do status hemodinâmico, empregos de vasopressores, transfusão de plasma e suporte respiratório. Contudo, as taxas de letalidade e morbidade desta infecção não se alteraram significativamente nas últimas três décadas. Anualmente, a Organização Mundial de Saúde estima que ocorram 1.2 milhões de novos casos da doença, resultando em 135.000 mortes. No Brasil, anualmente, há 3500 casos da doença com uma taxa de incidência igual a 2 casos por 100.000 habitantes e uma taxa de letalidade igual a 20%. No Instituto de Infectologia Emílio Ribas (IIER) há 100 casos por ano. Assim, nós observamos um amplo espectro clínico da infecção, incluindo manifestações dramáticas como purpura fulminans e complicações atípicas como peritonite. O propósito deste estudo foi avaliar as características clínicas e laboratoriais, assim como a severidade da doença nos pacientes hospitalizados no IIER entre 2003 e 2004. Assim, pacientes previamente hígidos com diagnóstico de infecção meningocócica foram incluídos neste estudo prospectivo. Durante o período de estudo um total de 91 (53 homens e 38 mulheres) pacientes foram identificados como casos confirmados de infecção meningocócica como previamente descrito em materiais e métodos. Culturas de sangue, líquor, ou biópsia de pele de 39 pacientes (43%) foram positivas para N. meningitidis. Todos pacientes tiveram o exame de contraimunoeletroforese ou teste de aglutinação do látex positivo. A idade mediana dos pacientes foi igual a 6 anos (variação, 2 a 16 anos). A letalidade foi igual a 14% (13/91) e seqüelas ou complicações clínicas ocorreram em 63% (49/78) dos sobreviventes. Todos pacientes morreram de choque séptico e o tempo mediano entre hospitalização e óbito foi igual a 24 horas (variação, 18-72 horas). Concluindo, os resultados deste estudo prospectivo criam um elo entre infecção meningocócica e uma constelação de fenômenos fisiopatológicos: hipocalemia, hipomagnesemia, hipocalcemia, hiponatremia, hipoglicemia, hiperglicemia, leucopenia, coagulopatia e plaquetopenia. Os níveis de IL-6 e IL-10 corresponderam bem com a classificação baseada em parâmetros clínicos. A letalidade foi igual a 14% (13/91) e seqüelas ou complicações clínicas ocorreram em 63% (49/78) dos sobreviventes. Uma complexa interação entre mediadores é responsável por determinar a severidade da infecção e tais observações podem ser utilizadas para identificar fatores associados com a gravidade na fase aguda da infecção meningococócica Scientific knowledge of meningococcal infection has increased greatly since the epidemic nature of the illness was first described by Vieusseux at the dawn of the nineteenth century. In fact, two centuries later, revolutionary advances have been made in public health measures, diagnostic procedures, antimicrobial therapy, and adjunctive therapies involving modulation of the inflammatory and coagulation cascades. In addition, supportive care facilities can maintain homeostasis by monitoring hemodynamic status, administering vasoactive agents and/or plasma exchange, and providing respiratory support. However, the prognosis of and case fatality rate among patients affected by meningococcal disease have not changed significantly over the past 3 decades. The World Health Organization estimates that there are 1.2 million cases of meningococcal disease and 135,000 related deaths annually. In Brazil, 3500 cases are reported annually, with a median incidence of 2 cases per 100,000 population and a case-fatality rate of 20%. At the Emílio Ribas Institute of Infectology (ERII), the incidence of meningococcal disease is approximately 100 cases per year. Therefore, we have observed a broad range of clinical presentations of N. meningitidis infection, including dramatic manifestations as purpura fulminans and atypical complications such as peritonitis. The purpose of this study was to evaluate the clinical features, laboratory features, and the severity of meningococcal disease in patients admitted to the ERII between 2003 and 2004. Therefore, consecutive previously healthy patients with a diagnosis of meningococcal disease were included in a prospective cohort study. During the study period a total of 91 (53 males and 38 females) patients were identified as confirmed cases of meningococcal infection as previously described in material and methods. Cultures of blood, CSF, or skin biopsy specimens from 39 patients (43%) yielded N. meningitidis. All patients had positive counterimmunoelectrophoresis or latex agglutination test in blood or CSF. The median age of the patients was 6 years (range, 2 years to 16 years). The case fatality rate was 14% (13/91) and sequelae or clinical complications occurred in 63% (49/78) of the survivors. All patients died of irreversible septic shock and the median duration from the hospitalization until death was 24 hours (range, 18-72 hours). In conclusion, results from this prospective cohort study support a link between meningococcal infection and a constellation of pathophysiological phenomena: hypokalemia, hypomagnesemia, hypocalcemia, hyponatremia, hypoglycemia, hyperglycemia, leukopenia, coagulopathy, and thrombocytopenia. Both pro-inflammatory IL-6 and anti-inflammatory IL-10 corresponded well with a classification based on clinical parameters. The case fatality rate was 14% (13/91) and sequelae or clinical complications occurred in 63% (49/78) of the survivors. A complex interplay of mediators is responsible for determining severity of disease and these observations can be used to identify factors associated with severity in the acute phase of meningococcal infection

We report the first case of Neisseria meningitidis -induced septic peritonitis diagnosed by PCR assay of peritoneal fluid. Concentrations of interleukin-6 were notably higher in the peritoneal fluid than in the blood. PCR diagnosis of septic meningococcal peritonitis and the pathogenesis of the disease are discussed.

Herein, we report a case of purulent pericarditis caused by Neisseria meningitidis serogroup C in a previously healthy 5-year-old boy, which was detected in pericardial fluid by polymerase chain reaction. The concentrations of interleukin-6, interferon-gamma and interleukin-10 in pericardial fluid were notably increased compared with serum. The role of polymerase chain reaction, counterimmunoelectrophoresis and latex agglutination test in the diagnosis, as well as the participation of cytokines in the pathogenesis of meningococcal pericarditis, are discussed.

We describe an unusual case of leptospirosis in a 54-year-old man presenting peripheral nerve palsy. The diagnosis of leptospirosis was confirmed by ELISA IgM and the microscopic agglutination test. Electrophysiological studies showed that no response could be obtained from the right fibular nerve. At 7 months after the initiation of treatment, additional electrophysiological studies and a neurological examination showed, respectively, a chronic axonal lesion of right fibular nerve with signs of re-innervation and a nearly complete clinical recovery. We feel that this case may serve to remind clinicians that peripheral nerve palsy is a potential clinical feature of leptospirosis.

An unusual case of leptospirosis is described in a 19-month-old male child presenting with meningitis and acute renal failure without jaundice. Some aspects concerning the pathogenesis and treatment of this potentially life-threatening disease are also discussed. Leptospirosis was diagnosed on the basis of history and serological tests.

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.

We here report the case of a previously healthy 20-y-old male with disseminated meningococcal disease and purulent pericarditis. Polymerase chain reaction was used to identify Neisseria meningitidis serogroup C as the causative agent in the pericardial fluid.

The human immunodeficiency virus (HIV) infection epidemics increased the prevalence, multi-drug resistance and disseminated forms of tuberculosis. The central nervous system (CNS) tuberculosis has high mortality and morbidity, and it is usually divided into diffuse (meningitis) and localized (tuberculoma and abscess) forms. We report three cases of cerebral tuberculomas in AIDS patients: one with definitive diagnosis, confirmed with histopathology, and two with probable diagnosis, based on clinical information, radiological images, Mycobaterium tuberculosis isolation out of the CNS and adequate response to antituberculous treatment. Further, we discuss diagnostic, therapeutic and prognostic issues of tuberculomas, with emphasis in the distinction from cerebral tuberculous abscesses. Despite of their infrequent presentation, tuberculomas should be considered in the differential diagnosis of cerebral expansive lesions in patients with AIDS. A epidemia da infecção pelo vírus da imunodeficiência humana (HIV) aumentou a prevalência, multiresistência e formas disseminadas da tuberculose. O acometimento neurológico da tuberculose apresenta elevada morbidade e mortalidade, classificando-se em formas difusas (meningite) e localizadas (tuberculoma e abscesso). Relatamos três casos de tuberculomas cerebrais em pacientes com AIDS: um deles com diagnóstico definitivo, confirmado com histopatologia e dois com diagnóstico provável, baseado em informação clínica, radiológica, isolamento de Mycobaterium tuberculosis fora do sistema nervoso central e adequada resposta ao tratamento tuberculostático. Discutimos também aspectos diagnósticos, terapêuticos e prognósticos dos tuberculomas, enfatizando suas diferenças com os abscesos tuberculosos cerebrais. Apesar de serem relatados de forma infreqüente, os tuberculomas devem sempre ser considerados no diagnóstico diferencial das lesões expansivas cerebrais em pacientes com AIDS.

There is evidence that systemic inflammatory response and infectious diseases are associated with an increased risk of vascular events such as stroke and myocardial infarction in humans. However, the potential triggering effect of infectious diseases in carciovascular phenomena is typically underreported, overlooked and unexplored. The remarkable discovery of the link between cytokine networks and the pathophysiology of infectious diseases, together with studies of the CD14+ Toll-like receptor 4 (TLR4), has increased our knowledge of the inflammatory cascade within the vascular compartment as well as of coronary artery disease. In addition, meningococcal sepsis can trigger an important host inflammatory response characterized by systemic production of cytokines and chemokines, as well as activation of complement and nitric oxide pathways. However, the exact mechanism involved and the multiple pathogenic links by which infection influences acute cardiovascular events have not been explored, presenting a challenging puzzle for researchers. Determining cytokine concentrations could prove to be a valuable tool in evaluating the pathophysiology of myocardial infarction during infectious processes. The knowledge gained could guide the development of new strategies for reducing the occurrence of adverse cardiovascular events.

To the Editor: The excellent review by Pelton of meningococcal disease highlights clinical and epidemiological factors affecting prevention and management in the United States [1]. I would like to draw attention to a key point made in this review. The author has stated that, ‘‘Primary meningococcal bacteremia is the presenting syndrome in 30%–40% of patients with meningococcal disease.’’ Historically, at the dawn of the twentieth century, the pioneer Herrick, in his classic article entitled ‘‘Extrameningeal meningococcus infections,’’ appropriately stated: ‘‘For a satisfactory understanding of the complications of epidemic cerebrospinal meningitis a proper knowledge of the fundamental nature of disease is necessary’’ [2]. Astutely, he also stated that ‘‘the result of the study of epidemic cerebrospinal meningitis in the camps has been the quite definitive establishment of the disease as primarily a meningococcic sepsis, a blood-stream invasion from the initial focus in the upper air-passages with usual but not constant localization in various susceptible parts of the body’’ [2]. In fact, meningococcal pathogenesis involves multiple links that interconnect in a complex web of phenomena from Neisseria meningitidis attachment to meningococcal sepsis or meningitis [3]. As the first step in the chain of events, meningococci attach to the microvillous surface of nonciliated columnar mucosal cells of the human nasopharynx, where they multiply (colonization process) [4]. Subsequently, N meningitidis penetrates the mucosa and gains access to the bloodstream, causing bacteremia, which is a critical step in the pathophysiology of neisserial disease [4, 5]. Therefore, colonization and invasion of the nasopharyngeal mucosa with subsequent bacteremia are primary events in the genesis of meningococcal infection [3–5]. However, meningococcal sepsis occurs in only 5%–20% of patients [4]. In fact, bacteremia without sepsis is one of four major clinical syndromes of neisserial infection [6]. Meningococcal sepsis is a N meningitidis bacteremia associated with a systemic inflammatory response syndrome (SIRS), including leukocytosis, cutaneous manifestations as petechial or purpuric lesions, myalgia, weakness, fever, and high levels of cytokines [6, 7].