Comparison of Pathogenicity of Invasive and Carried Meningococcal Isolates of ST-4821 Complex in China.

Serotype 4821 (ST-4821) clonal complex (cc4821) Neisseria meningitidis strains are divided into two groups (groups I and II) according to the core genome-based phylogenetic analysis. Group I contains the greater number of invasive disease isolates. However, the differences in pathogenicity between the two groups are unclear. In this study, the pathogenicity of cc4821 isolates (n = 28) belonging to group I and group II (each containing eight invasive isolates and six isolates from healthy carriers) was investigated, including adhesion, invasion, and induction of interleukin-6 (IL-6) and interleukin-8 (IL-8) release from host cells (Hep2 and A549). The invasive isolates had higher adhesion and invasion capabilities than the carried isolates in both groups. The carried cc4821 isolates in group I had stronger invasion capability than those in group II. Invasive isolates induced more IL-6 and IL-8 secretion than carried isolates in both groups. The carried cc4821 isolates stimulated higher levels of IL-8 in group I than in group II. The isolates were defined as hyperadherent and hypoadherent groups according to their adhesion ability and as hyperinvasive and hypoinvasive groups based on their invasion ability. The hyperadherent and hyperinvasive isolates mediated more IL-6 and IL-8 release than the hypoadherent and hypoinvasive isolates. There was no difference in the level of cytokine release when cc4821 isolates lost their adhesion and invasion capability after lysis. The results revealed that differences in pathogenicity existed between the two groups and that the differences were mainly determined by differences in adhesion and invasion capabilities.

Síndrome de waterhouse friderichsen secundario a meningoccocemia fulminante / Waterhouse friderichsen secondaria to fulminant meningococemia

Neisseria meningitidis (meningococo), es un diplococo Gram negativo específico del ser humano, único reservorio conocido hasta la fecha; se clasifica en 13 serogrupos en base a la composición química de polisacárido capsular, no obstante, la enfermedad epidémica es causada por los serogrupos A, B, C, Y y W-135. En el presente caso clínico el agente patógeno aislado corresponde a la especie Neisseria meningitidis serogrupo W-135, cuya cepa no había sido aislada en 21 años en nuestro país y dicha anatomía patológica reportó hemorragia intracapsular de ambas glándulas suprarrenales secundaria al shock séptico inducido por la endotoxina específica de este patógeno(AU)

Neisseria meningitidis (meningococcus) is a Gram negative diplococcus specific to human and the only reservoir known to date; it is classified into 13 serogroups according to the chemical composition of capsular polysaccharide, however, epidemic disease is caused by serogroups A, B, C, Y and W-135. In this case we report an isolated pathogen that corresponds to serogroup W-135,This strain had not been isolated in 21 years in our country and this pathology reported intracapsular bleeding from both secondary adrenal glands to septic shock induced endotoxin specified pathogen(AU)

[Meningococcemia without meningitis: A report of two cases]. / Méningococcémie sans méningite: à propos de deux observations.

INTRODUCTION: Meningococcemia without meningitis is an often under recognized clinical form of invasive Neisseria meningitidis infection. CASE REPORTS: We report two unusual cases of invasive meningococcal disease who presented with meningococcemia without distinct signs of meningitis or severe sepsis manifestation. In both cases, confirmation of the diagnosis is provided by meningococcal PCR performed on blood or skin lesion biopsy. CONCLUSION: Clinical recognition of this entity is crucial for early antibiotic treatment and to avoid delayed diagnosis and potentially dangerous complications.

Neisseria meningitidis induces brain microvascular endothelial cell detachment from the matrix and cleavage of occludin: a role for MMP-8.

Disruption of the blood-brain barrier (BBB) is a hallmark event in the pathophysiology of bacterial meningitis. Several inflammatory mediators, such as tumor necrosis factor alpha (TNF-alpha), nitric oxide and matrix metalloproteinases (MMPs), contribute to this disruption. Here we show that infection of human brain microvascular endothelial cells (HBMEC) with Neisseria meningitidis induced an increase of permeability at prolonged time of infection. This was paralleled by an increase in MMP-8 activity in supernatants collected from infected cells. A detailed analysis revealed that MMP-8 was involved in the proteolytic cleavage of the tight junction protein occludin, resulting in its disappearance from the cell periphery and cleavage to a lower-sized 50-kDa protein in infected HBMEC. Abrogation of MMP-8 activity by specific inhibitors as well as transfection with MMP-8 siRNA abolished production of the cleavage fragment and occludin remained attached to the cell periphery. In addition, MMP-8 affected cell adherence to the underlying matrix. A similar temporal relationship was observed for MMP activity and cell detachment. Injury of the HBMEC monolayer suggested the requirement of direct cell contact because no detachment was observed when bacteria were placed above a transwell membrane or when bacterial supernatant was directly added to cells. Inhibition of MMP-8 partially prevented detachment of infected HBMEC and restored BBB permeability. Together, we established that MMP-8 activity plays a crucial role in disassembly of cell junction components and cell adhesion during meningococcal infection.

Inhibition of macrophage apoptosis by Neisseria meningitidis requires nitric oxide detoxification mechanisms.

Host-driven macrophage apoptosis contributes to innate immunity during bacterial infection. Neisseria meningitidis inhibits apoptosis in a variety of cells, but its impact on macrophage apoptosis is unknown. We demonstrate that N. meningitidis prevents macrophage apoptosis via genes encoding nitric oxide detoxification and a porin, PorB.

Meningitis por N. meningitis en pediatría / N meningitidis meningitis in children

La meningitis producida por N. meningitidis (Nm) es la forma más frecuente de enfermedad invasiva. Con el objetivo de analizar las características clínicas, microbiológicas y de evolución de pacientes con diagnóstico de meningitis por Nm con o sin meningococcemia se realizó un estudio retrospectivo de 190 pacientes (P) internados durante el perído octubre 1992 a enero 2001. La mediana de edad fue de 24 meses (r:1-180m). Al sexo masculino correspondieron 170p (56 porciento). En 47p (25 por ciento) se pudo determinar el antecedente de infección viral previa y 23 p (12 por ciento) habían recibido antibióticos previos. En 5 p (3 por ciento) hubo contacto con convivientes con infeción por Nm. El diagnóstico fue de meningitis en 139 p (73 por ciento) y en 51p (27 por ciento) meningitis con meningococcemia. La fiebre 186p (98 por ciento) y el rash 124p (65 por ciento) fueron las manifestaciones clínicas más frecuentes. En 8 p (4 por ciento) no se detectó reacción inflamatoria en liquido cefalorraquideo, pero los cultivos fueron positivos. En 115p (81 por ciento) se realizó serotipificación, correspondiento al serogrupo B 74 cepas (48 por ciento). La mortalidad fue del 1 por ciento (2p), ambos con miningococcemia. Conclusiones: la fiebre y el rash fueron las manifestaciones clínicas más frecuentes, los serogrupos B y C fueron los predominantes. La mortalidad se relacionó con meningococcemia.

Matrix metalloproteinase (MMP)-8 and MMP-9 in cerebrospinal fluid during bacterial meningitis: association with blood-brain barrier damage and neurological sequelae.

To evaluate the spectrum and regulation of matrix metalloproteinases (MMPs) in bacterial meningitis (BM), concentrations of MMP-2, MMP-3, MMP-8, and MMP-9 and endogenous inhibitors of metalloproteinases (TIMP-1 and TIMP-2) were measured in the cerebrospinal fluid (CSF) of 27 children with BM. MMP-8 and MMP-9 were detected in 91% and 97%, respectively, of CSF specimens from patients but were not detected in control patients. CSF levels of MMP-9 were higher (P<.05) in 5 patients who developed hearing impairment or secondary epilepsy than in those who recovered without neurological deficits. Levels of MMP-9 correlated with concentrations of TIMP-1 (P<.001) and tumor necrosis factor-alpha (P=.03). Repeated lumbar punctures showed that levels of MMP-8 and MMP-9 were regulated independently and did not correlate with the CSF cell count. Therefore, MMPs may derive not only from granulocytes infiltrating the CSF space but also from parenchymal cells of the meninges and brain. High concentrations of MMP-9 are a risk factor for the development of postmeningitidal neurological sequelae.

Meningococcemia fulminante - Síndrome Waterhouse - Friderichsen: o mais grave espectro clínico da doença meningocócica / Fulminans meningococcemia - Waterhouse - Frderichsen's syndrome: the most serious spectrum of the meningococcal disease

É apresentado o caso de uma paciente adulta jovem, previamente sadia, que, em 24 horas, desenvolveu febre com mialgias e artralgias, intensa agitaçäo psicomotora e queda do nível de consciência, simultaneamente com o aparecimento de lesöes petioquiais, lesöes de púrpura fulminans e equimoses disseminadas, entrando em estado de choque refratário e falecendo duas horas após internaçäo. O estudo de necrópsia revelou os achados clássicos da síndrome de Waterhouse-Frederichsen, servindo o caso para demonstrar as características clínicas, patogênicas e anatomopatológicas do mais grave espectro clínico da doença meningocócica

Transplantation of cultured autologous epithelium after meningococcal septicaemia in a 4-year-old with 35% skin loss.

A 4-year-old girl with scattered full-thickness skin and soft tissue wounds mainly on the extremities and corresponding to roughly 35% of the total body surface area was treated with early excision and transplantation of cultured autologous epidermal grafts. The transplantation was accomplished in one stage, three weeks after admission. The epidermal cells were cultured in Stockholm, Sweden and the time of transportation of the grafts to Reykjavik, Iceland (seven hours) did not seem to affect the quality, as 85% had taken one week after transplantation. The patient healed completely without further transplantation, but a few local skin flaps were needed to cover exposed articular surfaces. The patient was discharged from hospital with stable grafts five weeks after transplantation.

Bilateral renal cortical necrosis in two patients with Neisseria meningitidis sepsis.

Two patients who developed bilateral renal cortical necrosis as a consequence of Neisseria meningitidis infections are described: 1 patient had meningococcemia and the other had meningococcal meningitis. Both patients developed a Shwartzman-like reaction, disseminated intravascular coagulation and irreversible renal failure. Renal biopsy showed sclerosis of the majority of glomeruli; some glomeruli showed capillary congestion, thrombosis and an increased number of neutrophils; the intralobular arterioles showed thrombotic occlusions.

Surgical management of life-threatening and disfiguring sequelae of fulminant meningococcemia.

In recent years, because of prompt diagnosis and effective, aggressive resuscitation, the majority of infants and children with fulminant meningococcemia are surviving. From 1974 through 1984, 135 patients with this diagnosis were treated, and 126 of them survived. Although a purpuric skin rash developed in almost all of these patients initially, in eight of them it progressed to multiple confluent areas of cutaneous gangrene, usually associated with extensive necrosis of underlying subcutaneous fat, fascia, skeletal muscle, and even bone. Tissue necrosis seemed to be most extensive in regions of reduced blood flow, such as the extremities, but it almost never followed a pattern of anatomic vascular distribution. A most significant microscopic finding was the presence of multiple fibrin thrombi in vessels, often in close proximity with the foci of tissue necrosis. Five children who ranged in age from 6 months to 12 years required operation. Initially, all surface wounds were treated like full-thickness burns with silver sulfadiazene (Silvadene) dressings. Once the patient's condition had stabilized and the extent of tissue necrosis was apparent, all necrotic tissue was excised and the resulting wounds were temporarily covered with biologic dressings to assure a clean, viable base for skin grafting. Because the resulting quality of life postoperatively in all five surviving patients has been satisfactory, we recommend an aggressive surgical approach in patients with fulminating meningococcemia, despite what may initially appear to be devastating and even lethal complications of this disease.

[Pathogenetic and pathomorphological problems of viral-bacterial associations in children dying of meningococcal infection]. / Nekotorye voprosy patogeneza i patomorfologii virusno-bakterial'nykh assotsiatsii u detei, umershikh ot meningokokkovoi infektsii.

The information on 63 children dying from hypertoxic forms of meningococcal infection is presented. Four groups of brain damage by respiratory viruses (RV) are distinguished on the basis of the results of morphological and virological examination: 1) with a recent RV generalization (26 cases); 2) with dissemination of an etiological agent but without clear-cut structural changes (6 cases); 3) with an isolated affection of the brain (13 cases); 4) without clear-cut brain damage. Experimental influenza-meningococcal infection was reproduced in 260 white rats. Enhancement of the animal death rate, multiplication of virus and the degree of brain damage in cases of combined action of both etiological agents is demonstrated. The ability of influenza virus, when inoculated intranasally together with meningococcus, to penetrate and to multiply in the brain provoking meningitis and choroiditis is shown virologically, histologically and electron microscopically.