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Meningococcal infections can present in diverse clinical forms ranging from fulminant, occult, chronic meningococcaemia to meningitis. Rare presentations may include conjunctivitis, sinusitis, pneumonia, pericarditis, arthritis, and osteomyelitis. We present a very unusual case of meningococcaemia presented as an endophthalmitis.
In recognition of the need for immunological memory-inducing components for future Neisseria meningitidis group B vaccines, we previously searched the proteome of N. meningitidis and identified T-cell-stimulating protein A (TspA). This study was designed to confirm the immunogencity of TspA and to examine the subset of T-helper cell responses to the protein in patients and nasopharyngeal carriers. The tspA gene was reconstructed, cloned, and expressed in Escherichia coli, and the recombinant TspA (rTspA) protein was affinity purified. T-cell proliferative responses to rTspA were detected in the peripheral blood mononuclear cells (PBMCs) of convalescent patients and carriers, confirming that TspA-specific T-cell responses were stimulated by invasive disease and nasopharyngeal colonization. Following stimulation of PBMCs with meningococcal lysate, increased frequencies of both Th1 and Th2 cells were observed, indicating that, as during carriage, invasive meningococcal disease induced an unbiased T-helper subset response. A similar unbiased T-helper response was also detected against rTspA in the PBMCs of convalescent patients. The response of PBMCs from the carriers to TspA stimulation, however, was very weak, and the frequencies of cytokine-positive CD4 cells were not significantly greater than the frequencies in unstimulated control cultures. All of the patients and carriers responded with serum antimeningococcal immunoglobulin G (IgG) antibodies, while four of six samples from patients and 5 of 14 samples from carriers contained detectable anti-rTspA IgG antibodies. Taken together, the results of this study confirmed the immunogenicity of TspA in humans during natural meningococcal infection, and therefore, TspA is worthy of further investigation as a possible T-cell stimulating component of future vaccines.
The present study describes the effect of plasma exchange or whole blood exchange (PEBE) on the survival rate among patients with fulminant meningococcal sepsis and on the level of circulating endotoxin. Since 1989 all patients with meningococcal disease and hypotension who were admitted to our intensive care unit were treated with PEBE. Results for our patients were compared with those for a historical control group conventionally treated between 1984 and 1989 (n = 10; mortality rate, 60%); the expected mortality rate, which was based on the Niklasson prognostic score and was calculated for seven patients in this control group, was 73%. A total of 15 patients were treated with PEBE, three (20%) of whom died, whereas the prognostic score (calculated for 14 patients) for this group was 62%. In two of the fatal cases, PEBE was started after a delay of greater than or equal to 40 hours. In the remaining 13 patients, PEBE was started within 5-30 hours after the first hospital admission. The mortality rate among this group was 8% (one of 13 patients); this rate was significantly different from that among the control group (P = .025). For seven patients treated with PEBE, plasma endotoxin concentrations were sequentially measured. The overall half-life (+/- SEM) of endotoxin was 181 +/- 18 minutes. This is approximately the same as reported values for patients who were not treated with PEBE. It is concluded that early initiation of PEBE may improve the rate of survival among patients with meningococcal infection and hypotension but that the mechanism of the beneficial effect is most likely not based on the elimination of endotoxin.
BACKGROUND: In recent years PCR has proven to be a highly sensitive and specific method for the diagnosis of infections caused by Neisseria meningitidis. STUDY DESIGN: We developed and evaluated a N. meningitidis LightCycler real-time duplex PCR (NM-LCdPCR) capable of simultaneously detecting and distinguishing between two separate genes on the N. meningitidis genome. METHODS: The NM-LCdPCR was developed on the LightCycler platform (Roche Diagnostics, Castle Hill, NSW, Australia) and comprised two primer pairs and two hybridization probe sets, enabling the detection of both the porA and ctrA genes within the same reaction mix. To distinguish between the fluorescence emitted by each hybridization probe set, each downstream probe was labeled with a different fluorophore (either LC-Red640 or LC-Red705). The results obtained by the NM-LCdPCR were then compared with the results obtained by a mono-specific LightCycler assay targeting the porA gene only (porA-LCPCR). PATIENTS: One-hundred and forty-eight clinical samples from patients with suspected meningococcal infection were evaluated. RESULTS: The results of the NM-LCdPCR and porA-LCPCR gave 100% agreement; N. meningitidis DNA was detected in 25 samples whereas 123 samples were negative by both assays. The breakdown of the NM-LCdPCR results show that both genes were detected in 26 of the 28 positive samples. DISCUSSION: By targeting two separate N. meningitidis genes, the NM-LCdPCR has the potential to prevent the false-positive results which may arise from sequence variation. In addition, the ability to detect and discriminate between the two different N. meningitidis genes within the same reaction mix offers a rapid means for confirming the presence of N. meningitidis DNA in clinical samples, thereby reducing the need for subsequent confirmatory assays to be performed. CONCLUSIONS: The sensitivity and specificity of the NM-LCdPCR assay, combined with its ability to detect and discriminate both the N. meningitidis porA and ctrA genes, make it suitable for the diagnosis of N. meningitidis infections in the routine clinical laboratory.
The degree of the antilysozyme activity (ALA) of 430 Neisseria meningitidis strains isolated from 379 healthy carriers in 11 closed groups with different epidemiological situation and in 3 family foci was studied by the method of delayed antagonism. 87% of the strains exhibited ALA in a concentration of lysozyme between 1 and 10 micrograms per ml of the medium; about 11% of them were highly active, inactivating 20 and 25 micrograms of lysozyme per ml. ALA was shown to be the constant sign of carriership. The ALA of 39 strains isolated in cases of prolonged carriership (exceeding 2 weeks) was essentially higher than the ALA of 20 strains obtained in a single isolation. N. meningitidis strains of groups A, B and C, mostly responsible for the appearance of the generalized forms of diseases, were essentially less active than N. meningitidis strains of groups X, Y, Z, 29E, W-135, as well as strains not classified with any group. No correlation between ALA and the presence or absence of hyaluronidase was noted. Analysis of the data obtained in this study revealed that the ALA of N. meningitidis strains isolated in closed groups and families was not linked with the presence or absence of morbidity in the generalized forms of meningococcal infection and the spread of carriership in these groups, but reflected only differences in the serological picture of strains circulating there. The role of ALA in the formation of prolonged N. meningitidis carriership requires further study.
The number of laboratory confirmed cases of meningococcal infection in England and Wales rose in 1995 for the first time since 1990. Culture confirmed cases rose to 1459, an increase of 29% over the 1994 total, due largely to increased disease activity in the last quarter of 1995. Cases diagnosed by non-culture methods totalled 431, giving a total of 1890 laboratory confirmed cases. Notifications reported to the Office of Population Censuses and Surveys also increased to a similar extent. Northern regions generally had higher rates of disease activity and greater increases in rates. Meningococcal disease caused by serogroup C strains accounted for the main increase in culture confirmed cases and made up 32% of the total in 1995. Disease caused by C2a strains showed a particularly large increase. A change in the age distribution was noted with a greater proportion of patients in older age groups. Among group B isolates, B4 P1.4 strains continued to be identified most commonly.
The present report describes two cases of dental complications of meningococcemia at an early age. The meningococcal infection in these young children resulted in limb amputation and significant plastic surgery. Dental treatment and psychological considerations are described in both cases. Similar dental complications, especially in the premaxilla, were found. Some of the severely affected teeth were extracted.
OBJECTIVES: To determine the association between the ability of a different strains of meningococci to survive in whole blood and the age of the donor. METHODS: A panel of serogroup B and a serogroup C strain of Neisseria meningitidis was tested in an ex vivo whole blood model. Blood from 81 healthy children and 20 adults and from children during convalescence from serogroup B (55 patients) or serogroup C (43 patients) meningococcal infection was assessed. RESULTS: Age-dependent acquisition of whole blood killing of serogroup B and C bacterial isolates was demonstrated in healthy children with an inverse relationship to the reported incidence of disease. After infection with serogroup B or C meningococci, evidence of whole blood killing of the bacteria was found even in blood from children <2 years of age, the survival of a serogroup B strain, MC58, being reduced compared with that in healthy children (median, 64% compared with 194.5% survival at 90 min). In both affected children and controls, there was a significant correlation between whole blood killing of strain MC58 and of other serogroup B and C meningococci. CONCLUSIONS: The whole blood model measures both humoral and cellular mechanisms responsible for the bactericidal activity of blood. The model was first described 80 years ago, but this is the first description of its age dependency. Acquisition of bactericidal activity was more rapid in children infected and is directed at various strains of meningococci, indicating the presence of a cross-reactive antigen(s).
The concentration of the elastase-alpha 1 proteinase inhibitor complex (E-alpha 1 PI) in a meningococcal infection in an index case with severe changes in haemostasis was measured. The concentration of the E-alpha 1 PI complex was increased throughout the duration of the illness, although concentrations of the blood clotting factors were severely decreased. The release of polymorphonuclear elastase activity may contribute to the depletion in clotting factors.
A 60-yr-old immunodepressed woman presented with acute perimyocarditis and cardiac tamponade complicating meningococcic infection. We had the opportunity to study her cardiac condition by injecting antimyosin during the acute phase. Images at 48 hr showed unexpected findings, with obvious localization of the tracer in the pericardial fluid, as well as myocardial uptake. Possible mechanisms for pericardial activity are discussed.
The onset of meningococcal infection in the first 72 hours after birth has only been reported on a few occasions; The authors describe a case where it was confirmed that the bacteria responsible, Neisseria meningitidis group B, grew in the newborn's blood and in the mother's lochia. The transmission mechanisms are also reviewed.
Hypoxia plays an important role in pathogenesis of infectious diseases. Therefore, its correction is an essential factor in pathogenetic antibacterial treatment. Hyperbaric oxygenation (HBO) as a leading method in current antihypoxic therapy was studied in combined medication for typhoid, diphtheria, meningococcal infection, viral hepatitis. HBO sessions were given to 331 patients, 363 controls did not receive HBO. Utilization of HBO provided much better saturation of blood with oxygen, eliminated metabolic disorders, warranted favorable course and outcomes of the diseases.
Nineteen children, who had been admitted to the Pediatric Hospital of Coimbra with severe meningococcal infection with DIC, were submitted to clinical and radiological examination, an average of 4.2 years after hospitalization, in order to demonstrate late skeletal lesions. Patellar dystrophy, to our knowledge previously unreported, was found in 4 children, all of whom had overlying cutaneous scarring.
BACKGROUND: An association has been described between mortality in children with meningococcal disease and functional polymorphisms in the interleukin-1 (IL1) cluster. We undertook a multicenter study to evaluate associations of these polymorphisms in a Central European population. PATIENTS AND METHODS: The study involved 95 Middle European pediatric hospitals. We collected blood samples from, and clinical information about, 285 previously healthy children with meningococcal infection. We used a newly developed multiplexed mutagenic separated PCR assay to analyze 6 polymorphisms within the IL1 cluster: IL1A (-889)C/T, IL1A (+4845)G/T, IL1B (-511)C/T, IL1B (-31)C/T, IL1B (+3954), and IL1RA (+2018)C/T. We studied the same polymorphisms in a comparison group of 481 healthy newborns. RESULTS: Genotype frequencies between patients and the comparison group differed significantly only for the IL1RA (+2018)C/T variant: The CC genotype was more frequent in patients (11%) than in healthy controls (5%; P = 0.008). In the patient group, the C allele was significantly more prevalent (67%) in nonsurvivors than in survivors (42%; P = 0.02). CONCLUSION: The IL1RA (+2018)C/T polymorphism is associated with the risk of meningococcal disease and with its outcome.
The action of two antibiotics, penicillin and chloramphenicol, on bacterial growth and endotoxin liberation was studied in 18 strains of Neissevia meningitidis isolated from blood and CSF of patients with meningococcal infections. The antibiotics were administered both separately and in combined form in doses equivalent to 1 MIC and 100 MIC. Penicillin was found to produce a faster and more intense bactericidal effect than chloramphenicol during the first hour, whereas at 12 h these differences were not significant. This could explain the initial worsening observed in some infected patients when large doses of penicillin are administered. An increased liberation of endotoxin after adding penicillin was observed in six of the strains studied, whereas the remaining 12 did not show significant increases. The six strains (belonging to serogroup B) were known to have an enhanced capacity for spontaneous endotoxin liberation.
A retrospective study of the pathology in 86 consecutive autopsies of fatal meningococcal infection in children, performed at the Red Cross War Memorial Children's Hospital during the 19-year period from 1973 to 1991, was undertaken. The most prominent pathological changes found at autopsy were those of an overwhelming bacterial infection with evidence of disseminated intravascular coagulopathy in many organs of the body. The skin, adrenal glands and central nervous system were most commonly involved. Acute myocarditis occurred in 23 cases (27%) and was diagnosed almost exclusively histologically. In only one case was it diagnosed clinically. In addition, the nutritional status and the morphological expression of immune reactivity of our hospital population was better than expected.
Scandinavia (Denmark, Finland, Iceland, Norway, and Sweden) comprises with mutual borders and 22.3 million inhabitants an area where the socioeconomic and cultural conditions are similar. Epidemic diseases, such as meningococcal infection, might therefore be expected to be uniformly distributed. An epidemiological study in the 10-year period 1970-9 shows, however, remarkable differences in the incidence, age, and serogroup and type distribution, as well as in the general dynamics of the disease. Three epidemics, two caused by different serotypes of group B (Norway and Iceland) and one by group A (Finland) occurred within the observation period. The annual overall incidence was generally around 3/100 000 but increased from fivefold (Finland) to eightfold (northern Norway) during epidemics. The epidemic strains caused infection in over 3000 patients and the loss of at least 250 lives. The overall case fatality rate was 8.6% (range 4.1-13.7%). Men were more susceptible and had a worse prognosis than women of the same age group. The group A epidemic in Finland was influenced by a large vaccination campaign, but this possibility was not feasible in the two other epidemics.
Analysis of the socioeconomic effectiveness of the use of immune antimeningococcal plasma in patients with the grave patterns of meningococcal infection has shown that introduction of the preparation into multimodality therapy results not only in a considerable medicosocial effect (reduction of lethality, lowering of the patients' stay at a hospital, a more rapid, as compared with the control group, removal of the symptoms of intoxication, elimination of hemodynamic disorders underlying the infectious toxic shock) but also in an appreciable economic effect.