Confirmation of meningococcal disease by urinary antigen testing.

The meningococcus is an important cause of morbidity and mortality and a rapid laboratory diagnosis is required through accurate, non-culture-based methods. Body fluids that are easily obtainable are preferred for this route of diagnosis and urine is the specimen of choice as it can be obtained non-invasively. Urine samples were tested from patients with suspected meningococcal disease and tested by latex agglutination and PCR. It was shown that urinary PCR is not useful for the laboratory confirmation of MD but latex agglutination testing may be useful in certain settings prior to confirmatory testing by a reference laboratory.

Degradation of albumin in meningococcal sepsis.

We postulate that the proteolytic degradation of albumin into fragments could link the rapidity of the shock, rash, and hypocalcaemia associated with meningococcal sepsis. We examined urine of children with meningococcal disease and urine from control children with no sepsis and found albumin fragments of about 45 kDa, 25 kDa, and less than 20 kDa only in the urine of children with meningococcal sepsis and associated purpura. Exogenous or endogenous proteases, or both, may be released in severe meningococcal sepsis and, in association with an inadequate antiprotease response, result in albumin degradation. This may be a contributory factor to the rapid shock, hypocalcaemia, and rash seen in meningococcal sepsis.

Increased excretion of urinary glycosaminoglycans in meningococcal septicemia and their relationship to proteinuria.

OBJECTIVES: Meningococcal septic shock is a devastating illness associated with an increase in vascular permeability leading to hypovolemia and accumulation of plasma proteins and fluid in tissues. The capillary leak syndrome is often associated with widespread thrombosis in the skin, limbs, and digits. We postulated that the increase in vascular permeability and the intravascular thrombosis might be caused by an inflammation-induced loss of endothelial and basement membrane glycosaminoglycans (GAGs), which play a role in the permeability and thromboresistant properties of the microvasculature. DESIGN: Prospective, single-center observational study. SETTING: University-affiliated meningococcal research unit and pediatric intensive care unit. PATIENTS: Eighteen children requiring intensive care for meningococcal sepsis, 18 children with steroid-responsive nephrotic syndrome, and 18 healthy control children. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Serum concentrations and urine excretion of glycosaminoglycans were measured and related to changes in glomerular permeability to plasma proteins. The size-distribution and nature of glycosaminoglycans were defined by Polyacrylamide Gel Electrophoresis and specific enzyme digestion. Urinary excretion of heparan sulfate, chondroitin-4-sulfate, and chondroitin-6-sulfate were significantly increased in meningococcal disease (MD) relative to healthy controls and children with steroid-responsive nephrotic syndrome. The urinary GAGs in MD were of similar size to those in controls when analyzed after pronase digestion. However, analysis of proteoglycan size before proteolytic digestion showed the urinary GAGs in MD were of lower molecular weight and unattached to proteins. The fractional excretion of albumin and immunoglobulin G in MD increased with severity of disease. Patients with severe or fatal MD had albumin clearances overlapping those seen in steroid-responsive nephrotic syndrome. There was a significant correlation between proteinuria in MD and urinary excretion of heparan sulfate (r2 = 0.611, p < .0001), chondroitin-4-sulfate (r2 = 0.721, p < .0001), and chondroitin-6-sulfate (r2 = 0.395, p < .0001). CONCLUSIONS: The capillary leak in meningococcal disease is associated with increased plasma and urine concentrations of GAGs, which may be proteolytically cleaved from endothelial and basement membrane sites. The correlation between the severity of protein leakage and the urine excretion of GAGs suggests that loss of GAGs may be causally related to the increase in permeability to proteins.

Effect of meningococcal endotoxin in a rabbit model of shock.

Endotoxin in the form of a lipooligosaccharide (LOS) plays a key role in the development of shock in meningococcal sepsis. To examine hemodynamic and biochemical alterations during meningococcal endotoxic shock, we established a rabbit model. Thirty-nine rabbits, weighing 2.5-4.4 kg, were studied. After anesthesia with intramuscular ketamine (20 mg/kg) and xylazine (4 mg/kg), femoral venous and arterial catheters were inserted. Control animals received only saline, while rabbits in each of four additional groups were given LOS in 10-fold increments from 0.1 microgram/kg to 100 microgram/kg. Mean arterial pressure (MAP), heart rate (HR), respirations (RR), temperature (T), urine output, and arterial blood gases (pH, PCO2, PO2, and bicarbonate) were determined at baseline and hourly. Endotoxin levels and TNF levels were measured at 30, 60, 120, 180, 240, 300, and 360 min post-LOS. Survival was recorded. One-way analysis of variance (ANOVA) and the Scheffe procedure, paired samples t-test, two-tailed t-test, and Fisher's exact test were used. Pearson's coefficients were calculated. Animals receiving meningococcal LOS developed tachycardia and compensated metabolic acidosis with an initially normal pH and MAP. With progression of the shock state, the pH decreased and hypotension ensued. Maximal levels of endotoxin were measured 30 min after LOS injection and declined during the ensuing 6 hr. TNF rose from undetectable to markedly elevated levels and peaked at 60-120 min post-LOS. Increasing the amount of injected endotoxin produced more profound degrees of shock until a dose of 10.0 micrograms/kg was reached. There was no correlation between serum TNF at 60 min and survival at 6 hr or 24 hr.(ABSTRACT TRUNCATED AT 250 WORDS)

[Evaluation of the coagglutination reaction with urine in generalized forms of meningococcal infection]. / Otsenka reaktsii koaggliutinatsii s mochoi pri generalizovannykh formakh meningokokkovoi infektsii.

The coagglutination test with concentrated urine was tried in 59 patients with validated generalized forms of meningococcal infection and in 23 ones with meningitides and pneumonia of a different etiology to assess the diagnostic value of this test. Positive results were obtained in 64.4% of the test group patient and in 4.3% of the reference patients (in a case with pneumococcal meningitis). The antigen serologic group in the urine coincided with the serologic group of the meningococcus that induced the disease in only 19 (50%) of the 38 patients in whom antigenuria+ was detected. In the rest cases urine samples reacted parallel with 2-7 antisera, in 5 patients with the antisera heterologic towards the serologic group of the meningococcus responsible for the disease. Antigenuria was observed between the second and ninth days of the illness, its peak was recorded on days 4-6. Repeated urine tests are more likely to yield positive results. The authors come to a conclusion that the test is simple and harmless for patients, but the presence of false positive results permits regarding it as but an auxiliary one.

[Functional state of the sympathetic-adrenal system in meningococcal infections]. / O funktsional'nom sostoianii simpatiko-adrenalovoi sistemy pri meningokokkovoi infektsii.

A study of the functional state of the sympathico-adrenal system by determining the diurnal urine excretion of catecholamines and DOPA was conducted in 29 patients with meningoencephalitis of a meningococcal etiology. These studies demonstrated a significant activation of its adrenal link and a tendency to an increase of activity in the sympathical link with a drop of the reserve possibilities. These changes were most distinctly expressed in cases with prevalent localization of the pathological process in the deep brain structures. These facts made it possible to conclude that there is a lesion in the link of a control of the sympathico-adrenal system. These data were confirmed by results of a study in 18 patients with meningococcal infections by physiological loadings with insulin and adrenalin and a study of the catecholamines and DOPA in the urine portions, which exert specific influence on the state of activity of the sympathico-adrenal system through the hypothalamus and reticular formation.