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Arguments are presented which indicate or show that: (1) Diagnostic precision and severity level of systemic meningococcal disease (MCd) both seem to rise exponentially with the developmental stage of the disease at referral. Lowering of the clinical admission threshold improves early coverage of vaguely suspected cases and should probably be implemented in Norway. (2) Fear that cell wall active bactericidal antibiotics could trigger important endotoxin release may cause unnecessary treatment delays. (3) Although risk of death due to meningococcal septicemia is the main indication for early treatment of MCd, the risk of sequelae may also become a major cause for very early treatment of MCd. (4) Treatment delays for MCd cases could have been substantially reduced by implementing reasonable guidelines. (5) In the relations between the public and the health service both organizational and psychological factors are operating. (6) Increased awareness among professionals and lay people of some key symptoms and signs may facilitate earlier diagnosis of MCd. (7) Earlier treatment of meningococcal disease is now feasible and does seldom preclude the possibility of etiological diagnosis. (8) More relevant studies and information on the early phases and rapid management of MCd are highly desirable. Rapid diagnosis and treatment of MCd are very important to reduce death, sequelae and community costs and should be more advocated in training of health personnel and in public information.

Results from our own and other published series of cases of meningococcal disease were used to study prognostic factors and to compose scores for assessment of severity of disease on admission to the hospital. The difference in risk for fatality was designated the factor fatality difference (FFD); the FFD was determined by subtracting the percent fatality for factor-negative patients from the percent fatality for factor-positive patients. FFD was useful for selection of good indicators of severity of disease. Blood pH of less than 7.35 was the best single factor; low platelet count came next, followed by low blood pressure, cyanosis, ecchymosis, and low blood leukocyte count. New scores were constructed based on multiple regression analyses. Several older and new scores seemed to be comparable. By combining age-adjusted systolic blood pressure (less than 100 mm Hg), cyanosis, ecchymosis, diarrhea before or at admission, cold extremities, absence of nuchal or back rigidity, and rectal temperature of greater than or equal to 40 degrees C, a simple bedside percentage score, the MenOPP bedside clinical score (MOC), was devised. Cross-evaluations on test materials generally confirmed the choice of score. The simplicity of this score made it more clinically suitable than laboratory or mixed laboratory and bedside scores.

Factor V (proaccelerin) concentration was measured in the plasma of 1016 regular and controlled blood donors. Age had a highly significant effect on factor V concentration. The median rose from 99 per cent at the age of 20 to 123 at the age of 60 years. Minor effects of sex and ABO blood groups were suggested. Interactions between these factors were found negligible. Accuracy and precision of the assay method and the use of percentiles in the laboratory reports are discussed. The results may support the hypothesis of relation between high concentration of coagulation factor V and predisposition to thrombosis.

Factor VIII (AHG) activity was assayed in the plasma specimens from 1016 regular and controlled blood donors. Age and ABO blood groups had highly significant effects on factor VIII concentrations, whereas the effect of sex was not significant. The median in the donors of blood group O rose from 87% at the age of 20 to 119% at the age of 60 years, and the median in blood groups A and B+AB of corresponding ages rose from 108 to 147%. An interaction effect of age and blood groups was present only at the 5% level of significance. The present data and the previous findings of others suggest the existence of an association between high factor VIII levels and thrombotic states.

The case coverage for meningococcal (MC) disease in the old notification system (ending 1974) in Norway was estimated at 52%. In contrast, an estimate for the new system (MSIS) is 76%. The latter is considered to verify the 72% found earlier. Adjustments for coverage resulted in a 160% increase in incidence from 1967-73 to 1974-79, whereas the unadjusted figure was 246%. A new estimate of MC death registration coverage is 78%, which verifies the 82% found earlier. Case fatality ratios in the two periods are 10.9% and 10.5% when adjusted, compared with 17.1% and 12.4% when unadjusted. Coverage estimates seem relatively stable, but if they were to be put under surveillance with the help of a sampling scheme, broader application and more appropriate confidence levels might be obtained for routine data.

As part of a greater project (MenOPP), the type, distribution and frequency of sequelae after meningococcal disease (MCd) were estimated on the basis of examinations carried out about six weeks after hospital admission. Well documented sequelae were found in about 18% of 102 MCd cases compared to about 3% in 61 control patients. In 18 control patients with meningitis/septicemia due to other bacteria, the sequelae frequency was 11%. Our MCd sequelae results correspond with many of those published during the last few years. The frequency of uncertain sequelae was about the same (16%) in the MCd and the control group patients. A routine examination six weeks and one year after a MCd episode seems to be useful for the individual patient and for the research on better prophylaxis and improved treatment.

To investigate the relative importance of the many possible influencing factors and developmental traits of systemic meningococcal disease (MCd) in the practical Norwegian context, a comprehensive multipurpose case control study was carried out during the winter of 1981-1982 on incident cases in the whole country. The design of the study, the MenOPP project, is outlined. The main inclusion criteria for patients were suspected bacterial meningitis and/or septicemia on referral to hospital. This resulted in 115 verified or probable cases of MCd and 61 patient controls. Randomly drawn from three age strata, 320 population controls were actually approached and 293 (92%) of these responded to the "environmental questionnaire". So did most of the patients (98%). The clinical data mainly comprised information from the commencement of the disease to a sequelae check about six weeks after hospital admission. Laboratory data on strain and serum characteristics were, and still are, collected. The results are to be published in several papers. Here, some epidemiological characteristics of the material are given. Regional, seasonal, and age/sex differences in case fatality are reported and discussed.

Gonococci were found by culture in 112 of 442 patients suspected of having gonorrhoea. Meningococci were cultured from the pharynx more than twice as often in patients harbouring gonococci (26%) than in patients from whom gonococci could not be cultured (11%). These results could indicate an individual susceptibility to Neisseria organisms or they could be caused by a difference in the behaviour of patients with and without gonorrhoea, the conduct of the former making them not only more likely to be infected with Neisseria gonorrhoeae but possibly more exposed to Neisseria meningitidis as well.

Using official notification figures for 1975-79, the recent meningococcal (MC) epidemic in Norway is described and related briefly to historical and international trends. This is the fourth major MC epidemic in Norway. Such epidemics have occurred at intervals of about 30 years. Apparent morbidity and mortality are presented in relation to time, region, serogroup, age and sex. Main characteristics of this epidemic are long duration, higher attack rates in North Norway and Mid-Norway, and in the winter/spring months, and a relatively high case fatality. The start of the epidemic coincided with a development of serogroup B predominance, following a shift from sulphonamide sensitivity to sulphonamide resistance in the majority of causative strains isolated shortly before. Morbidity peaks are observed in the second half of the first year of life (the highest rate) and among the age-group 14-17 years, with more male cases than female cases in the first three years of life. Case fatality appears to be high in the first five years of life, and even higher in the age-group 20 years and above. In the youngest age-groups and among adults, the case fatality is higher for males. The features of the epidemic are discussed in the light of coverage in official statistics of true occurrence of morbidity and mortality.

The occurrence of sequelae 3-15 years after meningococcal disease has been investigated in a study on 71 patients and 64 controls. The patients were young men, aged 18 to 24 years at the time the disease was contracted. Participants filled in a questionnaire on possible symptoms. Audiometry and EEG were also carried out. The response rates were 84% among patients and 75% among controls. We found that 61% of the patients had one or more symptoms of possible sequelae compared to 20% in the control group (p less than 0.001). The symptoms were generally light and of mental or neurological type. Among the patients 13% stated that they had obvious complaints commonly attributed to meningococcal disease, compared to 2% only in the controls (p less than 0.05). Twenty-nine per cent of the patients stated that the disease had affected their education or working capacity. No statistical differences between patients and controls were demonstrated by audiological or EEG examinations. In only one single ear could deafness unequivocally be attributed to the disease.

In a prospective study of 115 patients with systemic meningococcal disease, 61 control patients and 293 population controls, environmental and other factors which preceded the illness and which might have influenced the acquisition and case fatality rate of the meningococcal disease were investigated. Passive smoking in children under 12 year of age, stressful events, and symptoms and signs of preceding illness within the last two weeks were significantly more frequent in meningococcal patients than among the population controls. In contrast, those patients who had been exposed to stressful events, or who had symptoms or signs of ill-health preceding the meningococcal disease, had significantly reduced case fatality rates as compared to those who had not had any such experiences. Passive smoking remains a factor of great interest for further studies and intervention.

To elucidate pathogenic aspects and serodiagnostic possibilities for meningococcal disease, we investigated levels of specific antimeningococcal immunoglobulin G (IgG), IgA, and IgM in serum by using an enzyme-linked immunosorbent assay with outer membrane antigen prepared from a Neisseria meningitidis B:15:P1.16 strain. Serum samples were drawn on hospital admission as well as during convalescence from patients suspected of purulent meningitis or meningococcal septicemia, and single samples were drawn from population controls. A total of 637 samples were examined blindly. On admission, the average antimeningococcal immunoglobulin levels were about the same in the meningococcal disease patients as in the population controls. Septicemic patients, however, had significantly lower values. During one week the mean specific immunoglobulin levels in meningococcal-disease patients increased 6 times for IgG, 14 times for IgA, and 5 times for IgM. Children younger than 1 year showed a modest and more slowly developing antibody response. There were no statistically significant differences in average antibody responses among patients infected with meningococci of different serotypes. At 100% specificity, the increase in IgG, IgA, and IgM yielded diagnostic sensitivities for meningococcal disease of 84, 52, and 66%, respectively. One of seven serum pairs from the patient control group with unknown etiology was positive for meningococcal disease in this assay. The patients with meningococcal disease originally diagnosed only by clinical signs and symptoms showed a slightly lower rate of seroconversion than the patients in whom the diagnosis was supported by test results showing a systemic Neisseria meningitidis isolate.

The epidemiology of meningococcal disease in the Norwegian Armed Forces has been studied for the years 1974-79 and compared with the situation in the years 1967-73. The clustering of cases was examined with special reference to vaccination. The annual incidence rate increased from 24 to 43 cases per 100,000 men. However, this is only half the relative total increase in Norway in the same period. When 1975-79 figures were weighted according to the military age distribution, the combined rate for conscripts was four times the civilian rate. The weekly risk during the three month recruit training was three to ten times greater than later on. A malignancy change was demonstrated by a fourfold increase in the proportion of septicaemia and a fivefold increase in the case fatality.

In 71 males who survived acute meningococcal disease 3 to 15 years ago at an age of about 20, associations between acute clinical conditions (including a few pre- and post-admission variables) and late sequelae have been studied. There was a higher rate of sequelae symptoms (mainly light neurological and mental disturbances) among survivors from meningitis (76%) than among those who had had both meningitis and septicemia (58%) or pure septicemia (50%). Twenty percent of control persons experienced such symptoms. "Changed Life" because of serious educational and working problems followed in 29% of the meningitis cases and 70% of the septicemia cases. Most of the clinical and laboratory factors separately examined were not significantly correlated to the sequelae rates. However, less than 2.5 mmol/l glucose in the cerebrospinal fluid (CSF) on admission (p less than 0.01), more than 1000 X 10(6) white blood cells per 1 in the cerebrospinal fluid (p less than 0.05), fever for more than 8 days (p less than 0.05), and probable cerebral symptoms the first week (p less than 0.05), were all positively correlated to a high rate of late sequelae. Well documented early sequelae correlated with serious late sequelae (p = 0.05). No conspicuous associations between acute antibiotic treatment and late sequelae were found. A combination of CSF glucose, blood thrombocytes, and cells in CSF on admission yielded a multiple regression score which seems to be a moderately reliable predictor of sequelae (R = 0.46). Hospital treatment should both aim at avoiding death and escaping residual effects. Because many prognostic factors for sequelae on admission are different from those for lethality, scoring for sequelae may be helpful in such secondary prevention of sequelae. Early standardized registration of sequelae may also be of value in tertiary prevention.