BACTERIAL MENINGITIS AND OTHER DISEASES AFFECTING THE MENINGES—A Review of 349 Cases

Three hundred and forty-nine cases of disease affecting the meninges were observed at the San Bernardino County Charity Hospital in an eight year period.A total of 29 patients with meningococcal, H. influenzae and pneumococcal meningitis were treated. There were four deaths, of which three occurred during the first 24 hours in the hospital.Of 22 cases of unclassified meningitis, four probably were tuberculous, four probably were meningococcal and two probably were of virus origin.Under present treatment programs the differentiation between viral and bacterial meningitides is difficult and it is possible, therefore, that the reported incidence of the two groups may not represent the facts.Of 22 cases of unclassified meningitis, 12 had no specific characteristics which would permit a clinical diagnosis. One of the patients died.Of 70 cases of clinical meningitis, the infecting organism was identified in 69 per cent.Meningococcal meningitis made up only 17 per cent of 70 cases of purulent meningitis observed between July 1, 1945, and July 1, 1948.     

Prevention of secondary cases of meningococcal disease in household contacts by vaccination.

Household contacts of patients with group A meningococcal infection were vaccinated with either meningococcal vaccine or tetanus toxoid. Five of the 523 subjects who received tetanus toxoid developed meningococcal meningitis and another four probably had meningococcal disease. Only one possible case of meningococcal infection occurred among 520 contacts vaccinated with meningococcal vaccine. Vaccination had no effect on nasopharyngeal carriage of meningococci. Vaccination of household contacts of patients with group A meningococcal infections is an effective way of using limited supplies of meningococcal vaccine, though its value would be limited in an epidemic. Secondary cases of meningococcal infection often occur within a few days of the index case, and, although vaccine alone seemed to provide adequate prophylaxis in these Nigerian subjects, additional chemoprophylaxis may be needed to cover this critical period.     

Bacterial Meningitis in Brazil: Baseline Epidemiologic Assessment of the Decade Prior to the Introduction of Pneumococcal and Meningococcal Vaccines

Background

Bacterial meningitis is associated with significant burden in Brazil. In 2010, both 10-valent pneumococcal conjugate vaccine and meningococcal capsular group C conjugate vaccine were introduced into the routine vaccination schedule. Haemophilus influenzae type b vaccine was previously introduced in 1999. This study presents trends in demographics, microbiological characteristics and seasonality patterns of bacterial meningitis cases in Brazil from 2000 to 2010.

Methods and Findings

All meningitis cases confirmed by clinical and/or laboratory criteria notified to the national information system for notifiable diseases between 2000 and 2010 were analyzed. Proportions of bacterial meningitis cases by demographic characteristics, criteria used for confirmation and etiology were calculated. We estimated disease rates per 100,000 population and trends for the study period, with emphasis on H. influenzae, N. meningitidis and S. pneumoniae cases. In the decade, 341,805 cases of meningitis were notified in Brazil. Of the 251,853 cases with defined etiology, 110,264 (43.8%) were due to bacterial meningitis (excluding tuberculosis). Of these, 34,997 (31.7%) were due to meningococcal disease. The incidence of bacterial meningitis significantly decreased from 3.1/100,000 population in 2000–2002 to 2.14/100,000 in 2009–2010 (p<0.01). Among cases of meningococcal disease, the proportion of those associated with group C increased from 41% in 2007 to 61.7% in 2010, while the proportion of group B disease progressively declined. Throughout the study period, an increased number of cases occurred during winter.

Conclusions

Despite the reduction in bacterial meningitis incidence during the last decade, it remains a significant healthcare issue in Brazil. Meningococcal disease is responsible for the majority of the cases with group C the most common capsular type. Our study demonstrates the appropriateness of introduction of meningococcal vaccination in Brazil. Furthermore, this study provides a baseline for future evaluation of the impact of the vaccines introduction in Brazil and changes in disease epidemiology.     

Mumps and Enteroviral Meningitis in Toronto, 1966

Of 52 children admitted to hospital for apparently typical mumps meningitis in 1966, 50 had their cerebrospinal fluid (CSF) examined. In only 17 was the mumps virus isolated from the CSF. Mumps antihemagglutinin conversions or increments were detected in 32 subjects including 10 whose CSF yielded virus. Antibody conversions were found in 16 patients and fourfold increments in another nine whose serum pairs were collected only one to four days apart. Initial sera from 20 patients were obtained three days or less after the onset of meningitis. Antibody increments were frequently noted about one day after defervescence and clinical improvement. Interferon was detected in CSF from two of eight patients, both of whom yielded virus. Enteroviruses were isolated from CSF and/or feces in seven of 15 cases of aseptic meningitis which occurred between July and October. Six patients including three virus excretors showed enteroviral neutralizing antibody increments during convalescence. The dominant enteroviral serotype was coxsackievirus A9.     

Perforated gastric and duodenal ulcers; an analysis of 73 cases

In 73 cases of perforated gastroduodenal ulcers in which operation was done at St. Joseph's Hospital, San Francisco, during the ten-year period July 1939 to July 1949, the death rate was 13.7 per cent. In all but three of the cases, simple closure of the perforation was carried out. In 46 cases there were postoperative complications. Of this number, peritonitis and its sequelae comprised 35 per cent and pulmonary complications, 37 per cent. The mortality rate in the group in which these complications occurred was 35 per cent.     

SUBACUTE BACTERIAL ENDOCARDITIS—A Report on 57 Patients Treated with Massive Doses of Penicillin

Fifty-seven patients with subacute bacterial endocarditis were treated with doses of penicillin varying from 500,000 to 20,000,000 units per day. Diagnosis was confirmed in some cases by growths on blood culture, in others by postmortem examination. In those cases in which the diagnosis was established by blood culture, the in vitro sensitivity of the organism to penicillin was determined and penicillin then was administered by continuous intramuscular infusion in a dosage calculated to produce blood levels of penicillin four to five times that required for in vitro inhibition. Penicillin was given for a period of 21 days, and blood cultures were made periodically during and after treatment.Of the 57 patients, 38 were cured (66.7 per cent), and 19 died (33.3 per cent).Of the 19 who died, three did so within 48 hours of hospitalization and seven died despite adequate treatment. Of these seven, three died of cerebral emboli, two because of resistance to penicillin and streptomycin, one because of congestive heart failure, and one of undetermined cause. The remaining nine who died were considered to have been inadequately treated in that there was (1) failure to obtain sensitivity, (2) inadequate dossage of penicillin, (3) delay in starting treatment, or (4) failure to recognize mixed infections.There were five patients with repeatedly sterile blood cultures during life. In all of these cases, streptococcus viridans was recovered at postmortem examination. In an attempt to determine how long therapy should justly be withheld in patients with repeatedly sterile blood cultures, 140 cases of subacute bacterial endocarditis in which positive blood cultures had been obtained were reviewed. From the review it was determined that if blood cultures taken during the first two days are reported sterile, the chance of subsequent cultures proving positive is minimal. Therefore, for patients in whom the diagnosis seems otherwise obvious, delaying treatment for more than two days is not justified even though the blood culture be sterile. In cases in which blood cultures are repeatedly sterile, a dosage of 6,000,000 to 10,000,000 units of penicillin daily for 21 days is advisable.High bacterial resistance to penicillin and streptomycin was found in four fatal cases. In one of these, the infecting organism was streptococcus viridans, and in three it was staphylococcus albus. There was one patient with penumococcal meningitis complicated by unrecognized streptococcal viridans bacterial endocarditis.     

Subacute bacterial endocarditis; a report on 57 patients treated with massive doses of penicillin

Fifty-seven patients with subacute bacterial endocarditis were treated with doses of penicillin varying from 500,000 to 20,000,000 units per day. Diagnosis was confirmed in some cases by growths on blood culture, in others by postmortem examination. In those cases in which the diagnosis was established by blood culture, the in vitro sensitivity of the organism to penicillin was determined and penicillin then was administered by continuous intramuscular infusion in a dosage calculated to produce blood levels of penicillin four to five times that required for in vitro inhibition. Penicillin was given for a period of 21 days, and blood cultures were made periodically during and after treatment. Of the 57 patients, 38 were cured (66.7 per cent), and 19 died (33.3 per cent). Of the 19 who died, three did so within 48 hours of hospitalization and seven died despite adequate treatment. Of these seven, three died of cerebral emboli, two because of resistance to penicillin and streptomycin, one because of congestive heart failure, and one of undetermined cause. The remaining nine who died were considered to have been inadequately treated in that there was (1) failure to obtain sensitivity, (2) inadequate dossage of penicillin, (3) delay in starting treatment, or (4) failure to recognize mixed infections. There were five patients with repeatedly sterile blood cultures during life. In all of these cases, streptococcus viridans was recovered at postmortem examination. In an attempt to determine how long therapy should justly be withheld in patients with repeatedly sterile blood cultures, 140 cases of subacute bacterial endocarditis in which positive blood cultures had been obtained were reviewed. From the review it was determined that if blood cultures taken during the first two days are reported sterile, the chance of subsequent cultures proving positive is minimal. Therefore, for patients in whom the diagnosis seems otherwise obvious, delaying treatment for more than two days is not justified even though the blood culture be sterile. In cases in which blood cultures are repeatedly sterile, a dosage of 6,000,000 to 10,000,000 units of penicillin daily for 21 days is advisable.High bacterial resistance to penicillin and streptomycin was found in four fatal cases. In one of these, the infecting organism was streptococcus viridans, and in three it was staphylococcus albus. There was one patient with penumococcal meningitis complicated by unrecognized streptococcal viridans bacterial endocarditis.     

Allergic Complications of Meningococcal Disease II—Immunological Investigations

Immunological investigation of four patients with meningococcal meningitis who developed arthritis or cutaneous lesions showed circulating meningococcal antigen at the time of presentation in each patient. It was cleared from the circulation over the next few days. Circulating antibody was detectable in three of the four patients about a week after the onset of the illness. A marked fall in the serum C₃ level occurred in two patients at about that time. Deposits of meningococcal antigen, immunoglobulin, and C₃ were detected in the synovial fluid white cells of the two patients studied and in one of three skin biopsies examined. These findings suggest that the arthritis and cutaneous lesions of meningococcal meningitis may be due to immune complex formation.     

Evidence for familial immune defect in meningococcal meningitis.

Twenty-six patients who had recovered from group A meningococcal meningitis were vaccinated with group C meningococcal polysaccharide and tetanus toxoid. Their haemagglutinating antibody response was measured two weeks later and compared with those of 22 siblings and 39 controls. Patients and siblings had a significantly lower antibody response to the group C vaccine but not to tetanus toxoid. This suggests that patients susceptible to meningococcal disease may have an immune defect involving their response to meningococcal polysaccharides.     

A THERAPEUTIC REGIMEN FOR TUBERCULOUS MENINGITIS

The results of treatment of tuberculous meningitis in Highland Alameda County Hospital, since the advent of streptomycin, in 34 cases were: dead, 21 patients, or 61 per cent; alive, 10 patients, or 29 per cent. Three cases were excluded from the ultimate report due to inadequate follow-up. The mean survival time of the ten survivors at the time of report was 35 months, the longest being 74 months.The composite results of treatment elsewhere, as reported in the literature, have been: dead, 892, or 59 per cent; alive, 629, or 41 per cent.The pathogenesis of the disease and the effects of chemotherapy are discussed.A therapeutic regimen for tuberculous meningitis is presented, which has been used at Highland Hospital since INH became established as the most effective component in the combined chemotherapeutic attack on the disease.     

The role of external irradiation in the treatment of transitional cell carcinoma of the bladder-a review of fifty cases

Of 100 patients with carcinoma of the bladder seen in the Section of Therapeutic Radiology, University of California, San Francisco, between 1957 and 1962, 59 were accepted for radiation treatment. Fifty had transitional cell carcinoma and were treated with supervolt therapy (1 mev or cobalt-60).TWO TYPES OF TUMORS WERE AGAIN FOUND SUITABLE FOR EXTERNAL IRRADIATION: Papillary carcinomas Grades II and III, as long as they have not, or at least have not massively, invaded muscle; and undifferentiated carcinomas, Grade IV, regardless of degree of extension through the pelvis. The former type, if single, is treated by irradiation for the first recurrence after one attempt with radical transurethral resection. In the presence of multiple lesions at the first examination, radiation therapy is given immediately. The latter type is treated by radiation therapy without any attempt at surgical removal.Of 37 patients, Stages A to C, treated more than three years ago, 14 (38 per cent) lived more than three years and eight (22 per cent) had no cystoscopic or clinical signs of active disease and had normal bladder function. Of 23 patients treated more than five years ago, eight were alive after five years (35 per cent) and four (17 per cent) remained controlled by radiation therapy alone, with normal bladder function.No major complications were observed. In particular, no fibrosis of the bladder occurred. Doses ranged from 5,000 r in five and a half weeks to 6,000 r in seven weeks.A close cooperation between urologic surgeons and radiotherapists during recent years permits long-range treatment planning from the time of diagnosis, which is essential in the effective therapy of carcinoma of the bladder.     

The Role of External Irradiation in the Treatment of Transitional Cell Carcinoma of the Bladder—A Review of Fifty Cases

Of 100 patients with carcinoma of the bladder seen in the Section of Therapeutic Radiology, University of California, San Francisco, between 1957 and 1962, 59 were accepted for radiation treatment. Fifty had transitional cell carcinoma and were treated with supervolt therapy (1 mev or cobalt-60).Two types of tumors were again found suitable for external irradiation: Papillary carcinomas Grades II and III, as long as they have not, or at least have not massively, invaded muscle; and undifferentiated carcinomas, Grade IV, regardless of degree of extension through the pelvis. The former type, if single, is treated by irradiation for the first recurrence after one attempt with radical transurethral resection. In the presence of multiple lesions at the first examination, radiation therapy is given immediately. The latter type is treated by radiation therapy without any attempt at surgical removal.Of 37 patients, Stages A to C, treated more than three years ago, 14 (38 per cent) lived more than three years and eight (22 per cent) had no cystoscopic or clinical signs of active disease and had normal bladder function. Of 23 patients treated more than five years ago, eight were alive after five years (35 per cent) and four (17 per cent) remained controlled by radiation therapy alone, with normal bladder function.No major complications were observed. In particular, no fibrosis of the bladder occurred. Doses ranged from 5,000 r in five and a half weeks to 6,000 r in seven weeks.A close cooperation between urologic surgeons and radiotherapists during recent years permits long-range treatment planning from the time of diagnosis, which is essential in the effective therapy of carcinoma of the bladder.     

Direct PCR assay for detection ofNeisseria meningitidis in human cerebrospinal fluid

A PCR amplification was performed to detectNeisseria meningitidis insertion sequence1106 (IS-1106) in the humancerebrospinalfluid (CSF) in cases of meningitis. The study included 27 CSF samples from suspected meningitis patients. Although the inflammatory response in most of the samples was slightly increased, the results showed that 7 (26%) and 8 (30%) CSF samples were diagnosed as meningococcal meningitis by Gram staining and by culture, respectively. The primers of theIS-1106 were used for direct diagnosis ofN. meningitidis in the human spinal fluid after a minor treatment of the CSF samples. The sample was diagnosed as meningococcal meningitis, if a DNA band of about 600 bp was detected in the ethidium bromide-stained agarose gel. The 27 CSF samples were analyzed in a random manner. Of these, 18 samples including the Gram staining- and culture-positive samples were also positive in PCR amplification. However, a CSF sample, which was diagnosed to be meningococcal meningitis in culture was negative in both Gram staining and PCR analysis. The specificity of theIS-1106 primers was determined to be 95%, with 100% sensitivity in comparison to Gram staining and culture. The primers were sensitive to 10 pg or more of meningococcal DNA. In addition, the PCR amplification showed high predictive values (89 and 100%) in diagnosing meningitis in patients that were negative and positive responders when tested by culture and by Gram staining. In conclusion, the PCR amplification ofIS-1106 ofN. meningitidis is specific and sensitive to both culture-positive and-negative meningococcal meningitis. Hence, PCR assay is highly recommended for use in a rapid diagnosis of suspected meningitis patients.     

Incidence,Carriage and Case-Carrier Ratios for Meningococcal Meningitis in the African Meningitis Belt: A Systematic Review and Meta-Analysis

BackgroundTo facilitate the interpretation of meningococcal meningitis epidemiology in the “African meningitis belt”, we aimed at obtaining serogroup-specific pooled estimates of incidence, carriage and case-carrier ratios for meningococcal meningitis in the African meningitis belt and describe their variations across the endemic, hyperendemic and epidemic context.MethodsWe conducted a systematic review and meta-analysis of studies reporting serogroup-specific meningococcal meningitis monthly incidence and carriage in the same population and time period. Epidemiological contexts were defined as endemic (wet season, no epidemic), hyperendemic (dry season, no epidemic), and epidemic (dry season, epidemic).FindingsEight studies reporting a total of eighty pairs of serogroup-specific meningococcal meningitis incidence and carriage estimates were included in this review. For serogroup A, changes associated with the transition from endemic to hyperendemic incidence and from hyperendemic to epidemic incidence were 15-fold and 120-fold respectively. Changes in carriage prevalence associated with both transitions were 1-fold and 30-fold respectively.
For serogroup W and X, the transition from endemic to hyperendemic incidence involved a 4-fold and 1•1-fold increase respectively. Increases in carriage prevalence for the later transition were 7-fold and 1•7-fold respectively. No data were available for the hyperendemic-epidemic transition for these serogroups. Our findings suggested that the regular seasonal variation in serogroup A meningococcal meningitis incidence between the rainy and the dry season could be mainly driven by seasonal change in the ratio of clinical cases to subclinical infections. In contrast appearance of epidemic incidences is related to a substantial increase in transmission and colonisation and to lesser extent with changes in the case-carrier ratio.ConclusionSeasonal change in the rate of progression to disease given carriage together with variations in frequency of carriage transmission should be considered in models attempting to capture the epidemiology of meningococcal meningitis and mainly to predict meningitis epidemics in the African meningitis belt.     

Infectious Causes of Eosinophilic Meningitis in Korean Patients: A Single-Institution Retrospective Chart Review from 2004 to 2018

Eosinophilic meningitis is defined as the presence of more than 10 eosinophils per μl in the cerebrospinal fluid (CSF), or eosinophils accounting for more than 10% of CSF leukocytes in patients with acute meningitis. Parasites are the most common cause of eosinophilic meningitis worldwide, but there is limited research on patients in Korea. Patients diagnosed with eosinophilic meningitis between January 2004 and June 2018 at a tertiary hospital in Seoul, Korea were retrospectively reviewed. The etiology and clinical characteristics of each patient were identified. Of the 22 patients included in the study, 11 (50%) had parasitic causes, of whom 8 (36%) were diagnosed as neurocysticercosis and 3 (14%) as Toxocara meningitis. Four (18%) patients were diagnosed with fungal meningitis, and underlying immunodeficiency was found in 2 of these patients. The etiology of another 4 (18%) patients was suspected to be tuberculosis, which is endemic in Korea. Viral and bacterial meningitis were relatively rare causes of eosinophilic meningitis, accounting for 2 (9%) and 1 (5%) patients, respectively. One patient with neurocysticercosis and 1 patient with fungal meningitis died, and 5 (23%) had neurologic sequelae. Parasite infections, especially neurocysticercosis and toxocariasis, were the most common cause of eosinophilic meningitis in Korean patients. Fungal meningitis, while relatively rare, is often aggressive and must be considered when searching for the cause of eosinophilic meningitis.     

Ectopic pregnancy; early diagnosis,clinical errors and conservative operation

This report of eight years' experience with extrauterine pregnancy by a single gynecologist is an exposition of how the diagnosis was made or why it was missed. Of 26 diagnoses of ectopic pregnancy, five were false (20 per cent); and in three cases (10 per cent) the diagnosis was not made promptly-a total error of 30 per cent. Ectopic pregnancy will be discovered earlier if obstetric patients are always examined shortly after missing the first menstrual period.A palpable adnexal mass was present in 19 of 21 ectopic pregnancies (90 per cent). A mass was palpable in only one of five cases erroneously diagnosed as ectopic pregnancy (20 per cent).Decidual casts were passed by four patients, two of whom did not have ectopic pregnancy. If two gynecologists do not agree on the question of extrauterine pregnancy, a third opinion should be sought or culdoscopy employed. Enucleation of the conceptus and salvage of the oviduct is advocated.     

CEA, ZGM and EMA localization in cells of pleural and peritoneal effusion: a preliminary study

Carcinoembryonic antigen (CEA), the zinc glycinate marker (ZGM) and epithelial membrane antigen (EMA) have been described as epithelial or tumour markers of varying specificity. These antigens were studied by immunoperoxidase localization in selected cell blocks of 62 pleural or peritoneal effusions and compared to cytological findings and review of the clinical records. By cytological criteria, 25 of the cell blocks were positive for malignancy, 30 negative, and 7 inconclusive. CEA, ZGM, and EMA by immunoperoxidase staining were localized on the cell surface and often in the cytoplasm of malignant cells, in 11/25 (44 per cent), 17/25 (68 per cent) and 22/25 (88 per cent) of the positive cell blocks respectively. Ten (40 per cent) of these cases were positive for all three antigens, 7 (28 per cent) for two, and 6 (24 per cent) for one. Of the 7 cases which were inconclusive on routine cytological reporting, 5 were positive for at least one marker. In 3 of the 5 a diagnosis of malignancy was confirmed, and in the other two was strongly suspected as malignant on clinical grounds. Macrophages were sometimes positive for one or more markers (but showed cytoplasmic staining only) and mesothelial cells in some cases stained positively for EMA but were always negative for CEA and ZGM. Localization of the 3 antigens in cells of malignant effusions was compared with their localization in the primary tumours in 9 cases. Localization corresponded for CEA in 7 of 9 cases, for EMA in 8 of 8 an for ZGM in only 2 of 9. Effusion fluid levels for CEA were compared with the cytological and immunocytochemical findings in 30 cases. Mucin stains performed on the cell blocks were also compared with the immunoperoxidase findings.     

The diagnostic value of a meningococcal-B erythrocyte diagnostic agent based on the group-specific polysaccharide

In this work the diagnostic value of group B meningococcal erythrocyte diagnosticum was determined. 585 blood serum samples taken from adult donors were studied: 220 samples from practically healthy persons and 365 samples from 144 patients with meningococcal infection and purulent bacterial meningitis of nonmeningococcal etiology. Group B meningococcal erythrocyte diagnosticum was found to possess serological activity and to reveal the growth of specific antibodies in the sera of patients with meningococcal infection, serologically confirmed by the isolation of group B meningococcal culture, in 100% of cases on weeks 2-3 of the disease. Diagnostic characteristics--specificity and sensitivity--for group B erythrocyte diagnosticum were, respectively, 90.2% and 63.5%. The study revealed that antibodies to several group-specific meningococcal polysaccharides in blood sera can be simultaneously determined in the passive hemagglutination test with a set of erythrocyte diagnostica, which should be taken into consideration in the clinical interpretation of serological results.     

ECTOPIC PREGNANCY—Early Diagnosis,Clinical Errors and Conservative Operation

This report of eight years'' experience with extrauterine pregnancy by a single gynecologist is an exposition of how the diagnosis was made or why it was missed.Of 26 diagnoses of ectopic pregnancy, five were false (20 per cent); and in three cases (10 per cent) the diagnosis was not made promptly—a total error of 30 per cent.Ectopic pregnancy will be discovered earlier if obstetric patients are always examined shortly after missing the first menstrual period.A palpable adnexal mass was present in 19 of 21 ectopic pregnancies (90 per cent). A mass was palpable in only one of five cases erroneously diagnosed as ectopic pregnancy (20 per cent).Decidual casts were passed by four patients, two of whom did not have ectopic pregnancy.If two gynecologists do not agree on the question of extrauterine pregnancy, a third opinion should be sought or culdoscopy employed.Enucleation of the conceptus and salvage of the oviduct is advocated.     

Etiology of suppurative bacterial meningitis

The results of the laboratory examination of 2034 patients with meningococcal infection and purulent meningitides, hospitalized during the period of June 1980 to October 1983, revealed that three main etiological agents were responsible for these diseases: meningococci, pneumococci and Haemophilus influenzae. The susceptibility of the patients to different etiological agents was found to depend on their age. Children aged up to 3 years constituted 75% of the patients with meningitis caused by H. influenzae; 50% of the patients with meningococcal infection were children aged up to 5 years; pneumococcal meningitis occurred more frequently in adults. Serogroup A meningococci were found to prevail in patients with meningococcal infection. Besides, in children serogroup C meningococci could be isolated in 24% of cases. Since 1983 the cases of the isolation of strains belonging to serogroup B increased in number. Among the pneumococci responsible for the disease serotypes 1, 19, 6 and in children serotype 12 occurred most frequently.