Acute encephalitis and bacterial meningitis in children in Aichi Prefecture (1984-1993)

A survey was performed of acute encephalitis and bacterial meningitis in infancy and childhood from 1984 to 1993 using a questionnaire directed to departments of pediatrics in large hospitals in Aichi prefecture. The case records for 391 patients with acute encephalitis including related diseases and 328 patients with bacterial meningitis were obtained from 63 hospitals. Of 391 patients with acute encephalitis, 224 were male and 167 were female. Of 328 patients with bacterial meningitis, 200 were male and 128 were female. Sex ratio were 1.3, 1.6 respectively. Of the patients, 52.4% of encephalitis and 84.8% of meningitis were under 4 years of age and 0 year olds made up 53.7% of the latter. The causes of these diseases were confirmed in 38.7% and 82.9% of the encephalitis and meningitis patients, respectively, etiologically. In encephalitis, rubella virus was the most frequent with 29 cases, followed by measles virus (27 cases), herpes simplex virus (24) and varicella-zostervirus (19). In meningitis H. influenzae (95 cases), S. pneumoniae (56), Group B streptococcus (41) and E. coli (27) were frequently diagnosed. These diseases showed respective patterns of age distribution and clinical course, and moreover, the increases in their onset were clearly related to the prevalence of causal infections. Therefore, the results of this study should be utilized in the development of administrative measures for prevention of these diseases.     

Epidemiology of encephalitis in children. A prospective multicentre study

We found 175 cases with acute encephalitis in a population of 791,712 children aged 1 month-15 years during a 2-year surveillance period in 1993-1994. The overall incidence was 10.5/100,000 child-years with the highest figure in children < 1 year of age, 18.4/100,000 child-years. The microbial diagnosis was considered proven or suggested in 110 cases (63%); varicella zoster, respiratory and enteroviruses comprised 61% of these, and adeno, Epstein Barr-, herpes simplex and rota viruses comprised 5% each. A clearcut change seems to have occurred in the aetiology of encephalitis. Mumps, measles, and rubella virus associated encephalitides have been almost eliminated. Varicella zoster, respiratory, and enteroviruses have increased in frequency and occur in younger age groups. New causes were identified, especially Chlamydia pneumoniae and HHV-6. Our data should assist in making a specific diagnosis and defining appropriate antimicrobial therapy. CONCLUSIONS: The spectrum of encephalitis in children has changed due to vaccination programs. The incidence, however, appears to be about the same due to increasing frequency of other associated old and new microbes.     

Efficacy of measles vaccine during the 1993 measles epidemic in Korea

Immunization to eliminate measles is recommended at 15 months of age with the option of giving vaccine at 6 to 9 months of age during measles outbreaks in Korea. Because of the recent resurgence of measles and concern about the possibility of reduced vaccine efficacy caused by genomic differences between vaccine virus and contemporary wild measles viruses, we conducted a measles vaccine efficacy study involving children with household exposure ages 1 to 5 years during measles outbreak that had occurred 1993 in Seoul and Seong-nam city, with the demographic analysis of patients brought to the hospitals. A total of 380 patients (M:F = 216:164) were included in this study. Two hundred nine cases (55.0%) occurred in children less than 5 years of age, and 167 (43.9%) were younger than 16 months of age. The recorded age-specific incidence rates showed bimodal patterns, i.e. highest peak in those below 16 months of age and second peak in those ages 6 to 9 years of age. Only 9.6% (16 of 167) of the measles cases less than 16 months, 59.5% (25 of 42) of those 16 months to 4 years and 91.8% (157 of 171) of the cases in school age children have been vaccinated. Attack rates among the 122 vaccinated siblings and 12 unvaccinated siblings ages 1 to 5 years who contacted measles were 5.7 and 75%, respectively, and the clinical vaccine efficacy was 92.4% (95% confidence interval, 83.6, 96.4). The high vaccine efficacy in household exposures suggests that measles outbreaks in Korea are not caused by reduced vaccine efficacy.     

A measles epidemic controlled by immunisation

AIM: In 1997, an immunisation campaign, using measles-mumps-rubella vaccine, was planned for children aged 2-10 years to prevent a measles epidemic predicted by mathematical modelling. The epidemic started before the campaign and is described here. METHOD: Measles hospitalisation, notification and laboratory data were combined. RESULTS: The epidemic started in April 1997 and was largely over by January 1998. No deaths were identified and only one hospitalisation was coded as measles encephalitis, compared to seven deaths and ten cases of measles encephalitis in the 1991 epidemic. For the 12 months from 1 March 1997 there were 2,169 (60 per 100,000) measles cases identified, 314 (9 per 100,000) of whom were hospitalised. Two-thirds of hospitalised cases were notified. The age-standardised measles incidence rates were 33, 34, and 174 per 100,000 for Europeans, Maori and Pacific people, respectively. The respective age-standardised hospitalisation rates were 4, 9 and 32 per 100,000. Measles incidence was highest for under one-year-olds (904 per 100,000) and low for 11-16 year-olds (27 per 100,000)--the cohort previously offered a second vaccine dose. Most cases were aged 10 years and under, and this group were the main drivers of virus transmission. CONCLUSIONS: The immunisation campaign prevented 90-95% of predicted cases. The campaign was appropriately targeted at children aged 10 years and under.     

Novel methods for molecular dynamics simulations

HYPOTHESIS: Monovalent measles vaccine can be administered to children 6 to 11 months of age during an outbreak. Efficacy and effectiveness of this control measure still have to be assessed. METHODS: During and outbreak of measles, monovalent measles vaccine was administered as part of outbreak control to children aged 6 to 11 months. Active surveillance was used to detect cases of measles occurring during the following month. Children who did not develop measles were tested for measles antibody before their revaccination at 15 months of age. RESULTS: Of 81 children 6 to 11 months of age, 56 were vaccinated and two received immunoglobulins; the latter were excluded from the analysis. Measles occurred in 15 of the 79 children during and after the vaccination campaign, for an overall attack rate of 19%. The attack rate among unvaccinated children was 39% (9 of 23), compared with 11% (6 of 56) among those vaccinated (relative risk = 3.6, 95% confidence interval [CI] = 1.5 to 9.1). All of those who sustained measles in the vaccinated group developed the disease within 10 days after vaccination. The overall vaccine effectiveness was 73% (95% CI = 32% to 89%) when children were classified as vaccinated as soon as they were given measles vaccine. It rose to 96% (95% CI = 72% to 99%) when children were considered vaccinated 1 week postimmunization. Nineteen infants who were vaccinated and who did not develop measles during the outbreak were tested for measles antibody status at 15 months of age before revaccination. All had plaque reduction neutralizing antibody titers greater than 120. CONCLUSION: This study confirms that measles vaccination of infants aged 6 to 11 months is an effective intervention measure during measles outbreaks.     

Measles outbreaks in the Bern canton

Currently, overall vaccination coverage against measles among infants ranges between 77% and 89% in Switzerland. Experience in other countries has shown that this level of vaccination is not sufficient to prevent measles outbreaks, especially among schoolchildren. During 1992 surveillance for measles outbreaks in closed populations was conducted in the Canton of Berne. Outbreaks were investigated for vaccine efficacy. Two measles outbreaks in schoolchildren were observed during the study period. In 2 Bernese suburban schools 6 measles cases in children (median age 12.5 years) occurred over a period of 37 days. One of the cases had been vaccinated. Vaccination rate in the healthy control children was 89.7%. Estimated vaccine efficacy was 97.7% (95% confidence interval [CI]: 68%, 99%). The second outbreak occurred in a rural region and comprised 21 measles cases (median age 7.5 years) within 43 days. 10 (47.6%) of the cases attended the same school. None of the cases had been vaccinated. Of the healthy control children 82.6% had received measles vaccine. Estimated vaccine efficacy was 100% (CI: 87%, 100%). These two measles outbreaks were due to failure to vaccinate rather than low vaccine efficacy. Surveillance for measles cases is currently not sufficient for the detection of measles outbreaks in our population. Laboratory confirmation of measles, especially in vaccinated persons, has become more important in a time of relatively low measles incidence.     

The neuropathology of HIV-infected African children in Abidjan, C?te d'Ivoire

In an autopsy study of HIV-infected children in Abidjan, C?te d'Ivoire, the neuropathology of 76 HIV-1- and 2 HIV-2-positive children was compared with that of 77 frequency-matched HIV-negative children, in whom the systemic pathology was also known. Seventy of the 78 HIV-seropositive children were confirmed as HIV-infected, as determined by combined serology, IgA Western blots and clinicopathological criteria. The HIV-negative children showed a high background level (n = 49, 64%) of neuropathological abnormalities, including nonspecific inflammatory infiltrates, micromineralization, and bacterial and lymphocytic meningitis. In the HIV-positive children, HIV encephalitis was found in 4 (6%), cytomegalovirus in 2 (3%), toxoplasmosis in 3 (4%) and measles encephalitis in one (1%). Bacterial meningitis was equally common in both groups, but cerebral malaria was less common (n = 2, 3%) in HIV-positive than in HIV-negative children (n = 11, 14%). The low prevalence of HIV encephalitis may reflect comparatively early death in HIV infection in Africa as compared with our experience in Europe and the US.     

Prognostic factors of early sequelae and fatal outcome of Japanese encephalitis

A clinical case control study to identify prognostic factors present at hospital admission associated with early sequelae and fatal outcome of acute Japanese encephalitis (JE) was carried out in Gusi county, Henan Province, central China from June to September 1991. A total of 70 patients with laboratory-confirmed acute JE were studied, of whom 3 cases died and 33 cases had neurological or psychiatric sequelae at the end of three months follow-up. The results showed that acute JE at younger age, with higher body temperature, high white cell count in CSF, and deep coma present at hospital admission were markers for unfavorable outcomes (sequelae or fatal). A history of the vaccination was not correlated with the early sequelae and fatal outcome of the disease. The paper suggests that early diagnosis and treatment and universal JE vaccination for all susceptible populations are keys for decreasing incidence of sequelae and fatal outcome of acute JE.     

Diethylstilbestrol in beef production: what is the risk to consumers?

Acute measles encephalitis with severe sequelae in a 25-year-old man was studied. A transient appearance of oligoclonal IgG in cerebrospinal fluid and of intrathecally produced measles antibodies was found during 2 months after the onset of the disease. On the basis of this finding of local hyperimmunization it is proposed that in the case studied the measles virus infection may have been directly responsible for the disease process in the central nervous system.     

Measles vaccine effectiveness in standard and early immunization strategies, Niger, 1995

BACKGROUND: An Expanded Programme on Immunization was started in late 1987 in Niger, including vaccination against measles with one dose of standard titer Schwarz vaccine given to infants after 9 months of age. During epidemics an early two-dose strategy was implemented (one dose between 6 and 8 months and one dose after 9 months). From January 1, 1995, until May 7, 1995, 13 892 measles cases were reported in Niamey, Niger. METHODS: A retrospective cohort study was conducted in a crowded area of Niamey at the end of the outbreak to assess the effectiveness of measles vaccine in standard (after 9 months) and early (before 9 months) immunization strategies under field conditions. RESULTS: Highest measles incidence rates were observed among children <1 year of age. Vaccine effectiveness estimates increased with age at vaccination from 78% with a single dose administered at 6 months of age to 95% at 9 months. Vaccine effectiveness with the early two dose strategy was 93%. CONCLUSIONS: Immunization with a single dose of standard titer Schwarz vaccine before 9 months of age provided higher clinical protection than expected from seropositivity studies. The early two dose strategy is justified in contexts where measles incidence is high before 9 months of age. Our results raise the issue of lowering the recommended age for measles vaccination in developing countries.     

New systemic drugs in the treatment of gastrointestinal cancer

Our objective was to study the antibody response to the parotiditis, rubella, measles and tetanus vaccines in HIV infected children. Forty-four children of HIV positive mothers, of which 14 were infected (SG) and 33 HIV negative (CG) were studied when they were between 2 and 3 years of age. Their response to vaccinations of four doses of tetanus toxoid and one dose of measles, rubella and parotiditis vaccines was assessed. Children in the SG were tested at the age of 5-6 years to study the evolution of the response. At the age of 2-3 years, all children had optimal protection against tetanus toxoid. The response to measles, parotiditis and rubella was poor (adequate levels of antibodies in 50%, 25% and 21%, respectively) in infected children and good (93%, 75% and 90%, respectively) in the CG. At 5-6 years of age, a decreased level of antitetanus antibodies were found in the SG, maintaining low protection levels. There was no evidence of any changes in the response to measles, while the number of cases with a good response to parotiditis and rubella increased. Further results are necessary to know the effectiveness of the booster. We conclude that: 1) The immunological response to vaccination is poor in HIV infected children. 2) There was no evidence of side effects or changes in the HIV symptoms after vaccination.     

The "other" parvovirus: first description of the minute virus of canines (Canine parvovirus type 1) in Germany

OBJECTIVE: We present seven cases of acute encephalitis following measles, which were diagnosed during the epidemic that occurred in Spain in 1986. PATIENTS AND METHODS: We studied seven patients diagnosed of encephalitis due to measles. The diagnosis of measles was a made by the presence of a characteristic morbiliform rash and the detection of specific IgM antibodies. The diagnosis of encephalitis was based on the symptoms and the routine examinations of blood, CSF, EEG, CT, ophthalmic exploration and the study of the audiovisual evoked potentials. RESULTS: The patients were between 5 and 9 years of age. None of them had been previously vaccinated for measles. The symptoms of encephalitis occurred 1 to 12 days after the appearance of the rash and the most frequent symptoms were drowsiness and vomiting. All of the patients had EEG abnormalities that returned to normal 1 to 18 months after the diagnosis. One patient presented CT abnormalities. CSF examination revealed an increase of the cell count in one case. The ophthalmic exploration was normal except in one of the patients which had optic neuritis. There were no abnormalities in the audiovisual evoked potentials. All of the cases showed good evolution. Five years later, all of the patients have had a normal development. CONCLUSIONS: The correct vaccination of measles can eradicate this disease.     

Measles inclusion-body encephalitis in a child with treated acute lymphoblastic leukaemia

A child with acute lymphoblastic leukaemia, being treated in the UKALL II Trial, had while in remission an attack of measles and made a normal recovery. Four months later she developed an acute encephalopathy and died within two weeks. The brain showed mild inflammatory features and widespread inclusion bodies in neurones and glial cells. Immunofluorescence proved an infection with measles virus. Similar cases have been called SSPE; reasons are given for preferring the term "measles inclusion-body encephalitis".     

Encephalitis in ferrets caused by a nonproductive strain of measles virus (D.R.) isolated from patient with subacute sclerosing panencephalitis

A nonproductive, syncytiogenic strain (D.R.) of measles virus, isolated from a patient with subacute sclerosing panencephalitis (SSPE), was inoculated intracerebrally into ferrets in an attempt to induce subacute encephalitis. Inoculation of freeze-thawed syncytia before immunization was the least effective procedure, and inoculation of live syncytia after immunization with measles virus vaccine was the most effective procedure, for induction of subacute or persistent subclinical encephalitis in the animals. After the latter procedure three of five ferrets developed subacute or subclinical encephalitis, whereas ferrets inoculated with live syncytia without prior immunization consistently contracted acute fatal encephalitis in one to two weeks. The subacute encephalitis in ferrets was characterized by high titers of antibody to measles virus in serum. At the time of sacrifice 1.25, 4.5, or 8.0 months after inoculation, brains of the ferrets showed histologic lesions similar to those characteristic of SSPE, and nonproductive syncytiogenic measles virus was recovered from the brains of two of the animals. All three ferrets had greatly increased concentrations of gamma-globulin in their brains and high levels of neutralizing and hemagglutination-inhibiting antibodies to measles virus. Only one of these animals developed clinical signs 1.25 months after inoculation.     

Vaccination status of children in the Vienna area (author's transl)

The vaccination status was investigated in 1482 patients between the ages of 1 and 14 years admitted to hospital with scarlet fever. Most of the patients were vaccinated against tuberculosis (97.7%), diphtheria, tetanus and whooping-cough (95.3%) and poliomyelitis (94.1%), relatively few against measles (21.1%) and very few indeed against mumps (0.7%) and tick-borne encephalitis (1.9%). The booster vaccination against tetanus and diphtheria had been omitted in more than 40%. Although the beneficial results of vaccination against tuberculosis, diphtheria-pertussis-tetanus and poliomyelitis remained more or less the same, the tendency towards vaccination did not spread as might have been anticipated. On the contrary, the extent of vaccination decreased, especially during the past years. In the same way the tendency towards vaccination against measles showed a sudden slowing down after a period of rapid increase. This implies that vaccination of children does not tend towards perfection. The vaccination rates differ widely between foreign children living in Vienna and natives. Although the foreigners show a similar vaccination distribution pattern as the natives, the numbers of unvaccinated children are much higher.     

Laboratory diagnosis of subacute and acute encephalitis probably of viral origin: seven years of experience

The results obtained in the laboratory diagnosis of 609 cases of acute or subacute encephalitis, studied during a period of time of even years, is briefly presented. Diagnostic methods included virus isolation from stools and cerebrospinal fluid (CSF); specific serology in serum; detection of intrathecal production of IgG antibody; and, in the last two years, detection of viral genome sequences in CSF by the polymerase chain reaction. Significant results were obtained in 196 cases (32.2%) and the alfa-herpesviruses were responsible for a major part of them (77.5%). Furthermore, 18 cases were likely to respond to dual infection by both herpes simplex and varicella-zoster viruses. Epstein-Barr virus and Human herpesvirus 6 were found in CSF from three immunocompetent patients. Besides the current vaccination program, measles virus is still responsible for an important part (22/196, 11.2%) of cases of viral encephalitis.     

Podiatric casts used for surgery and trauma. Part II: Boot cast

Between April 18 and May 20, 1975, 16 cases of measles occurred in pupils in an elementary school in Baltimore County, Md., and 1 case occurred in a sibling at a junior high school. Measles was serologically confirmed in 16 of these pupils. Attack rates were determined by grade and by vaccine status. The measles attack rate was 2.1 percent for the 377 children who had been given measles vaccine at 1 year of age or later. The rates were 27.8 percent (13 times higher) for those vaccinated at less than 10 months of age and 20.0 percent (10 times higher) for those with no definite history of vaccine. The higher attack rates for children who were vaccinated only before 10 months of age supports the 1972 recommendation of the Public Health Service Advisory Committee on Immunization Practices that children vaccinated before this age need to be revaccinated with live measles virus vaccine to assure full protection. The finding that 2 of 10 children with a history of measles became ill during the outbreak suggests that such histories are not a totally reliable indicator of immunity. Containment of the outbreak was attributed to the high level of immunity in the community and prompt initiation of control measures.     

A case of paradoxical brain embolism in a 17-year-old boy

OBJECTIVE: To estimate the proportion of 1-4-year-old New South Wales children immune to measles and compare the documented immunization history with serologically defined immune status. DESIGN: Population based seroprevalence survey piggybacked onto the National Survey of Lead in Children. Immune status was determined by two different enzyme immunoassays on plasma samples from subjects. SETTING: New South Wales, February-March 1995. OUTCOME MEASURES: Documented measles immunization collected by interview survey and serologically defined immunity. RESULTS: Of 689 survey subjects, 430 (62.4%) provided a blood sample. Adequate plasma remained for both assays for 347 children, of whom 279 (80.4%) were immune by both assays. Parents of 330 stated that their children were immunised, of whom 211 (63.9%) were able to produce corroborating records. Of these 211 subjects, 178 (84.4%) were immune compared to 87 (76.3%) of 114 without records (P = 0.07). CONCLUSIONS: We estimate the prevalence of true measles immunity in 1-4-year-old NSW children to be only 80%, a level inadequate to prevent outbreaks of measles in urban populations. Both long term and immediate strategies are required to increase the prevalence of immunity among NSW children; these may include lowering the age of the routine second measles dose and mounting a mass measles immunisation campaign to include preschool aged children.     

Granulomatous hepatitis: aetiological study of 107 cases (author's transl)

In this series, the commonest aetiology was tuberculosis (30 cases, 28%), followed by sarcoidosis (18 cases, 17,7%), mediterranean fever (Olmer's disease) (13 cases, 12,1%), brucellosis (8 cases, 7,4%), typhoid fever (7 cases, 6,6%) and idiopathic forms (8 cases, 7,4%). These were followed by Hodgkin's disease, toxoplasmosis, adenosarcoma, and leprosy. Finally, there were single cases due to infectious mononucleosis, B.C.G. reaction, hypogammaglobulinaemia, coeliac disease and temporal arteritis. Half of the patients had hepatomegaly and an increase, in general moderate, in hepatic enzymes (transaminases, alkaline phosphatase). The highest enzyme levels were seen in cases of brucellosis, hepatic enzymes being normal in patients with sarcoidosis.     

Measles control in the United States: problems of the past and challenges for the future

Elimination of indigenous measles from the United States has been a public priority since 1978. To assess the progress made toward this goal, we review the epidemiology of measles from 1963 to the present. From the 1970s through early into the recent measles epidemic, the majority of measles cases were in highly vaccinated, school-age children. This was due primarily to a 1 to 5% primary measles-mumps-rubella vaccine failure rate and nonrandom mixing patterns among school-age populations. To eliminate susceptible individuals in the school-age populations, a second dose of measles vaccine is now recommended between 5 and 6 years or 11 and 12 years by both the Advisory Committee on Immunization Practices and the American Academy of Pediatrics. Later in the epidemic, measles cases surged among unimmunized preschool children, especially among the poor in inner-city areas. Immunization rates have been documented to be low among preschool populations because of missed opportunities to administer vaccines at all health visits and barriers to access to immunizations. To raise immunization rates, the age for the first measles-mumps-rubella immunization was lowered to 12 to 15 months of age, federal immunization funding has increased, and new standards for immunization delivery have been developed and promulgated.