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 and its complications in Hamburg from 1960 to 1973 (author's transl)

A study of measles was undertaken from the case histories of 3 093 children under 15 years of age, treated in the children's clinics of Hamburg between 1960 to 1973. 562 children were suffering from pneumonia (18,2%), 230 had otitis (7,4%) and 229 (7,4%) showed neural affections (143 cases with fits and 86 patients with encephalopathy or encephalitis), Various parameters were analysed: age, sex, seasonal distribution, fatality, age disposition to convulsions and measles encephalitis, "incubation period" of neural affections, sequelae. Permanent sequelae due to measles encephalitis were seen in 14% of the cases. A plea is made for an universal immunisation against measles.     

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.     

Meningococcal disease in childhood--a regional study in Ireland

A retrospective study of microbiology laboratory records of culture-confirmed cases of meningococcal disease in children under 14 years of age, admitted to four Dublin hospitals, was conducted for the period 1981-1991 inclusive. The study aimed to describe the epidemiology of meningococcal disease in childhood and to assess the potential of meningococcal group A and C vaccine in preventing disease. There were 406 cases of meningococcal disease of which 319 (78.6%) were in children under 5 years of age. The meningitis to septicaemia ratio was almost 4:1 (320 vs. 86 cases). Of the 406 cases, 216 (53.2%) cases occurred during the period November to March. The age-specific annual incidence rates for the Eastern Health Board region served was 64.2 per 100,000 under 1 year of age and 24.6 per 100,000 under 5 years of age. A relative increase in disease caused by meningococcal serogroup C was observed during the period of the study. Only 15% all cases could have been prevented by a policy of universal meningococcal group A and C immunisation at 2 years of age. Such a policy, therefore, is not recommended. A vaccine for preventing disease caused by meningococcal group B is urgently required.     

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.     

Modelling the incidence of measles in Canada: an assessment of the options for vaccination policy

A range of vaccination policy options for improving the control of measles in Canada is investigated using a mathematical model to simulate transmission of the disease. Results suggest that a catch up campaign giving a second dose of vaccine to children aged up to 18 years would have an immediate impact on transmission, which could be maintained by the introduction of a routine second dose at either 18 months or 5 years of age. Introducing a routine second dose of vaccine without a catch up campaign would allow continued endemic transmission of measles among older children for at least 10-15 years.     

Epidemiological investigations on measles in unvaccinated and vaccinated children (author's transl)

A national study, with participation of 82 paediatricians, was carried out on 9472 children over medium observation periods of between 3.13 and 5.46 years with evaluation of the history of measles, incidence of complications and details of vaccination procedure performed. The protection rate of primary vaccination with live vaccine was 0.89, with split vaccine (3 times) 0.67 and after a combination of split vaccine (3 times) with live vaccine (9 to 12 months later) 0.94. Complications due to measles in unvaccinated children were found in 5.9% of cases. Measles complications after failure of vaccination were found in 2.9% and 2.8% of children vaccinated with live or split vaccine, respectively. No such complications were observed in children vaccinated with a combination of split and live vaccines.     

The influence of the HLA-DRB1*13 allele on measles vaccine response

BACKGROUND: Measles remains a public health threat in the United States with over 50,000 cases being reported from 1989 through 1991 with continued smaller outbreaks. Measles vaccine failure is in part to blame for these large-scale outbreaks. The human leukocyte antigen (HLA) genes are important determinants of immune response to measles virus and vaccine. To examine the influence that HLA polymorphisms may have on measles vaccine antibody response, we compared the distribution of HLA-DRB1 alleles between measles vaccine nonresponders and hyper-responders. METHODS: We determined the seroprevalence of measles antibody in 881 school children immunized with measles-mumps-rubella-II at age 15 months using a whole virus IgG EIA. We performed class II HLA-DR typing by PCR with sequence specific primers (PCR-SSP) on 81 nonresponders (IgG seronegative) and 65 hyper-responders (from the upper 10th percentile of IgG levels of all subjects). We then compared the distribution of alleles between nonresponders and hyper-responders. RESULTS: The distribution of HLA-DRB1 alleles among nonresponders compared to hyper-responders was significantly different (p = 0.014). Nonresponders were significantly less likely to carry the HLA-DRB1*13 alleles than were hyper-responders (7.4% vs 16.2%;p = 0.02). Nonresponders also had an excess of HLA-DRB1*07 alleles (15.4% vs 6.2%; p = 0.015). CONCLUSIONS: The absence of HLA-DRB1*13 alleles is associated with measles vaccine nonresponse. The absence of this allele has also been associated with susceptibility to other infectious diseases. The role of this gene in the immunogenetic response to infectious diseases requires further study.     

Prevention and control of hepatitis B virus infection in Singapore

Hepatitis B virus (HBV) accounted for 24% to 54% of the reported acute viral hepatitis cases in Singapore from 1982 to 1996. The prevalence of HBV infection, as indicated by the presence of markers of HBV, increased from 9.3% in children below 5 years of age to 54.6% in adults above 55 years. The overall hepatitis B surface antigen (HBsAg) prevalence was 5.7% for males and 3.4% for females, with the highest rate among the Chinese. About 39% of the HBsAg carriers were hepatitis B 'e' antigen positive. The main mode of transmission during the first year of life was perinatal, with 43% of the babies born to HBsAg-positive mothers developing the carrier state. Horizontal transmission within the infected household was significantly associated with sharing of personal and household articles. Based on the findings of seroprevalence surveys in various population groups and clinical trials on the safety, immunogenicity and efficacy of various doses and schedules with the plasma-based and yeast-derived hepatitis B vaccines in newborn babies, a national childhood hepatitis B vaccination programme was formulated and implemented in phases, starting with babies born to carrier mothers on 1 October 1985 and finally extending to all newborns on 1 September 1987. The hepatitis B prevention and control programme has been successful. During the period 1994 to 1996, more than 90% of children completed the full schedule of immunisation by below one year of age, and 85% had evidence of vaccination at school entry at age six. Follow-up of 2 cohorts of vaccinated children showed that perinatal transmission has been reduced by 80% to 100%. Horizontal transmission has also declined through other public health measures. The efficacy of the hepatitis B vaccine and the adequacy of reduced doses in the long-term protection of chronic carrier state have been shown in children and adults. The incidence of acute hepatitis B has declined from 10.4 per 100,000 in 1985 to 4.8 per 100,000 in 1996. There is a noticeable reduction in HBsAg prevalence in selected population (school children, national servicemen and antenatal women). The age-standardised incidence rate of primary liver cancer among males had also dropped from 27.8 per 100,000 per year during 1978 to 1982 to 19.0 per 100,000 per year during 1988 to 1992.     

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.     

HLA-DRB1 molecules and antigenic experience shape the repertoire of CD4 T cells

BACKGROUND: During an epidemic of early syphilis, social networks were used for an intervention campaign. GOAL OF THIS STUDY: To characterize the epidemic and describe the yield of new cases from index-case interviews. METHODS: Analyses of morbidity data collected by the Montgomery County, Alabama, sexually transmitted disease program determined the course of the epidemic and characterized the new case yields from social networks identified via index-case interviews (partner notification investigations) and interviews with sex partners and their associates (cluster investigations). Results and costs were compared to a noncampaign period. RESULTS: The number of reported syphilis cases nearly doubled from 1990 to 1991 (201 to 348 per 100,000 residents). During the 21-week campaign, 373 case-patients had partner notification/cluster investigations; 113 (11%) of 984 sex partners and 41 (3%) of 1,146 high-risk associates (persons identified during cluster investigations) had syphilis. No subgroup of case-patients for which the partner notification/cluster investigation yielded more infected persons than other subgroups was identified. The cost per case detected was more than twice that during a noncampaign period ($1,627 vs. $771). CONCLUSION: Partner notification investigations yielded more infected persons than cluster investigations. Further evaluation is needed to determine the role of intense partner notification/cluster investigators' efforts in the control of epidemic syphilis.     

An economic analysis of alternatives for childhood immunisation against Haemophilus influenzae type b disease

Cost-effectiveness and cost-utility analyses of immunisation strategies against invasive Haemophilus influenzae type b (Hib) disease in Australia were based on a hypothetical birth cohort of 250,000 non-Aboriginal Australian children. The model predicted that, without immunisation, 625 cases of invasive Hib disease would occur in under-five-year-olds, with direct costs of $10.2 million. Universal public sector vaccination beginning before six months of age (6MVAC) prevented 80 per cent of cases; vaccination at 12 months (12MVAC) 62 per cent and at 18 months (18MVAC) 46 per cent. At a vaccine cost of $15 per dose, 18MVAC gave the lowest cost per quality-adjusted life year (QALY) over a wide range of model assumptions, with 6MVAC the 'best' alternative. The best estimate ($ per QALY) for 6MVAC was $6930 (three doses), for 12MVAC $9136 (two doses) and for 18MVAC $1231 (one dose). The cost per QALY of single dose catch-up immunisation of older children was estimated at $8630 at two years, $27,000 at three years and $117,000 at four years if done at a scheduled visit; these values were increased if an additional medical visit was included. The threshold cost per vaccine dose at which an immunisation program became cost-saving was estimated for 6MVAC, 12MVAC and 18MVAC as $11, $10 and $14. Even under a worst-case scenario, an immunisation program at 6, 12 or 18 months became cost-saving if indirect costs of death were included. Comparison with previous analyses revealed the importance of the incidence and age distribution of disability and assumptions about vaccine administration costs in determining model outcomes.     

Clinical aspects of human Venezuelan equine encephalitis in Texas

The Venezuelan equine encephalitis epidemic which occurred in Texas in 1971 produced a wide range of predominantly mild clinical symptoms. This epidemic, which peaked on 13-14 July, was most intensely felt in the far-south counties of Cameron and Hidalgo. In all, 88 laboratory-confirmed human cases were reported to the U.S. Center for Disease Control by the Texas State Department of Health. The ratio of male to female cases was about two to one. An attack of 20.8 cases per 100,000, observed in both the 20-29 and 30-39 age groups, was higher than attack rates experienced by other age groups and by the population at large. Together, Cameron and Hidalgo counties experienced a much higher overall attack rate (21.7 cases por 100,000) than did affected counties in the Corpus Christi area (4.9 cases per 100,000). Knowledge about when various patients were first exposed points to an incubation period ranging from 27.5 hours to four days. In those 79 cases for which clinical data were available, the most common clinical manifestations were found to be fever, severe headache, myalgia, and chills. Evidence of mild to moderate central nervous system involvement was found in 10 out of 25 children and young people under 17 years of age, and in six out of 54 adults. Two children still had residual paralysis six weeks after onset of illness, but by 10 months these sequelae had disappeared. Seven of the 54 adults, however, still complained of tiring easily a year after onset of illness. Leukopenia, as demonstrated by a count of less rhan 4,500 white blood cells per cubic millimeter, was observed in 75 per cent of the patients examined.     

Transformation by v-Jun prevents cell cycle exit and promotes apoptosis in the absence of serum growth factors

Data was collected about 49 newly diagnosed cases of SSPE in the years 1993-1995 in Poland. In the analyzed period of time a falling of tendency the incidence of SSPE was maintained. Overall incidence--0.42 per million population, was lower than the incidence in years 1990-1992, when it was 0.72. The tendency of a shift towards older age group was maintained--the peak incidence was observed among 19 year olds, as opposed to 15 year olds in the previous analyzed time period. The authors explain the dropping SSPE incidence in Poland with a drop in measales incidence, which is a consequence of growing measles vaccine coverage rates. The influence of a big measles epidemic which occurred in 1989-1990 on a potential rise in number of SSPE cases has not been noted, but further observations are needed.     

Chickenpox immunisation in New Zealand

PREVENTION: The appropriate use of varicella vaccine, effective in the prevention of chickenpox, has been considered by a Ministry of Health Working Party in 1996 and 1997, including discussion at a workshop held in Wellington, 26-27 June 1996. The introduction of varicella vaccine into the routine childhood immunisation schedule was not supported at this stage. The use of the only varicella vaccine for which the Minister of Health has given consent for distribution in New Zealand, Varilrix (SmithKline Beecham Limited), in healthy children aged nine months to 13 years inclusive, was supported. Consent has not been given for the use of Varilrix in immunocompromised people or in adults. This report discusses other groups that could be candidates for vaccination, such as children with deteriorating renal function and susceptible health care workers who regularly come into contact with especially vulnerable patients. In these cases, the vaccine would need to be administered on a named patient basis. The use of Varilrix in immunocompromised people was not supported. SURVEILLANCE: Enhanced surveillance of chickenpox and zoster are required in New Zealand. Adverse reactions to Varilrix should be carefully monitored. OUTBREAK CONTROL: There are insufficient data at present to support the use of Varilrix in outbreak control. The frequency, cost and current management of nosocomial outbreaks should be ascertained. This information may also assist in the decision whether to incorporate a varicella vaccine into the routine childhood immunisation schedule in the future.     

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.     

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.     

Challenges of traction in critical care: a case study

PROBLEM/CONDITIONS: Despite widespread availability of a safe and effective vaccine against tetanus, 124 cases of the disease were reported during 1995-1997. Only 13% of patients reported having received a primary series of tetanus toxoid (TT) before disease onset. Of patients with known illness outcome, the case-fatality ratio was 11%. REPORTING PERIOD COVERED: 1995-1997. DESCRIPTION OF SYSTEM: Physician-diagnosed cases of tetanus are reported by state and local health departments to CDC's National Notifiable Diseases Surveillance System. In addition, since 1965, supplemental clinical and epidemiologic information for cases has been provided to CDC's National Immunization Program. RESULTS: From 1995 through 1997, a total of 124 cases of tetanus were reported from 33 states and the District of Columbia, accounting for an average annual incidence of 0.15 cases per 1,000,000 population. Sixty percent of patients were aged 20-59 years; 35% were aged > or =60 years; and 5% were aged <20 years, including one case of neonatal tetanus. For adults aged > or =60 years, the increased risk for tetanus was nearly sevenfold that for persons aged 5-19 years and twofold that for persons aged 20-59 years. The case-fatality ratio varied from 2.3% for persons aged 20-39 years to 16% for persons aged 40-59 years and to 18% for persons aged > or =60 years. Only 13% of patients reported having received a primary series of TT before disease onset. Previous vaccination status was directly related to severity of disease, with the case-fatality ratio ranging from 6% for patients who had received one to two doses to 15% for patients who were unvaccinated. No deaths occurred among the 16 patients who previously had received three or more doses. Tetanus occurred following an acute injury in 77% of patients, but only 41% sought medical care for their injury. All patients who sought care were eligible for TT as part of wound prophylaxis, but only 39% received it. Tetanus in injecting-drug users (IDUs) with no known acute injury comprised 11% of all cases, compared with 3.6% during 1991-1994. None of the IDU-associated tetanus cases occurred among persons who were known to have been vaccinated. Sixty-nine percent of IDU-associated tetanus cases were reported from California, and 77% of these cases occurred in heroin users. INTERPRETATION: Tetanus remains a severe disease that primarily affects unvaccinated or inadequately vaccinated persons. Adults aged > or =60 years continue to be at highest risk for tetanus and for severe disease. However, the overall incidence of tetanus has decreased slightly since the late 1980s and early 1990s, from 0.20 to 0.15, a result primarily of a decreased incidence among persons aged > or =60 and <20 years. ACTIONS TAKEN: Tetanus is preventable through both routine vaccination and appropriate wound management. In addition to decennial booster doses of diphtheria and tetanus toxoids during adult life, the Advisory Committee on Immunization Practices (ACIP) recommends vaccination visits for adolescents at age 11-12 years and for adults at age 50 years to enable health-care providers to review vaccination histories and administer any needed vaccine. Every contact with the health-care system, particularly among older adults and IDUs, should be used to review and update vaccination status as needed.     

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.     

Dose adequacy in measles vaccinations in Tabora region, Tanzania

A study was carried out in Tabora region between July 1991 and September 1991, with the aim of determining the adequacy of measles vaccine given to children in Maternal Child Health clinics. Measles vaccine dose used per child was found to be 0.485 ml, which is about 0.385 ml when wastage due to removal of air bubbles is subtracted. Workers in the field need to be trained on the exact volume of vaccine required to be drawn into the syringe before vaccination, to ensure that a dose measuring exactly 0.5 ml of vaccine is injected to a child.