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.     

A comparison of alternate immunization regimes for measles in vaccinated populations

Infants today lose maternal measles antibody sooner than in the past. This is related to demographic changes in maternal immunization. Data for rates of decay of maternal antibody and seroconversion after measles vaccination for infants born to naturally immune (Group 1) or vaccinated (Group 2) mothers have been used to evaluate two vaccination schedules: Regime 1, measles-mumps-rubella (MMR) at 1 year of age and Regime 2, monovalent measles at 6 months followed by MMR at 15 months of age. Regime 2 costs less because MMR can be administered at 15 months with the last pentavalent booster. Months of protection/1000 children aged 0-15 months (child-months of protection) were estimated for infant populations ranging from 0 to 100% Group 1 for Regimes 1 and 2. Regime 1 provides more child-months of protection only for 100% Group 1 populations. For the study population Regime 2 provided at least 17% more child-months of protection than Regime 1. Regime 2 provides increased medical and financial benefits in proportion to the number of Group 2 infants in the population and thus is ever more advantageous for today's increasingly vaccinated populations.     

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.     

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.     

A dynamic, multi-level analysis of recent immunization trends in Colombia

During 1985-91, Latin American ministries of health carried out the ultimately successful Regional Polio Eradication Initiative. Unprecedented vaccine coverage levels were attained through a combination of mass campaigns, house-to-house vaccinations, and improvements in routine immunization services. Little is known, however, about the effects of these interventions on immunization demand; whether they reached so-called high-risk households and, if so, whether program effects were sufficient to offset the household risk factors. This paper examines the probability and timing of full immunization over this period in one case country, Colombia. Information on the immunization status of 3,609 vaccine-eligible children born 1985-90 was extracted from Colombia's 1990 Demographic and Health Survey. Annual immunization coverage estimates from the Colombian Ministry of Health for 1985-90 for 148 sample municipios were appended to each child record, along with household-level data. Initial non-parametric regressions showed that five of six observed risk factors negatively influenced full immunization probability. Multivariate logit models showed that parents who had already lost a child were significantly less likely to obtain immunization cards (a proxy for exposure to the routine immunization program), despite rising cardholdership rates over the period. Among 1,376 immunization cardholders, waiting times to full immunization fell monotonically over the period. Local program coverage of 80 per cent or higher and prior use of prenatal services both increased the probability of full immunization. However, three of five maternal occupational categories decreased the probability, as did three of six observed household risk factors. The results show that demand for routine immunizations rose over the period, that only the highest-risk households were not exposed to the routine program, and that routine program participation partially offset negative risk factor effects on the probability of full immunization. While targeted PHC interventions may increase health production by recruiting high-risk households into the routine PHC services, further health production increases will require more intensive follow-up of such households through routine PHC services.     

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.     

A non-specific, beneficial effect of measles vaccination. Analysis of mortality studies from developing countries

The study examined whether the reduction in mortality after standard titre measles immunization in developing countries can be explained by the prevention of acute measles and its long-term consequences. All studies comparing mortality of unimmunised children and children immunised with standard titre measles vaccine in developing countries were included; ten cohort and two case-control studies from Bangladesh, Benin, Burundi, Guinea-Bissau, Haiti, Senegal, and Zaire. We examined the protective efficacy of standard titre measles immunization against all cause mortality. Furthermore, by restricting the analysis to children who had not developed measles, we examined how much of the difference in mortality between immunised and unimmunised children could be explained by prevention of measles disease. In the ten cohort studies, protective efficacy against death after measles immunization was found to be in the range of 30-86%. Efficacy was highest in the studies with short follow-up and where children were immunised in infancy (range: 44-100%). Vaccine efficacy against death was much greater than the proportion of deaths attributed to acute measles disease. In four studies from Guinea-Bissau, Senegal and Burundi, vaccine efficacy against death remained almost unchanged when measles cases were excluded from the analysis. Hence, the reduction in mortality among immunized children cannot be explained by the prevention of acute and long-term consequences of measles. In contrast to the effect of measles vaccine, studies from Guinea-Bissau, Senegal and Benin suggest that diphtheria-tetanus-pertussis and polio vaccinations are not associated with reduction in mortality. These observations suggest that standard titre measles vaccine may confer a beneficial effect which is unrelated to the specific protection against measles disease.     

Impact of maternal and child health strategy on child survival in a rural community of Pondicherry

OBJECTIVE: To determine the impact of Maternal and Child Health (MCH) services on child survival in a socio-economically backward rural community. SETTING: Twelve villages in Pondicherry with a population of 16,803. DESIGN: Prospective study. SUBJECTS: A birth cohort of 356 live births (LB) born between January 1st and December 31st 1988. METHODS: The live births were followed-up from birth to five years age (1988-1993). The health care received by this cohort and the antenatal services received by the cohort mothers was reviewed. Outcome measures related to child survival were determined and their changing trend since 1967 was examined. RESULTS: Fifty-four per cent of the cohort children were from families below the poverty line. Antenatal registration and tetanus immunization coverage of the mothers of the cohort was 100%. Immunization coverage of the cohort children was more than 98% for BCG, DPT (three doses) and OPV (three doses) and 82% for measles. The infant mortality rate had reduced from 201/1000 LB in 1967 to 64/1000 LB (95% CI 58.9-68.1) in 1989. The child death rate decreased from 29.4/1000 children 1-4 years of age (1970) to 18/1000 (95% CI 13.9-22.1) in 1992. There were no deaths due to neonatal tetanus or measles. Neonatal mortality (35/1000 LB; 95% CI 29.9-40.1) was higher than the post-neonatal mortality (29/1000 LB; 95% CI 24.1-33.9). Fifty eight per cent of the neonatal deaths were due to non-infective causes like prematurity, birth asphyxia, birth injuries and congenital anomalies. Eighty per cent of post neonatal deaths were due to infections. Overall, the child survival index was high (91.27%; 95% CI 88.14-94.26). This was inspite of the low socio-economic background of the children's families. CONCLUSIONS: Good MCH services can substantially improve child survival inspite of prevailing low socio-economic situations. Inputs for neonatal care need to be strengthened to further enhance child survival.     

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 study of maternally derived measles antibody in infants born to naturally infected and vaccinated women

Maternal, cord and infant measles antibody levels were measured and compared in a group of 411 vaccinated mothers and 240 unvaccinated mothers, and their babies, between 1983 and 1991. Maternal and cord sera were tested by haemagglutination inhibition and/or enzyme-linked immunosorbent assay, and plaque reduction neutralization tests were also used to test infant sera. Geometric mean titres were significantly higher in the unvaccinated than in the vaccinated mothers (P < 0.001). Infants born to mothers with a history of measles had higher antibody levels at birth than infants of vaccinated mothers and, although the difference narrowed over time, continued to have higher levels up to 30 weeks of age. Between 5 and 7 months of age significantly more of the children of vaccinated mothers had plaque reduction neutralization antibody levels below that which would interfere with vaccination. As the boosting effect of circulating natural measles disappears, earlier measles vaccination may need to be considered, perhaps as part of a two-dose policy.     

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.     

Testicular cancer risk and maternal parity: a population-based cohort study

The aim was to study, in a population-based cohort design, whether first-born sons run a higher risk of testicular cancer than later born sons; to investigate whether this difference in risk was affected by birth cohort, age of the son, maternal age, interval to previous delivery and other reproductive factors; and, finally, to evaluate to what extent changes in women's parity over time might explain the increasing incidence of testicular cancer. By using data from the Civil Registration System, a database was established of all women born in Denmark since 1935 and all their children alive in 1968 or born later. Sons with testicular cancer were identified in the Danish Cancer Registry. Among 1015994 sons followed for 15981 967 person-years, 626 developed testicular cancer (443 non-seminomas, 183 seminomas). Later born sons had a decreased risk of testicular cancer (RR = 0.80, 95% CI = 0.67-0.95) compared with first-born sons. The RR was 0.79 (95% CI = 0.64-0.98) for non-seminomas and 0.81 (95% CI = 0.58-1.13) for seminomas. There was no association between testicular cancer risk and overall parity of the mother, maternal or paternal age at the birth of the son, or maternal age at first birth. The decreased risk of testicular cancer among later born sons was not modified by age, birth cohort, interval to the previous birth, sex of the first-born child, or maternal age at birth of the son or at first birth. The increased proportion of first-borns from birth cohort 1946 to birth cohort 1969 only explained around 3% of an approximated two-fold increase in incidence between the cohorts. Our data document a distinctly higher risk of testicular cancer in first-born compared with later born sons and suggest that the most likely explanation should be sought among exposures in utero. The increase in the proportion of first-borns in the population has only contributed marginally to the increase in testicular cancer incidence.     

The effect of neonatal universal hearing screening in a health surveillance perspective--a controlled study of two health authority districts

The contribution describes the effect of a neonatal hearing screening program in terms of estimated prevalence rate of congenital hearing impairment and age at identification in two five-year cohorts born between 1990 and 1994 as a function of health authority districts (HADs). In addition, identically defined five-year birth cohorts from 1970 to 1974 and 1980 to 1984 living in the same HADs evaluated previously are used in the analysis, offering longitudinal data. In 1990 a non-targetted neonatal hearing screening program based on EOAE was introduced in the County-HAD, whereas the City-HAD continued its child hearing health surveillance program unchanged. Assuming an unchanged prevalence estimate of 1.5 per 1000 of congenital or early acquired (i.e. neonatal period) hearing disability, i.e. > or = 25 dB HL for the better ear at 0.5-4 kHz in both HADs, an underestimate of 68 per cent in the City and of 20 per cent in the County, respectively, was found at the time of data collection (January 1995). Significant longitudinal improvements in the early identification from the 1970-1974 cohort compared to the 1980-1984 cohort has been demonstrated, but the improvement in the proportion of children identified as a function of both 6 and 12 months of age in the 1990-1994 cohort is significantly greater, showing a median age at identification of 11 months in the County-HAD. The cross-sectional and longitudinal comparisons between the HADs imply that a neonatal universal hearing screening program with a 20 per cent coverage may add significantly to the early identification of children with early-onset hearing impairment.     

Beh?et''s disease and chronic neutropenia

This paper reviews the Indian data on age distribution of measles prior to large scale immunization. In metropolitan areas, the median age was about 24 months and virtually all the cases were recorded in children under 5, whereas median age in most of rural studies was < 4-< 5 years and all the persons were not affected until 10 years of age. The situation was in between in other areas. Since less than 10 per cent of the cases occurred before 9 months of age, this age is appropriate for routine measles immunization. The results also suggested the choice of age groups to be immunized during measles mass campaigns; the upper age may be 3 years in metropolitan city, 10 years in rural areas, and 5 years in the rest of the population.     

Effects of cocaethylene on dopamine and serotonin synthesis in Long-Evans and Sprague-Dawley brains

BACKGROUND: Primary liver cancer is an important health problem in Korea, where hepatitis B virus (HBV) infection is prevalent. The authors conducted a prospective cohort study to evaluate the protective effect of HBV vaccination against liver cancer in adults. METHODS: A total of 370,285 males aged > or = 30 comprised the study population. They were clinically free of liver diseases, and had not been vaccinated against HBV at enrolment. The results of HBV surface antigen (HBsAg) and antibody to HBsAg (anti-HBs) marker positivity and those of the vaccination programme which took place during 1985 were used for the construction of the cohort. About 5% (n = 18,914) were HBsAg positive, 78,094 were anti-HBs positive, and 273,277 were negative for both. Among the candidates for HBV vaccination (n = 273,277), 35,934 (13.2%) people had been vaccinated against HBV during 1985. Cases of liver cancer were ascertained by record linkage and from medical records covering 1986-1989. A multivariate log-linear model was used to test statistical significance and to estimate relative risks (RR). RESULTS: The total follow-up period was 1,404,566 person-years, with an average of 3 years and 10 months. A total of 302 incident cases were ascertained. The overall incidence rate of liver cancer was 21.7 per 100,000 person-years. With reference to the incidence level among the unvaccinated and uninfected, the RR of primary liver cancer among the chronically infected and that of the unvaccinated and infected was 18.1 (95% CI: 14.2-22.9) and 0.34 (95% CI: 0.19-0.60), respectively. The RR among the vaccinated group was 0.58 (95% CI: 0.31-1.09). CONCLUSIONS: This study suggested that artificial immunization through HBV vaccination, even in adulthood, reduces the risk of liver cancer. It might also offer a practicable means of primary prevention, especially in areas with hyperendemicity of HBV infection.     

Cervical cancer mortality in Belgium, 1955-1989. A descriptive study

This study describes trends in cervical cancer mortality among women in Belgium from 1954 to 1989. Data are analysed by means of the standardised mortality rate, age- and cohort-specific mortality rates and standardised cohort mortality ratios. The age-standardised mortality rate decreased progressively from 6.3/100,000 women-years in the first period (1955-1959) to 3.8/100,000 in 1985-1989, indicating a decline of 39.7% over the seven quinquennial periods. A decrease was observed in almost all age groups between 30 and 69 years. In the last 15 years, no further decline, but even a discrete increase, occurred for the age categories younger than 50 years. The successive cohorts born between 1915 and 1939 expressed a continuing lower risk of cervical cancer mortality. This trend was not observed for the most recent generations, for whom even a slight increase of the standardised cohort mortality ratio could be distinguished.     

Bacterial meningitis in the United States in 1995. Active Surveillance Team

BACKGROUND: Before the introduction of the conjugate vaccines, Haemophilus influenzae type b was the major cause of bacterial meningitis in the United States, and meningitis was primarily a disease of infants and young children. We describe the epidemiologic features of bacterial meningitis five years after the H. influenzae type b conjugate vaccines were licensed for routine immunization of infants. METHODS: Data were collected from active, population-based surveillance for culture-confirmed meningitis and other invasive bacterial disease during 1995 in laboratories serving all the acute care hospitals in 22 counties of four states (total population, more than 10 million). The rates were compared with those for 1986 obtained by similar surveillance. RESULTS: On the basis of 248 cases of bacterial meningitis in the surveillance areas, the rates of meningitis (per 100,000) for the major pathogens in 1995 were Streptococcus pneumoniae, 1.1; Neisseria meningitidis, 0.6; group B streptococcus, 0.3; Listeria monocytogenes, 0.2; and H. influenzae, 0.2. Group B streptococcus was the predominant pathogen among newborns, N. meningitidis among children 2 to 18 years old, and S. pneumoniae among adults. Pneumococcal meningitis had the highest case fatality rate (21 percent) and in 36 percent of cases was caused by organisms that were not susceptible to penicillin. From these data, we estimate that 5755 cases of bacterial meningitis were caused by these five pathogens in the United States in 1995, as compared with 12,920 cases in 1986, a reduction of 55 percent. The median age of persons with bacterial meningitis increased greatly, from 15 months in 1986 to 25 years in 1995, largely as a result of a 94 percent reduction in the number of cases of H. influenzae meningitis. CONCLUSIONS: Because of the vaccine-related decline in meningitis due to H. influenzae type b, bacterial meningitis in the United States is now a disease predominantly of adults rather than of infants and young children.     

Opinions and practices of family physicians regarding measles-mumps-rubella vaccination

BACKGROUND: Measles-mumps-rubella immunization rates among young children depend on the awareness and responsibility of parents and physicians. In order to improve immunization programmes, it is important to enhance our knowledge about attitudes of physicians in regard to MMR immunization. A random sample of 1013 general practitioners was interviewed by telephone in December 1994, with the collaboration of the BVA Institute. The large majority of French physicians (86%) have a favourable opinion about MMR immunization that they systematically propose to each child aged 12-24 months. However, barriers remain among some physicans. Favourable opinion about MMR immunization to infants was less frequent among physicians aged 41-50 years, homeopaths, those practicing in Southern France, those asking for higher payment to patients, those who are treating a small proportion of patients receiving public medical aid, those not convinced about the role of physicians in health education, those who experienced side-effects of immunization and those who are not personnally immunized against hepatitis B. Eradication of measles, mumps and rubella in France will be only achieved through a stronger and well-argumented information of physicians supported by health professional organizations.