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An outbreak of measles among a predominantly unvaccinated and susceptible Amish population in Lebanon County, Pennsylvania, offered the opportunity to test the hypothesis that secondary cases in households are more severe than primary cases because the former have more intense exposure and receive a greater virus inoculum. Of 130 measles cases reported between April and June 1988, 119 (92%) constituted a study of disease severity. Severity was assessed by determining frequency and duration of symptoms, length of any hospitalization, and number of days in bed. In a univariate analysis, fewer secondary cases had conjunctivitis (relative risk [RR], 0.67; 95% confidence interval [CI], 0.48-0.96) and headache (RR, 0.37; CI, 0.15-0.86), but more had earache (RR, 9.69; CI, 1.8-202.9) compared with primary cases. Secondary cases had a shorter mean duration of coryza (4.0 vs. 5.0 days, Student's t test, P = .08). However, a logistic regression model that matched by family and controlled for age and sex indicated that there were no significant differences in measles severity among primary and secondary cases in households.

In recent years, measles outbreaks have occurred among unimmunized children in inner cities in the United States. From May 1988 through June 1989, 1214 measles cases were reported in Los Angeles, and from October 1988 through June 1989, 1730 cases were reported in Houston. More than half of cases were in children younger than 5 years of age, most of whom were unvaccinated. Of cases of measles in preschool-aged children, nearly one fourth in Los Angeles and more than one third in Houston were reported by one inner-city emergency room. To evaluate whether emergency room visits were a risk factor for acquiring measles, in Los Angeles, 35 measles patients and 109 control patients with illnesses other than measles, and in Houston, 49 measles patients and 128 control patients, who visited these emergency rooms, were enrolled in case-control studies. Control patients were matched to case patients for ethnicity, age, and week of visit. Records were reviewed to determine whether case patients had visited the emergency room during the period of potential measles exposure, which was defined as 10 to 18 days before rash onset, and whether control patients had visited 10 to 18 days before their enrollment visit. In Los Angeles, 23% of case patients and 5% of control patients (odds ratio = 5.2, 95% confidence interval = 1.7, 15.9; P less than .01), and in Houston, 41% of case patients and 6% of control patients (odds ratio = 8.4, 95% confidence interval = 3.3, 21.2; P less than .01), visited the emergency room during these periods.(ABSTRACT TRUNCATED AT 250 WORDS)

A school blood drive before a measles outbreak permitted correlation of preexposure measles antibody titers with clinical protection using the plaque reduction neutralization (PRN) test and an EIA. Of 9 donors with detectable preexposure PRN titer less than or equal to 120, 8 met the clinical criteria for measles (7 seroconfirmed) compared with none of 71 with preexposure PRN titers greater than 120 (P less than .0001). Seven of 11 donors with preexposure PRN titers of 216-874 had a greater than or equal to 4-fold rise in antibody titer (mean, 43-fold) compared with none of 7 with a preexposure PRN titer greater than or equal to 1052 (P less than .02). Of 37 noncases with preexposure PRN titer less than 1052, 26 (70%) reported one or more symptoms compared with 11 (31%) of 35 donors with preexposure PRN titers greater than or equal to 1052 (P less than .002). By EIA, no case had detectable preexposure antibody; the preexposure geometric mean titer of asymptomatic donors (220) was not significantly higher than that of symptomatic donors who did not meet the clinical criteria for measles (153) (P = .10). The study suggests that PRN titers less than or equal to 120 were not protective against measles disease and illness without rash due to measles may occur in persons with PRN titers above this level.

Persons who received measles vaccine between 12 and 14 months of age have been found to be at increased risk of measles compared with those vaccinated at greater than or equal to 15 months of age. Because of this, in 1987 the Immunization Practices Advisory Committee of the US Public Health Service recommended that, during measles outbreaks, revaccination of persons vaccinated at 12-14 months of age be considered. During a school-based outbreak in New Mexico in 1987, the authors evaluated the effect of a mandatory revaccination policy in affected schools. Before the effect of revaccination, the overall attack rate in persons vaccinated at greater than or equal to 12 months of age was 4.1 cases/1,000 students; afterward, the risk was significantly reduced by 73%, to 1.1/1,000 students. The attack rate among students targeted for revaccination declined 100%, compared with 41% among those not revaccinated. Overall, attack rates were significantly lower in schools conducting revaccination early compared with schools holding later revaccination. In a retrospective cohort study of single-dose vaccines in one school, age at vaccination was not associated with risk of disease; however, persons vaccinated greater than or equal to 10 years before the outbreak were at increased risk, independently of age at vaccination. Revaccination of persons whose most recent vaccination was between 12 and 14 months of age appeared to control transmission in this outbreak. Further studies are needed to confirm these observations and to evaluate the effect of other revaccination efforts during outbreaks.

Measles vaccine is one of the safest and most effective vaccines currently available. Use of the vaccine has decreased the incidence of measles in both developed and developing countries. Nevertheless, preventable morbidity and mortality continue to occur. In the United States, the measles problem differs when it occurs among preschool-aged children or school-aged children. The former is a due to insufficient vaccine delivery. For measles in school-aged and college students, the problem is primarily vaccine failure, which should eventually be solved by a two-dose schedule. In developing countries, the major problem is vaccine delivery. Use of Edmonston-Zagreb measles vaccine in developing countries offers the promise of reducing disease rates in young infants; however, in both the United States and in developing countries, increasing immunization levels is essential.

Because measles causes an estimated 2 million deaths per year among children in developing countries, including a substantial proportion of infants less than nine months old--the age at which vaccination is recommended--there has been interest in using different strains of vaccine and higher doses to achieve immunization of younger infants. We conducted a randomized trial of three different doses of Edmonston-Zagreb and of Schwarz measles vaccines in infants to evaluate the effect of the strain and dose of vaccine on the serologic response and acute adverse reactions to vaccination. Six-month-old infants received a standard, medium, or high dose of one of the vaccines, and nine-month-old infants received a standard dose. Antibody levels were measured before and after vaccination, by means of a plaque-reduction neutralization assay, in 1061 six-month-olds and 299 nine-month-olds. Edmonston-Zagreb vaccine produced higher rates of seroconversion and seropositivity than comparable doses of Schwarz vaccine. Among the six-month-old infants, the seroconversion rate 18 weeks after vaccination with the standard dose of Edmonston-Zagreb vaccine was 92 percent, that with the medium dose was 96 to 97 percent, and that with the high dose was 98 percent; the rates for the corresponding doses of Schwarz vaccine were 66 percent, 76 percent, and 91 percent, respectively. Higher seroconversion rates were observed with an increase in the dose of either Edmonston-Zagreb (P less than 0.01) or Schwarz (P less than 0.001) vaccine. The seroconversion rates produced by high and medium doses of Edmonston-Zagreb vaccine in six-month-olds were equal to or significantly higher than the rate produced by a standard dose of Schwarz vaccine in nine-month-olds (87 percent). Clinical adverse reactions were not associated with the strain or dose of a vaccine. We conclude that Edmonston-Zagreb vaccine is more immunogenic than Schwarz vaccine in infants and can induce effective immunization against measles at six months of age.

State immunization laws which exempt religious groups present difficult problems in disease control in measles epidemics. Two outbreaks are described, 136 cases in a college for Christian Scientists, and 51 cases associated with a camp attended by Christian Scientists. Control measures at the college included immunization and quarantine. An alternative strategy at the camp consisted of dispersal of exposed persons from the camp and their being quarantined in their home States. Three deaths (case-fatality ratio = 2.2 percent) were reported at the college; no serious complications were reported from the camp-associated epidemic. No transmission into the general community occurred in either epidemic. Public health officials are encouraged to be aware of the legal rights and obligations of religiously exempt groups so that outbreaks in these groups can be effectively controlled, even if standard immunization strategies are not possible. Early reporting and rapid case identification, investigation, and quarantine or vaccination procedures by public health workers are necessary for disease control in these settings.

During the first six months of 1983, an epidemic of serogroup A meningococcal meningitis occurred in the Kathmandu valley of Nepal, resulting in 875 cases and 95 deaths. The annual attack rate was 103 cases per 100,000 population, with a peak attack rate occurring in April. Epidemic meningococcal disease had not been recognized previously in Nepal. Early in 1984, a review of hospital-based data on pyogenic meningitis in Kathmandu showed three times as many cases per month compared with the same period the previous year, suggesting that a recurrent epidemic was unfolding. Beginning in February 1984, a vaccination campaign directed at a high-risk target population of people aged 1-24 years was launched; over 329,000 doses of bivalent A/C meningococcal vaccine were given, achieving approximately 64% coverage of the target population. A dramatic decline in the number of new meningitis cases occurred coincident with the initiation of the mass vaccination campaign. This experience demonstrates that it is possible, with appropriate surveillance efforts, to detect an evolving epidemic of meningococcal disease early in its course and to institute control measures in advance of the expected epidemic peak.

During 1983-1986, 5,016 cases of Lyme disease were reported to the Centers for Disease Control. Cases were acquired in 31 states; however, 86% of the cases were acquired in seven states: Massachusetts, Rhode Island, Connecticut, New York, New Jersey, Wisconsin, and Minnesota. For 63% of patients the disease began in summer; 52% recalled a tick bite. Erythema chronicum migrans (ECM) occurred in 91% of the patients; arthritis, in 57%; neurologic complications, in 18%; and cardiac manifestations, in 10%. When serum samples were obtained greater than or equal to 21 days after onset of symptoms, 14% (6 of 42) with ECM alone and 19% (17 of 89) with complicated Lyme disease (ECM plus organ-system involvement) had positive serologic tests. Antimicrobial therapy did not appear to affect serologic response. Lyme disease is now the most commonly reported tick-borne illness in the United States and has been reported from 32 states since 1980. Physicians nationwide need to be familiar with the protean signs and symptoms associated with Lyme disease and with the limitations of current serologic techniques in diagnosing early illness.

This study compares the cost-effectiveness of six vaccination strategies during a measles outbreak: vaccination of all susceptibles 15 months of age or older and born after 1956 (the current routine strategy); lowering the recommended age at vaccination from 15 to 12 months (plus current routine strategy); lowering the recommended age at vaccination to six months (plus current routine strategy); revaccination of those vaccinated at 12-14 months of age (plus current routine strategy); vaccination of all students in school regardless of immune status; and vaccination of all residents 15 months to 28 years of age in the community regardless of immune status. The analysis is based on the hypothetical, early application of these strategies to a 1985 measles outbreak in Montana, which occurred despite appropriate application of current prevention and control recommendations. Although the results are applicable only to this particular outbreak, this analysis provides an approach which can be used in other settings to assess measles outbreak control strategies. Similar studies would need to be performed in a variety of settings to determine the most cost-effective measles outbreak control strategies overall.

Recently studies conducted in several countries using Edmonston-Zagreb vaccine administered subcutaneously to infants younger than 9 months of age have shown high seroconversion rates, approaching or equaling those routinely achieved at 9 months of age with the more widely used Schwarz vaccine. These results have raised expectations that the Edmonston-Zagreb vaccine can play an important role in helping to prevent measles in young infants in highly endemic areas. Because of the implications of changing the measles vaccine recommendations, vaccine advisory groups and vaccine manufacturers will require additional studies to confirm the preliminary findings and to answer new questions which have been raised. The needed data will probably be collected over the next year or two in studies already under way or being planned in the hope that a more effective vaccine for young infants can be introduced before the end of this decade.

Data from the Commission on Professional and Hospital Activities, Professional Activities Study were used to estimate the incidence and geographic distribution of hospitalized patients with toxic shock syndrome (TSS) in the United States in 1981 and 1982. There were 1004 discharges with a diagnosis of TSS from hospitals participating in the study. These discharges could not be validated using clinical criteria. Using these data, the projected incidences for the United States were 0.78/100,000 and 0.84/100,000 total population in 1981 and 1982, respectively. Female patients, 15 to 19 years of age, had the highest age-specific incidence (4.8/100,000). Race, sex, and geographic distributions of cases reported to the national surveillance system were similar to those of patients discharged with a diagnosis of TSS from hospitals participating in the study.

In 1982, national surveillance for Lyme disease was established by the Centers for Disease Control to monitor trends and determine endemic geographic areas. Initially, the endemic areas corresponded to the known distribution of Ixodes dammini, a five-state area of the northeastern seaboard (New York, New Jersey, Connecticut, Rhode Island, and Massachusetts) and Wisconsin and Minnesota. Increasing numbers of cases have been reported outside these areas, however, 86% of the provisional 5731 cases reported to CDC were acquired in these seven states. The number of reported cases increased from 491 in 1982 to approximately 1500 per year in 1984-1986, making Lyme disease the most commonly reported tick-borne illness in the United States. The apparently widening distribution of Lyme disease indicates that physicians in all regions of the country should be familiar with its signs and symptoms. Investigations of the vector in areas endemic for Lyme disease where Ixodes ticks are not found are warranted.

Since 1982 seven patients at Stanford University Medical Center have been shown to have prosthetic-valve endocarditis caused by Legionella pneumophila or L. dumoffii. We studied the clinical features of legionella endocarditis at the time of diagnosis and performed a case-control study to analyze risk factors for the infection. All patients with endocarditis had a chronic course (3 to 19 months after surgery) of fever, night sweats, weight loss, and anemia, but no embolic events or immune-complex deposition disease. Five patients required surgical replacement of their infected prosthetic valves. The case-control study revealed that during the early postoperative period, patients who later contracted legionella endocarditis were more likely to have had symptoms and signs attributable to postcardiomyotomy syndrome than were patients who did not contract endocarditis (P less than 0.013). Examination of the legionella isolates by means of molecular techniques demonstrated that the Stanford L. pneumophila isolates were genotypically identical to isolates from the hospital drinking water. L. dumoffii isolates from patients with endocarditis were derived from a single strain apparently unique to this medical center. We conclude that legionella infection was nosocomially acquired in the perioperative period. These cases demonstrate an expanding spectrum of illness caused by legionella species and emphasize the need to consider legionella as a cause of "culture-negative" endocarditis.

In 1985, 69 secondary cases, all in one generation, occurred in an Illinois high school after exposure to a vigorously coughing index case. The school's 1,873 students had a pre-outbreak vaccination level of 99.7% by school records. The authors studied the mode of transmission and the risk factors for disease in this unusual outbreak. There were no school assemblies and little or no air recirculation during the schooldays that exposure occurred. Contact interviews were completed with 58 secondary cases (84%); only 11 secondary cases (19%) of these may have had exposure to the index case in the classrooms, buses, or out of school. With the use of the Reed-Frost epidemic model, only 22-65% of the secondary cases were likely to have had at least one person-to-person contact with the index case during class exchanges, suggesting that this mode of transmission alone could not explain this outbreak. A comparison of the first 45 cases and 90 matched controls suggested that cases were less likely than controls to have provider-verifiable school vaccination records (odds ratio (OR) = 8.1) and more likely to have been vaccinated at less than age 12 months (OR = 8.6) or at age 12-14 months (OR = 7.0). Despite high vaccination levels, explosive measles outbreaks may occur in secondary schools due to 1) airborne measles transmission, 2) high contact rates, 3) inaccurate school vaccination records, or 4) inadequate immunity from vaccinations at younger ages.

Between 1980 and 1985, 89-121 international measles importations were reported annually in the US, accounting for 0.7-6.9% of the annual number of reported measles cases. These measles cases were acquired in more than 70 different countries. Three countries accounted for over one third of all imported cases: Mexico, the UK and the Philippines. Thirty-six states reported importations. However, over half of all importations were reported from only six states: California, New York, Maryland, Florida, Texas and Hawaii. Most measles importations did not cause transmission in the US. In 1982 and 1985 only 16% and 29% of importations resulted in any spread cases. Until there is better control of measles worldwide, high immunization levels are crucial for continued measles control in the US.

From January 4 to May 13, 1985, an outbreak of 137 cases of measles occurred in Montana and persisted for 12 generations of spread. A total of 114 cases occurred on the Blackfeet Indian reservation in northwest Montana. Of the 137 cases, 82 (59.9%) were in school-aged children (aged 5-19 years). Of the 114 cases on the reservation, 108 (94.7%) were classified as programmatically nonpreventable. A total of 64 (82.1%) of the 78 patients on the reservation who were born after 1956 and were above the recommended age at vaccination had a history of adequate measles vaccination. Additionally, an audit of immunization records at the schools in Browning, Montana, where most of the cases occurred, showed that 98.7% of students were appropriately vaccinated. A retrospective cohort study in the Browning schools failed to identify age at vaccination or time since vaccination as significant risk factors for vaccine failure. Overall vaccine efficacy was 96.9% (95% confidence interval = 89.5-98.2%). None of 80 Browning students who were vaccinated at less than 12 months of age and revaccinated at 15 months of age or older became infected. A case-control study showed a significant association between attendance at Browning basketball games and infection early in the outbreak. This outbreak suggests that measles transmission may persist in some settings despite appropriate implementation of the current measles elimination strategy.

Between June 1 and July 15, 1984, twenty persons with glandular tularemia were identified on the Lower Brule and Crow Creek Indian reservations in South Dakota. The median age of the patients was 6 years (range, 2 to 20 years). The clinical illness was mild, consisting of fever, headache, and lymphadenopathy. All lymphadenopathy was in the head and neck area. Dermacentor variabilis ticks were identified as the vector. Although the mild clinical illness suggested Francisella tularensis, type B, was the agent, both type A and type B strains of F tularensis were isolated from ticks collected from dogs in the area. Tularemia is generally thought to be a severe systemic illness in North America. This outbreak illustrates that it can be a mild disease and that both type A and type B strains can be tick-borne and coexist in the same ecosystem.

Lyme disease is an increasingly recognized tick-borne illness caused by a spirochete, Borrelia burgdorferi. Because the etiologic agent of Lyme disease is a spirochete, there has been concern about the effect of maternal Lyme disease on pregnancy outcome. We reviewed cases of Lyme disease in pregnant women who were identified before knowledge of the pregnancy outcomes. Nineteen cases were identified with onset between 1976 and 1984. Eight of the women were affected during the first trimester, seven during the second trimester, and two during the third trimester; in two, the trimester of onset was unknown. Thirteen received appropriate antibiotic therapy for Lyme disease. Of the 19 pregnancies, five had adverse outcomes, including syndactyly, cortical blindness, intrauterine fetal death, prematurity, and rash in the newborn. Adverse outcomes occurred in cases with infection during each of the trimesters. Although B burgdorferi could not be implicated directly in any of the adverse outcomes, the frequency of such outcomes warrants further surveillance and studies of pregnant women with Lyme disease.

Since the licensing of measles vaccine in 1963, the incidence of reported measles in the United States has declined to less than 2 percent of previous levels. To characterize the current epidemiology of measles in the United States, we analyzed measles outbreaks that occurred during 1985 and 1986. There were 152 outbreaks (defined as five or more cases related epidemiologically), which accounted for 88 percent of the cases reported during those two years. There were two major types of outbreaks: those in which most of the cases occurred among preschool-age children (those under 5 years of age) (26 percent) and those in which most of the cases occurred among school-age persons (those 5 to 19 years of age) (67 percent). The outbreaks among preschool-age children ranged in size from 5 to 945 cases (median, 13); a median of only 14 percent of the cases occurred in vaccinated persons, and a median of 45 percent of the cases were classified as preventable according to the current strategy. Outbreaks among school-age persons ranged in size from 5 to 363 cases (median, 25); a median of 60 percent of the cases occurred in vaccinated persons, and a median of only 27 percent of the cases were preventable. The outbreaks among preschool-age children indicate deficiencies in the implementation of the national measles-elimination strategy. However, the extent of measles transmission among highly vaccinated school-age populations suggests that additional strategies, such as selective or mass revaccination, may be necessary to prevent such outbreaks.

Trends in measles discharges from hospitals participating in the Commission on Professional and Hospital Activities, Professional Activities Study (CPHA-PAS) from 1977 to 1984 reflected the rapid decline in measles morbidity indicated by national surveillance data with an 88 per cent decrease in hospitalizations and a 95 per cent decrease in reported cases from 1977 to 1984. Overall trends in number, age, and seasonal distribution were also generally similar. Thirty-four per cent of the hospitalizations listed respiratory complications, 8.5 per cent otitis media, and 3.4 per cent neurologic complications.

A measles outbreak in an inner-city area primarily involved preschool-aged children younger than 5 years of age. The reasons why 31 unvaccinated preschool children with measles disease had not been vaccinated were investigated. For some patients, health care providers missed opportunities to vaccinate eligible patients against measles. Of the 26 patients whose full immunization status was known, ten (38%) were vaccinated with diphtheria and tetanus toxoids and pertussis vaccine and/or oral poliovirus vaccine at a time when they could have received measles vaccine simultaneously, according to recommendations of the Immunization Practices Advisory Committee and the American Academy of Pediatrics. In addition, five of ten health care providers interviewed missed at least one opportunity to administer measles vaccine because of a minor illness that was not a contraindication to vaccination. Unvaccinated patients were more likely to receive health care in the public sector, have single mothers, and have parents who had no knowledge of existing vaccines; they were less likely to be age-appropriately immunized with other antigens. If measles immunization levels among preschool children in the United States are to be increased, education of both health care providers and parents, coupled with innovative strategies targeted to preschool children, particularly of low socioeconomic groups in inner cities, are needed.

Treatment with high dose vitamin A has recently been recommended for children with measles in communities where vitamin A deficiency is a recognized problem. However, the relationship between vitamin A and measles mortality has not been clearly established. We studied serum vitamin A levels in 283 children less than or equal to 5 years of age admitted to Mama Yemo and Kalembe Lembe Hospitals in Kinshasa, Zaire, between January and March, 1987. Vitamin A levels were determined by high performance liquid chromatography. Vitamin A levels ranged from less than 5 to 63 micrograms/dl (median, 8). The overall case-fatality rate was 26 per cent. On univariate analysis, age less than 24 months, pneumonia on admission, lymphopenia (less than 2000/mm3), and lower vitamin A levels were associated with death during hospitalization. In a multivariate logistic regression model, a vitamin A level less than 5 micrograms/dl was associated with fatal outcome for children younger than 24 months old (relative risk = 2.9, 95 per cent CI 1.3, 6.8), but not for older children. Further studies are needed to determine whether low vitamin A levels predispose children to severe measles and the role of vitamin A supplements in the prevention of measles mortality.