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Objective To compare the economic costs and benefits associated with using either diphtheria and tetanus toxoids and acellular pertussis vaccine (DTaP) or diphtheria and tetanus toxoids and whole-cell pertussis vaccine (DTwP) in the United States in 1997. Design Standard cost-benefit analysis, from both the societal and health care system perspectives, was performed for each combination vaccine as well as for the pertussis components singly. Setting A simulated cohort of 4.1 million children from birth to age 15 years. Main outcome measures Net costs (savings) and benefit-cost ratios (BCRs) Results Without a vaccination program, diphtheria, tetanus, and pertussis disease caused more than 3 million cases and more than 28,000 deaths, at a cost of $23.6 billion. From the societal perspective, net savings because of the use of DTaP and DTwP were $22.510 million and $22.623 million, respectively. The net savings from the acellular pertussis component and the whole-cell pertussis component only were $4.362 million and $4.474 million, respectively. Benefit-cost ratios for DTaP from a societal and health care system perspective were 27:1 and 9:1, respectively. Sensitivity analyses of key variables did not result in appreciable changes in results. Conclusions Compared with no program, vaccination with DTaP or DTwP resulted in substantial savings, regardless of the perspective taken and for all sensitivity analyses conducted. Compared with DTwP, use of DTaP generated a small cost increase that might be offset by the value of other factors, such as increased confidence in pertussis vaccination resulting from reduced adverse events.

Context. —A review by the Institute of Medicine found a possible relationship between rubella vaccination and chronic arthritis among women. Objective. —To evaluate the risk of persistent joint and neurologic symptoms in rubella seronegative women subsequently vaccinated with RA 27/3 rubella vaccine. Design. —Retrospective cohort study based on computerized laboratory data and medical record review. Records were reviewed for symptoms occurring within 2 years before and after the date of serological testing and to identify vaccinees. Possible cases were evaluated by a rheumatologist blinded to serological findings and vaccination status. Setting. —Large health maintenance organization in northern California. Patients. —Women aged 15 to 59 years serotested for rubella during 1990 with continuous health plan membership for 2 years before and after the date of their serological test. Seronegative women immunized within 1 year of serotesting (n=971) were defined as exposed. Primary comparison groups included all unvaccinated, seronegative women (n=924) and randomly selected seropositive, unvaccinated women (n=2421) matched to exposed subjects on serological test date and age (±3 years). Main Outcome Measures. —Prevalence and incidence of chronic joint and neurologic symptoms during 1-year follow-up period stratified by age and serological findings, immunization, and postpartum status. Results. —No significantly increased risk was associated with receipt of rubella vaccine for any outcome except for prevalence of carpal tunnel syndrome in vaccinated women at least 30 years old compared with seropositive, unvaccinated women (2.9% vs 1.4%;P=.03). A total of 34 women had onset of conditions within the 1-year follow-up period; 9 of these were in the group of seronegative, immunized women, of whom 6 had onset of symptoms within 6 weeks of vaccination. Among these 6 women, symptoms included transient arthritis or arthralgias ( Conclusions —In this large retrospective cohort analysis there was no evidence of any increased risk of new onset chronic arthropathies or neurologic conditions in women receiving the RA 27/3 rubella vaccine. These data support the continued vaccination of rubella-susceptible women to reduce the risk of congenital rubella syndrome.

Objectives. —To describe patterns among imported measles cases to the United States. Design. —Descriptive analysis of national case-based surveillance data on measles cases. Setting. —United States in the period 1986 through 1994. Patients. —All reported confirmed cases of measles. Main Outcome Measures. —Demographic variables, immunization history, country of exposure, and reporting state. Results. —The number of reported imported cases of measles to the United States has dropped from an average of 99 cases annually in 1986 through 1988 and 190 cases in 1989 through 1991 to 61 cases in 1992 through 1994. Since 1990, the number of imported cases originating in Latin America declined by 98%, despite continued increase in the number of travelers to this region; cases from other regions remained relatively constant. This decrease paralleled the rapid decrease in measles incidence in the Western Hemisphere associated with national measles elimination programs. Most imported cases occurred among children, although 22% of cases occurred among young adults. Rates of measles cases per 1 million travelers are higher among non-US citizens than among US citizens. Conclusion. —The sharp decline in importations into the United States from Latin America since 1991 provides evidence of the success of measles control efforts undertaken there. The decrease in imported cases has been associated with a decline in total measles cases in the United States. Sustained elimination of measles in the United States will require improved measles control in other countries in addition to a high level of population immunity.

In Reply. —Two recent reviews 1,2 have updated our understanding of the epidemiology of VAPP in the United States and the relative proportions of recipient, contact, and immunologically abnormal cases. These data as well as a review of immunologically abnormal VAPP cases were considered by the Delphi panel. 3 With respect to immunologically abnormal VAPP cases, the panel noted the following: (1) 95% of such patients were associated with B-cell disorders, and IPV administration would not be expected to induce an effective immune response in these individuals; (2) the median age at onset of paralytic disease among recipients was 11.2 months; and (3) with the exception of 1 contact case, VAPP was the precipitating event that led to the diagnosis of immunodeficiency. In addition, few cases of agammaglobulinemia (the most severe form of B-cell disorders) are diagnosed in the first year of life. In one study the mean age at diagnosis of

Objective. —To assess the impact of different interventions to increase measles vaccination coverage among preschool children enrolled in the Special Supplemental Food Program for Women, Infants, and Children (WIC). Design. —Public health intervention trial. Setting. —Six volunteer WIC sites in New York City. Study Participants. —Children aged 12 to 59 months presenting for WIC certification between April 1 and September 30, 1991, who were eligible for measles vaccination. Interventions. —Two WIC sites were assigned at random to one of three immunization strategies: (1) escort: child was escorted to a nearby pediatric clinic for immunization; (2) voucher incentive: the family returned monthly, rather than every 2 months, to pick up WIC food vouchers until the child was immunized; or (3) referral: the family was passively referred for immunization. Main Outcome Measure. —Proportion of eligible children receiving measles vaccination. Results. —Of children eligible for measles immunization, 74% (618/836) were immunized. Children at escort sites were 5.5 times (relative risk [RR]=5.5; 95% confidence interval [CI], 3.7 to 8.1) and those at voucher incentive sites were 2.9 times (RR=2.9; 95% CI, 1.9 to 4.5) more likely to be immunized than children at referral sites. Children were immunized more rapidly at escort sites (median, 14 days) and voucher incentive sites (median, 26 days) than at referral sites (median, 45 days;P Conclusions. —Both escort and voucher incentive models resulted in more children being immunized more rapidly than passive referral. Because of ease of administration, voucher incentives may be a more suitable immunization intervention for use at WIC sites, with addition of escort where feasible. (JAMA. 1995;274:312-316)

In Reply. —A single tetanus booster for adults at the age of 65 years, as proposed by Drs Balestra and Littenberg,1may appear to be an appropriate tetanus prevention policy on the basis of cost-effectiveness analysis. For several reasons, however, we do not recommend changing the vaccination policy of decennial booster doses of tetanus and diphtheria toxoid (Td) at this time. First, neither person who developed tetanus in Kansas in 1993 had a history of receiving any tetanus vaccination.2Furthermore, serologic surveys have indicated that 31% to 71% of older adults (who may have never received the primary three-dose Td series) lack protective levels of antibody against tetanus.3Although compliance with the decennial Td vaccination policy recommended by the Advisory Committee on Immunization Practices (ACIP)4may be suboptimal, these doses may provide catch-up immunizations to people who never received the primary series. Second, many persons, such

Background: Retrospective immunization coverage surveys conducted during 1991 and 1992 demonstrated that coverage levels for the routine childhood vaccines by 24 months of age in selected urban areas of the United States ranged from 10% to 52%, far below the US Public Health Service goal of 90%. Therefore, appropriate programmatic changes must be identified and incorporated. Methods: We analyzed coverage survey data collected from 21 sites to measure the potential impact on coverage levels of implementing selected changes in vaccination practices. In a multistaged cluster survey design, school health records of kindergarten or first-grade students were randomly selected and dates of vaccination assessed. We evaluated changes in the vaccination practices, such as eliminating missed opportunities for simultaneous administration of vaccines and ensuring that children initiated the vaccination series on time (ie, by 3 months of age). We then calculated potential increases in coverage levels for a best-case scenario. Results: From 77% to 96% of all children in the 21 sites had received at least one vaccination by their first birthday. Children were 2.3 to 17 times more likely to be up to date on their vaccinations by 24 months of age if they were up to date at 3 months of age. Each child had many opportunities for the simultaneous administration of diphtheria and tetanus toxoids and pertussis (DTP) vaccine, oral polio vaccine (OPV), and measles-mumps-rubella (MMR) vaccine that, if used appropriately, could have potentially raised coverage levels by 12% to 22% (median, 17%). The highest coverage levels could have been attained if all children had started the series on time and if advantage had been taken of all opportunities for simultaneous vaccination. Coverage levels for four doses of DTP vaccine, three doses of OPV, and one dose of MMR vaccine would have increased from a baseline of 10% to 52% to levels of 54% to 83%. Conclusions: Although the majority of children received a vaccination by their first birthday, the coverage level at 24 months of age was low. Tracking systems are needed to ensure that children do not drop out of the system once they have begun the vaccination series. In addition, all children who are late in beginning their vaccination series are at increased risk of not completing the recommended vaccination series on time, and these children need intensive follow-up and recall efforts. Also, providers need to administer all needed vaccines simultaneously. (Arch Pediatr Adolesc Med. 1994;148:943-949)

MMWR. 1993;42:102-104 SINCE 1983, the Centers for Disease Control and Prevention (CDC) has published the CDC Surveillance Summaries under separate cover as part of the MMWR series. Each report published in the CDC Surveillance Summaries focuses on public health surveillance; surveillance findings are reported for a broad range of risk factors and health conditions. Summaries for each of the reports published in the November 20,1992, issue of the CDC Surveillance Summaries 1 are provided below. All subscribers to MMWR receive the CDC Surveillance Summaries , as well as the MMWR Recommendations and Reports , as part of their subscriptions. MEASLES SURVEILLANCE—UNITED STATES, 1991 A total of 9643 measles cases was reported from the United States in 1991, a 65.3% decrease from the 27 786 cases reported in 1990. The overall incidence of measles was 3.9 cases per 100 000 population. The highest age-specific incidence was among children younger than 12 months

Objective. —To evaluate heterosexual transmission of hepatitis B virus (HBV) and the prevalence of hepatitis delta virus (HDV) infection in female prostitutes. Design. —Survey. Setting. —Sexually transmitted disease clinics, drug treatment programs, detention centers, and/or outreach efforts in eight areas in the United States. Participants. —A total of 1368 female prostitutes 18 years of age or older. Outcome Measures. —Seropositivity for HBV and HDV infection. Results. —The overall prevalence of past or present HBV infection was 56%: 74% in women who were injecting-drug users (IDUs), 38% in women reporting no history of injecting-drug use (non-IDUs), 51% in whites, 55% in blacks, and 67% in Hispanics. Of 21 HBV carrier IDUs, 21% had HDV infection; of 18 HBV carrier non-IDUs, 6% had HDV infection. In non-IDUs (49%), risk factors for HBV infection were a history of having penile-anal intercourse (odds ratio [OR], 3.1; 95% confidence limits [CL], 1.3, 7.3) and seropositivity for syphilis and human immunodeficiency virus (HIV) infection. In IDUs, factors associated with an increased risk of infection, in addition to behaviors related to injecting-drug use, were the number of lifetime sexual partners, having sexual partners from groups at high risk for HBV infection, and seropositivity for syphilis and HIV infection; spermicide and/or diaphragm use was associated with a markedly decreased risk of HBV infection among blacks (OR, 0.1; 95% CL, 0.03,0.4) and Hispanics (OR, 0.2; 95% CL, 0.06, 0.9). Conclusion. —This is the first study to suggest that having anal intercourse and failing to use vaginal contraceptives may facilitate transmission of HBV to women. Our data support guidelines that recommend hepatitis B vaccination for prostitutes and persons with a history of sexually transmitted diseases or multiple sexual partners. ( JAMA . 1992;267:2477-2481)

Objective. —To describe the geographic distribution of measles cases in the United States by county for the 10-year period from 1980 through 1989. Design. —Ecological analysis of national measles surveillance data. Methods. —Measles cases reported to theMorbidity and Mortality Weekly Reportfrom 1980 through 1989 were analyzed. Data from the 1980 and 1990 US censuses were used to produce demographic profiles for each of the 3137 counties. Outcome variables examined included mean annual incidence and number of years reporting measles, with use of Spearman's rank correlation coefficients to examine the association between the demographic and the two outcome variables. Results. —A total of 56775 measles cases were reported during the decade. Of the nation's 3137 counties, 1690 (53.9%) did not report any cases; only 17 (0.5%) reported measles in all 10 years. Counties reporting measles more frequently during the decade had higher median populations, population densities, and percentage of black and Hispanic populations than those counties reporting less frequently. Population size, population density, and percentage of Hispanic population were associated with number of years reporting measles and mean annual measles incidence rate. Measles cases in counties reporting measles every year predominately occurred in unvaccinated preschoolers; cases in counties reporting less frequently predominately occurred in vaccinated school-aged children. Conclusions. —This analysis illustrates the focal nature of measles in the United States during the past decade. Most counties have not reported a single case of measles during the entire decade, and only 17 counties reported measles every year. Targeted strategies are needed to improve age-appropriate immunization levels among preschool-aged children living in large inner-city areas. (JAMA. 1992;267:1936-1941)

The Centers for Disease Control conducted intensive surveillance for acute non-A, non-B hepatitis in four sentinel counties over a 7-year period. Testing for antibody to hepatitis C virus was performed with the newly developed enzyme immunoassay. The incidence of non-A, non-B hepatitis remained relatively stable (average, 7.1 cases per 100 000), but there were significant changes in disease transmission patterns. The proportion of patients with a history of blood transfusion declined from 17% to 6%, but the proportion with a history of parenteral drug use increased from 21% to 42%. The proportion of patients with histories of sexual exposure (6%), household exposure (3%), occupational exposure to blood (2%), or hemodialysis (0.6%) did not change over time. Antibody to hepatitis C virus was found in 45% of patients within 6 weeks of onset of illness and in 68% of patients followed up for at least 6 months. Patients with no history of transfusions were just as likely to be positive for antibody to hepatitis C virus as patients with transfusion-associated hepatitis, indicating that hepatitis C virus is the major causative agent of all non-A, non-B hepatitis in the United States. ( JAMA . 1990;264:2231-2235)

Outbreaks of acute hepatitis occurred in Huitzililla and Telixtac, two rural villages 70 miles south of Mexico City, Mexico, in late 1986. The first outbreak began in Huitzililla in June of that year, 1 month after the start of the rainy season. A census revealed 94 icteric case subjects, for an attack rate of 5%; two women died. Attack rates were higher for persons older than 15 years (10%) than for younger persons. A case-control study showed that illness was highly associated with water-related factors. The second outbreak began in August 1986 in Telixtac. There were 129 case subjects, for an attack rate of 6%; one woman died. Epidemiologic findings were similar to those in Huitzililla, except that most disease transmission was not linked to unsafe water sources. None of 62 case subjects in Huitzililla and only 2 of 53 case subjects in Telixtac tested had serological evidence for recent infection with hepatitis A or B. Two of eight stool samples from Huitzililla and one of eight stool samples from Telixtac were positive by immune electron microscopy for 32- to 34-nm viruslike particles similar to those seen in cases of enterically transmitted non-A, non-B hepatitis from Asia. To our knowledge, these investigations document for the first time the epidemic transmission of enterically transmitted non-A, non-B hepatitis virus in the Americas. (JAMA. 1990;263:3281-3285)

To determine the risk of hepatitis B virus infection for rural hospital employees, we obtained serum and a completed questionnaire from each of 2,064 employees of 11 rural hospitals. Only 96 (4.7%) employees had hepatitis B virus markers. Increased marker prevalence was significantly associated with prior residence in a city with a population of greater than 100,000 (odds ratio, 2.9; 95% confidence interval, 1.6 to 5.2) and increasing blood contact (odds ratio, 1.6; confidence interval, 1.2 to 2.3); however, the association with blood contact was not significant when we limited analysis to the 836 employees who had never lived in a city. We conclude that the risk of hepatitis B virus infection for these rural hospital employees is low, probably because the incidence of hepatitis B in rural areas is low. ( JAMA 1984;252:3270-3272)

Five patients developed acute hepatitis B (HB) within four months after major operations by the same obstetric-gynecologic surgeon. Investigation documented that the surgeon was HB surface antigen and HB e antigen positive; all five patients had an HB subtype matching that of the surgeon and no other identifiable risk factors for HB viral infection. A seroprevalence study comparing exposed surgical and obstetric patients with a control group showed no significant additional subclinical HB transmission. The surgeon resumed his surgical practice but was required to obtain written informed consent from patients, to double-glove, and to employ appropriate surgical techniques to avoid self-injury. Seven months later, acute HB occurred in a patient two months after a cesarean section, resulting in exclusion of the surgeon from major operations. This is the fifth outbreak of nosocomial HB linked to an obstetric-gynecologic surgeon, and it reinforces the need for health care workers to receive preexposure prophylaxis with HB vaccine to prevent such occurrences. ( JAMA 1986;255:934-937)

In Reply.— Dr Ross questions two issues discussed in the ACIP 1 recommendations for routine HBsAg screening of pregnant women: the scientific justification that treatment for infants born to hepatitis B virus carrier mothers be initiated within 24 hours of birth and the feasibility of obtaining HBsAg test results within 24 hours for women who come to the hospital to deliver without prior HBsAg screening. The scientific basis of the need for rapid treatment of exposed infants stems from early studies of the efficacy of hepatitis B immune globulin (HBIG) in the prevention of perinatal hepatitis B virus transmission. One study showed that a single dose of HBIG had a 50% efficacy if given within the first 48 hours of life but had no efficacy if given later. 2 On the basis of this information, in all subsequent studies of HBIG and hepatitis vaccine researchers administered the HBIG as soon

In 1981, a hepatitis B virus vaccine demonstration project was conducted in 1630 Yupik Eskimos in southwest Alaska. Levels of antibody to hepatitis B surface antigen and markers for hepatitis B virus infection in vaccinees were monitored yearly for 5 years. After 5 years of follow-up, 19% of those who initially had an immune response to vaccine of 10 sample ratio units or greater subsequently had levels of antibody to hepatitis B surface antigen lower than 10 sample ratio units. During the 5 years after the first dose of vaccine, in three responders and one person with an antibody to hepatitis B surface antigen response lower than 10 sample ratio units, antibody to hepatitis B core antigen developed, and the level of antibody to hepatitis B surface antigen was boosted. Hepatitis B surface antigen did not develop in any subjects, and none had clinical hepatitis. In the 5 years following the demonstration project, the annual incidence of hepatitis B virus infection decreased from 50 cases per 1000 population before the vaccine trial to 0.45 per 1000. ( JAMA . 1989;261:2362-2366)

To define more exactly the epidemiology of delta virus infection and confirm its role in causing fulminant Labrea hepatitis in the Amazon Basin, we studied the prevalence of delta virus infection among persons with acute and chronic hepatitis B virus infection in the Boca do Acre district of the southern Amazon Basin. Delta virus infection was found in 24% of asymptomatic hepatitis B virus carriers, 29% of acute nonfulminant hepatitis B cases, 74% of fulminant hepatitis B cases, and 100% of chronic hepatitis B cases. Chronic delta virus infection occurred primarily in older children and adults, while acute and fulminant delta virus infection occurred in young children as well. In fulminant hepatitis cases, delta virus superinfection of hepatitis B virus carriers was the most common serological pattern; histopathologic examination showed features identical to those described in fulminant hepatitis cases of similar etiology in Colombia and Venezuela. Delta virus infection is highly endemic in the southern Amazon Basin and is the principal cause of Labrea hepatitis. ( JAMA 1987;258:479-483)

Over a 21-month interval, we investigated the effectiveness of immunoglobulin (Ig) in preventing hepatitis A spread in day-care centers. Immunoglobulin was given to all center children and employees whenever hepatitis occurred in one center child or employee or parents in two families. Immunoglobulin programs were completed in 91 centers during the trial within an average of 17 days of onset of illness in the index case. Immunoglobulin intervention caused significant reduction in the average size of a day-care hepatitis outbreak, from 7.3 cases in historically untreated centers to 6.0 cases in Ig-treated centers. Cases in center children and employees virtually ceased two weeks after Ig intervention, while those in household contacts decreased significantly within six weeks. Reported cases of hepatitis types A or unspecified in the community decreased 75% and the number of new hepatitis outbreaks decreased 77% during the trial. A decrease occurred not only in day-care-associated cases, but in cases not directly associated with centers, probably due to decreased tertiary spread from day-care families into the community. Use of Ig to prevent hepatitis spread in day-care centers seems to be an excellent means of controlling this disease, both within the centers and in the general community. (JAMA1983;249:48-53)

In Reply.— The points raised by Dr Holmes are well taken. The works of Capps and colleagues in the 1950s not only served as models for recent studies of hepatitis A in day-care centers but helped to inspire initiation of these studies. 1 The lessons in both postexposure treatment and preexposure prevention have not been lost to those persons who deal with this problem. Certainly the cornerstone of disease control in a day-care setting must be educational programs aimed at maximizing hygienic standards in day-care centers. Such programs must be broadly conceived to be applicable not only for hepatitis A but also for the other enteric diseases—shigellosis and rotavirus, Giardia , and Campylobacter infections—that have been recognized as disease threats in day-care centers. 2 Such programs should be primarily for day-care employees and directors who are directly responsible for establishing and implementing appropriate hygienic practices in a day-care setting. But to

Transmission of the hepatitis B virus (HBV) during the perinatal period leads to the most devastating consequences of HBV infection. Women who test positive for hepatitis B surface antigen (HBsAg) at the time of delivery and who have hepatitis B e antigen in their sera have a 70% or greater chance of transmitting infection to their newborn infants. At least 90% of these infected infants become HBV chronic carriers. These HBV-carrier children have a 25% lifetime risk of dying from primary hepatocellular carcinoma or cirrhosis, usually during adulthood.1In addition, they serve as a reservoir of HBV infection in their families and communities. Many become carrier mothers themselves and perpetuate the cycle of perinatal transmission. Fortunately, treatment of these newborns shortly after birth with a combination of hepatitis B immune globulin and hepatitis B vaccine is 85% to 95% effective in preventing development of the HBV—chronic carrier state.2

Between April 1, 1984, and Feb 1, 1985, nine cases of hepatitis B occurred in the patients of a dentist practicing in a rural Indiana county (population, 35,000). This was over 20 times the mean annual incidence for the county in the previous decade. All of the patients had been treated by the dentist two to five months before illness. Although the dentist had never had hepatitis symptoms, his serum was positive for hepatitis B surface antigen and hepatitis B e antigen and negative for anti-hepatitis B core IgM antibody, indicating that he was probably a hepatitis B carrier. Two patients (22%) died of fulminant hepatitis; the case-fatality ratio was over ten times the reported US mean for hepatitis B. Using a case definition based on anti-hepatitis B core IgM antibody positivity and exposure to the dentist during a defined time period, a serosurvey of the dentist's patients identified 15 asymptomatic cases (overall attack rate, 3.2%). Infection risk was related to the amount of trauma involved in the cases' dental procedures. No cause was found for the unusual lethality of the outbreak. ( JAMA 1986;255:3260-3264)

To identify previously unrecognized sources for acquiring acute hepatitis B and non-A, non-B (NANB) hepatitis, we interviewed patients with these types of hepatitis who were reported to two county health departments in the United States and matched control subjects for known and potential risk factors for acquiring hepatitis. Of 218 patients with hepatitis B and 140 patients with NANB hepatitis, 46% and 53%, respectively, had no commonly recognized source for infection. When these patients were compared with control subjects, significantly more patients with hepatitis B had multiple heterosexual partners, accounting for 14% of all hepatitis B infections; more patients with NANB hepatitis either had sexual or household contact with a person who had hepatitis in the past or had multiple heterosexual partners, accounting for 11% of all NANB infections. This is the first study to suggest that heterosexual transmission may play an important role in the spread of NANB hepatitis. ( JAMA . 1989;262:1201-1205)