Mixture model framework facilitates understanding of zero-inflated and hurdle models for count data.

In this note, we comment on the zero-inflated and hurdle models for count data presented by Rose et al., 2006, J. Biopharma. Stat. 16:463-481. By viewing these models as finite mixture models, one gains a better understanding of the components of the models, including assumptions about the latent variable(s) in the finite mixture models. Deciding whether a zero-inflated or hurdle model is appropriate for a given data set requires close collaboration with subject matter experts. For instance, in modeling vaccine adverse event count data, the pharmacokinetic rationale for the occurrence of an adverse event and the likelihood of detecting or reporting the adverse event are important considerations for mixture model development.

Enhancing vaccine safety surveillance: a capture-recapture analysis of intussusception after rotavirus vaccination.

The Vaccine Adverse Event Reporting System (VAERS) is the passive reporting system for postmarketing surveillance of vaccine safety in the United States. The proportion of cases of an adverse event after vaccination that are reported to VAERS (i.e., VAERS reporting completeness) is mostly unknown. Therefore, the risk of such an event cannot be derived from VAERS only. To study whether its reporting sensitivity and risks could be estimated, VAERS was linked to data from a case-control and a retrospective cohort study in a capture-recapture analysis of intussusception after rotavirus vaccination (RV). Cases of intussusception after RV were selected from the common time frame (December 1998 through June 1999) and the common geographic area (19 states) of the three sources. Matching occurred on birth date, gender, state, date of vaccination, and date of diagnosis. Thirty-five matches were identified among a total of 84 cases. The estimated VAERS reporting completeness was 47%. The relative risks of intussusception in the periods 3-7 and 8-14 days after RV (relative risk = 22.7 and 4.4, respectively) were comparable with those reported in the two studies. Linkage of VAERS to complimentary data sources may permit more timely postmarketing assessment of vaccine safety.

Vaccination practices, policies, and management factors associated with high vaccination coverage levels in Georgia public clinics. Georgia Immunization Program Evaluation Team.

BACKGROUND: Controlling vaccine-preventable diseases by achieving high childhood vaccination coverage levels is a national priority. However, there are few, if any, comprehensive evaluations of state immunization programs in the United States, and little attention has been given to the importance of vaccination clinic management style and staff motivation. OBJECTIVE: To evaluate the factors associated with the increase in childhood vaccination coverage levels from 53% in 1988 to 89% in 1994 in Georgia's public health clinics. DESIGN: A 1994 mail survey obtaining information on clinic vaccination policies and practices and management practices. SETTING: All 227 public health clinics in Georgia. PARTICIPANTS: Clinic nurses responsible for vaccination services. OUTCOME MEASURE: The 1994 clinic-specific coverage level for 21- to 23-month-old children for 4 doses of diphtheria and tetanus toxoids and pertussis vaccine, 3 doses of polio vaccine, and 1 dose of a measles-containing vaccine as determined by an independent state assessment of clinic coverage levels. RESULTS: Univariate analysis showed that higher coverage levels were significantly (P<.05) associated with smaller clinic size, higher proportions of clientele enrolled in the Special Supplemental Nutrition Program for Women, Infants, and Children (WIC), being a nonurban clinic, and numerous vaccination practices and policies. Multivariable analysis showed that only 8 of greater than 150 factors remained associated with higher coverage levels, including having no waiting time to be seen, having telephone reminder systems, conducting home visits for defaulters, and restricting WIC vouchers when a child was undervaccinated. Motivational factors related to higher coverage included clinic lead nurses receiving an incentive to raise coverage and lead nurses participating in assessments of clinic coverage levels by state immunization staff. CONCLUSIONS: No single factor is responsible for raising vaccination coverage levels. Efforts to improve coverage should include local assessment to provide feedback on performance and identify appropriate local solutions. Coordinating with WIC, conducting recall and reminder activities, motivating clinic staff, and having staff participate in decisions are important in raising vaccination levels.

Increased susceptibility to measles in infants in the United States.

BACKGROUND: Women born in the United States after measles vaccine licensure in 1963 transfer less measles antibody to their infants than do older women. This may result in increased susceptibility to measles among infants. OBJECTIVE: To determine the effect of maternal year of birth on the risk for measles in infants. METHODS: We enrolled 128 unvaccinated infants

Impact of measurement and feedback on vaccination coverage in public clinics, 1988-1994.

OBJECTIVE: To investigate whether a reported rise in vaccination coverage in Georgia public clinics during the period 1988 through 1994 was artifactual or real and, if real, to determine the extent to which the rise could be associated with a program of measurement and feedback. DESIGN: Examination of data from Georgia public clinics, doses-administered records, and National Health Interview Surveys. SETTING/PARTICIPANTS: Children attending Georgia public clinics. INTERVENTION: Measurement of vaccination coverage and feedback to providers. MAIN OUTCOME MEASURE: Vaccination coverage rates. RESULTS: For the period 1988 through 1994, 136 004 Georgia public clinic vaccination records for children 21 to 23 months of age were reviewed. Median series-completion rates at public clinics rose from 53% to 89%, while indexes of under-vaccination fell: missed opportunities for simultaneous vaccination (6% to 0%), lost contact for more than 12 months (14% to 1%), and first vaccination more than 1 month late (19% to 8%). According to the independent doses-administered database, the proportion of children starting the primary series very late (> or =12 months old) fell from 14% to 6%, and the series-completion index rose from 64% to 83%, suggesting that improvements could not be wholly ascribed to better clinic record keeping. In 1988, vaccination coverage of children 24 months of age in the National Health Interview Survey (NHIS) was 53%, identical to median public clinic coverage in Georgia; in 1993, NHIS coverage was 60%, while median public clinic coverage in Georgia was 90%, suggesting that the rise in coverage in Georgia public clinics exceeded national trends. Patterns within the coverage changes suggest an association with the process of measurement and feedback. CONCLUSIONS: A marked increase in vaccination coverage occurred in Georgia public clinics associated with a program of annual measurement and feedback.

Seroprevalence of antibody against poliovirus in inner-city preschool children. Implications for vaccination policy in the United States.

OBJECTIVES: To assess susceptibility to poliomyelitis in selected inner-city preschool children in the United States and to estimate the contribution of secondary spread of live attenuated oral poliovirus vaccine virus to type-specific immunity. DESIGN: Cross-sectional seroprevalence study. METHODS: Serum neutralizing antibody levels against poliovirus types 1, 2, and 3 were analyzed according to vaccination status, age, and other sociodemographic variables. SETTING: Hospital and satellite clinics serving inner-city populations in Houston, Tex, and Detroit, Mich, 1990 to 1991. PARTICIPANTS: A total of 526 children aged 12 to 47 months seeking medical care were enrolled in the seroprevalence study; 144 children aged 12 to 35 months without a history of previous oral poliovirus vaccination were enrolled in the secondary spread study. RESULTS: Seropositive rates were similar in children in both cities, ranging from about 80% for types 1 and 3 in 12- to 23-month-old children to more than 90% in those aged 36 to 47 months. The most important predictor of seropositivity was the number of doses of oral poliovirus vaccine received (P < .01), with levels approximately 90% for all 3 serotypes among children who had received 3 or more doses. In children likely to have been unvaccinated, seropositive rates ranged from 9% to 18% for poliovirus types 1 and 3 and from 29% to 42% for type 2; secondary spread of vaccine virus appeared to have occurred among children who had previously received 1 dose or less but not those with 2 or more doses. CONCLUSIONS: Levels of immunity to poliovirus among inner-city preschoolers are high and may be predicted by the number of doses of oral poliovirus vaccine received. Secondary spread of the vaccine virus plays a modest role in increasing polio immunity in inner-city populations, especially against types 1 and 3. This role will decrease in importance if the recently attained high levels of immunization coverage in the United States are sustained and if the risk of importation of wild poliovirus continues to diminish.

An evaluation of measles revaccination among school-entry-aged children.

BACKGROUND: A two dose measles vaccination schedule is recommended routinely for all school-entry-aged children. We evaluated this recommendation by determining both measles antibody seroprevalence and the response to revaccination in seronegative children in this age group. METHODS: Children 4 to 6 years of age who had received a single dose of measles vaccine between the ages of 15 to 17 months were tested for measles antibody by using enzyme-linked immunosorbent assay (ELISA) microneutralization technique. Seronegative children were revaccinated and again tested for measles antibody (immunoglobulin M [IgM] and neutralizing). RESULTS: Of 679 children tested, 37 (5.4%) were seronegative. Seronegativity was not significantly associated with age, sex, race, age at initial vaccination, time since vaccination, or maternal year of birth. However, children mothers with a college degree were 12 times more likely to be seronegative than children of mothers who never attended college (P < .01). Of the 37 seronegative children, 36 seroconverted after revaccination--33 producing IgM measles antibody, suggestive of a primary immune response. The cost per seroconversion would have been an estimated $415 if all 679 children had been revaccinated. CONCLUSIONS: Revaccination reduces the pool of children who are susceptible to measles. Although the cost per seroconversion is high, a two-dose schedule should reduce the substantial costs of controlling measles out breaks by reducing the number of outbreaks.

Measles antibody in vaccinated human immunodeficiency virus type 1-infected children.

OBJECTIVES: The goals of this study were to evaluate the proportion of previously vaccinated human immunodeficiency virus (HIV) type 1-infected children with detectable postvaccination measles antibody; to assess risk factors for vaccine failure; and to evaluate the response to reimmunization. METHODS: A total of 81 perinatally HIV-infected children receiving medical care in the Bronx, New York who had previously received measles vaccine were enrolled. The Centers for Disease Control and Prevention (CDC) HIV class, lymphocyte subsets, and measles antibody were determined upon enrollment. Additional data abstracted from medical records included dates and number of prior measles vaccinations and CDC HIV class at the time of vaccination. Measles antibody was determined by microneutralization enzyme-linked immunosorbent assay (ELISA). RESULTS: The median age at time of study was 42 months (range, 9 to 168 months). Overall, 58 (72%) subjects had detectable measles antibody (microneutralization ELISA titer > 1:5). Children studied within 1 year of vaccination were more likely to have detectable measles antibody than children evaluated more than 1 year after vaccination (83% vs 52%, P < .01). The proportion of children with detectable measles antibody was higher among children with no or moderate immunosuppression compared to those with severe immunosuppression when immune status was based on CD4%. Children vaccinated at 6 to 11 months of age appeared to have a higher proportion of detectable measles antibody than those who received a first measles vaccination after age 1. Only 1 (14%) of 7 previously vaccinated children who were seronegative or had very low titers experienced a four-fold rise in measles antibody when reimmunized. CONCLUSION: These results support current recommendations to vaccinate HIV-infected children against measles. The proportion of children with detectable measles antibody among vaccinated HIV-infected children is considerably lower than in vaccinated healthy children. HIV-infected children may respond better to measles vaccine when it is administered before the first birthday. From our limited data it appears that reimmunization of previously vaccinated HIV-infected children with moderate to severe immunosuppression does not result in an antibody recall response.

Risk factors for pertussis in young infants during an outbreak in Chicago in 1993.

Because young infants are at highest risk for severe pertussis and death and are also too young to have received the minimal protective series of three doses of diphtheria-tetanus-pertussis (DTP) vaccine, we conducted a matched case-control study to assess risk factors for pertussis among young infants during a pertussis outbreak in Chicago in 1993. We enrolled 39 cases < 7 months of age from a single teaching hospital and 96 controls, individually matched for age, from the well-child clinic at the same hospital. Demographic characteristics, immunization status, and opportunities for disease exposure were analyzed by means of conditional logistic regression. Cases and controls were similarly up to date with their DTP vaccinations (87% and 89%, respectively). Infants of adolescent mothers (matched odds ratio [OR], 6.4; 95% confidence interval [CI], 1.3-41.4) and infants of mothers who suffered > or = 7 days of cough during the child's incubation period (matched OR, 12.0; 95% CI, 1.4 to infinity) were significantly more likely to have pertussis. Young mothers and mothers with a cough lasting > or = 7 days may be an important source of pertussis infection for their young infants.

A standardized instrument to assess hazards for falls in the home of older persons.

Hazards in the home are implicated in up to half of all falls among older persons. Yet, the instruments used to identify these hazards usually have been unstandardized, have lacked specific definitions of hazards, and have not been evaluated. Therefore, in 1988, as part of the Study to Assess Falls among the Elderly, in Miami Beach, Florida, the authors evaluated the reliability of a standardized instrument used for assessing the training of evaluators and assessing home environments. Based on up to 176 observations for each potential hazard, the interviewers' assessment of hazards such as throw rugs, tripping hazards, light switch hazards, and hazardous bath surfaces had good overall reliability (kappa = 0.65-0.92). Their assessment of grab-bars and hazardous furniture was unreliable (kappa = 0.18-0.35). Variations in the reliability reflect the difficulty in creating definitions that are simple to be understood and used, yet detailed enough to produce sensitive and specific survey items. Investigators studying falls among older persons should use standardized definitions to train evaluators and assess environmental hazards.

Vaccine-associated paralytic poliomyelitis in the United States: no evidence of elevated risk after simultaneous intramuscular injections of vaccine.

During the past 30 years, Romania reported rates of vaccine-associated paralytic poliomyelitis (VAPP) approximately 10-fold higher than in the United States. The elevated VAPP risk was largely caused by multiple intramuscular (im) injections with antibiotics given within 30 days of onset of paralysis. Because it is not known whether im injections contribute to the VAPP risk in the United States, we examined VAPP cases reported since 1980. We reviewed injection histories of VAPP cases reported to the Centers for Disease Control and Prevention from 1980 to 1993: with vaccines for 1980 to 1987; and for all substances for 1988 to 1993. Rates of VAPP by number of im injections with vaccines were calculated from 1988 to 1993 with estimated vaccine coverage data from the National Health Interview Survey. From 1980 to 1993 a total of 119 cases of poliomyelitis were reported to the Centers for Disease Control and Prevention. Of these, 87 (73%) were vaccine-associated and immunologically normal: 41 were oral polio vaccine (OPV) recipient cases; 40 were OPV contact cases; and 6 were community-acquired cases. A history of im injections in the 45 days before onset of paralysis was obtained from 28 (72%) of 39 recipient cases reported from 1980 to 1993 for which dates of paralysis onset could be determined and from 1 (8%) of 13 contact cases reported from 1988 to 1993. With one exception all substances administered intramuscularly were routine childhood vaccines. No clustering of im injections in the "high risk" windows, 0 to 3 and 8 to 21 days before onset of paralysis, was observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Intramuscular injections within 30 days of immunization with oral poliovirus vaccine--a risk factor for vaccine-associated paralytic poliomyelitis.

BACKGROUND: In Romania the rate of vaccine-associated paralytic poliomyelitis is for unexplained reasons 5 to 17 times higher than in other countries. Long ago it was noted that intramuscular injections administered during the incubation period of wild-type poliovirus infection increased the risk of paralytic disease (a phenomenon known as "provocation" poliomyelitis). We conducted a case-control study to explore the association between intramuscular injections and vaccine-associated poliomyelitis in Romania. METHODS: The patients were 31 young children in whom vaccine-associated paralytic poliomyelitis developed from 1988 through 1992. Eighteen were vaccine recipients, and 13 had acquired the disease by contact with vaccine recipients. Each of these children was matched with up to five controls according to health center, age, and in the case of vaccine recipients, history of receipt of the live attenuated oral poliovirus vaccine. Data were abstracted from medical records that documented the injections administered in the 30 days before the onset of paralysis. RESULTS: Of the 31 children with vaccine-associated disease, 27 (87 percent) had received one or more intramuscular injections within 30 days before the onset of paralysis, as compared with 77 of the 151 controls (51 percent) (matched odds ratio, 31.2; 95 percent confidence interval, 4.0 to 244.2). Nearly all the intramuscular injections were of antibiotics, and the association was strongest for the patients who received 10 or more injections (matched odds ratio for > or = 10 injections as compared with no injections, 182.1; 95 percent confidence interval, 15.2 to 2186.4). The risk of paralytic disease was strongly associated with injections given after the oral polio virus vaccine, but not with injections given before or at the same time as the vaccine (matched odds ratio, 56.7; 95 percent confidence interval, 8.9 to infinity). The attributable risk in the population for intramuscular injections given in the 30 days before the onset of paralysis was 86 percent (95 percent confidence interval, 66 to 95 percent); that is, we estimate that 86 percent of the cases of vaccine-associated paralytic poliomyelitis in this population might have been prevented by the elimination of intramuscular injections within 30 days after exposure to oral poliovirus vaccine. CONCLUSIONS: Provocation paralysis, previously described only for wild-type poliovirus infection, may rarely occur in a child who receives multiple intramuscular injections shortly after exposure to oral poliovirus vaccine, either as a vaccine recipient or through contact with a recent recipient. This phenomenon may explain the high rate of vaccine-associated paralytic poliomyelitis in Romania, where the use of intramuscular injections of antibiotics in infants with febrile illness is common.

The impact of college prematriculation immunization requirements on risk for measles outbreaks.

OBJECTIVE: To assess whether prematriculation immunization requirements (PIRs) affect the number of measles cases on college campuses. DESIGN: We surveyed a stratified random sample of 880 colleges and universities to determine their immunization policies and practices and occurrence of measles outbreaks from 1988 through 1991. We merged national measles surveillance data with survey data by county to determine the risk for measles introduction on college campuses. We used logistic regression methods to estimate the effect of PIRs and assess risk factors for college measles outbreaks. SETTING: A total of 3205 US colleges and universities listed in standard guides. RESULTS: Of selected schools, 91 (11%) of the 796 responding schools reported one or more measles cases occurring from 1988 through 1991. Schools with a state-mandated PIR were significantly less likely to report measles outbreaks of two or more cases than other institutions (adjusted relative risk [RR] = 0.30; 95% confidence interval [Cl], 0.11 to 0.84). None of the 14 schools that reported outbreaks of 10 or more cases was subject to state regulation or had a PIR specifying two doses of measles vaccine in place. Of schools with introduction of measles, residential colleges were more likely to report extensive spread of measles (five or more cases) than nonresidential colleges (RR = 35.8; 95% Cl, 2.08 to 617.0). Of public schools, 4-year programs had a higher risk of a large outbreak (five or more cases) than 2-year programs. CONCLUSIONS: These results strongly support current recommendations for requiring proof of vaccination of college students to decrease the risk for measles outbreaks on college campuses. State regulations mandating PIRs ensure the best protection against widespread measles transmission.

Prematriculation immunization requirements of American colleges and universities.

The authors surveyed a stratified sample of 880 colleges and universities in the United States to assess the status and characteristics of their prematriculation immunization requirements (PIRs). On the basis of a 90% return (796 responses), they estimated that 55% of US colleges and universities had implemented a PIR at the time of the survey. Among schools with PIRs, measles vaccine was almost universally required, with 74% requiring two doses, mumps vaccine was required by 70%, and rubella vaccine by 92%. Hepatitis B vaccine was rarely required and was usually recommended only for students in health-profession programs. The strongest determinant of having a PIR was the presence of a state law or regents' policy. PIRs implemented under the aegis of a state law were, on average, less comprehensive but better enforced. Other factors associated with the implementation of a PIR included membership in the American College Health Association (ACHA), the presence of a student health clinic, and availability of record-keeping personnel.

Pertussis in Missouri: evaluation of nasopharyngeal culture, direct fluorescent antibody testing, and clinical case definitions in the diagnosis of pertussis.

No diagnostic test for pertussis in routine use in the United States has both high sensitivity and high specificity. During a statewide increase in the incidence of pertussis in Missouri, we studied the clinical features of 153 patients with suspected pertussis in the Greater St. Louis area from whom a specimen for pertussis culture had been taken between 15 May and 19 September 1989. In this cross-sectional study, nasopharyngeal cultures were more likely to be positive for persons whose specimens were collected < 21 days after cough onset (adjusted rate ratio [RRa] and 95% confidence interval = 3.4; 1.5-8.0) and who were not receiving erythromycin/sulfamethoxazole prior to the culture [RRa = 5.8; 0.8-40.6], who had received fewer than three prior doses of pertussis vaccine [RRa = 1.8; 0.8-4.2], and whose specimen was in transit to the laboratory for < 4 days [RRa = 2.0; 0.8-5.5]. Among children < 5 years of age, spasmodic cough plus a lymphocytosis of > 10,000/mm3 was the acute symptom complex associated with the highest predictive value for a positive culture result (67%). Cough for > or = 14 days plus whoop was sensitive (81%) and specific (58%) for identifying children with culture-confirmed pertussis. Direct fluorescent antibody staining performed well as a screening test for pertussis but requires substantial commitment of personnel and resources. In the absence of a positive culture result, clinical case definitions should be used for decision making (e.g., initiation of antimicrobial therapy and routine case reporting).

The geographic distribution of measles in the United States, 1980 through 1989.

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 the Morbidity and Mortality Weekly Report from 1980 through 1989 were analyzed. Data from the 1980 and 1990 US censuses were used to produce demographic profiles for each of the 3137 countries. 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 56,775 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 predominantly occurred in unvaccinated preschoolers; cases in counties reporting less frequently predominantly 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.

Measles herd immunity. The association of attack rates with immunization rates in preschool children.

OBJECTIVE: To examine the association between incidence of measles and immunization coverage among preschool-age children. DESIGN: An ecological study in which measles incidence was compared with immunization coverage among census tracts. The independent effects of race and population density were controlled for. SETTING: A recent measles outbreak in Milwaukee, Wis. Immunization coverage data were estimated from a retrospective, school-based survey of Milwaukee grade school students. PATIENTS: One thousand eleven persons (less than or equal to 17 years) who had confirmed measles from September 1989 through June 1990. MAIN OUTCOME MEASURES: Confirmed measles cases grouped by census tract, corresponding census tract preoutbreak immunization coverage, racial breakdown, and population density. RESULTS: Census tracts stratified into four levels, with mean immunization rates of 50.4%, 60.2%, 69.9%, and 81.0%, had respective median attack rates of 11.6, 5.0, 1.7, and 0.0 cases per 1000 persons (P less than .01). The association between immunization coverage and measles attack rate remained significant even after controlling for race and population density. CONCLUSIONS: Modest improvements in low levels of immunization coverage among 2-year-olds confer substantial protection against measles outbreaks. Coverage of 80% or less may be sufficient to prevent sustained measles outbreaks in an urban community.

The independent associations of parity, age at first full term pregnancy, and duration of breastfeeding with the risk of breast cancer. Cancer and Steroid Hormone Study Group.

Although the important influence of a woman's reproductive history on her risk of breast cancer is widely recognized, it is not clear whether this is wholly accounted for by the age at her first full-term pregnancy, or whether there are additional, independent influences of breastfeeding or number of children. To examine the respective contributions to the risk of breast cancer of these reproductive factors, we used logistic regression methods to analyze data from a multicenter case-control study, the Cancer and Steroid Hormone Study. Included in the analysis were 4599 women, 20-55 years of age, identified as having an initial diagnosis of breast cancer by one of eight collaborating population-based cancer registries. The 4536 controls were women of similar ages selected by random dialing of households with telephones in the same eight areas. As expected, age at first full-term pregnancy exerted a strong influence on the risk of breast cancer. However, after it and other potentially confounding factors had been controlled for, parity and duration of breastfeeding also had a strong influence on the risk of breast cancer. Compared with women of parity one, women of parity seven or greater had an adjusted relative risk of breast cancer of 0.59 (95% CL, 0.44-0.79). Compared with parous women who never breastfed, women who had breastfed for 25 months or more had an adjusted relative risk of 0.67 (0.52-0.85). These results do not support the supposed preeminent importance of age at first full-term pregnancy among the reproductive determinants of breast carcinogenesis. Resolution of this issue may have important implications for elucidating hormonal influences on breast cancer and for projecting future trends in the disease.