Immunogenicity of a heptavalent pneumococcal conjugate vaccine in Apache and Navajo Indian, Alaska native, and non-native American children aged <2 years.

High rates of invasive pneumococcal disease have been described among infants living in various Native American communities. In this study, we evaluated the immunogenicity of a 7-valent pneumococcal vaccine consisting of serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F covalently linked to the outer membrane protein complex of Neisseria meningitidis in Apache and Navajo Indian, Alaska Native, and non-Native American children. The vaccine was administered at ages 2, 4, and 6 months; a booster dose was given at age 15 months. Levels of serotype-specific immunoglobulin G (IgG) were measured by a standardized enzyme-linked immunosorbent assay. The responses after 3 primary doses of vaccine were similar in all 3 groups of children, except for those to serotypes 14 and 23F. One month after the booster dose, geometric mean concentrations (GMCs) of serotype-specific IgG antibodies increased significantly in all 3 groups of children, compared with GMCs of IgG antibodies to pneumococcal serotypes before the booster dose.

Right away and all at once: how we saved Continental.

In 1993, when Greg Brenneman started working at Continental Airlines, it was the most dysfunctional company he had ever seen. It had been through two bankruptcies and ten presidents in ten years. There was next to no strategy. The company was burning through money. And employee morale couldn't get any worse. Today Continental is flying high. It posted revenues of $7.2 billion and a net income of $385 million in 1997. It regularly ranks as one of the top five U.S. airlines for key performance measures such as dispatch reliability. And employee turnover has been drastically reduced. What happened? In this first-person account, Brenneman, now Continental's president and COO, describes how he and the new team at Continental's helm transformed the company "right away and all at once." More specifically, he describes the five lessons he learned during this dramatic turnaround. At the beginning, there was so much wrong with Continental that he felt as if any one misstep could bring the whole effort down. But in a time of crisis, when time is tight and money is tighter, you can't afford to mull over complex strategy. With Gordon Bethune, Continental's chairman and CEO, Brenneman devised the Go Forward Plan, a straightforward strategy focused on four key elements: understanding the market, increasing revenues, improving the product, and transforming the corporate culture. He admits that the plan wasn't complicated--it was pure common sense. The tough part was getting it done. "Do it now!" became the rallying cry of the movement, and the power of momentum has carried Continental to success.

Efficacy and safety of high-dose rhesus-human reassortant rotavirus vaccine in Native American populations.

OBJECTIVES: We compared the efficacy, safety, and immunogenicity of a rhesus rotavirus tetravalent vaccine (RRV-TV), a rhesus rotavirus monovalent (serotype 1) vaccine (RRV-S1), and placebo in healthy American Indian infants for two rotavirus seasons. STUDY DESIGN: Infants aged 6 to 24 weeks were enrolled in a randomized, double-blind efficacy study. Infants were orally administered RRV-TV (4 x 10(5) plaque-forming units per dose), RRV-S1 (4 x 10(5) plaque-forming units per dose), or placebo at 2, 4, and 6 months of age. Stools collected during episodes of gastroenteritis were tested for detection of rotavirus antigen. A total of 1185 infants received at least one dose of a study vaccine or placebo, and 1051 received all three doses according to the protocol. RESULTS: During the first year of surveillance, the estimates of vaccine efficacy (with 95% confidence interval) for preventing rotaviral gastroenteritis were 50% (26, 67) for RRV-TV and 29% (-1, 50) for RRV-S1. In this population only 6% of rotaviral gastroenteritis episodes among placebo recipients were associated with type G1 disease. For severe disease the estimates of vaccine efficacy were higher: 69% (29, 88) for RRV-TV and 48% (-4, 75) for RRV-S1. CONCLUSIONS: These data indicate that RRV-TV is moderately efficacious in preventing all episodes of gastroenteritis caused by rotavirus and is most efficacious against the severe disease characteristic of rotaviral illness.

Case-cohort analysis of case-coverage studies of vaccine effectiveness.

Evaluation of vaccine field effectiveness may be performed by combining surveillance data on incident cases with an immunization coverage survey. Although many methods have been used for the analysis of studies of similar design, they are not always desirable or optimal. The authors discuss these approaches and propose use of a case-cohort analysis for such a study design when appropriate. The case-cohort analytic approach is illustrated with data from studies of a vaccine for Haemophilus influenzae type b (Hib) disease in children living on a southwestern Native American reservation during 1988-1993.

Postlicensure effectiveness of the Haemophilus influenzae type b polysaccharide-Neisseria meningitidis outer-membrane protein complex conjugate vaccine among Navajo children.

The incidence of invasive Haemophilus influenzae type b (Hib) infection was decreased significantly among Navajo children since the licensure of Hib conjugate vaccines, even though two lots of Hib (polyribosylribitol phosphate)-meningococcal B outer-membrane protein conjugate vaccine (PRP-OMP) widely used among the Navajo were later found to be of low immunogenicity. We measured the effectiveness of all Hib conjugate vaccines combined, PRP-OMP alone, and the PRP-OMP lots with lower-than-expected immunogenicity among Navajo infants and children. This was a matched case-control study using active, laboratory-based surveillance for the ascertainment of Navajo children 2 1/2 to 59 months of age with invasive Hib infection; 45 patients with infection and 180 control subjects were enrolled. The effectiveness of one, two, and three doses, respectively, of all Hib conjugate vaccines combined was 96% (95% confidence interval (CI) 65%, 99%), 99% (95% CI, 69%, 100%), and 99% (95% CI - 57%, 100%). The effectiveness of one or more doses of PRP-OMP was 95% (95% CI, 66%, 99%). The effectiveness of a single dose of the lots of lower-than-expected immunogenicity was 89% (95% CI, -8%, 99%). The Hib conjugate vaccine coverage increased from 49% during 1991 to 94% during 1992; no control subjects younger than 18 months of age were enrolled during 1993. The occurrence of invasive Hib infections in this population after licensure of Hib conjugate vaccines was the result of gradual vaccine uptake, not poor vaccine effectiveness. The use of PRP-OMP has been highly effective despite concerns about the immunogenicity of several lots.

The urban American Indian oversample in the 1988 National Maternal and Infant Health Survey.

Although more than two-thirds of American Indians and Alaska Natives (AI) live outside reservations and Tribal lands, few data sets describe social and maternal-child health risk factors among urban AI. The Indian Health Service sponsored a special effort to survey mothers of AI infants as part of the 1988 National Maternal and Infant Health Survey (NMIHS), a comprehensive national study conducted by the National Center for Health Statistics, Centers for Disease Control. The authors analyzed questionnaires completed by mothers residing in selected locations served by urban Indian health programs and compared the data with those for women of other races residing in metropolitan areas. After adjusting the sample for non participating States, the response rate in the Urban Indian Over sample was 60.8 percent (763 of 1,254). More than 45 percent of AI and black respondents, compared with 15 percent of white respondents, reported an annual household income of less than $10,000. About half of AI and black women, compared with nearly three-quarters of white women, reported having insurance or health maintenance organization coverage during pregnancy. Despite having a similarly low rate of health insurance coverage and low household income, AI respondents were far less likely than black respondents to have Medicaid coverage. A higher proportion of AI women than of black or white women reported difficulties in obtaining prenatal care, and AI women were less likely to obtain prenatal care. AI women were also less likely than white women to obtain prenatal care in the first trimester. Although a similar proportion of Al and white women reported that they consumed alcohol during the year before pregnancy, a higher proportion of Al drinkers than of white drinkers reported consuming one or more drinks weekly after finding out they were pregnant. The proportion of unwanted pregnancies was higher among Al women than among white women, but lower than among black women. Al and black women had a higher prevalence of depressive symptoms than did white women.The data suggest that urban Al mothers experience a disproportionate burden of economic, social, and behavioral risk factors for adverse pregnancy outcome.In spite of some data limitations, the Urban Indian Over sample of the NMIHS provides important information about social and health risk factors among urban Al mothers.

Mortality of American Indian and Alaska native infants.

Accurate determination of infant mortality rates among Indians in seriously hampered by variations in the identification of Indian persons and use of different subsets of the Indian population for various purposes. Lack of consistency in the reporting of racial origin on birth and death records is a source of substantial error. Because of these factors, more than the usual care must attend comparisons and inferences drawn from data in which these differences are present. At present, it would seem prudent to regard all data about American Indians as provisional. Even though Indian infant mortality remains higher than that for US all races, regardless of techniques used for estimates, the decline of Indian infant mortality by more than 80% since the establishment of the IHS is a truly remarkable achievement. This success has been ascribed to a combination of activities, including the provision of safe drinking water, especially as an integral part of the IHS program; the nearly universal immunization of Indian children; and emphasis upon comprehensive, community-oriented programs focused on maternal and child care. These successes have contributed to changes in the distribution of the leading causes of Indian infant mortality, so that the most prominent causes now are SIDS, congenital anomalies, injuries, and various infections. Because of these changes and advances in knowledge, the IHS has recently revised its five-year plan for dealing with infant mortality to provide greater attention to injuries and infections and has embarked upon a series of discussions with the American Academy of Pediatrics to address postneonatal deaths and the difficult problem of SIDS. Low socioeconomic conditions, so important in influencing mortality rates (7, 14, 29), have thus far proved to be intractable. In the meantime, success will depend upon ensuring optimal prenatal care, reducing those risk factors amenable to correction, and solving the problem of SIDS.

Limited efficacy of a Haemophilus influenzae type b conjugate vaccine in Alaska Native infants. The Alaska H. influenzae Vaccine Study Group.

BACKGROUND: The prevention of invasive Haemophilus influenzae type b disease requires a vaccine that is effective when administered during the first six months of life. The infants of Alaska Natives are at particularly high risk of invasive H. influenzae type b disease. METHODS: To evaluate the protective efficacy of a H. influenzae type b polysaccharide-diphtheria toxoid conjugate vaccine (polyribosylribitol phosphate-diphtheria toxoid [PRP-D]), we enrolled 2102 Alaska Native infants in a randomized, double-blind, placebo-controlled trial in which either the vaccine or a saline placebo was administered at approximately two, four, and six months of age. RESULTS: After 3969 subject-years of follow-up and 32 episodes of H. influenzae type b disease, the overall incidence of invasive disease was not reduced significantly in the vaccinated subjects (6.0 cases per 1000 patient-years), as compared with the placebo controls (9.6) or with other Alaska Native infants (6.0). After one, two, or three doses there was no significant protective efficacy with the vaccine; after three doses the efficacy was only 35 percent (95 percent confidence interval, -57 to 73). The lack of efficacy was not related to the age at onset of disease, age at immunization, type of disease, degree of Alaska Native heritage, time after immunization, or year of the study. Levels of H. influenzae type b anticapsular antibody in recipients of the vaccine became significantly higher than levels in those who received placebo only after the second and third doses. Even after the third dose, only 48 percent of the vaccinated infants had antibody levels of more than 0.1 microgram per milliliter (geometric mean titer, 0.18). Antibody responses did not vary with the level of maternally acquired antibody, degree of Alaska Native ancestry, or age at time of the first or second immunizations, but they increased with increasing age at time of the third dose (P less than 0.001). CONCLUSIONS: We found no evidence that the PRP-D vaccine provides significant protection, at least for Alaska Native infants, against invasive diseases caused by H. influenzae type b. The ineffectiveness of the vaccine paralleled its limited immunogenicity.

Haemophilus influenzae type b anticapsular antibody responses to PRP-pertussis and PRP-D vaccines in Alaska native infants.

To evaluate immune responses in Alaska Native infants at high risk for invasive Haemophilus influenzae type b (Hib) disease, we studied PRP-pertussis and PRP-D conjugate vaccines in this population relative to responses in white infants in California and New York. Infants were immunized at two, four, and six months of age (both vaccines). In the PRP-pertussis trial, there were no significant differences in antibody levels at any age between Alaska Native infants and infants from California. Only 50% of the infants had a twofold or greater antibody rise after three doses. In the PRP-D trial, antibody levels at two months of age (presumably maternally acquired) were significantly higher for Alaska Native infants compared with infants from New York (P = .002). There were no significant differences in antibody levels after any of the three doses. Among Alaska Native infants there was no significant difference in antibody response based upon degree of ethnic purity.

Recurrent invasive Haemophilus influenzae type b disease in Alaskan Natives.

Alaskan Natives (Indians and Eskimos) have an extraordinary incidence of invasive Haemophilus influenzae type b (Hib) disease (500 cases/100,000 children younger than 5 years of age) and also an increased incidence of recurrent disease. However, the incidence of primary Hib disease and recurrent disease are not excessive in non-Native children in Alaska (mainly Caucasian). Twelve recurrent cases in Alaskan Natives were studied, 10 of which were detected in surveillance activities between 1971 and 1984. These recurrent episodes occurred 23 to 197 days after the initial episodes (median, 51 days); the overall rate of recurrent disease was 3.5%. The ages of the patients with recurrent disease were significantly younger than single episode cases. To determine if disease recurrence was a manifestation of the high disease incidence and earlier age at onset of disease, we calculated an expected number of recurrent cases for our study population, based on the incidence observed in children with first episodes and the period of observed follow-up. The expected number of recurrent cases was only 1.9, significantly fewer than the 10 observed, indicating that age and the high incidence of disease alone were not the only factors contributing to the recurrent disease. No other significant clinical or epidemiologic risk factors could be identified. Patients who develop recurrent invasive Hib disease may represent a subset of this population with unusual disease susceptibility.