Challenges to vaccine safety.

The end of the 20th century saw the realization of a goal that was previously only dreamed about: the near elimination of many deadly infectious diseases through universal vaccination. As one disease after another has been driven from memory, it is vaccination programs themselves that have come to occupy the public's mind. With increased scrutiny comes the promise that vaccines will become even safer, but there is also the threat that ill-founded concerns will result in reduced immunization rates, and diseases will resurge. This article reviews scientific data relating to current vaccine safety concerns.

Do parents understand immunizations? A national telephone survey.

BACKGROUND: Immunization may now be undervalued because vaccines have largely eliminated the threat of serious infectious diseases in childhood. As the incidence of vaccine-preventable diseases has declined, concern about vaccine safety has increased. Significant erosion of public confidence in vaccine safety could lead to reduced immunization rates and a resurgence of vaccine-preventable diseases. OBJECTIVE AND METHODS: To assess parents' understanding of vaccine-preventable diseases, vaccines, immunization practices, and policies, we conducted a telephone survey in the United States with a nationally representative sample (n = 1600) of parents with children

Invasive Haemophilus influenzae disease in Alaskan residents aged 10 years and older before and after infant vaccination programs.

CONTEXT: The introduction of Haemophilus influenzae type b (Hib) vaccination of children has led to a decline in incidence of Hib disease in young Alaskan children. However, the impact of vaccination on unimmunized Alaskan adolescents and adults has not been studied. OBJECTIVE: To characterize trends in incidence of and mortality due to invasive H influenzae disease in Alaskan residents aged 10 years and older prior to and after the introduction of a statewide Hib infant vaccination program. DESIGN AND SETTING: Population-based, descriptive correlational study conducted 1980-1996 in Alaska. SUBJECTS: One hundred twenty-nine individuals (31 Alaska Natives and 98 nonnative Alaska residents) aged 10 years and older in whom H influenzae was cultured from a normally sterile site. MAIN OUTCOME MEASURES: Incidence of H influenzae infection before (1980-1990) vs after (1991-1996) vaccination program initiation; serotype, biotype, and beta-lactamase production of isolates. RESULTS: The overall annual incidence of invasive H influenzae in those aged 10 years and older declined 33%, from 2.1 per 100,000 persons per year to 1.4 per 100,000 persons per year (P=. 03) after initiation of statewide infant Hib vaccination programs in 1991. This reduction appeared to be the result of a decrease in serotype b disease (82%; P<.001). Infection with other H influenzae serotypes and nontypeable strains increased from 0.5 per 100,000 persons per year to 1.1 per 100,000 persons per year (P=.01). Incidence declined from 4.2 per 100,000 persons per year to 1.2 per 100,000 persons per year in Alaska Natives (P=.005) and from 1.7 per 100,000 persons per year to 1.4 per 100,000 persons per year in nonnative Alaska residents (P=.37). Pneumonia (43%), sepsis (26%), and meningitis (16%) were the most common clinical presentations. Alcohol/drug abuse was comorbid in 15% of patients, while 13% of patients were pregnant women. beta-Lactamase production occurred in 35% of isolates and was stable throughout the surveillance. The overall case-fatality rate was 15%. CONCLUSION: The overall statewide incidence of invasive H influenzae infections in unimmunized persons aged 10 years and older decreased after the initiation of an infant Hib vaccine program, perhaps by decreasing Hib carriage in child reservoirs. An increase in non-serotype b strains was observed. This trend justifies the need for continued surveillance of invasive disease caused by H influenzae. JAMA. 2000.

Immunogenicity of two doses of yeast recombinant hepatitis B vaccine in healthy older adults.

To determine the immunogenicity of two doses of yeast recombinant hepatitis B virus (HBV) vaccine containing surface (S) protein, an open-label, multicenter trial was conducted in 199 healthy HBV-seronegative adults > or = 40 years old. Volunteers were randomly assigned to 1 of 5 groups to receive a total of three 10-microg doses, at 0, 1, and 6 months, or a total of two doses of 20 microg and 10 microg, 20 microg and 20 microg, 40 microg and 10 microg, or 40 microg and 20 microg at 0 and 6 months. The 40-microg/20-microg regimen elicited the highest rate of seroprotection (96.2%), with a geometric mean titer of antibody against the S protein of 369 mIU/mL, not significantly different from the 536 mIU/mL achieved with three doses. These results suggest that a two-dose regimen can achieve seroprotection similar to that of the three-dose regimen. Whether a shorter interval can be used or a booster dose will be needed later to confer durable immunity are unknown.

Fungal infections: a growing threat.

THE EMERGENCE OF newly identified fungal pathogens and the reemergence of previously uncommon fungal diseases is primarily related to increases in the numbers of susceptible persons: people with HIV infection, bone marrow and organ transplant recipients, cancer patients being treated with chemotherapy, critically ill persons, and very low birth weight ( < or = 1500 g) infants. These immunocompromised populations are at risk for infection not only with opportunistic pathogens (for example, Pneumocystis, Candida, Cryptococcus, Trichosporon, Malassezia, Aspergillus, Penicillium marneffei, and numerous other moulds or yeasts) but also with fungal pathogens that usually infect otherwise healthy persons not previously exposed to endemic fungi (for example, Coccidioides immitis, Histoplasma capsulatum, and Blastomyces dermatitidis) and Sporothrix schenckii. Morbidity, mortality, and health care costs associated with fungal infections are high. Addressing the emergence of fungal diseases will require increased surveillance coupled with the availability of rapid, noninvasive diagnostic tests; monitoring the development of resistance to antifungal agents; and research focused on the understanding, prevention, and control of fungal infections.

Global DTP manufacturing capacity and capability. Status report: January 1995.

A recently completed survey of 63 manufacturers of diphtheria-tetanus-pertussis (DTP) vaccine and its components in 42 countries shows that there is potentially a large excess installed capacity for DTP production. However, many manufacturers are not producing to capacity, and demand and supply for this vaccine are not matched in individual countries. About half of all countries producing DTP vaccine and its components do not have fully functional national control systems, and some countries are performing none of the critical functions for an effective control of quality. Thus, potential for export of excess capacity is limited. The data collected indicate much homogeneity in the preparation of diphtheria and tetanus toxoids. Nearly all manufacturers use the same seeds and similar purification methods, but there is variability in whether purification is done before or after conversion of toxin to toxoid. About 10% of all manufacturers do not meet WHO-defined standards of purity for these toxoids. There is much more heterogeneity in the pertussis seed strains and the methods of purification used. The formulation of DTP vaccine differs considerably among producers. Potency testing is not being done by the WHO-recommended method by about 50% of manufacturers on lots of diphtheria and tetanus toxoids for release. Testing of irreversibility of conversion of toxin to toxoid, a WHO-specified safety test, is also not being done on each lot of diphtheria toxoid by 15% of manufacturers surveyed nor on each lot of tetanus toxoid vaccine by 30% of manufacturers surveyed. Access to technology to develop new DTP-based combination vaccines will be delayed if these manufacturers cannot ensure consistent high quality vaccine for their target populations. The results and conclusions suggest areas for future activities to strengthen the supply and quality of DTP and DTP-based combination vaccines.

Cardiac mortality in Alaska's indigenous and non-Native residents.

Cardiac disease mortality in Alaska, from both ischaemic and rheumatic heart disease, is of interest given the high consumption of fish and high streptococcal disease rates in the indigenous population. Uniformly coded underlying cause-of-death data for the period 1979-1988, compared with that from 1955-1965, indicated that deaths from all cardiac diseases combined, have been increasing in Alaska Natives over the past 30 years. Recent mortality from all cardiac, ischaemic, and rheumatic heart diseases in Alaska Natives were 80%, 61%, and 202% of those corresponding levels in Alaskan whites, whose cardiac mortality closely profiles US whites. Alaska Native men aged 30-45 years had higher overall mortality rates for cardiac diseases than did whites because of higher mortality rates of rheumatic heart disease and cardiomyopathy. Elderly Alaska Native men had lower rates than whites, reflecting less ischaemic heart disease mortality. The lowest levels of ischaemic heart disease mortality, less than one-third that of US whites, occurred in Alaskan Eskimos who lived in an area with documented patterns of high salmon consumption by individuals with high blood concentrations of omega-3 fatty acids. Elevated mortality from non-ischaemic heart disease and previously documented genetic markers suggest associations deserving further study.

Severity and frequency of sequelae of bacterial meningitis in Alaska Native infants. Correlation with a scoring system for severity of sequelae.

OBJECTIVES: To (1) determine the frequency and severity of sequelae of Haemophilus influenzae type b and Streptococcus pneumoniae meningitis in Alaska Native children, (2) compare morbidity and mortality of H influenzae b and S pneumoniae meningitis, and (3) evaluate the applicability of the Herson-Todd prognostic score (HTPS) to both H influenzae b and S pneumoniae meningitis in this population. DESIGN: A retrospective study of all cases of H influenzae b and S pneumoniae meningitis in Alaska Native children younger than age 5 years. Data on meningitis sequelae, obtained from medical charts and records of the Infant Learning Program, were collected, and incidence of sequelae tabulated. Data obtained on admission to the hospital were used to calculate HTPS. SETTING: Indian Health Service facility for the Yukon-Kuskokwin Delta region of southwest Alaska. STUDY SUBJECTS: 51 of 63 Alaska Native children with H influenzae b meningitis and 13 of the same 63 Alaska Native children with S pneumoniae meningitis occurring between 1980 and 1988. One child was infected with both organisms, producing a total of 64 cases for study. SELECTION PROCEDURES: Cases were identified by surveillance for these diseases between January 1, 1980, and December 31, 1988, maintained by the Arctic Investigations Program, Centers for Disease Control. MEASUREMENTS AND RESULTS: Sequelae of bacterial meningitis caused by H influenzae b were equal to or exceeded rates of sequelae described in other children in the United States. After H influenzae b meningitis, motor abnormalities (29%) and hydrocephalus (7%) occurred two to four times more often in Alaska Native children than in children in other parts of the United States. Differences in severity of H influenzae b sequelae could not be accounted for by microbiologic markers of the H influenzae b strain, including ampicillin sensitivity, biotype, outer membrane protein type, or electropherotype. Numbers of cases of S pneumoniae meningitis were too small for statistically valid comparison, but sequelae of S pneumoniae meningitis occurred in roughly equal proportion as sequelae of H influenzae b meningitis. The HTPS was applied to Alaska Native children with H influenzae b meningitis and was found to be very accurate in predicting children with major sequelae. Analysis of the prognostic factors used in deriving the HTPS revealed a unique set of predictors for sequelae in Alaska Native children: seizures at admission, glucose levels in cerebrospinal fluid of less than 1.1 mmol/L; and male gender, with a significant predictive interaction between male gender and age less than 6 months at admission. CONCLUSIONS: Alaska Native children suffer greater neurologic morbidity as a result of H influenzae b meningitis than do their non-Native counterparts. The HTPS was a good predictor of major sequelae in Alaska Native children with H influenzae b or S pneumoniae meningitis and could be useful in determining which patients need referral to a tertiary care center.

Characterization of Neisseria meningitidis serogroup C by multilocus enzyme electrophoresis and ribosomal DNA restriction profiles (ribotyping).

We compared multilocus enzyme electrophoresis (MEE) and ribosomal DNA fingerprinting (ribotyping) for subtyping 44 strains of Neisseria meningitidis serogroup C that were isolated in Los Angeles County, California, between December 1985 and July 1986. The isolates were divided into six enzyme types (ETs) by MEE, but 36 of the isolates were clustered in one ET, 3. The same isolates were divided into 17 ribotypes by use of restriction endonucleases ClaI, EcoRI, and XhoI. Twenty of the 36 ET 3 isolates were divided into 17 ribotypes by use of restriction endonucleases ClaI, EcoRI, and XhoI. Twenty of the 36 ET 3 isolates were grouped in a single ribotype, J. The rate of infection with ribotype J strains was higher in the southern part of the study area than in the northern part. Isolates from each of eight pairs (each isolate pair was cultured from the same patient from the same or different sites) were found identical by MEE, but ribotyping revealed a difference in one pair. In this study, ribotyping showed a greater discriminating capacity than MEE for subtyping N. meningitidis serogroup C, but the epidemiologic relevance of this increased sensitivity needs further assessment.

Coccidian infections in AIDS. Toxoplasmosis, cryptosporidiosis, and isosporiasis.

Cryptosporidium sp. and Isospora belli are coccidian protozoan parasites that were long recognized as pathogens for many animal species. The medical community became acquainted with these organisms with the advent of AIDS. Both parasites are associated with persistent, debilitating enteritis and, in the case of Cryptosporidium, biliary tract involvement in patients with AIDS. For the immunocompetent host, infection with these two pathogens usually results in self-limited diarrhea. Cryptosporidiosis appears to occur more often than isosporiasis, but the true prevalence of both infections for various populations of humans is unknown. Clinically, cryptosporidiosis is indistinguishable from isosporiasis. Diagnosis is based on finding the acid-fast (red staining oocyst in stained fecal specimens). There is no known effective therapy for cryptosporidiosis, whereas patients with isosporiasis respond promptly to treatment with trimethoprim-sulfamethoxazole. Patients with AIDS and isosporiasis have a high relapse rate after achieving complete remission and therefore need to be maintained on suppressive therapy. Much more needs to be learned about these two fascinating, "newly recognized" parasites.

Meningococcal disease in the United States--1986. Meningococcal Disease Study Group.

Active surveillance for invasive meningococcal disease was conducted during 1986 and 1987 in six areas of the United States with a total population of approximately 34 million persons. The incidence of meningococcal disease was 1.3:10(5). The highest incidence of disease among the surveillance areas was in Los Angeles County (1.65:10(5). Neisseria meningitidis serogroups B and C caused about equal amounts of disease, which reflects a recent increase in the incidence of group C disease. Group C caused more than half of the cases of meningococcal disease in Los Angeles and Tennessee but less than one-third of the cases in Missouri and Oklahoma. Multilocus enzyme electrophoresis demonstrated that a group of closely related isolates of N. meningitidis was prevalent in Los Angeles during the surveillance period and was associated with an increased incidence of meningococcal disease there.

The epidemiology of listeriosis in the United States--1986. Listeriosis Study Group.

To determine the morbidity and mortality due to listeriosis in the United States, the authors undertook an active surveillance project in 1986 to identify all cases in which Listeria monocytogenes was isolated from cultures of ordinarily sterile sites in a population of 34 million persons. The authors estimated that at least 1,700 cases of listeriosis and 450 deaths occurred in the United States in 1986; 27% of these cases occurred in pregnant women, with 22% of perinatal cases resulting in stillbirths or neonatal deaths. The risk of listeriosis in adults (0.5 per 100,000 population) was similar in all regions studied; the incidence of perinatal listeriosis was three times higher in Los Angeles County, California, than in the other areas (24.3/100,000 live births vs. 7.8/100,000 live births). Geographic variation may have resulted from underdiagnosis of perinatal listeriosis in five of the study areas. Multilocus electrophoretic enzyme typing was useful for elucidating the molecular epidemiology of L. monocytogenes; perinatal listeriosis was significantly associated with one group of related strains. Multilocus electrophoretic enzyme typing also identified three clusters representing possible common-source outbreaks. These findings document the substantial morbidity due to listeriosis in the United States; to the extent that sporadic listeriosis is foodborne, this morbidity could be reduced by appropriate preventive measures, particularly in persons known to be at increased risk of infection.