Think globally, act locally: the role of local demographics and vaccination coverage in the dynamic response of measles infection to control.

The global reduction of the burden of morbidity and mortality owing to measles has been a major triumph of public health. However, the continued persistence of measles infection probably not only reflects local variation in progress towards vaccination target goals, but may also reflect local variation in dynamic processes of transmission, susceptible replenishment through births and stochastic local extinction. Dynamic models predict that vaccination should increase the mean age of infection and increase inter-annual variability in incidence. Through a comparative approach, we assess national-level patterns in the mean age of infection and measles persistence. We find that while the classic predictions do hold in general, the impact of vaccination on the age distribution of cases and stochastic fadeout are mediated by local birth rate. Thus, broad-scale vaccine coverage goals are unlikely to have the same impact on the interruption of measles transmission in all demographic settings. Indeed, these results suggest that the achievement of further measles reduction or elimination goals is likely to require programmatic and vaccine coverage goals that are tailored to local demographic conditions.

Molecular epidemiology of Bordetella pertussis by pulsed-field gel electrophoresis profile: Cincinnati, 1989-1996.

Reported cases of pertussis have increased in the United States, with peaks occurring every few years. Bordetella pertussis isolates collected in Cincinnati from 1989 to 1996 were analyzed with pulsed-field gel electrophoresis (PFGE), to evaluate trends. Among 496 isolates, 30 PFGE profiles were identified; 32% were CYXXI-010, the profile that predominated each year. Eighteen profiles (198 strains) were identified in 1989-1992, 20 profiles (197 strains) were identified during the 1993 epidemic, and 11 profiles (101 strains) were identified in 1994-1996. From 1989 to 1996, among 42 patients, isolates from household members in 17 (89%) of 19 households had concordant PFGE profiles. There was no association between PFGE profile and seasonality, age, and hospitalization or pneumonia in infants <1 year old. The 1993 epidemic was associated primarily with an increased prevalence of PFGE profiles that circulated before and after 1993, which suggests that the epidemic was due to factors other than the emergence of a novel B. pertussis strain.

Measles eradication: is it in our future?

Measles eradication would avert the current annual 1 million deaths and save the $1.5 billion in treatment and prevention costs due to measles in perpetuity. The authors evaluate the biological feasibility of eradicating measles according to 4 criteria: (1) the role of humans in maintaining transmission, (2) the availability of accurate diagnostic tests, (3) the existence of effective vaccines, and (4) the need to demonstrate elimination of measles from a large geographic area. Recent successes in interrupting measles transmission in the United States, most other countries in the Western Hemisphere, and selected countries in other regions provide evidence for the feasibility of global eradication. Potential impediments to eradication include (1) lack of political will in some industrialized countries, (2) transmission among adults, (3) increasing urbanization and population density, (4) the HIV epidemic, (5) waning immunity and the possibility of transmission from subclinical cases, and (6) risk of unsafe injections. Despite these challenges, a compelling case can be made in favor of measles eradication, and the authors believe that it is in our future. The question is when.

Molecular epidemiology of Bordetella pertussis by DNA fingerprinting with pulsed-filled gel electrophoresis, 1989-1996

Pertussis is an endemic disease in the United States of America, with epidemics occurring every three to four years. In Cincinnati, Bordetella pertussis isolates collected from 1989 to 1996 were analysed by genomic subtyping with pulsed-field gel electrophoresis (PFGE) to evaluate the B pertussis population before, during and after a large epidemic of epidemiologically relevant changes. Among the 496 B pertussis isolates, 31 PFGE profiles were identified; 32 percent of isolates were CYXXI-010 and this profile predominated in each year. Nineteen, 20 and 12 PFGE profiles were identified in the pre-epidemic period (n=198), during the epidemic (n = 197) and in the post-epidemic period (n = 101), resulting in genotypic diversities of 0.82, 0.83 and 0.76 respectively. From 1989 to 1996, among 19 households clusters of 42 patients, 17 (89 percent) households had concordant PFGE profiles among isolates from household members. There was no association between PFGE type and seasonality, age, hospitalisation or pneumonia in infants. The 1993 epidemic was primarily associated with increased prevalence of B pertussis PFGE profiles that circulated before and after the epidemic, suggesting increased susceptibility to pertussis rather than a novel strain as a cause of the outbreak.(Au)

Economic evaluation of use of diphtheria, tetanus, and acellular pertussis vaccine or diphtheria, tetanus, and whole-cell pertussis vaccine in the United States, 1997.

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. Arch Pediatr Adolesc Med. 2000;154:797-803

Factors determining prevalence of maternal antibody to measles virus throughout infancy: a review.

The effectiveness of vaccination against measles, the leading cause of vaccine-preventable deaths in infants globally, is greatly impacted by the level of maternal antibody to measles virus (or "measles maternal antibody"; MMA) during infancy. Variation in the prevalence of maternal antibody to measles virus between infant populations across countries and sociodemographic strata is poorly understood. We reviewed the literature on the prevalence of MMA, focusing on 3 principal determinants: starting level of maternal antibody, placental transfer of maternal antibody, and rate of decay of maternal antibody after birth. Our review identified placental transfer as an important determinant, with greater efficiency found in studies performed in developed countries. Placental transfer was influenced by gestational age, human immunodeficiency virus infection, and malaria. Antibody levels in mothers varied widely between countries, although predictably according to vaccination status within populations. Rates of antibody decay across studies were similar. Future studies should evaluate the utility of the cord blood level of MMA as a predictor of vaccine efficacy in infancy; inclusion of World Health Organization international reference sera will facilitate comparisons. Greater understanding of the determinants of the prevalence of MMA will help national policy makers determine the appropriate age for measles vaccination.

Epidemic diphtheria in the Kyrgyz Republic, 1994-1998.

The Kyrgyz Republic experienced a widespread diphtheria epidemic during 1994-1998. National diphtheria surveillance and vaccination coverage information were used to describe the course of the epidemic. The epidemic began in August 1994, reached a peak in 1995 with 704 cases (incidence rate: 15.4/100,000 population) and 30 deaths, and declined to an incidence rate of 4.0/100,000 during the first 8 months of 1998. Age-specific incidence was highest in 1995 among persons 15-19 and 20-29 years old. Three rounds of mass vaccination with tetanus and diphtheria toxoids for adult use (Td) were conducted; reported coverage was 69% in 1995 and >95% in 1996 and 1997. Reported routine vaccination coverage with three doses of diphtheria toxoid by age 12 months increased from 62% in 1989 to 98% in 1997. Mass vaccination of the adult population with Td and improvements in childhood vaccination coverage played a major role in controlling the epidemic.

Clinical characteristics and management of 676 hospitalized diphtheria cases, Kyrgyz Republic, 1995.

The Kyrgyz Republic experienced a widespread resurgence of diphtheria during 1994-1998. To describe the clinical characteristics and management of diphtheria patients hospitalized in 1995, a retrospective chart review was conducted. Physician-diagnosed cases of diphtheria were classified according to the system recommended by the World Health Organization and UNICEF. Among 676 patients hospitalized with respiratory diphtheria, 163 (24%) were carriers, 186 (28%) had tonsillar forms, 78 (12%) had combined types or delayed diagnosis, and 201 (30%) had severe forms of diphtheria. The highest age-specific incidence rates occurred among persons 15-34 years old, and 70% of cases were among those >/=15 years of age. Myocarditis occurred among 151 patients (22%), and 19 patients died (case fatality ratio: 3%). Diphtheria antitoxin was administered to 507 patients (75%), and all patients received antibiotics (penicillin or erythromycin). Respiratory diphtheria remains a potentially fatal disease, commonly presenting with a typical membranous pharyngitis. Early diagnosis and treatment of cases with diphtheria antitoxin and antibiotics are the cornerstones of effective treatment.

Risk factors for diphtheria: a prospective case-control study in the Republic of Georgia, 1995-1996.

The large-scale resurgence of diphtheria in the former Soviet Union offered a unique opportunity to evaluate risk factors for the transmission of respiratory diphtheria; therefore, a prospective case-control study was done in the republic of Georgia. In total, 218 diphtheria cases (hospitalized between October 1995 and March 1996) and 408 matched controls participated. One hundred cases (45%) were /=15 years of age (range: <1 to 75 years). In the multivariate analyses, the following risk factors were found to be significant: lack of vaccination (matched odds ratio [mOR]=19.2), household exposure to diphtheria (mOR=7.4), exposure to skin lesions (mOR=5.8), history of eczema (mOR=3.4), fever with myalgia prior to illness (mOR=2.6), having tonsils (mOR=4.4), sharing a bed (mOR=1.9), sharing cups and glasses (mOR=2.7), and taking a bath less than once a week (mOR=2.6). These findings emphasize primary prevention through immunizations, secondary prevention following exposure to diphtheria (and to suspicious skin lesions), and adherence to strict standards of personal hygiene.

Epidemic diphtheria in the Republic of Georgia, 1993-1996: risk factors for fatal outcome among hospitalized patients.

Epidemic diphtheria reemerged in the republic of Georgia in November 1993. To identify risk factors for fatal outcomes, clinical and epidemiologic data on all hospitalized diphtheria patients were examined. Medical charts of patients from 1993-1995 were reviewed. A total of 659 cases and 68 deaths were identified (case fatality rate [CFR] = 10.3%). Fifty-two percent of all cases and 68% of deaths were in children 3 days) between onset of symptoms to antitoxin treatment were significantly associated with fatal outcomes. Immunization of children and 40- to 49-year-old adults was required to rapidly control the epidemic.

Measles epidemic in Romania, 1996-1998: assessment of vaccine effectiveness by case-control and cohort studies.

A measles epidemic occurred in Romania with 32,915 cases and 21 deaths reported between November 1996 and June 1998, despite high vaccination coverage since the early 1980s. Most cases were unvaccinated children aged <2 years and vaccinated school-aged children. A case-control study among preschool children and a cohort study among primary-school children were conducted to estimate effectiveness of Romanian-produced measles vaccine, and to evaluate age at vaccination and waning immunity as risk factors for vaccine failure. Both studies indicated that measles vaccine was highly effective. One dose reduced the risk for measles by 89% (95% confidence interval (CI) 85, 91); two doses reduced the risk by 96% (95% CI 92, 98). Children vaccinated at <1 year of age were not at increased risk for measles compared with children vaccinated at > or =1 year. Waning immunity was not identified as a risk factor since vaccine effectiveness was similar for children vaccinated 6-8, 9-11, and 12-14 years in the past. Because specific groups were not at risk for vaccine failure, an immunization campaign that targets all school-aged children who lack two doses may be an effective strategy for preventing outbreaks. A mass campaign followed by increased first-dose coverage should provide the population immunity required to interrupt indigenous measles virus transmission in Romania.

PIP: Two studies examined the effectiveness of measles vaccines in Romania during the measles epidemic between 1996 and 1998. A case control study among preschool children and a cohort study among primary school children were conducted to estimate Romanian-produced vaccine effectiveness and to identify risk factors for measles among these age groups. Both studies found that measles vaccine was highly effective. Single-dose vaccine effectiveness was 89% and double-dose vaccine effectiveness was 96%. Univariate analysis of the case-control study indicated that being unvaccinated and being born of itinerant parents were significant risk factors for measles among preschool children. Children vaccinated at less than 1 year of age were not at increased risk for measles compared with children who receive the vaccine at 1 year or older. Because specific groups were not at risk for vaccine failure, an immunization campaign targeting all school-aged children who lacks two doses of measles vaccine may be an effective measure to prevent outbreaks in Romania.

Changing epidemiology of pertussis in the United States: increasing reported incidence among adolescents and adults, 1990-1996.

Since 1990, the reported incidence of pertussis has increased in the United States with peaks occurring every 3-4 years. On the basis of analysis of pertussis cases reported to the Centers for Disease Control and Prevention, the incidence remained stable among children aged younger than 5 years, most of whom were protected by vaccination. In contrast to 1990-1993, during 1994-1996, the average incidence among persons aged 5-9 years, 10-19 years, and 20 years or older increased 40%, 106%, and 93%, respectively. Since 1990, 14 states reported pertussis incidences of > or =2 cases per 100,000 population during at least 4 years between 1990 and 1996; seven of these states also reported that a high proportion of cases occurred in persons aged 10 years or older. Analysis of national data on pertussis did not provide sufficient information to fully elucidate the relative importance of multiple possible explanations for the increase in the incidence of pertussis in adolescents and adults. Improvement in diagnosis and reporting of pertussis in this age group, particularly in some states, is an important factor contributing to the overall increase.

Epidemiology of epidemic diphtheria in three regions, Russia, 1994-1996.

BACKGROUND: A massive diphtheria epidemic which began in the former Soviet Union in 1990 is the first large-scale diphtheria epidemic in developed countries in more than 30 years and has primarily affected adults. In response, health authorities attempted to maximize vaccination for children and conducted an unprecedented campaign to vaccinate adults. METHODS: We analyzed diphtheria surveillance data (case report forms and diphtheria vaccine coverage data) from three Russian regions from January 1994 to December 1996 and estimated vaccine effectiveness by the screening method. RESULTS: We reviewed records from 2243 (97.2%) of 2307 reported cases. The highest cumulative incidence in the period was among children aged 5 to 9 years (106 cases per 100,000 population); adults aged 40-49 years had the highest adult incidence for disease (88 cases per 100,000) and the highest incidence of any age group of clinically severe disease (29 cases per 100,000) and death (5.1 deaths per 100,000). The incidence among women aged 2049 years (82 per 100,000 women) was higher than among men (47 per 100,000, p<0.01). The annual incidence decreased from 25.2 cases per 100,000 population in 1994 to 9.4 cases per 100,000 in 1996. The decrease occurred as adult coverage increased from an estimated 25-30% in December 1992 to 88% in December 1995. Vaccine effectiveness was high among both children and adults. CONCLUSIONS: The Russian diphtheria epidemic primarily affected adults, especially women; this pattern is likely representative of diphtheria epidemics in immunized populations. Raising childhood immunization coverage and mass adult vaccination was effective in controlling the Russian epidemic. An improved understanding of the current epidemiology of diphtheria will be useful to design public health responses to prevent or control modern epidemics.

Risk of diphtheria among schoolchildren in the Russian Federation in relation to time since last vaccination.

BACKGROUND: Between 1990 and 1996, more than 110,000 cases and 2900 deaths from diphtheria were reported in the Russian Federation. In 1994, because disease rates were high among children aged 7-10 years, the age of administration of the second booster dose of diphtheria vaccine was lowered from 9 years to 6 years, the age of school entry. To assess the impact of this policy change, we did a matched case-control study in three Russian cities. METHODS: Children aged 6-8 years who had diphtheria between September, 1994, and December, 1996, were each matched with five to seven children acting as controls who were within 3 months of age of the case and were from the same class at school. We did a matched analysis using conditional logistic regression. FINDINGS: We analysed the immunisation records of 58 cases and 306 controls. All but one case and all controls had received at least three doses of diphtheria-toxoid vaccine. 19 (33%) cases and 144 (47%) controls had received a booster dose of diphtheria toxoid within the previous 2 years. Cases were more likely than were controls to have received only four doses rather than five (odds ratio 2.8 [95% CI 1.2-6.5]) and to have a time since the last dose of diphtheria toxoid of 3-4 years (3.1 [1.1-9.1]) or 5-7 years (15.0 [2.5-89.0]), compared with children for whom it was 2 years or less. On multivariate analysis only a time since the last dose of 5-7 years remained significantly associated with disease (matched odds ratio adjusted for total number of doses 10.9 [1.6-75.1]). CONCLUSION: A booster dose of diphtheria-toxoid vaccine given to children in the Russian Federation at 6-8 years of age reduced the interval since the last dose of diphtheria toxoid and improved protection against diphtheria.

PIP: More than 110,000 cases and 2900 deaths from diphtheria were reported in the Russian Federation in 1990-96. In response to the high disease rates in children 7-10 years of age, the timing of the second booster dose of diphtheria vaccine was lowered in 1994 from 9 to 6 years of age--the age of school entry. The impact of this change was assessed in a matched, retrospective, case-control study conducted in three Russian cities. 58 children 6-8 years old who had diphtheria between September 1994 and December 1996 were matched with 306 controls within 3 months of age and from the same school class. All but one case and all controls had received at least three doses of diphtheria toxoid vaccine and 19 cases (33%) and 144 controls (47%) had received a booster dose of the vaccine within the previous 2 years. Cases were more likely than controls to have received 4 rather than 5 doses (odds ratio (OR), 2.8; 95% confidence interval (CI), 1.2-6.5) and to have an interval since the last vaccine dose of 3-4 years (OR, 3.1; 95% CI, 1.1-9.1) or 5-7 years (OR, 15.0; 95% CI, 2.5-89.0) compared with children for whom it was 2 years or less since the last dose. In the multivariate analysis, only time since the last vaccine dose of 5-7 years was significantly associated with disease (matched OR adjusted for total number of doses, 10.9; 95% CI, 1.6-75.1). These findings indicate that a booster dose of diphtheria toxoid at the age of school entry is effective in preventing diphtheria among school-aged children. This evidence should be considered in the development of routine childhood immunization schedules in countries where diphtheria remains endemic.

Haemophilus influenzae invasive disease in the United States, 1994-1995: near disappearance of a vaccine-preventable childhood disease.

We analyzed national Haemophilus influenzae (Hi) surveillance data from 1994 and 1995 to describe the epidemiology of Hi invasive disease among persons of all ages. Serotype data were available for 376 (56%) of 669 reported Hi cases among children aged 4 years or younger; 184 (49%) were H. influenzae type b (Hib). Among children aged 4 or younger, incidence (per 100,000) of all Hi invasive disease was 1.8 in 1994 and 1.6 (p < 0.05) in 1995. Children aged 5 months or younger had the highest average annual incidence rate of Hib invasive disease (2.2 per 100,000); children aged 6 to 11 months had the next highest rate (1.2 per 100,000)(p < 0.05). Of 181 children with Hib invasive disease whose age in months was known, 85 (47%) were too young (aged 5 months or younger) to have completed a primary series with an Hib-containing vaccine. Of the 83 children with known vaccination status who were eligible to receive a primary series (aged 6 months or older), 52 (63%) were undervaccinated, and the remaining 31 (37%) had completed a primary series in which vaccine failed. Among persons aged 5 years or older with Hi invasive disease, the lowest average annual incidence was among those 20 to 39 years of age (0.15 per 100,000), and the highest was among those aged 80 years or older (2.26 per 100,000). Among persons aged 5 years or older, serotype data were available for 1,372 (71%) of the 1,940 Hi invasive disease cases; 159 (28%) of the 568 Hi cases with known serotype were due to Hib.

Respiratory diphtheria in the United States, 1980 through 1995.

OBJECTIVES: The purpose of this study was to describe the epidemiologic, laboratory, and clinical features of respiratory diphtheria cases reported in the United States during 1980 through 1995. METHODS: Respiratory diphtheria cases reported to the Centers for Disease Control and Prevention were reviewed. Cases were defined as physician-diagnosed cases with signs and symptoms compatible with respiratory diphtheria, including the presence of a pseudomembrane without other apparent cause. RESULTS: From 1980 through 1994, 41 respiratory diphtheria cases were reported; none were reported in 1995, and no secondary cases were identified. Nine (22%) case patients were 4 years of age or younger, and 28 (68%) were 15 years of age or older. None of the case patients were up to date with diphtheria vaccination; 4 unvaccinated children died. Seventeen (43%) of 40 case patients had positive culture results. CONCLUSIONS: Available surveillance data suggest that respiratory diphtheria has become a rare disease in the United States. However, importation and circulation of toxigenic strains continue to present a threat and require achieving and maintaining high coverage with diphtheria toxoid-containing vaccines in both children and adults.