Impact of a vaccination campaign on adult immunity to diphtheria

OBJECTIVES: to raise the level of immunity to diphtheria in the adult population of Stockholm by a vaccination campaign. The rationale behind the campaign, conducted during 1995-1996, was the re-emergence of epidemic diphtheria in the countries of the former Soviet Union and earlier surveys of immunity to diphtheria showing low levels of protection in adults. DESIGN AND MAIN OUTCOME MEASURES: the impact of the vaccination campaign was measured by recording the age and sex of vaccinees, the type and number of vaccine doses given and any side-effects. The effect on immunity was evaluated in 1998-1999 by measuring the neutralising antibodies in blood samples from 1863 inhabitants, chosen by random stratified sampling. Vaccines and vaccinations: three doses of diphtheria (D) or diphtheria-tetanus (DT) vaccine were given to those without documented previous vaccination; others received a booster dose. The DT vaccine, with the D component purified before toxoiding, contained 15 Lf of D and 7.5 Lf of T per ml, and was given in 0.5 ml doses for the two priming doses and 0.25 ml as booster. RESULTS: 184969 doses of D or DT vaccine were given to 99939 individuals. Of the vaccinees, 65% were 50 years of age or older and 60% were women. The highest rates of reported local reactions were 1.8-5.4% and of systemic reactions, such as fever, 0.2-0.8%. The campaign resulted in a significant increase in antitoxin concentrations in the age cohorts targeted, and especially in women, less well protected than men. CONCLUSIONS: a vaccination campaign, targeting the adult part of a population, can result in a major improvement in immunity to diphtheria with only a few and minor side-effects with a DT vaccine where the D component was purified prior to toxoiding. Extending national immunisation programmes to include adults would, however, seem preferable.     

Side Effects of Diphtheria-Tetanus Toxoid in Adults

During a mass diphtheria-tetanus immunization campaign in November 1975, more than 220,000 doses of diphtheria-tetanus toxoid, adult type were administered to adults throughout Alaska. In Anchorage, where more than 87,000 doses were given, a survey was conducted to determine the frequency of side effects. Postcard questionnaires were mailed to 2,000 randomly selected Anchorage residents; 467 questionnaires were returned by the post office as undeliverable, and 697 questionnaires were completed and returned. A follow-up survey was done of a random sample of the 836 non-responders.Of those responding, 57.8 per cent reported at least one reaction to the toxoids. The most frequent side effects were sore arm (42.7 per cent), swelling at the site of injection (34.8 per cent), and itching (24.2 per cent). Serious side effects occurred less frequently-swelling of the arm below the elbow (1.1 per cent) and abscess or infection (0.7 per cent). Of those vaccinated, 0.5 per cent saw a physician. There were no statistically significant differences in reaction rates by age group, except for sore arms. The jet injector produced more arm swelling at the site of injection, hives, and itching. More women than men reported adverse reactions, especially sore arm, swelling at the site of injection, and itching. Fear of adverse side effects should not preclude mass vaccination of adults. (Am. J. Public Health (69:246-249,1979.)     

Surveillance of adverse events following immunisation: Australia 2002 to 2003.

Reports of suspected adverse events following immunisation (AEFI) are reviewed by the Adverse Drug Reactions Advisory Committee and collated in a central database. We analysed AEFI records for vaccines administered during October 2002 to December 2003, and assessed AEFI reporting trends for 2000 to 2003. AEFI reporting rates were calculated using denominator data from the Australian Childhood Immunisation Register and the annual national influenza vaccination coverage survey. A total of 1,744 AEFI records were analysed for October 2002 to December 2003. The majority described non-serious events; 9 per cent (n=149) described AEFIs defined as 'serious'. Four deaths were reported but none were causally related to immunisation. Dose-based AEFI reporting rates were 2.1 per 100,000 doses of influenza vaccine for adults aged 40 years or over and 19.8 per 100,000 doses of scheduled vaccines for children aged <7 years. The most frequently reported individual AEFI was injection site reaction in children after a fourth or fifth dose of an acellular pertussis-containing vaccine (54 and 98 reports per 100,000 doses respectively). The most frequently suspected vaccine was meningococcal C conjugate vaccine (34% of reports-mostly injection site reactions, gastrointestinal symptoms and headaches). The average annual reporting rate was 7.0 per 100,000 population, the highest to date. The increase in the AEFI reporting rate was due to a greater number of children becoming eligible to receive a fourth or fifth consecutive dose of acellular pertussis vaccine and the introduction of the meningococcal C vaccination program in January 2003 for those aged 1-19 years. The low reporting rate of serious AEFIs demonstrates the high level of safety of vaccines in Australia.     

Short-term booster effect of diphtheria toxoid in initially long-term protected individuals

The main objective of this study was to investigate the booster antibody response in individuals with initially high levels of diphtheria antitoxin. Sixty individuals eligible for the routine booster by the age of 18 years each received a single dose of 5 Lf of diphtheria toxoid in diphtheria-tetanus vaccine. A double antigen ELISA was used for the assessment of the antibody levels. Chaotropic disruption in paired ELISA was used to test antibody avidity. The ratio between initial and maximum antibody concentrations after 1 month was >10 times higher and after 6 months still four times higher in those with initial antibody levels <1 IU/ml. In individuals with initial antibody levels >/=1 IU/ml a two-fold decrease was observed after 6 months compared to the initial levels. Thus, vaccination of individuals with initial long-term protection against diphtheria (antibody levels >/=1 IU/ml) is unnecessary and should be avoided.     

Surveillance of adverse events following immunisation: Australia, 2000-2002.

The Adverse Drug Reactions Advisory Committee (ADRAC) database collates notifications of adverse events following immunisation (AEFI) from across Australia. The data were analysed for vaccines received between 1 January 2000 and 30 September 2002. Dose-based AEFI reporting rates were calculated using denominator data from the Australian Childhood Immunisation Register and annual national influenza vaccination coverage surveys. The majority of the 2,409 AEFI records analysed described non-serious events, principally injection site reactions; 10.5 per cent (n = 253) described AEFIs with outcomes defined as 'serious'. Ten deaths were recorded but only one, following yellow fever vaccine, was causally related to immunisation. The average annual population-based reporting rate was 4.5 per 100,000 population. Vaccine dose-based AEFI reporting rates were 2.2 per 100,000 doses of influenza vaccine for adults aged 40 years and over and 14.6 per 100,000 doses of all scheduled vaccines for children aged less than 7 years. The most frequently reported type of adverse event was injection site reaction following receipt of an acellular pertussis-containing vaccine, particularly among children in the age groups scheduled to receive their fourth or fifth doses of the vaccine (overall reporting rate 67 per 100,000 doses). The data highlight the safety of vaccines in Australia, and illustrate both the utility of available immunisation coverage data to estimate dose-based AEFI reporting rates and the value of the ADRAC database as a surveillance tool for monitoring AEFIs nationally.     

河北省2013—2017年疑似预防接种异常反应监测分析

目的 了解河北省2013—2017年疑似预防接种异常反应(adverse events following immunization,AEFI)的发生特征,评价所用疫苗的安全性和预防接种服务工作质量。方法 采用描述性流行病学方法分析河北省2013—2017年AEFI数据。结果 河北省2013—2017年报告AEFI病例57 028例,年均报告发生率为44.48/10万剂。男女性别比为1.33∶1,集中在1岁年龄组,报告时间集中在夏、秋两季;绝大多数AEFI报告已痊愈或好转,约85%的不良反应报告发生在接种后24 h内。一般反应、异常反应报告分别占97.56%、2.00%。AEFI报告发生率较高的疫苗是无细胞百白破联合疫苗(diphtheria,tetanus and acellular pertussis combined vaccine,DTaP)(189.91/10万剂)、23价肺炎球菌多糖疫苗(23-valent pneumococcal polysaccharide vaccine, PPV23)(182.45/10万剂)和无细胞百白破-灭活脊灰-b型流感嗜血杆菌联合疫苗(diphtheria,tetanus and acellular pertussis, inactivated poliomyelitis and Haemophilus influenza type b conjugate combined vaccine, DTaP-IPV-Hib)(150.67/10万剂)。过敏性皮疹(5.48/10万剂)是报告发生率最高的异常反应类型。结论 河北省2013—2017年AEFI监测工作质量逐年提高,所用疫苗安全性良好。     

Vaccination of infants with a four-dose and a three-dose vaccination schedule

Swedish infants were vaccinated with diphtheria, tetanus and pertussis toxoids, inactivated poliovirus vaccine and a Haemophilus influenzae type b - tetanus toxoid conjugate vaccine at 2, 4, 6 and 15 months (US vaccination program, 'US arm', n=118) or at 3, 5 and 12 months of age (Swedish vaccination program, 'Swedish arm', n=103). The antigen amounts in the diphtheria and tetanus vaccines were higher in the Swedish than in the US arm while the amounts in the other vaccines were the same in both arms. There were no serious side effects. Local reactions increased with the numbers of doses but did not differ significantly between the groups. Serum was obtained at 2, 7, 15 and 16 months in the US arm and at 3, 6, 12 and 13 months of age in the Swedish arm. A fifth serum was obtained in both groups at 4 yr of age. For vaccines with the same antigen amount the following was observed: a. three doses at 2, 4 and 6 months were more immunogenic than two doses at 3 and 5 months; b. the third dose in the Swedish arm was more immunogenic than the third dose in the US arm; c. the fourth dose in the US arm induced higher antibodies than the third dose in the Swedish arm (except for pertussis toxin antibodies that were similar in both groups) and the differences tended to remain at the age of 4 yr. Children in the Swedish arm received a higher diphtheria toxoid dose (25 Lf) than in the US arm (15 Lf) which led to higher diphtheria toxin antibodies in the Swedish arm at comparable ages. Children in the Swedish arm received a higher tetanus toxoid dose (7 Lf) than in the US arm (6 Lf). Tetanus antibodies were similar at comparable ages. In conclusion, the immunogenicity of vaccines in infancy can be improved by increasing the number of doses, by prolonging the intervals between doses and by increasing the antigen amount in the vaccine.     

Vaccine safety implications of Ontario,Canada's switch from DTaP–IPV to Tdap–IPV for the pre-school booster

Ontario, Canada, replaced the 4–6 year old diphtheria (D, d), tetanus (T), acellular pertussis (aP, ap) and polio (IPV) booster from DTaP–IPV to Tdap–IPV in May 2012. We assessed the impact of this replacement on the rate and types of reported adverse events following immunization (AEFIs). We used AEFIs reported among 4–6 years olds, through the provincial surveillance system, following administration of DTaP–IPV or Tdap–IPV from 2009 to 2013. Reporting rates per 100,000 doses distributed were calculated using publicly funded doses distributed as the denominator. A total of 204 AEFIs were reported (DTaP–IPV, n = 182; Tdap–IPV, n = 22). AEFI reporting rates were 33.1 and 6.3 per 100,000 doses distributed for DTaP–IPV and Tdap–IPV, respectively. Injection site reaction rate was lower for Tdap–IPV compared with DTaP–IPV (1.7 vs 20.6 per 100,000 doses). The replacement resulted in a decline in the number of reports and AEFI reporting rates, most notably a substantial decrease in injection site reactions.     

Adverse events following booster doses of diphtheria-tetanus-inactivated poliovirus and acellular pertussis vaccines for 4-year-old children in The Netherlands

The aim of the study was to assess the incidence and severity of local reactions and systemic events among 4-year-old children receiving a fifth dose of diphtheria-tetanus-inactivated poliovirus (dT-IPV) and acellular pertussis (aP) vaccines. Of 810 children, 483 had no adverse events following immunization. Of the reported local reactions of 281 children, pain was the most frequent (n=246). Eighty-one children developed redness, and 54, swelling. Pain, reduced use of the arm, redness, and swelling occurred significantly more often at the dT-IPV injection site than at the aP injection site (p<0.05). Local reactions were mainly mild and transient. Among the 104 reported systemic events, fever was the most frequent (n=42). In general, the vaccinations for the 4-year-olds are well tolerated.     

U.S. Postlicensure safety surveillance for adolescent and adult tetanus,diphtheria and acellular pertussis vaccines: 2005–2007

Background

Pre-licensure clinical trials for two U.S. licensed tetanus toxoid, reduced diphtheria toxoid and acellular pertussis (Tdap) vaccines did not reveal any major safety concerns. However, routine use in large adolescent and adult populations could reveal rare and potentially serious adverse events (AEs).

Methods

To characterize reported AEs following Tdap vaccination and identify potential safety concerns warranting further evaluation, we analyzed data from the Vaccine Adverse Event Reporting System (VAERS) and assessed the frequency and proportions of AEs and reporting rates (reports per 100,000 vaccine doses distributed).

Results

A total of 2090 reports (7% were serious; 55% listed Tdap alone) involving Tdap vaccines were submitted to VAERS May 2005–June 2007. The crude reporting rate was 10.2 per 100,000 vaccine doses distributed. The median age of vaccinees was 22 years, and the female to male ratio was about 2 to 1. The majority of reports described common local and systemic signs and symptoms, such as injection site reactions, fever, and headache. Rarely reported AEs included myopericarditis, demyelinating diseases of the central nervous system, Guillain–Barré Syndrome, syncope, encephalopathy/encephalitis, seizure, Bell's palsy, anaphylaxis, and thrombocytopenia.

Conclusions

Because adolescents and adults were not routinely vaccinated against pertussis in the past, this surveillance summary provides important – and reassuring – information about the use of Tdap in these age groups. Although subject to the limitations of passive surveillance, the findings of this VAERS review support the pre-licensure clinical trial data with regard to the safety of the U.S. licensed Tdap vaccines. Continued monitoring of clinically significant AEs that are temporally associated with Tdap vaccination and further assessment of such events using controlled observational studies may provide additional information about the safety of these vaccines.     

Adverse events after Japanese encephalitis vaccination: review of post-marketing surveillance data from Japan and the United States. The VAERS Working Group

We determined the reporting rates for adverse events following the administration of inactivated mouse-brain derived Japanese encephalitis vaccine (JEV) based on post-marketing surveillance data from Japan and the United States. The rate of total adverse events per 100,000 doses was 2.8 in Japan and 15.0 in the United States. In Japan, 17 neurological disorders were reported from April 1996 to October 1998 for a rate of 0.2 per 100,000 doses. In the United States, no serious neurological adverse events temporally associated with JEV were reported from January 1993 to June 1999. Rates for systemic hypersensitivity reactions were 0.8 and 6.3 per 100,000 doses in Japan and the United States, respectively. Passively collected VAERS surveillance data indicate that characteristic hypersensitivity reactions with a delayed onset continue to occur among JEV recipients and that conservative recommendations limiting its use to travelers at high risk of infection with Japanese encephalitis are appropriate.     

A randomised controlled trial with a diphtheria-tetanus-acellular pertussis (dTpa) vaccine in adults

The aim of this assessor-blinded trial was to compare the immunogenicity and reactogenicity of a candidate diphtheria, tetanus toxoids and acellular pertussis vaccine with reduced antigen content for diphtheria and pertussis (dTpa) with a licensed reduced adult-type diphtheria-tetanus vaccine Td (reduced diphtheria content) and with an experimental candidate monovalent acellular pertussis vaccine with reduced antigen content (pa). The dTpa and pa vaccines had identical pertussis antigen content. A total of 299 healthy adults (> or =18 years, mean age: 30.1 years+/-10.7) were randomised into 3 groups to receive a single dose of one of the study vaccines. In all groups, clinically significant reactions (severe) were infrequent (0-6%) and no serious adverse events were reported during the study. The incidence of local and systemic reactions following the administration of dTpa was comparable to the Td vaccine group. Of the total study group, prior to vaccination 52. 3 and 93.2% of the subjects had anti-diphtheria and anti-tetanus antibody levels > or = 0.1 IU/ml, respectively; and 73.1, 98.2 and 74.5% of the subjects were seropositive for pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (PRN) antibodies, respectively. One month after vaccination, a similar percentage of subjects in the dTpa and Td groups had anti-diphtheria (88.4% vs 90. 1%) and anti-tetanus (100% vs 98.9%) antibody levels > or =0.1 IU/ml. Similar anti-FHA (100%) and anti-PRN (98.9%) vaccine response rates were seen in the dTpa and pa groups, while the anti-PT vaccine response rates were 96.8 and 100.0%, respectively. The dTpa vaccine is as well tolerated and immunogenic as the licensed Td vaccine, and additionally, can also boost antibodies against pertussis.     

Diphtheria antitoxin titres six years after basic immunization of adults

Diphtheria antitoxin titres were analysed in 160 adults (median age 59 years, range 34–70), who completed basic vaccination with three doses of 7.5 Lf or 15 Lf of diphtheria toxoid (D) in a previous vaccination trial in 1987, in serum samples drawn 6 years later. The median titre had decreased from 3.2 IU ml⁻¹ in the post vaccination samples to 0.2 IU ml⁻¹ after 6 years in the 15 Lf group and 0.1 IU ml⁻¹ in the 7.5 Lf group. An antitoxin titre of <0.01 IU ml⁻¹, a level usually considered to give no safe protection, was found in 21/73 (29%) individuals, who had received 7.5 Lf and in 12 of 87 (14%), who received 15 Lf diptheria toxoid (P<0.05). In the orginal study, the vaccinees were enrolled as unimmunized based on their own vaccination histories, but many participants had serological evidence of previous immunization. In the subgroup of 48 truly nonimmune participants, i.e. without prevaccination titres and without booster response after the first injection, 46% (32% in the 15 Lf group and 58% in the 7.5 Lf group) had antitoxin levels of <0.01 IU ml⁻¹ 6 years after basic vaccination. Therefore, individuals who have received basic vaccination with three doses of diphtheria toxoid need at least one booster injection 5–10 years later.     

Annual report on surveillance of adverse events following immunisation in Australia, 2006

This report summarises Australian passive surveillance data for adverse events following immunisation (AEFI) reported to the Adverse Drug Reactions Advisory Committee for 2006, and describes reporting trends over the seven-year period 2000 to 2006. There were 779 AEFI records for vaccines administered in 2006. This is an annual AEFI reporting rate of 3.8 per 100,000 population, the lowest since 2002 and a 10% decrease compared with 2005 (869 AEFI records; 4.3 records per 100,000 population). Dose-based AEFI reporting rates in 2006 were 1.9 per 100,000 doses of influenza vaccine for adults aged > or = 18 years, 19.1 per 100,000 doses of pneumococcal polysaccharide vaccine for those aged > or = 65 years and 12.5 per 100,000 doses of scheduled vaccines for children aged < 7 years. Trend data showed transient increases in reporting of AEFI following the introduction of DTPa-IPV combination vaccines in November 2005 for children aged < 7 years. The majority of the 779 AEFI records for 2006 described non-serious events while 11% (n = 85) described AEFIs defined as serious. There was one report of death temporally associated with receipt of dTpa-IPV and typhoid vaccines in an adult with a history of a chronic medical condition. The most frequently reported individual AEFI was injection site reaction in children following a fourth or fifth dose of acellular pertussis-containing vaccine (70 reports per 100,000 doses). The data confirm the low rate of AEFI reported in Australia and demonstrate the ability of the system to detect and investigate signals such as those associated with changes in immunisation programs.     

Surveillance of Vaccine Safety: Comparison of parental reports with routine surveillance and a clinical trial

One way to maintain confidence in vaccination programmes is to improve monitoring of immunisation safety. We studied active parental reporting of adverse events after a booster dose of diphtheria-tetanus toxoid (DT). 7193 children received the vaccine. Questionnaires were submitted by 84.2% of the parents, who reported reactions for 9.2% of the children. Four percent of events were classified as moderate/severe by interviews. Relative risk of redness and swelling reported was 0.24 (95% CI, 0.13–0.42) compared to a clinical trial, while it was 71.0 (44–114) compared to passive surveillance. Active surveillance by parental reports is a useful complement to passive surveillance of childhood immunisations to generate hypotheses for evaluation in controlled studies.     

Safety and immunogenicity of single dose of tetanus–diphtheria (Td) vaccine among non/partially immune children against diphtheria and/or tetanus,Hyderabad, India, 2007

In Hyderabad, India, diphtheria is common among children aged 5–19 years. On account of low coverage of diphtheria vaccine boosters recommended under the universal immunization programme, a large proportion of children were susceptible/partially immune against diphtheria and/or tetanus. We evaluated immunogenicity and safety of single dose of indigenously developed tetanus–diphtheria (Td) vaccine (diphtheria–toxoid ≤5 Lf) among 483 school children from Hyderabad aged 7–17 years and susceptible/partially immune against diphtheria and/or tetanus. Serological testing 6 weeks after vaccination indicated that vaccine was highly immunogenic with >96% sero-protected against both antigens. The immune response observed indicated a booster response to previously acquired immunity. Administration of additional dose of Td vaccine to the older school children and replacing the tetanus toxoid vaccine with Td in the school health programme would considerably reduce diphtheria burden in Hyderabad.     

Epidemiological features of an outbreak of diphtheria and its control with diphtheria toxoid immunization.

An outbreak of diphtheria primarily involving adults occurred in seven townships and one farm in Jiangling county, Hubei, China from September 1988 to January 1989. Of the 103 reported cases, 80 were aged over 16 years, and there were two deaths. One hundred cases were reported in Jingzhou and its surrounding townships, only three occurred in townships distant from Jingzhou. The incidence and case fatality rates were 11.54/100,000 and 1.94% respectively. Twenty-one strains of diphtheria bacillus were isolated from 68 patients. A special immunization programme using adsorbed diphtheria toxoid was conducted 1 month into the outbreak, following which the incidence declined rapidly. Five vaccinees subsequently developed diphtheria.     

The dose-response lines for diphtheria toxoid fractions precipitated at various concentrations of ammonium sulfate

Three diphtheria toxoid preparations, fractionated at various concentrations of ammonium sulfate, having various grades of purity, and showing striking differences in immunizing potency when compared at the same Lf dose, were examined for similarity of the effective constituents in the fractions. No evidence of deviations from parallelism of the dose-response regression lines was observed; thus the statistical criteria for qualitative similarity were satisfactory met.     

Assessment of Tdap Administration Rates from 2009 to 2012 at a Large Urban Nonteaching Hospital

Due to the significant rise in pertussis cases reported in 2012, these authors investigated the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine administration at our institution from 2009 to 2012 to determine if changes in prescribing practices reflected published updates from the Advisory Committee on Immunization Practices (ACIP). A single large, urban, private, non-teaching hospital. Documented Tdap vaccines administered from January 2009 through December 2012 were retrieved using an electronic data pull. The incidence of Tdap vaccine administration was reported as number of events per 1,000 patient visits. This data pull served to provide the longitudinal context to prescribing pattern changes at our facility, which were then compared to ACIP vaccination recommendation changes. Tdap administrations increased from 1,365 vaccinations in 2009 to 3,048 vaccinations in 2012. Tdap vaccine administration increased significantly each successive year from 2009 to 2012 from 23.96 ± 1.25 to 47.15 ± 1.63 vaccines per 1,000 patient visits to the facility. Confidence intervals did not overlap for consecutive years representing statistically significant differences between vaccination rates from year to year. Review of Tdap administrations demonstrates a clear and significant increase over consecutive years from 2009 to 2012. Over this time period there were no institutional initiatives aimed at increasing appropriate Tdap use at our institution. This study suggests a correlation between ACIP vaccination recommendations and provider prescribing of Tdap, although no definitive association can be made.     

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 20–49 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.