Diphtheria.

Diphtheria is a contagious upper respiratory illness that was a major cause of childhood mortality in the prevaccine era. In the early twentieth century, an effective toxoid vaccine was developed. Implementation of childhood vaccination virtually eliminated diphtheria from developed countries after the Second World War and implementation of the Expanded Program on Immunization in developing countries led to rapid declines in diphtheria globally in the 1980s. However, in the 1990s, a massive epidemic of diphtheria spread throughout the countries of the former Soviet Union. Unlike the prevaccine era, most cases of severe disease and deaths were reported among adults. Multiple factors contributed to the epidemic, including increased susceptibility among both adults and children; suboptimal socioeconomic conditions; high population movement; and delay in implementing appropriate control measures. Mass immunization was the key element in the epidemic control strategy developed and implemented in a well-coordinated response by an international public health coalition. This strategy focused on rapidly raising population immunity of both adults and children; the immunization of more than 140,000,000 adults and adolescents and millions of children successfully controlled the epidemic. While improved coverage of children in developing countries with diphtheria toxoid has led to progressive decreases in diphtheria; eradication is unlikely in the foreseeable future and gaps in immunity among adult population exist or are developing in many other countries. Routine childhood immunization with diphtheria toxoid is the key to controlling diphtheria while the role of routine adult reimmunization is less established; mass immunization will remain an important control measure for widespread diphtheria outbreaks.

Diphtheria in Thailand in the 1990s.

Diphtheria remains endemic in developing countries, but there are limited published data on the subject. Thailand's diphtheria surveillance data are relatively complete and may give a fuller picture of the situation in similar countries. After routine immunization began in 1977, the incidence of reported diphtheria decreased by >98% to <0.1 case per 100,000 persons annually in the 1990s. Despite infant immunization coverage of >90%, diphtheria cases were reported throughout the 1990s, primarily among children <15 years old. Outbreaks were linked to both persistent endemic circulation and to importation of toxigenic Corynebacterium diphtheriae; suboptimal immunization coverage in minority and disadvantaged groups contributed. A serologic survey found 25% of adults 20-39 years old and 14% of adolescents 10-19 years old lacked immunity to diphtheria; these data indicate an accumulation of susceptible adolescents and adults. Diphtheria remains a threat in Thailand; improvements in diphtheria control will depend on improving childhood immunization coverage in Thailand and the surrounding region.

Diphtheria surveillance and control in the Former Soviet Union and the Newly Independent States.

The Newly Independent States (NIS) inherited a common approach to diphtheria control from the Soviet Union and maintained a centralized system of surveillance and control managed by Soviet-trained epidemiologists with a shared professional culture. This system had controlled a diphtheria resurgence in the 1980s. In response to the epidemic of the 1990s, NIS health authorities responded with a set of control measures based on the Soviet-era experience. These measures included intensified childhood vaccination, aggressive case investigation, widespread diphtheria screening in institutions, and vaccination of adults in high-risk occupation groups. These measures proved insufficient due to high levels of susceptibility among adults, excessive contraindications to childhood vaccination, and insufficient resources in many countries. After these initial delays in implementing effective measures in some countries, most of the NIS health authorities rapidly and successfully implemented mass immunization of the population against diphtheria once the strategy was adopted and sufficient vaccine was available.

Diphtheria in the Russian Federation in the 1990s.

A resurgence of diphtheria spread throughout the Russian Federation in the early 1990s; diphtheria had been well controlled, but circulation of toxigenic strains of Corynebacterium diphtheriae had persisted since the implementation of universal childhood vaccination in the late 1950s. More than 115,000 cases and 3,000 deaths were reported from 1990 to 1997, and, in contrast to the situation in the prevaccine era, most of the cases and deaths occurred among adults. Contributing factors included the accumulation of susceptible individuals among both adults and children and probably the introduction of new strains of C. diphtheriae. Vaccine quality, vaccine supply, or access to vaccine providers did not significantly contribute to the epidemic. Mass vaccination of adults and improved childhood immunization controlled the epidemic. High levels of population immunity, especially among children, will be needed to prevent and control similar outbreaks in the future.

Epidemic diphtheria in Belarus, 1992-1997.

In 1990, epidemic diphtheria reemerged in Russia and spread to Belarus in 1992, when 66 cases were reported. Diphtheria cases doubled each year in 1993 and 1994 and peaked in 1995, when 322 cases were reported. Intensified routine immunization of young children and mass vaccination of older children and selected groups of adults were conducted in 1995 and were followed by mass vaccination campaigns targeting all adults in 1996. By the end of 1996, full immunization of >95% of children and coverage of>87% of adults with >/=1 dose resulted in a rapid decline in diphtheria cases. In 1998, only 36 cases of diphtheria were reported. More than 70% of the 965 cases and 26 fatalities reported during 1990-1998 occurred among persons >14 years of age. High levels of immunity among the entire population are needed for rapid control of diphtheria epidemics in the vaccine era.

Epidemic diphtheria in the 1990s: Azerbaijan.

The diphtheria epidemic in the former Soviet Union reached Azerbaijan in 1991, when 66 cases of diphtheria were reported, a number that compared with 4 cases in 1990. From 1990-1996, 2182 cases of diphtheria and 286 diphtheria fatalities (case fatality rate: 13.1%) were reported in Azerbaijan, primarily among persons 5-39 years of age. Almost 45% of cases and 61% of deaths occurred among children 5-14 years of age. The high burden of severe disease among children and young adults suggested a different pattern of preexisting immunity against diphtheria in the Azerbaijani population than was observed in the concurrent diphtheria epidemic in Russia. Because resources were limited in Azerbaijan, mass immunization of the population was carried out in stages, focusing initially on school-aged children. Mass immunization campaigns targeting children were moderately successful in stabilizing the epidemic; mass immunization campaigns targeting both adults and children were eventually needed to fully stop the epidemic.

Diphtheria epidemic in the Republic of Uzbekistan, 1993-1996.

The Republic of Uzbekistan, like the other Newly Independent States in the 1990s, experienced epidemic diphtheria during the 1990s. The outbreak in Uzbekistan began in 1993 in southern regions that bordered areas of Tajikistan that were experiencing a very intense diphtheria epidemic. However, the Uzbek epidemic rapidly spread and threatened to involve the entire country. From 1993-1996, 1169 cases of diphtheria were reported, compared with 58 in 1990-1992. Unvaccinated or only partially vaccinated cases were more likely to have clinically severe forms of diphtheria than those who were fully vaccinated. Strong epidemiologic links with the Tajik diphtheria epidemic and the predominance of mitis biotype strains of Corynebacterium diphtheriae in Uzbekistan make it likely that the Uzbek outbreak arose independently of the predominantly biotype gravis epidemic that began in Russia. The epidemic appeared to be due to low population immunity and the large-scale reintroduction of toxigenic strains of C. diphtheriae. Several mass vaccination campaigns and general enhancement of routine immunization procedures led to control of the epidemic in 1996.

Increased protections during a measles outbreak of children previously vaccinated with a second dose of measles-mumps-rubella vaccine.

BACKGROUND: In 1989 a second dose of measles vaccine was recommended for US children to prevent school outbreaks of measles. Coverage of school age children with a second dose remains incomplete, and data on the effectiveness of this recommendation are limited. We investigated a measles outbreak in Mesa County, CO, in December, 1994, and evaluated the efficacy of preoutbreak immunizations at an elementary school (School A) where many students had received two doses. METHODS: All reported suspected cases of measles were investigated; cases that met a clinical case definition were tested by a measles IgM antibody assay. A confirmed case required laboratory confirmation or had to meet the clinical case definition and be epidemiologically linked to a confirmed case. Vaccination records of students at School A were reviewed. The effectiveness of one and two doses of measles vaccine was estimated using logistic regression. RESULTS: Sixty-two confirmed cases were reported, including 17 at School A. At School A the attack rate in unvaccinated children (7 of 16, 44%) was higher than in those with 1 dose (10 of 320, 3%) or 2 doses (0 of 289, 0%). Estimated vaccine effectiveness was 92% for 1 dose and 100% for 2 doses. Two doses were better than one dose in decreasing the likelihood of acquiring measles (P = 0.003). CONCLUSIONS: The lower attack rate among two dose recipients provides evidence that a two dose strategy can help prevent measles in schools. Administering the second dose at elementary school entry can help prevent the persistence of susceptible cohorts of children and is likely to be important in sustaining elimination of indigenous transmission of measles in the United States.

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.

Diphtheria in the former Soviet Union: reemergence of a pandemic disease.

The massive reemergence of diphtheria in the Newly Independent States of the former Soviet Union marked the first large-scale diphtheria epidemic in industrialized countries in 3 decades. Factors contributing to the epidemic included a large population of susceptible adults; decreased childhood immunization, which compromised what had been a well-established childhood vaccination program; suboptimal socioeconomic conditions; and high population movement. The role of a change in the predominant circulating strains of Corynebacterium diphtheriae in this epidemic remains uncertain. Massive, well-coordinated international assistance and unprecedented efforts to vaccinate adults were needed to control the epidemic.

Trends in importation of measles to the United States, 1986-1994.

OBJECTIVES: To describe patterns among imported measles cases to the United States. DESIGN: Descriptive analysis of national case-based surveillance data on measles cases. SETTING: United States in the period 1986 through 1994. PATIENTS: All reported confirmed cases of measles. MAIN OUTCOME MEASURES: Demographic variables, immunization history, country of exposure, and reporting state. RESULTS: The number of reported imported cases of measles to the United States has dropped from an average of 99 cases annually in 1986 through 1988 and 190 cases in 1989 through 1991 to 61 cases in 1992 through 1994. Since 1990, the number of imported cases originating in Latin America declined by 98%, despite continued increase in the number of travelers to this region; cases from other regions remained relatively constant. This decrease paralleled the rapid decrease in measles incidence in the Western Hemisphere associated with national measles elimination programs. Most imported cases occurred among children, although 22% of cases occurred among young adults. Rates of measles cases per 1 million travelers are higher among non-US citizens than among US citizens. CONCLUSIONS: The sharp decline in importations into the United States from Latin America since 1991 provides evidence of the success of measles control efforts undertaken there. The decrease in imported cases has been associated with a decline in total measles cases in the United States. Sustained elimination of measles in the United States will require improved measles control in other countries in addition to a high level of population immunity.

Evidence against infection with hantaviruses among forest and park workers in the southwestern United States.

To determine if individuals with extensive exposure to rodent habitats were infected with Sin Nombre hantavirus (SNV), we evaluated forest and park service personnel from the region of endemicity in the southwestern United States. Information about work and recreational activities, including exposure to rodents and a history of recent illnesses, was obtained via a standardized questionnaire. Serum specimens were also collected. Of 140 participating workers, 84 (60%) were primarily engaged in outdoor work activities, 14 (10%) were office-based supervisors, and 42 (30%) were office workers. Of the 140 employees, 89 (64%) reported repeated exposures to rodents, rodent nests, and/or rodent droppings; 22 (16%) reported trapping or handling wild rodents. Hantavirus antibodies were not detected in any park employee. These data suggest that transmission of SNV is a rare event even among persons in the southwestern United States who have a high level of exposure to this virus. Although park employees and visitors in this region are at low risk of infection with SNV, these persons should continue to use recommended measures for risk reduction.

Evidence against person-to-person transmission of hantavirus to health care workers.

Unusual, primarily pulmonary, manifestations of hantaviral illness occurring in the southwestern United States raised the possibility of person-to-person transmission of a recently recognized hantavirus, Sin Nombre virus. To determine whether such transmission had occurred among health care workers (HCWs) exposed to patients with confirmed hantavirus pulmonary syndrome, we evaluated HCWs who had cared for patients with hantavirus pulmonary syndrome or who had processed specimens from these patients. Information about exposure to these patients and about recent illnesses was obtained via a standardized questionnaire. Serum specimens were tested for IgM and IgG antibodies to hantaviruses with use of ELISAs. Of the 396 HCWs, 266 (67%) reported that they had been exposed to patients with hantavirus pulmonary syndrome or to their body fluids or that they had processed laboratory specimens from these patients. Although 108 (27%) of the HCWs reported fever, myalgias, or respiratory illnesses during the 3 months before the serum specimens were obtained, hantavirus antibodies were not detected in any HCW. These data suggest that person-to-person transmission of Sin Nombre virus is unlikely to occur in health care settings.

Evidence for sexual and mother-to-child transmission of human T lymphotropic virus type II among Guaymi Indians, Panama.

Guaymi Indians, a non-intravenous drug-using population in which human T cell lymphotropic virus type II (HTLV-II) is endemic, were studied in Changuinola, Panama, to identify the prevalence and modes of transmission of HTLV-II. A population-based survey showed that 352 (9.5%) of the 3686 participants were seropositive for HTLV-II. Infection rates were the same for male and female subjects and increased significantly with age, beginning in young adulthood. HTLV-II infection status was highly concordant among spouses (P < .001) and between mother and child; of children aged 1-10 years, 36 of 219 born to seropositive mothers were seropositive compared with 3 of 997 born to seronegative mothers (P < .001). The strong associations of HTLV-II infection with age and with an infected spouse in adults and of infection in children with infection in their mothers strongly suggest sexual and mother-to-child transmission of HTLV-II in this population.