Diphtheria toxoid vaccine effectiveness: A case-control study in Russia

Prior to the completion of this and other studies, low effectiveness of diphtheria toxoid-containing vaccine was suspected to be a major contributing factor to the diphtheria epidemic that began in the Russian Federation in 1990. A vaccine effectiveness study was done in Moscow by enrolling physician-diagnosed cases and 10 control subjects per case. Controls were matched to cases by age (+/-3 months) and clinic registration. Vaccination history was abstracted from a standardized form for case-patients and from clinic vaccination records for control subjects. Two hundred seventeen case-patients and 2169 matched controls were included in the study. Most controls (92%) had received three or more doses of a diphtheria toxoid vaccine, compared with 72% of case-patients. The vaccine effectiveness for three or more doses was 97% (95% confidence interval: 94.3-98.4). Low vaccine effectiveness was not a contributing factor to the diphtheria epidemic in the Russian Federation. To control and prevent diphtheria epidemics, it is necessary to achieve and maintain high vaccination coverage with three or more doses of diphtheria toxoid among adults and children.     

An HIV type 1 subtype A strain of low genetic diversity continues to spread among injecting drug users in Russia: study of the new local outbreaks in Moscow and Irkutsk

An explosive epidemic of human immunodeficiency virus type 1 (HIV-1) has been documented among injecting drug users (IDUs) in the former Soviet Union republics. In 1999, the two largest local IDU outbreaks of HIV-1 infection in the Russian Federation were registered in the Moscow and Irkutsk regions, where 13,004 HIV-1 cases were identified (44% of the total number of HIV-1 infections in Russia in 1999). To study the prevailing genetic variants and to estimate the genetic diversity of HIV-1 in these outbreaks, 60 samples from Moscow (n = 36) and from Irkutsk (n = 24) were analyzed using the gag/env heteroduplex mobility assay, and the env gp120 V3 encoding regions obtained from 23 individuals were sequenced. Both virus populations were highly homogeneous (the means of pairwise nucleotide distance were 1.75 +/- 0.83 and 2.35 +/- 1.59 for Irkutsk and Moscow, respectively), and similar to the subtype A viruses obtained earlier from IDUs in the former Soviet Union. The subtype A HIV-1 variant thus dominates in the largest HIV-1 outbreaks among IDUs in the Russian Federation.     

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.     

HIV seroprevalence among new TB patients in the civilian and prisoner populations of Donetsk Oblast, Ukraine

After the Russian Federation, Ukraine is the country of the Former Soviet Union experiencing the greatest epidemics of tuberculosis (TB) and HIV, although complete official data are not available. This study investigates the prevalence of HIV among new TB patients in the civilian and penitentiary populations of Donetsk Oblast. A cross-sectional survey was undertaken of 1507 new patients with TB (1351 civilians, 156 prisoners) between January and June 2006. The prevalence of HIV among patients with TB was 15.5% (95% confidence interval 13.7-17.6) and 23.7% (95% CI 17.3-31.2) in the civilian and penitentiary sectors, respectively. Reported injecting drug use was the strongest independent predictor for HIV infection, followed by young age (25-44 y). Being prisoners was also found a significant independent predictor for HIV infection (OR: 1.5, 95% CI 1.1-2.1). In conclusion, the prevalence of HIV in the TB population is the highest ever reported in Ukraine, almost 2 times higher than the World Health Organization estimates for 2005 (7.9%), and 3 percentage points higher than the official data reported. These findings call for urgent measures to control HIV and, consequently, HIV-related TB.     

Survival bias in observational studies of the impact of routine immunizations on childhood survival

OBJECTIVES: In situations with vaccination coverage high enough to control pertussis, observational studies have reported divergent effects of diphtheria-tetanus-pertussis (DTP) vaccination on childhood survival. We examined whether this could be because of methodological differences. METHODS: Some studies of the impact of DTP updated information on vaccination retrospectively (retrospective updating approach) while others kept vaccination status fixed for the time between follow-up visits (landmark approach). First, we conducted simulations with these approaches to investigate the impact of different mortality levels, vaccination incidence rates, intervals between data collection visits, and the proportion of children whose vaccination card had not been seen after death. Second, we re-analysed data from Guinea-Bissau using the retrospective updating approach. RESULTS: In simulations, the retrospective updating approach produced rate ratio (vaccinated/unvaccinated) estimates biased towards zero because of a differential misclassification which created survival bias as risk-free observation time was allocated to the vaccinated group. The landmark approach produced rate ratio estimates biased towards one. Biases increased with interval between data collection visits and incidence of vaccination, but were unaffected by the underlying mortality level. Survival bias increased with the proportion of dead children whose vaccination status could not be updated. The re-analysis of data from Guinea-Bissau changed the estimated impact of DTP from an 84% higher mortality using the landmark approach to a 37% lower mortality using the retrospective updating approach. CONCLUSIONS: The apparent contradiction between DTP studies could be because of methodological differences. To assess child survival associated with routine vaccinations, studies minimizing the effect of biases are warranted.     

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.     

Sexually transmitted infections in Estonia--syndromic management of urethritis in a European country?

Sexually transmitted infections (STIs) are considered a major public health problem, globally. In particular, increasing STI rates have been documented throughout eastern Europe and central Asia. The Russian Federation and adjacent countries have, traditionally, managed STIs on an aetiological basis. This approach is expensive in terms of laboratory costs and it may lead to delayed diagnosis and treatment. To overcome the limitations of the aetiological management of STIs, the World Health Organization (WHO) has placed an increased emphasis on integrated care using syndromic management at the primary care level, especially in developing countries. This article reviews the current aetiology of STIs in Estonia, an eastern European country bordering the Baltic Sea and formerly a part of the Soviet Union, with the aim of defining whether infection with Trichomonas vaginalis is common enough to include its management in a syndromic management protocol. The use of syndromic management, in general, is also discussed.     

Ukraine, 1992: first assessment of diphtheria vaccine effectiveness during the recent resurgence of diphtheria in the Former Soviet Union

A case-control study in Ukraine provided the first data on the field effectiveness of Russian-produced vaccine during the 1990 diphtheria resurgence in the former Soviet Union. For each of 262 diphtheria cases <15 years of age who were reported from January through October 1992, 2 controls, matched by age and clinic, were selected. The effectiveness of three doses of diphtheria vaccine was 98.2% (95% confidence interval: 90.3-99.9). Among controls, 84% had received three or more vaccinations by 2 years of age. These results suggest that the following five hypothesized causes of the outbreak appeared unlikely: appearance of a new "mutant" diphtheria strain, low potency of the Russian-produced diphtheria vaccine, inadequate cold chain, poor host immunogenicity due to radiation exposure from Chernobyl, and low routine childhood vaccination coverage. It is concluded that initial priority for scarce resources for controlling this outbreak should be placed on vaccination of persons susceptible to diphtheria (e.g., adults) rather than revaccination of children.     

BCG vaccination in the world

BCG vaccination programme and BCG vaccination coverage in the world were summarized mainly based on the published informations from official organizations, such as World Health Organization (WHO), International Union Against Tuberculosis and Lung Disease (IUATLD) and Centers for Disease Control and Prevention (CDC). From this review, we can see how widely BCG has been used for the prevention of tuberculosis in the world. In most of the developing countries, especially in Africa, the Americas, and Pacific Region, BCG vaccination is carried out to newborn babies soon after birth by intradermal injection according to the recommendations from WHO, but some of the developing countries in Asia and Europe have their own modified BCG vaccination programmes. In economically developed countries, BCG vaccination programme has been established according to the tuberculosis status of each countries. Some countries have general vaccination policy, and other countries have selected vaccination policy, but there is no country where BCG vaccination is not carried out at all. Among G8 contries, as representatives of the economically developed countries, Japan, United Kingdom, France and Russian Federation have BCG general vaccination policy for the specified age group. In these 4 countries revaccination (s) of BCG are still carried out. In Germany, some provinces have general vaccination policy and some others have selected vaccination policy. In the United States of America, BCG vaccination is recommended to selected high risk infants and health care workers by CDC. There are many debates as for the efficacy and safety of BCG vaccination, and the development of new vaccine better than BCG has been actively discussed and some encouraging results in animal models have been reported from several laboratories. But, there is almost no possibility to be able to use a new vaccine in the routine practice within a couple of years. From the practical point of view, therefore, the operational researches for the better and more appropriate usage of BCG are equally important and more practical than the researches for the development of new vaccines.     

从第三次流调结果探讨我国卡介苗接种工作

通过对全国第三次结核病流行病学调查资料的再次分析来评价我国卡介苗接种工作。分析结果表明１９９０年调查时０～４岁儿童的卡介苗接种率为６５．０％，低于以往报道。０～４岁有卡介苗接种史儿童的结素阳性率仅为２６．３％，城市的阳性率最高也仅５５．８％，表明接种质量不高，必须找到原因而迅速改进。我国目前卡介苗接种的保护效果对０～４岁儿童是明显的，但对５～９岁儿童即不明显，因此必须进一步调查研究卡介苗复种的必要性。     

Measles epidemiology and elimination strategies in Turkey

In Turkey, 15,000-30,000 measles cases have been reported annually since the 1990s. Epidemics occur every 3-4 years, and >/=90% of cases are <15 years old. The high incidence is due to inadequate vaccination coverage (nationally 84% in 2001) and immunity provided by the first dose of vaccine administered at age 9 months. The second dose, which has been recommended for first grade students since 1998, has been insufficient to provide the herd immunity necessary to control measles. The Ministry of Health launched a comprehensive program for 2002-2010 targeting measles elimination. This plan calls for a national vaccination campaign among all children aged 9 months to 14 years and routine two-dose vaccination coverage will be increased to >/=95% or follow-up campaigns will be conducted in areas not achieving high coverage levels. Also, all military recruits in 2002-2009 will be vaccinated and case-based, laboratory supported surveillance will be initiated.     

Non‐specific effects of diphtheria‐tetanus‐pertussis and measles vaccinations? An analysis of surveillance data from Navrongo,Ghana

Objectives Studies from low‐income countries have suggested that routine vaccinations may have non‐specific effects on child mortality; measles vaccine (MV) is associated with lower mortality and diphtheria‐tetanus‐pertussis (DTP) with relatively higher mortality. We used data from Navrongo, Ghana, to examine the impact of vaccinations on child mortality. Methods Vaccination status was assessed at the initiation of a trial of vitamin A supplementation and after 12 and 24 months of follow‐up. Within the placebo group, we compared the mortality over the first 4 months and the full 2 years of follow‐up for different vaccination status groups with different likelihoods of additional vaccinations during follow‐up. The frequency of additional vaccinations was assessed among children whose vaccination card was seen at 12 and 24 months of follow‐up. Results Among children with a vaccination card, more than 75% received missing DTP or MV during the first 12 months of follow‐up, whereas only 25% received these vaccines among children with no vaccination card at enrolment. Children without a card at enrolment had a significant threefold higher mortality over the 2‐year follow‐up period than those fully vaccinated. The small group of children with DTP3‐4 but no MV at enrolment had lower mortality than children without a card and had the same mortality as fully vaccinated children. In contrast, children with 1–2 DTP doses but no MV had a higher mortality during the first 4 months than children without a card [MRR = 1.65 (0.95, 2.87)]; compared with the fully vaccinated children, they had significantly higher mortality after 4 months [MRR = 2.38 (1.07, 5.30)] and after 2 years [MRR = 2.41 (1.41, 4.15)]. Children with 0–2 DTP doses at enrolment had higher mortality after 4 months (MRR = 1.67 (0.82, 3.43) and after 2 years [MRR = 1.85 (1.16, 2.95)] than children who had all three doses of DTP at enrolment. Conclusions As hypothesised, DTP vaccination was associated with higher child mortality than measles vaccination. To optimise vaccination policies, routine vaccinations need to be evaluated in randomised trials measuring the impact on survival.     

Measles antibody prevalence rates among young adults in Israel

BACKGROUND: In Israel, vaccination coverage against measles is high, yet seroepidemiologic studies have shown that more than 15% of the 18-year-old population were unprotected against the disease. A 2-dose program of vaccination against measles, mumps, and rubella at the ages of 1 and 6 years was begun in 1990, supplemented by a measles catch-up plan for all 13-year-olds. The aim of this study was to assess the prevalence of antimeasles antibodies at induction to the Israel Defense Forces in the first doubly vaccinated birth-cohort. METHODS: In 1996, serum samples of 540 recruits, 339 men and 201 women, were tested for measles virus antibody. Findings were compared with surveys conducted in 1987 and 1990. RESULTS: Measles antibodies were present in 95.6% (95% CI, 93.5-97.1) of the recruits. Antibody prevalence was higher in women than in men (99% vs 93.5%; P =.0096). A slightly lower seroprevalence was found in recruits born in the former Soviet Union. The results were substantially higher than the seroprevalence rates found in 1987 (73.3%) and 1990 (84.6%). CONCLUSIONS: The high prevalence of antimeasles antibodies in the young adult population in Israel points to the success of the double-vaccination policy in promoting immunity against the disease.     

DTP vaccination and child survival in observational studies with incomplete vaccination data

BACKGROUND: Observational studies of diphtheria-tetanus-pertussis (DTP) vaccine from longitudinal study sites have reported divergent effects on child survival, ranging from 10-fold reduction to threefold increased mortality. None of these studies had complete information on DTP vaccinations from both survivors and children who died. We reviewed the data analysis methodology to assess whether methodological differences could explain the divergent results. DESIGN: Studies have used case-control design, survival analysis with interval-fixed vaccination status (landmark approach), and survival analysis with retrospective updating of vaccination status. RESULTS: Seven studies using a case-control design or a landmark approach found a negative effect of DTP on child survival. Eight of nine survival analyses with retrospective updating of vaccination status reported a beneficial effect. This beneficial effect of DTP increased with the length of the interval between data collection visits. Studies with long interval between visits had very high mortality rates among unvaccinated children, low mortality rate ratios for vaccinated compared with unvaccinated children, and strongly beneficial estimates of DTP. CONCLUSION: The divergent results in observational studies of the impact of DTP on child survival are partly because of methodological differences. To assess the impact on mortality of routine vaccinations, observational study designs which minimize the effect of bias are warranted. Randomized trials should be considered.     

Diphtheria in Estonia, 1991-1996

Clinical diphtheria reappeared in Estonia in 1991. Between 1991 and 1996, 61 cases and 5 deaths occurred; 19 cases were among children 5-9 years of age, and 11 were among persons 40-49 years of age. From 1993-1995, vaccine supplies donated by Finland were used in vaccination programs. In 1995, the International Federation of Red Cross and Red Crescent Societies and the Estonian Red Cross launched a mass vaccination campaign targeting the adult population. By the end of 1997, it was estimated that 46% of adults had received at least one dose of vaccine. Although the vaccination campaigns did not target the pediatric population, vaccination coverage in school-aged children remained high due to continuing routine vaccination programs. The reappearance and epidemic of clinical diphtheria cases and the mass vaccination campaign efforts demonstrated that preventive measures are important and must be maintained in order to keep diphtheria under control.     

Diphtheria in the WHO European Region, 2010 to 2019

BackgroundDiphtheria is uncommon in the World Health Organization (WHO) European Region. Nevertheless, sporadic cases, sometimes fatal, continue to be reported.AimTo report on diphtheria cases and coverage with first and third doses of diphtheria, tetanus and pertussis vaccines (DTP1 and DTP3, respectively) for 2010–19 in the Region with a focus on 2019.MethodsData on diphtheria cases were obtained from WHO/United Nations International Children''s Emergency Fund (UNICEF) Joint Reporting Forms submitted annually by the Region’s Member States. WHO/UNICEF Estimates of National Immunization Coverage for DTP1 and DTP3 were summarised for 2010–19. For 2019, we analysed data on age, and vaccination status and present data by country on DTP1 and DTP3 coverage and the percentage of districts with ≥ 90% and < 80% DTP3 coverage.ResultsFor 2010–19, 451 diphtheria cases were reported in the Region. DTP1 and DTP3 coverage was 92–96% and 95–97%, respectively. For 2019, 52 cases were reported by 11 of 48 countries that submitted reports (including zero reporting). Thirty-nine countries submitted data on percentage of their districts with ≥ 90% and < 80% DTP3 coverage; 26 had ≥ 90% districts with ≥ 90% coverage while 11 had 1–40% districts with < 80% coverage.ConclusionLong-standing high DTP3 coverage at Regional level probably explains the relatively few diphtheria cases reported in the Region. Suboptimal surveillance systems and inadequate laboratory diagnostic capacity may also be contributing factors. Still, the observed cases are of concern. Attaining high DTP3 coverage in all districts and implementing recommended booster doses are necessary to control diphtheria and prevent outbreaks.     

Progress toward measles elimination in the Russian Federation, 2003-2009

Successful implementation of the Russian Federation's national measles elimination program has been ensured by high vaccine coverage (>95%) of the target population (with 2 doses of measles-containing vaccine), case-based laboratory investigation of measles, and active surveillance of measles cases among patients with rashes and/or fever. As a result, the incidence of measles has decreased to <1 case per 1,000,000 population (2007-2009); no circulation of D6 genotype, which was endemic in the Russian Federation, has been observed since the second half of 2007; and the proportion of imported measles cases of different genotypes increased to 19.8% in 2007 from 1% in 2003. To confirm successful elimination of indigenous measles, a documentation system was initiated in the Russian Federation.     

Mandatory influenza vaccination of health care workers: A first-year success implementation by a community health care system

Poudre Valley Health System is a private, not-for-profit health care system of more than 5,300 employees. Poudre Valley Health System increased its influenza vaccination coverage rate among health care workers from 68% in 2009 to 95.5% in 2010 after implementing a mandatory influenza vaccination program.     

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.