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The experience of stamping out the Diphtheria epidemic in the Republic of Moldova and optimization of Diphtheria infection surveillance

Author: Melnic Anatolie
Degree:doctor of medicine
Speciality: 14.00.30 - Epidemiology
Scientific adviser: Valeriu Chicu
doctor, associate professor (docent), Nicolae Testemitanu State University of Medicine and Pharmacy of the Republic of Moldova
Scientific consultant: Victoria Bucov
doctor habilitat, professor
Scientific council:


The thesis was presented on the 26 August, 2009
Approved by NCAA on the 5 November, 2009


Adobe PDF document0.58 Mb / in romanian


diphtheria, C.diphtheriae, toxigenic, vaccination coverage, immune stratum, epidemiological surveillance


The work presents the results of a detailed analysis of the epidemic situation concerning diphtheria in the Republic of Moldova for the period of 1991-2008. As a result of the study of particularities of the epidemic process of diphtheria, it was determined, that 20 years of epidemic wellbeing (1971-1990 with approximately 3 cases of diphtheria reported annually) were followed, in 1994-1996, on the background of relatively high coverage of children with vaccination against diphtheria (85-90%) and 7 years of immunization of adults, by an epidemic of diphtheria infection. The highest indices of morbidity were registered in 1994-1995 – 8.64%000 and 9.61%000, and carrier state of toxigenic C.diphtheriae comprising 14.18%000 and 11.68%000, with 82.4% of administrative territory of the country being affected.

Specific characteristics of diphtheria in the period of its epidemic spreading were as follows: high rate of adult patients (47.2%) with maintenance of the maximum intensity of children affected (40.3%000), almost equal incidence in rural and urban areas (21.3%000 and 19.5%000 correspondingly). Pharyngeal diphtheria was registered as a dominant clinical form – 97% of cases. Mortality rate was 5.3%.

From the total number of patients, non-vaccinated and persons with unknown vaccination history comprised 20% (12.2% in age group of 5-14 years, 35% among 20-29 years old and 33% among patients older than 50 years). Incidence among non-vaccinated persons of age group 0-4 years – 54.2%000; 389.4%000 in age group of 5-10 years, 241.6%000 in age group of 11-14 years, 116.8%000 in age group of 15-17 years and 7.5%000 among adults, was correspondingly 9; 29; 16; 20 and 3 times higher than incidence in the same age groups of vaccinated persons.

During the epidemic period and in the first year following it (1994-1997), strains C.diphtheriae gravis dominated – 78.3% from total number and 95.2% from toxigenic strains. Epidemic spread of diphtheria infection was accompanied by dynamic change of phage picture of C.diphtheriae. At the beginning of the epidemic, (4th quarter of the year 1994 and 1st quarter of 1995), their dominant strains were non-lysed by phags, and strains of phagovariant VI, and in 2-3 quarter of the year 1995 - strains of phagovariant XIV. In general, phagotyping of 494 strains of C.diphtheriae, isolated in 31 out of 44 administrative territories of the country, shows that phagovariant VI comprised 26.9%, phagovariant XIV – 25.7% and 47.0% of strains were non-lysed by phages in relation to 55 phages from collection of Cantacuzino Institute, Bucharest, Romania.

During molecular genetic investigation, conducted in the Cantacuzino Institute, Romania and Pasteur Institute, France, strain identity was determined for strains (ribotypes С1 and С5, electric field profile Р1, RAPD-A test) that circulated in the Republic of Moldova and in the Russian Federation, and absence of their circulation on the territory of Romania, not involved in the diphtheria epidemic.

The main causes for the diphtheria epidemic development were as follows: decline in vaccination coverage of children due to unfounded medical contraindications and refusals to vaccinate, insufficient supply of vaccine, wide use of Td toxoid for primary vaccination of children, insufficient efficiency of booster scheme with a single Td dose for adults against diphtheria, in the conditions of mass impotr of infection sources from countries earlier affected by diphtheria epidemic.

Mass supplementary immunization campaign of 1995 served as a decisive factor for stopping of spread of diphtheria infection. During the first years following the epidemic (1997- 2000) incidence has decreased by 11.5 times.

Mass immunization campaign and following routine immunization against diphtheria with DTP vaccine (2; 4; 6 and 22-24 months), DT at age of 7 and Td at 15; 20; 25; 30; 35; 40; 50 and 60 years, with coverage of over 95% of children and 80-85% of adults, gave positive epidemiological effect, expressed in eliminating morbidity and lack of cases of diphtheria carrier in the country during 2003-2008.

For the purpose of maintaining of epidemic wellbeing regarding diphtheria, a set of proposals was developed for optimization of the diphtheria epidemiological surveillance and control.