VN Antipov, VL Semiotrochev, NB Tselikova, GJ Tseneva, NN Kurova.
Western Interdistrict State Sanitary-Epidemiological Surveillance Centre and Pasteur Institute, St. Petersburg, Russia
Obligatory pertussis vaccination of all children beginning in 1959 resulted in a dramatic decrease in the incidence of the disease. From an incidence of 710 per 100,000 in St. Petersburg during 1958, the incidence decreased to a low of 18.8 per 100,000 in 1973. Mortality resulting form pertussis was almost eliminated.
However, during the early 1990s vaccination coverage decreased and a ride in pertussis was again noted. This change in policy resulted from medical contraindications for vaccination lacking a sound scientific basis. Large cities such as St. Petersburg suffered the most. The peak of this new epidemic was seen in 1994, when the incidence was 32.6 and 143.2 per 100,000 population in the Russian Federation and St. Petersburg, respectively. In the following years, measures to increase the vaccination coverage among children under three years of age were implemented. Vaccination coverage in St. Petersburg rose to 84.6 % in 1999, as compared with 35.7 % in 1992. As a result, the incidence of the disease decreased, but has remained stable at a level 3 to 4 times greater than the mean incidence level in the Russian Federation. The clinical manifestations of the disease among vaccinated and among non-vaccinated children in St. Petersburg do not differ from those observed in other places .
In many countries with high vaccination coverage against pertussis, an increase in incidence in the recent years has been observed [2,3]. Studies of Bordetella pertussis strains from different periods throughout the vaccination era has revealed various genetic mutations driven by vaccination in circulating strains [4-7].
The aim of this study was to determine the epidemiological and microbiological patterns of pertussis infection in the Krasnoselsky district of St. Petersburg.
Materials and methods.
Pertussis and acute respiratory infection incidence data registered for the territory of Krasnoselsky district in 1986-2001 were used in this study. During this period there were no significant changes in the patient registration system at the outpatient clinics. The number of inhabitants was based on the population registration at the outpatient clinics in the district. The mean population for the follow-up period was 309 641 persons.
Epidemiological analysis was performed using the available statistical data on pertussis incidence in the Krasnoselsky district (population 310,000) for the period 1986 to 2001. Bacteriological investigation of 3,348 pertussis patients was conducted using standard methods (serological and bacteriological investigations for pertussis and parapertussis). We used a bacteriological method including culture on casein-coal agar and serotyping of cultures with mono-factor Russian-produced serums. Genetic studies of Bordetella pertussis strains were conducted using pulsed-field gel electrophoresis (PFGE) and sequencing .
The incidence rates per 100,000 and 1,000 population were calculated. In addition, cases among persons vaccinated against pertussis were determined. Data on the number of vaccinated against pertussis and the number of B. pertussis isolates of different serotypes from infected persons are stated in percent. These data were used as the basis for dynamic rows formation which were used to analyze the tendencies of distribution. A graphical display method was employed to show the materials. Grouping of statistical data was used to calculate derivative values: Pearson correlation coefficient (r) and its minimal error (mr), which allow an estimate of the reliability of the correlation coefficient; comparison coefficient. Calculation of the above mentioned coefficients allowed an estimation of the level of interaction between the monitoring phenomena
Results and discussion.
There was an increase in the pertussis incidence in the study area from 1986 to 2001. Three epidemic peaks were registered in the period: 1990-91, 1993-94 and 1999, with high disease incidences of 96.6, 153.3 and 93.6 per 100,000, respectively. Periodic peaks of pertussis incidence in the Krasnoselsky district correlated with a general increase in incidence observed in the majority of districts in St. Petersburg and in the entire Russia (Fig. 1).
Fig. 1. Pertussis incidence in the Krasnoselsky district of St. Petersburg, and the Russian Federation.
The incidence levels in the Krasnoselsky district were higher during nine years and lower during seven years than the overall incidence for St. Petersburg. For the entire period, the incidence in the region was 1.2 times higher than the average in the city.
Cyclic waves of pertussis incidence were revealed with a mean inter-peak period of 7-8 years. There were three periods of high and three periods of low incidence in the 16-year observation period. The duration of the seasonal incidence was 8 months, from July to March. The maximum numbers of patients with pertussis were observed in November and December.
The epidemiology of three B. pertussis serotypes (1.2.3, 1.2.0, and 1.0.3) showed circulation cycles of four years (Fig. 2).
Fig. 2. Dynamics of B. Pertussis serovars, isolated from patients in the Krasnoselsky district
Serotype 1.0.3 was primarily recovered from children. The same dynamics of B. pertussis serotypes have been noted in the territory of Leningrad . The 1.0.3 serotype was also predominant in earlier years  while co-circulating with serotypes 1.2.3 and 1.2.0.
Improved regional immunization programs against pertussis have led to a considerable decrease in the incidence of this infection among the youngest children aged 1-2 years. In contrast, increasing incidences were seen in older children aged 3-14 years (Fig. 3).
Fig. 3. Pertussis incidence in Krasnoselsky district by age.
The considerable differences of pertussis incidence in the various age groups may be explained in part by older children's wide range of activities and contacts. Children in the first year of life have limited contact primarily with close relatives. These contacts may provide a possible source of infection through throat carriage , and thus explain the stable incidence of pertussis observed among the youngest age group during the 16-year observation period (Fig. 3.)
Pertussis incidence correlation coefficient's index of children under one year and children of 2 years of age is 0,6. It shows the presence of direct connection of mean strength in the disease incidence of the children from these groups. Correlation index is reliable, because it exceeds it's triple error (mr = 0,48). Incidence correlation coefficient's index for children under 1 year, first years of life and dynamics of the disease incidence among children at the age of 3-6 years and 7-14 years is 0,1. This level shows a slight connection of these children age groups incidence dynamics.
Pertussis infects young children at times when other acute respiratory diseases are observed. When analyzing the monthly incidence dynamics of children pertussis and acute respiratory diseases in adults, a total correlation could be noticed (Fig.. 4), a correlation coefficient is statistically proven (r = 0,6), it increases it's triple error 0,5 (mr = 5), and the correlation index of the dynamics correlation is 100 % (h = 100 %). It shows the important role of respiratory diseases in the spread of pertussis cases.
Fig. 4. Long-term monthly incidence of acute respiratory infections of adults and pertussis among children on the territory of Krasnoselsky district
Data on the effectiveness of increasing vaccination coverage among children were obtained. For the period of observation from 1993 to 200, the correlation coefficient was 0.8, indicating a strong relation between vaccinations against pertussis and incidence decrease. The correlation coefficient is statistically reliable because it exceeds it's triple error (mr = 0,4). However, among children under 1 year the correlation coefficient was 0.68 (mr = 0.5), indicating that the correlation connection has a mean strength of dependence. It is necessary to mention that instead of increasing vaccination coverage against pertussis among children, there is a stable incidence of diseases among them every year (Pic. 5). The incidence of pertussis among vaccinated children is on the level of 1.0 per 1,000. These data indicate that preventive vaccinations decreased the incidence of pertussis among children, but did not influence the standard flow of the epidemic.
It is possible that the increase in pertussis incidence among vaccinated and non-vaccinated children is due to a modified causative agent. In the 40-year period of preventive vaccination against pertussis, there have been genetic changes of B. pertussis arising from "the pressure" of the host immune response and possibly resulting in changes in its antigen structure. While investigating the genome of the strains obtained from patients and contacts in the Krasnoselsky district in 1999-2000 by PFGE, it was clear that their profiles differed considerably from vaccines strain profiles (results submitted for publication). DNA sequencing of the pertussis toxin and partakrin genes (representatives of B. pertussis toxins and adhesion families) showed changes in the loci for pertussis toxin genes in almost all of the modern strains and in the loci for the partakrin gene's in the majority of the strains.
The incidence of pertussis among children attending and not attending institutions was the same. However, there was a higher proportion of symptomatic infections in among children at institutions. There was an intensive hitting process and high share of forms with clinical manifestation in the children institutions. Asymptomatic infections were not included in the report. At the same time, the percentage of clinical pertussis cases confirmed by bacteriological methods decreased from 51 % in 1997 to 31.5 % in 2001.
Reduction of bacteriological confirmation of clinical forms of pertussis could also indicate the circulation of unknown serotypes among children of the older age groups. It is known that while immunity protects the vaccinated person from the disease, it doesn't eliminate the causative agent from the body. It could be postulated that circulation of B. pertussis bacilli with modified antigens has resulted from the influence of the immune responses of vaccinated persons . In this case it would be difficult to detect the bacteria by serodiagnostic methods.
Even in settings with known cases, i.e. kindergarten, less than 2 % of the bacteriological samples tested were positive for pertussis during the total period of observation. Epidemiological surveillance of pertussis needs special diagnostics methods with increased sensitivity.
Fig 5. Pertussis incidence among vaccinated children at the age from 3 months to 3 years.
The epidemiology of pertussis in the Krasnoselsky district of St. Petersburg showed a periodic increase of incidence among older children and adults, indicating an intensive spread of the disease among these groups and a high number of cases with clinical manifestations.
Stable pertussis incidences among children up to one year of age and increasing incidences among children of older age groups, make it necessary for medical staff pay special attention to non-specific prevention along with vaccination against pertussis. For example, it is necessary to provide education regarding hygiene to the families of newborns and to the staff of childcare institutions in order to protect newborns and young children from acute respiratory diseases. While organising preschool institutions, children of different age groups and staff should be accommodated in different rooms isolated from each other. The same strategy should be followed while teaching children in the primary and secondary schools.
It is necessary to provide high pertussis vaccination coverage among children from three months of age.
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