Eurosurveillance

ECDC

Congenital Rubella Syndrome Prevalence Study among Infants with Birth Defects in Saint-Petersburg

 Rediger
  Published: 06.05.09 Updated: 06.05.2009 10:29:37

L. Lyalina1, M. Bichurina1, Ye. Breus1, N. Khrustaleva2

1 Saint-Petersburg Pasteur Institute of Epidemiology and Microbiology, Russia
2 Municipal Children’s Hospital No. 1, Saint-Petersburg, Russia

Citation:  Lyalina L., Bichurina M., Breus Ye., Khrustaleva N. Congenital Rubella Syndrome Prevalence Study among Infants with Birth Defects  in Saint-Petersburg EpiNorth. 2009;10(1): 13-18.

Summary
The study was conducted in Saint-Petersburg during 2006-2007. One hundred sixty nine infants aged less than 1 year who were admitted to the Municipal Children’s Hospital with severe birth defects (BD) for surgical treatment were included in the study. Rubella virus IgM was determined using the Dade Behring assay recommended by WHO. Ninety one and 78 infants were tested for rubella virus IgM during 2006 and 2007, respectively. Congenital heart defect (CHD), jaundice, developmental delay and splenomegaly were represented in 19.5%, 15.4%, 8.9% and 4.7% of the cases, respectively. In 5.3% of cases, severe pathology compatible with congenital rubella syndrome (CRS) including CHD, cataract, hearing disorders and glaucoma with other symptoms was observed. Eighty-nine percent of the tested infants were less than 3 months of age.
During 2007 in Saint-Petersburg, one case of CRS was diagnosed that was not detected by the routine rubella epidemiological surveillance that covers pregnant women. Clinical signs of CRS included congenital heart defect, cataract of the right eye, jaundice, splenomegaly, developmental delay and congenital defect of brain. Rubella was not detected in the mother during her pregnancy; no contact with persons exhibiting exanthematous diseases was reported and the woman was not vaccinated against rubella. In the 10th to 12th weeks of pregnancy  the woman developed a sudden high fever (39.8º). The results indicate that it is necessary to improve epidemiological surveillance and diagnostics for congenital rubella.

Introduction
The strategic plan of the World Health Organization (WHO) Regional Office for Europe for 2005-2010 defines key strategies and actions for the improvement of national immunization programmes and epidemiological surveillance systems for rubella. The primary objectives include elimination of endemic rubella by 2010 and prevention of congenital rubella infection. For a quantitative assessment the goal is to reduce the incidence to less than 1 case of congenital rubella syndrome (CRS) per 100,000 live newborns (1). Many European countries have provided rubella vaccination since the 1980s (2). In Russia, prophylactic rubella vaccination was included in the national immunization programme at the end of 1997 and national registration of rubella and congenital rubella has been performed since 1979 and 1991, respectively. Due to the lack of a locally produced rubella vaccine, the immunization coverage in the first years of implementation was low. While in 1999-2000, the immunization coverage among children aged 24 months was only 9.9-16.6%, the coverage reached 98% in 2006 (3). In the Northwestern region of the Russian Federation, immunization coverage rates among young children, children aged 6 years (both genders) and girls aged 13 years were significantly different thus causing major difference in rubella incidence rates. An analysis of the national registration data showed that during 1991-2006, CRS was detected only in two of the 11 regions of the Northwestern Federal District (8 cases during 15 years in Saint-Petersburg and 3 cases in Vologda oblast). The data was collected as part of the routine rubella epidemiological surveillance that includes rubella incidence analysis among different age and socio-occupational groups, and pregnant women. In Russia, the surveillance system did not cover infants with congenital disorders compatible with the standard clinical case definition of CRS if the infant’s mother did not have rubella during pregnancy. The annual incidence of rubella in Saint-Petersburg varied from 778.4 (1998) to 90.7 (2006) per 100,000 population (4).
The National Measles Elimination Programme, which is currently being implemented in Russia, requires developing an integrated system of epidemiologic surveillance for measles and rubella, and improvement of congenital rubella surveillance. This work is conducted under the supervision of the National Methodological Center (Moscow) and the WHO/ Europe (Copenhagen) (5).
The purpose of this study was to determine the prevalence of CRS among children with birth defects that were not deteсted during the routine epidemiological surveillance of rubella in Saint-Petersburg.

Materials and methods
The study was conducted in Saint-Petersburg during 2006-2007. One hundred sixty nine infants aged less than 1 year who were admitted to the Municipal Children’s Hospital with severe birth defects for surgical treatment were included in the study. This hospital admits most of the children in the city presenting with the above pathology. Organisation of work, methodological support, analysis of information and laboratory analysis by an enzyme-linked immunosorbent assay (ELISA) of blood serum from infants were provided by the Federal State Institution of Science “Saint-Petersburg Pasteur Research Institute of Epidemiology and Microbiology”. A system of active epidemiological surveillance was implemented in four hospital departments to detect infants with the birth defects thought to be caused by CRS. The surveillance included a daily review of the medical case notes of admitted infants, selection of the infants with symptoms compatible with CRS, blood serum collection for rubella virus IgM testing, collection of maternal rubella history during pregnancy, and completion of a specific epidemiological survey form. Within the routine epidemiological surveillance these activities were performed only if the woman was diagnosed with rubella and refused termination of pregnancy. Clinical, epidemiological and laboratory diagnostic methods for CRS were conducted. A CRS case definition and epidemiological investigation form recommended by WHO were used in the study (1). Rubella virus IgM was detected using the Dade Behring assay recommended by the WHO. The ELISA test was conducted in the WHO-certified virology laboratory of the Saint-Petersburg Pasteur Institute. All study results were analyzed and summarized in the epidemiology laboratory of the Pasteur Institute. The work was performed with the international cooperation of the Norwegian Institute of Public Health (Department of Infectious Disease Epidemiology).

Results
An analysis of rubella incidence data was performed in the Russian Federation, the Northwestern Federal District and in Saint-Petersburg to provide a rough estimate of the potential number of CRS cases (Table 1).

Table 1. Rubella incidence in the Russian Federation, Northwestern Federal District and Saint-Petersburg during 2006-2007 (per 100,000 population)

Territory / Территория

2006

2007

Totall population / Все население

Children under the age of 14 / Дети в возрасте до 14 лет

Total population / Все население

Children under the age of 14 / Дети в возрасте до 14 лет

Russian Federation / РоссийскаяФедерация

93.1

399.3

21.6

97.9

NorthwesternFederalDistrict / Северо-Западный федеральный округ

56.7

314.4

34.6

186.8

Saint-Petersburg / Санкт-Петербург

90.7

603.2

38.6

252.4

 

Despite the recent success in rubella immunisation, the results indicate that rubella incidence is primarily defined by a high incidence in the child population. The disease was mostly reported in unvaccinated children. Cases of rubella among immunised children were not confirmed by laboratory tests. It is important to note that until 2008 in the Russian Federation, rubella was typically reported on the basis of clinical findings. During 2006-2007, the proportion of adolescents and adults among rubella patients (all age groups, both genders) was 18.1-24.2 % and 31.8-35.4% in Saint-Petersburg and the Russian Federation, respectively.

An analysis of data obtained by the routine rubella epidemiological surveillance showed that during 2006-2007 neither cases of the disease in pregnant women exposed to rubella nor CRS in infants were reported in Saint-Petersburg.
Ninety one and 78 infants were tested for rubella virus IgM in 2006 and 2007, respectively. The distribution of infants by diagnosis is shown in Table 2. CHD and jaundice of unknown etiology was observed among the largest portion (36.1%) of the examined children. CHD, jaundice, developmental delay and splenomegaly were represented in 19.5%, 15.4%, 8.9% and 4.7% of the children, respectively. In 5.3% of children, severe pathology compatible with CRS including CHD, cataract, hearing disorders and glaucoma with other symptoms was observed.

Table 2. Distribution by diagnosis of infants with suspected CRS in Saint-Petersburg, 2006-2007

 

Symptoms / Симптомы

Number of patients / Количество

больных

%

1

CHD* + jaundice of unknown etiology / ВПС* + желтуха неясной этиологии

61

36.1

2

CHD + jaundice + developmental delay / ВПС + желтуха + отставание в развитии

33

19.5

3

CHD + jaundice + developmental delay + splenomegaly / ВПС + желтуха + отставание в развитии + спленомегалия

26

15.4

4

CHD + jaundice + splenomegaly / ВПС + желтуха +  спленомегалия

15

8.9

5

CHD + developmentaldelay / ВПС + отставание в развитии

8

4.7

6

CHD + microcephaly, jaundice, developmental delay / ВПС + микроцефалия, желтуха, отставание в развитии

5

3.0

7

CHD + cataract + meningoencephalitis + jaundice + splenomegaly + developmental delay / ВПС + катаракта + менингоэнцефалит +желтуха + спленомегалия + запаздывание в развитии

5

3.0

8

CHD + meningoencephalitis + jaundice + developmental delay / ВПС + менингоэнцефалит + желтуха + отставание в развитии

5

3.0

9

CHD + hearing disorder + microcephaly + jaundice + splenomegaly + developmental delay / ВПС + нарушения слуха + микроцефалия + желтуха + спленомегалия + запаздывание в развитии

3

1.7

10

CHD + meningoencephalitis + jaundice / ВПС + менингоэнцефалит + желтуха

4

2.4

11

CHD + glaucoma + jaundice + developmental delay / ВПС + глаукома + желтуха + запаздывание в развитии

1

0.6

12

Diagnosisnotconfirmed / Диагноз не подтвержден

3

1.7

 

TOTAL / ВСЕГО

169

100

 * CHD - congenital heart defect / ВПС  -  врожденный порок сердца

 

No laboratory-confirmed cases of CRS were reported among infants examined in 2006. One case of CRS was detected in 2007 as part of the routine rubella epidemiological surveillance system that covers pregnant women.
To evaluate the reliability of the results obtained, the age distribution of infants examined was analysed (Table 3). For the analysis the published data was used that rubella virus-specific IgM antibodies are detectable in almost all infants with CRS during the first 6 months of life, and in 50-60% of infants these antibodies are also detectable during the second half of the first year of life (7-12 month). The results indicate that the virus may be carried throughout the first year of life and thus, the infants may be a source of rubella infection.

Table 3. Characteristics of tested infants with suspected CRS by age and testing results, Saint-Petersburg, 2006-2007

Age of infants (months) / Возраст детей (мес.)

Frequency of detecting rubella virus IgM in infants with CRS (%), (1) / Частота обнаружения IgM к вирусу краснухи у детей с СВК (%), (1)

2006

2007

Number of infants with suspected CRS / Количество обследованных детей с подозрением на СВК

 

Number of infants positive to rubella virus IgM / Из них (+)IgM к вирусу краснухи

 

 

 Number of tested infants with suspected CRS / Количество обследованных детей с подозрением на СВК

 

Number of infants positive to  rubella virus IgM / Из них (+)IgM к вирусу краснухи

 

 

0-6

100

83

0

74

1

7-12

  60

 8

0

 4

0

TOTAL / ВСЕГО

91

0

78

1

 

Summary of information about the patient with CRS detected in Saint-Petersburg in 2007:

  • Born in May 2007 and examined seven days later.
  • Clinical signs: CHD, cataract of the right eye, jaundice, splenomegaly, developmental delay, congenital defect of brain.
  • Information about maternal rubella during pregnancy: rubella was not reported; no contact with persons exhibiting exanthematous diseases reported; the woman was not vaccinated against rubella; in the 10th to 12th weeks of pregnancy, the woman developed a sudden high fever (39.8º C).

Discussion
The results of the study showed that the Northwestern region of Russia tends to have a low incidence of rubella; however, in several areas, including Saint-Petersburg, the incidence exceeded 30 per 100,000 population in 2007. Sporadic cases of rubella have been reported among pregnant women. The case of CRS detected in Saint-Petersburg during the active screening of infants hospitalized at the Children’s Hospital for surgical treatment of birth defects could not be diagnosed as there was no history of rubella infection in mother. Fourteen infants aged 4-12 months were examined. It is possible that CRS may have been detected if these infants were examined at the earlier age. Epidemiological surveillance to determine the true prevalence of congenital rubella should be conducted in several ways including surveillance of rubella among pregnant women with mandatory laboratory confirmation, screening of infants with birth defects suspected to be CRS, testing for  rubella virus IgM in stillborn infants with birth defects and investigation of other signs of congenital rubella infection.
The implementation of the international project aimed at determining CRS prevalence in infants with severe congenital pathology has a significant scientific and practical importance. It promoted integration of international standards of epidemiological surveillance and laboratory diagnostics for CRS in Saint-Petersburg and helped to detect a CRS case. As part of this initiative, two seminars were held for paediatricians, epidemiologists, immunologists, gynaecologists and nurses. A study visit was made to the Norwegian Institute of Public Health within the frame of the bilateral cooperation.
The study has demonstrated data on the high prevalence of birth defects corresponding to the CRS standard clinical case definition, the need to study intrauterine infections and the possible role of other risk factors.

Acknowledgement
The authors would like to acknowledge the managers and paediatricians of the Saint-Petersburg Municipal Children’s Hospital No. 1, Dr. Preben Aavitsland, Director of the Department of Infectious Disease Epidemiology, and Dr. Stein Andresen, Project Manager, for assistance in organizing the study.

References

  1. Руководство по организации эпидемиологического надзора за корью и врожденной краснушной инфекцией в Европейском регионе ВОЗ. Copenhagen, 2003.
  2. Galazka A. Rubella in Europe. Epidemiol Infect 1991;107: 43-54.
  3. Иммунизация против инфекционных заболеваний населения Российской Федерации в 2002-2006 годах. Информационный сборник Федерального центра гигиены и эпидемиологии. Москва, 2007.
  4. Инфекционная заболеваемость в Российской Федерации. Информационный сборник статистических и аналитических материалов Федерального центра гигиены и эпидемиологии. Москва, 2008.
  5. Measles and Rubella Surveillance Bulletin, WHO/Europe, March 2008.
  6. Best J.M., Enders G. In. Perspectives in Medical Virology, ed J.E. Banatvala. Elsevier, 2006.

 Print