- Email: [email protected]
The epidemiology of paediatric tuberculosis in Europe
ARTICLE IN PRESS Current Paediatrics (2004) 14, 258–262
www.elsevierhealth.com/journals/cuoe
The epidemiology of paediatric tuberculosis in Europe Tony Wallsa,b,*, Delane Shingadiac, Vas Novellid a
Paediatric Infectious Diseases, Royal Australasian College of Physicians, Australasia Department of Infectious Diseases, Hospital for Sick Children, Great Ormond Street Hospital for Children, Great Ormond Street, London WC1N 3JH, UK c Paediatric Infectious Diseases, Academic Department of Child Health, Royal London Hospital, 1st Floor Luckes House, Stepney Way, Whitechapel, London E1 1BB, UK d Paediatric Infectious Diseases, Great Ormond Street Hospital for Children, Great Ormond Street, London WC1N 3JH, UK b
KEYWORDS Tuberculosis; Epidemiology; Paediatric
Summary Tuberculosis is one of the major infections affecting children world-wide. The epidemiology of paediatric tuberculosis in Europe reflects world-wide trends, with significant differences in rates of disease between resource-poor nations and those with well-funded tuberculosis control programmes. The highest rates of disease occur in Eastern European countries, with increasing rates of disease in children resulting from increasing numbers of infectious adults within communities. Western European nations continue to have low rates of tuberculosis, with a large proportion of disease occurring in recent immigrants from high-burden countries, particularly those in Sub-Saharan Africa. & 2004 Elsevier Ltd. All rights reserved.
Practice point *
*
*
*
Paediatric TB is a direct result of ongoing transmission of TB in communities Fewer than 15% of infected children will be sputum-smear-positive and will therefore not be included in WHO case notifications There are alarming disparities in rates of TB between Eastern and Western Europe High rates of disease in Eastern Europe are partly due to inadequate TB control programmes
*Corresponding author. Department of Infectious Diseases, Hospital for Sick Children, Great Ormond Street Hospital for Children, Great Ormond Street, London WC1N 3JH, UK. Tel.: þ 44-20-7813-8504; fax: þ 44-20-7813-8552. E-mail address: [email protected] (T. Walls).
*
In low-prevalence countries a significant proportion of cases are recent immigrants from high-prevalence countries, particularly Sub-Saharan Africa
Introduction Tuberculosis (TB) continues to be one of the most devastating and widespread infections in the world. In Europe there is a huge disparity in the rates of TB between the western and eastern nations, and this appears to be worsening. Young children are often the worst affected by TB epidemics, as they are the most likely to develop disease after infection, and are at greatest risk of developing extrapulmonary
0957-5839/$ - see front matter & 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.cupe.2004.02.009
ARTICLE IN PRESS Paediatric tuberculosis in Europe and severe disseminated disease.1 Children also develop disease sooner after infection than adults, and thus the incidence of disease in children provides an early indication of the overall patterns of transmission and disease within communities. This review will focus on the epidemiology of paediatric TB in Europe.
Tuberculosis notifications to the world health organisation The recently published World Health Organisation (WHO) Global Report on tuberculosis shows that TB case notifications in the WHO European region make up less than 10% of worldwide notifications to the WHO.2 While these are an excellent source of information on adult disease, an accurate description of the burden of TB in children is very difficult to obtain. The WHO notification criteria include only cases that are sputum-smear-positive. Fewer than 15% of children with culture-proven TB will be sputum-smear-positive, meaning that only a small percentage of children with TB are notified to the WHO. The quality of information provided to the WHO can also vary, and in many countries surveillance data are often unreliable because of poor diagnostic facilities and reporting systems. Because of these issues the International Union against Tuberculosis and Lung Disease has stated that reliable information on the incidence of TB in childhood can only be obtained in developed countries.3 WHO case notifications reveal alarming disparities in the overall rates of TB between countries in Western Europe and those in Eastern Europe, comprising mostly states of the former Soviet Union (Table 1). For example, WHO figures for 2001 show that both France and the UK had notification rates for all cases of 10 per 100,000 population.2 This is compared to Romania and the Russian Federation whose rates are greater than 90 per 100,000 and Kazakhstan with rate of 163/100,000. Case notification rates in France and the UK have fallen since 1980 and in the last 5 years remained relatively unchanged. In contrast, many Eastern European countries have had steadily increasing rates of TB notifications. In 1995 the Russian Federation had 84,980 notifications, increasing by 64% to 132,477 by 2001. In the same time period notifications in Kazakhstan increased by 43% from 11,310 to 26,224. TB notifications in the countries of Central Europe fall somewhere in between these two extremes, and while many of these countries have falling rates of TB, increases of between 2% and 4%
259
Table 1 2001 TB case notifications to WHO. Population ( 1000)
Western Europe Denmark France Germany Italy United kingdom Central Europe Albania Bosnia and Hertzegovina Poland Slovenia Eastern Europe Kazakhstan Republic of Moldova Russian federation Tajikistan Ukraine
TB case notifications per 100,000 population
5333 59,453 82,007 57,503 59,542
9 10 8 7 10
3145 4067
18 61
38,577 1985
26 18
16,095 4285
163 84
144,664
92
6135 49,112
57 75
annually since 1995 have occurred in Bosnia– Herzegovina and Bulgaria.
Paediatric TB in Eastern Europe Information from Eastern European countries on paediatric TB is limited. The WHO had 601 notifications of smear-positive children aged 0–14 years in the European region for 2001, with one in five of these children living in Kazakhstan. These figures are likely to significantly underestimate the true rate of smear-positive TB in children for several reasons. Firstly, in Kazakhstan the total numbers of paediatric notifications makes up just over 1% of all notifications, with even lower reported rates in children for the Russian Federation. This is substantially lower than in the UK where children make up 2.5% of all notifications,suggesting that these figures may reflect poor detection or reporting of paediatric cases. Another reason that higher rates of paediatric TB notifications might be expected in these high-burden countries is the age distribution of adult TB. In many Eastern European countries
ARTICLE IN PRESS 260
T. Walls et al.
Kazakhstan
France
UK
Germany
30
Percentage of notifications
25
20
15
10
5
0 0-14
15-24
25-35
35-44
45-54
55-64
65+
Age Group
Figure 1 TB notification rates by age group.
particularly high rates of adult disease occur in younger adults in the 25–44 years age group compared to countries such as the UK, France and Germany (Fig. 1). More younger adults in Eastern Europe having active TB is likely to mean that more children are exposed to TB from their parents or carers, and hence higher rates of disease can be expected in children.4 The explanations for the high rates of TB in Eastern Europe are complex and vary between countries. Shilova and Dye investigated the reasons for the resurgence of TB in Russia during the 1990s.5 They found that overall there had been an increasing incidence of disease as shown by the increase in cases reported, yet there was also evidence that the detection of TB was declining. This was primarily due to a deterioration in TB control services, with a significant reduction in funding for TB control leading to drug shortages and a less effective system for patient diagnosis and management. Treatment success rates had also declined over the decade, while case fatality rates for TB had significantly increased. The rates of disease in children had dropped more rapidly (6.1% per year) than in the rest of the population (3.7% per year) leading up to the beginning of the 1990s. Since that time, however, increasing rates in the overall population have been mirrored in the rates of TB in children, which have increased at approximately 9.0% per year. The authors attributed these increases to a combination of deteriorating TB control services and changes in the social and economic conditions that have had an overall negative effect on Russian health in general.
TB in low-prevalence countries In most of the low-prevalence countries in Europe, such as the UK, notification rates for TB have declined over the last 20 years.2 National survey data from the UK show a decrease in TB rates in all age groups from 1978/1979 onwards, reaching their lowest levels in the mid-1980s before beginning to rise again. Rates in children and young people overall have remained relatively constant over the last 5 years.6 However, there have been specific changes in the pattern and distribution of paediatric tuberculosis in the UK that are not reflected in national data. Overall, TB notifications have increased substantially in London, which accounts for 40% of national cases. Several boroughs in London now have TB notification rates greater than 60 per 100,000, with some having rates greater than 120 per 100,000.7 Cases in children under 16 in London have risen almost every year since 1988, with increases across all age groups. Some areas have recorded rates of 440 per 100,000 in children. The proportion of Black African children with TB in 1998 (44%) had increased substantially from 1993 (23%), whereas the proportion of paediatric cases from the Indian Subcontinent (ISC) had fallen (21% in 1998 compared to 50% in 1993).8 The change in proportions is largely related to the increase in numbers of infected Black African children, with 95% of TB cases in this group resident in London. The data from 1998 show that 66% of the African children with TB were born abroad and that the majority of those developed disease within 5 years of entering the UK.
ARTICLE IN PRESS Paediatric tuberculosis in Europe
Similar patterns have occurred in other lowprevalence countries in Europe. Erickson et al. reviewed the epidemiology of paediatric TB in Stockholm between 1976 and 1995.9 They found the overall rates of TB in children increased from less than 1 per 100,000 early in the study to 5.8 per 100,000 between 1991–1995. The increase in case notifications was mostly due to children who were born outside the country (50% of children with TB were from Africa) or who had at least one parent who was born abroad. There were no cases of TB in children whose parents were both Swedish born in the years 1991–1995. A similar study in Copenhagen between 1984 and 1993 found that 70% of children with TB had immigrant parents.10
TB and immigration During the latter half of last century there has been an unprecedented movement of people between nations. Molecular epidemiological studies undertaken in Norway and the UK both suggest that many of the new TB cases in immigrants are due to reactivation of infections acquired abroad.11,12 Immigrant children born in countries with high rates of TB are at much higher risk of developing TB for several reasons. Firstly, those who are recent arrivals may have been exposed to TB in their home country. The long time between infection and reactivation of TB in adults means that this increased risk of disease in children extends to those whose parents were born overseas, even if they themselves are born in a low-risk country.
Human immunodeficiency virus and TB Human immunodeficiency virus (HIV) infection has had a profound effect on the incidence of TB globally, particularly in Sub-Saharan Africa where HIV/AIDS has been the major driving force behind the recent increases in the incidence of adult TB. HIV is known to greatly increase the annual risk of progression from TB infection to active disease. Increased rates of TB in children have been associated with increased rates of disease among HIV-infected adults in the community.13 This effect may be indirect, rather than due to the their own HIV infection, these children being more likely to have close contact with a smear-positive adult than non-infected children.14 At present there is little information on how the HIV pandemic has affected the incidence of TB in children in the European
261
region. It seems likely, however, that with increasing rates of adult HIV infection throughout Europe the numbers of children exposed to and developing TB will increase. These children are also more likely to be exposed to TB, either by visiting their home country or from close contact with infectious adults visiting from abroad.
Conclusion Although TB in Europe makes up a small percentage of the disease globally, its epidemiology reflects worldwide trends. There are major disparities between the rates of disease between resourcepoor Eastern countries and those nations in Western Europe who have the resources to fund TB control programmes. In the countries of Western Europe increasing rates of paediatric TB in some areas can be largely attributed to transmission of infection from immigrants who developed infection in other countries. Rates of TB in children give early indication of changes in the pattern of TB within communities because of the short time between infection and the development of disease. It is essential, therefore, that improvements be made across Europe in the diagnosis and monitoring of TB in this high-risk group.
References 1. Miller F, Seal R, Taylor M. Tuberculosis in children. Boston: Little, Brown and Co.; 1963. 2. WHO. Global tuberculosis control. Geneva: World Health Organisation; 2003. 3. Hershfield E. Tuberculosis in children: guidelines for diagnosis, prevention and management (a statement of the scientific committees of the IUATLD). Bull Int Union Tuberc Lung Dis 1991;66:61–7. 4. Walls T, Shingadia D. Global epidemiology of paediatric tuberculosis. J Infect 2004;48:13–22. 5. Shilova V, Dye C. The resurgence of tuberculosis in Russia. Philos Trans R Soc London 2001;356:1069–75. 6. PHLS. Tuberculosis surveillance in England, Wales, 2001, www.phls.org.uk/topics az/tb/data menu.htm. 7. Atkinson P, Taylor H, Sharland M, Maguire H. Resurgence of paediatric tuberculosis in London. Arch Dis Child 2002;86:264–5. 8. Balasegaram S, Watson J, Rose A, et al. A decade of change tuberculosis in England and Wales 1988–98. Arch Dis Child 2003;88:772–7. 9. Eriksson M, Bennet R, Danielsson N. Clinical manifestations and epidemiology of childhood tuberculosis in Stockholm 1976–95. Scand J Infect Dis 1997;29:569–72. 10. Rosenfeldt V, Paerregaard A, Fuursted K, Braendholt V, Valerius N. Childhood tuberculosis in a Scandinavian metropolitan area 1984–93. Scand J Infect Dis 1998;30: 53–7.
ARTICLE IN PRESS 262
11. Dahle U, Sandven P, Heldal E, Caugant D. Molecular epidemiology of Mycobacterium tuberculosis in Norway. J Clin Microbiol 2001;39:1802–7. 12. Maguire H, Dale J, McHugh T, Butcher P, et al. Molecular epidemiology of tuberculosis in London 1995–7 showing low rate of active transmission. Thorax 2002;57: 617–22.
T. Walls et al.
13. Cantwell M, Binkin N. Impact of HIV on tuberculosis in SubSaharan Africa: a regional perspective. Int J Tuberc Lung Dis 1997;1:205–14. 14. Thomas P, Bornschlegel K, Singh T, et al. Tuberculosis in human immunodeficiency virus-infected and human immunodeficiency virus-exposed children in New York City. Pediatr Infect Dis J 2000;19:700–6.
www.elsevierhealth.com/journals/cuoe
The epidemiology of paediatric tuberculosis in Europe Tony Wallsa,b,*, Delane Shingadiac, Vas Novellid a
Paediatric Infectious Diseases, Royal Australasian College of Physicians, Australasia Department of Infectious Diseases, Hospital for Sick Children, Great Ormond Street Hospital for Children, Great Ormond Street, London WC1N 3JH, UK c Paediatric Infectious Diseases, Academic Department of Child Health, Royal London Hospital, 1st Floor Luckes House, Stepney Way, Whitechapel, London E1 1BB, UK d Paediatric Infectious Diseases, Great Ormond Street Hospital for Children, Great Ormond Street, London WC1N 3JH, UK b
KEYWORDS Tuberculosis; Epidemiology; Paediatric
Summary Tuberculosis is one of the major infections affecting children world-wide. The epidemiology of paediatric tuberculosis in Europe reflects world-wide trends, with significant differences in rates of disease between resource-poor nations and those with well-funded tuberculosis control programmes. The highest rates of disease occur in Eastern European countries, with increasing rates of disease in children resulting from increasing numbers of infectious adults within communities. Western European nations continue to have low rates of tuberculosis, with a large proportion of disease occurring in recent immigrants from high-burden countries, particularly those in Sub-Saharan Africa. & 2004 Elsevier Ltd. All rights reserved.
Practice point *
*
*
*
Paediatric TB is a direct result of ongoing transmission of TB in communities Fewer than 15% of infected children will be sputum-smear-positive and will therefore not be included in WHO case notifications There are alarming disparities in rates of TB between Eastern and Western Europe High rates of disease in Eastern Europe are partly due to inadequate TB control programmes
*Corresponding author. Department of Infectious Diseases, Hospital for Sick Children, Great Ormond Street Hospital for Children, Great Ormond Street, London WC1N 3JH, UK. Tel.: þ 44-20-7813-8504; fax: þ 44-20-7813-8552. E-mail address: [email protected] (T. Walls).
*
In low-prevalence countries a significant proportion of cases are recent immigrants from high-prevalence countries, particularly Sub-Saharan Africa
Introduction Tuberculosis (TB) continues to be one of the most devastating and widespread infections in the world. In Europe there is a huge disparity in the rates of TB between the western and eastern nations, and this appears to be worsening. Young children are often the worst affected by TB epidemics, as they are the most likely to develop disease after infection, and are at greatest risk of developing extrapulmonary
0957-5839/$ - see front matter & 2004 Elsevier Ltd. All rights reserved. doi:10.1016/j.cupe.2004.02.009
ARTICLE IN PRESS Paediatric tuberculosis in Europe and severe disseminated disease.1 Children also develop disease sooner after infection than adults, and thus the incidence of disease in children provides an early indication of the overall patterns of transmission and disease within communities. This review will focus on the epidemiology of paediatric TB in Europe.
Tuberculosis notifications to the world health organisation The recently published World Health Organisation (WHO) Global Report on tuberculosis shows that TB case notifications in the WHO European region make up less than 10% of worldwide notifications to the WHO.2 While these are an excellent source of information on adult disease, an accurate description of the burden of TB in children is very difficult to obtain. The WHO notification criteria include only cases that are sputum-smear-positive. Fewer than 15% of children with culture-proven TB will be sputum-smear-positive, meaning that only a small percentage of children with TB are notified to the WHO. The quality of information provided to the WHO can also vary, and in many countries surveillance data are often unreliable because of poor diagnostic facilities and reporting systems. Because of these issues the International Union against Tuberculosis and Lung Disease has stated that reliable information on the incidence of TB in childhood can only be obtained in developed countries.3 WHO case notifications reveal alarming disparities in the overall rates of TB between countries in Western Europe and those in Eastern Europe, comprising mostly states of the former Soviet Union (Table 1). For example, WHO figures for 2001 show that both France and the UK had notification rates for all cases of 10 per 100,000 population.2 This is compared to Romania and the Russian Federation whose rates are greater than 90 per 100,000 and Kazakhstan with rate of 163/100,000. Case notification rates in France and the UK have fallen since 1980 and in the last 5 years remained relatively unchanged. In contrast, many Eastern European countries have had steadily increasing rates of TB notifications. In 1995 the Russian Federation had 84,980 notifications, increasing by 64% to 132,477 by 2001. In the same time period notifications in Kazakhstan increased by 43% from 11,310 to 26,224. TB notifications in the countries of Central Europe fall somewhere in between these two extremes, and while many of these countries have falling rates of TB, increases of between 2% and 4%
259
Table 1 2001 TB case notifications to WHO. Population ( 1000)
Western Europe Denmark France Germany Italy United kingdom Central Europe Albania Bosnia and Hertzegovina Poland Slovenia Eastern Europe Kazakhstan Republic of Moldova Russian federation Tajikistan Ukraine
TB case notifications per 100,000 population
5333 59,453 82,007 57,503 59,542
9 10 8 7 10
3145 4067
18 61
38,577 1985
26 18
16,095 4285
163 84
144,664
92
6135 49,112
57 75
annually since 1995 have occurred in Bosnia– Herzegovina and Bulgaria.
Paediatric TB in Eastern Europe Information from Eastern European countries on paediatric TB is limited. The WHO had 601 notifications of smear-positive children aged 0–14 years in the European region for 2001, with one in five of these children living in Kazakhstan. These figures are likely to significantly underestimate the true rate of smear-positive TB in children for several reasons. Firstly, in Kazakhstan the total numbers of paediatric notifications makes up just over 1% of all notifications, with even lower reported rates in children for the Russian Federation. This is substantially lower than in the UK where children make up 2.5% of all notifications,suggesting that these figures may reflect poor detection or reporting of paediatric cases. Another reason that higher rates of paediatric TB notifications might be expected in these high-burden countries is the age distribution of adult TB. In many Eastern European countries
ARTICLE IN PRESS 260
T. Walls et al.
Kazakhstan
France
UK
Germany
30
Percentage of notifications
25
20
15
10
5
0 0-14
15-24
25-35
35-44
45-54
55-64
65+
Age Group
Figure 1 TB notification rates by age group.
particularly high rates of adult disease occur in younger adults in the 25–44 years age group compared to countries such as the UK, France and Germany (Fig. 1). More younger adults in Eastern Europe having active TB is likely to mean that more children are exposed to TB from their parents or carers, and hence higher rates of disease can be expected in children.4 The explanations for the high rates of TB in Eastern Europe are complex and vary between countries. Shilova and Dye investigated the reasons for the resurgence of TB in Russia during the 1990s.5 They found that overall there had been an increasing incidence of disease as shown by the increase in cases reported, yet there was also evidence that the detection of TB was declining. This was primarily due to a deterioration in TB control services, with a significant reduction in funding for TB control leading to drug shortages and a less effective system for patient diagnosis and management. Treatment success rates had also declined over the decade, while case fatality rates for TB had significantly increased. The rates of disease in children had dropped more rapidly (6.1% per year) than in the rest of the population (3.7% per year) leading up to the beginning of the 1990s. Since that time, however, increasing rates in the overall population have been mirrored in the rates of TB in children, which have increased at approximately 9.0% per year. The authors attributed these increases to a combination of deteriorating TB control services and changes in the social and economic conditions that have had an overall negative effect on Russian health in general.
TB in low-prevalence countries In most of the low-prevalence countries in Europe, such as the UK, notification rates for TB have declined over the last 20 years.2 National survey data from the UK show a decrease in TB rates in all age groups from 1978/1979 onwards, reaching their lowest levels in the mid-1980s before beginning to rise again. Rates in children and young people overall have remained relatively constant over the last 5 years.6 However, there have been specific changes in the pattern and distribution of paediatric tuberculosis in the UK that are not reflected in national data. Overall, TB notifications have increased substantially in London, which accounts for 40% of national cases. Several boroughs in London now have TB notification rates greater than 60 per 100,000, with some having rates greater than 120 per 100,000.7 Cases in children under 16 in London have risen almost every year since 1988, with increases across all age groups. Some areas have recorded rates of 440 per 100,000 in children. The proportion of Black African children with TB in 1998 (44%) had increased substantially from 1993 (23%), whereas the proportion of paediatric cases from the Indian Subcontinent (ISC) had fallen (21% in 1998 compared to 50% in 1993).8 The change in proportions is largely related to the increase in numbers of infected Black African children, with 95% of TB cases in this group resident in London. The data from 1998 show that 66% of the African children with TB were born abroad and that the majority of those developed disease within 5 years of entering the UK.
ARTICLE IN PRESS Paediatric tuberculosis in Europe
Similar patterns have occurred in other lowprevalence countries in Europe. Erickson et al. reviewed the epidemiology of paediatric TB in Stockholm between 1976 and 1995.9 They found the overall rates of TB in children increased from less than 1 per 100,000 early in the study to 5.8 per 100,000 between 1991–1995. The increase in case notifications was mostly due to children who were born outside the country (50% of children with TB were from Africa) or who had at least one parent who was born abroad. There were no cases of TB in children whose parents were both Swedish born in the years 1991–1995. A similar study in Copenhagen between 1984 and 1993 found that 70% of children with TB had immigrant parents.10
TB and immigration During the latter half of last century there has been an unprecedented movement of people between nations. Molecular epidemiological studies undertaken in Norway and the UK both suggest that many of the new TB cases in immigrants are due to reactivation of infections acquired abroad.11,12 Immigrant children born in countries with high rates of TB are at much higher risk of developing TB for several reasons. Firstly, those who are recent arrivals may have been exposed to TB in their home country. The long time between infection and reactivation of TB in adults means that this increased risk of disease in children extends to those whose parents were born overseas, even if they themselves are born in a low-risk country.
Human immunodeficiency virus and TB Human immunodeficiency virus (HIV) infection has had a profound effect on the incidence of TB globally, particularly in Sub-Saharan Africa where HIV/AIDS has been the major driving force behind the recent increases in the incidence of adult TB. HIV is known to greatly increase the annual risk of progression from TB infection to active disease. Increased rates of TB in children have been associated with increased rates of disease among HIV-infected adults in the community.13 This effect may be indirect, rather than due to the their own HIV infection, these children being more likely to have close contact with a smear-positive adult than non-infected children.14 At present there is little information on how the HIV pandemic has affected the incidence of TB in children in the European
261
region. It seems likely, however, that with increasing rates of adult HIV infection throughout Europe the numbers of children exposed to and developing TB will increase. These children are also more likely to be exposed to TB, either by visiting their home country or from close contact with infectious adults visiting from abroad.
Conclusion Although TB in Europe makes up a small percentage of the disease globally, its epidemiology reflects worldwide trends. There are major disparities between the rates of disease between resourcepoor Eastern countries and those nations in Western Europe who have the resources to fund TB control programmes. In the countries of Western Europe increasing rates of paediatric TB in some areas can be largely attributed to transmission of infection from immigrants who developed infection in other countries. Rates of TB in children give early indication of changes in the pattern of TB within communities because of the short time between infection and the development of disease. It is essential, therefore, that improvements be made across Europe in the diagnosis and monitoring of TB in this high-risk group.
References 1. Miller F, Seal R, Taylor M. Tuberculosis in children. Boston: Little, Brown and Co.; 1963. 2. WHO. Global tuberculosis control. Geneva: World Health Organisation; 2003. 3. Hershfield E. Tuberculosis in children: guidelines for diagnosis, prevention and management (a statement of the scientific committees of the IUATLD). Bull Int Union Tuberc Lung Dis 1991;66:61–7. 4. Walls T, Shingadia D. Global epidemiology of paediatric tuberculosis. J Infect 2004;48:13–22. 5. Shilova V, Dye C. The resurgence of tuberculosis in Russia. Philos Trans R Soc London 2001;356:1069–75. 6. PHLS. Tuberculosis surveillance in England, Wales, 2001, www.phls.org.uk/topics az/tb/data menu.htm. 7. Atkinson P, Taylor H, Sharland M, Maguire H. Resurgence of paediatric tuberculosis in London. Arch Dis Child 2002;86:264–5. 8. Balasegaram S, Watson J, Rose A, et al. A decade of change tuberculosis in England and Wales 1988–98. Arch Dis Child 2003;88:772–7. 9. Eriksson M, Bennet R, Danielsson N. Clinical manifestations and epidemiology of childhood tuberculosis in Stockholm 1976–95. Scand J Infect Dis 1997;29:569–72. 10. Rosenfeldt V, Paerregaard A, Fuursted K, Braendholt V, Valerius N. Childhood tuberculosis in a Scandinavian metropolitan area 1984–93. Scand J Infect Dis 1998;30: 53–7.
ARTICLE IN PRESS 262
11. Dahle U, Sandven P, Heldal E, Caugant D. Molecular epidemiology of Mycobacterium tuberculosis in Norway. J Clin Microbiol 2001;39:1802–7. 12. Maguire H, Dale J, McHugh T, Butcher P, et al. Molecular epidemiology of tuberculosis in London 1995–7 showing low rate of active transmission. Thorax 2002;57: 617–22.
T. Walls et al.
13. Cantwell M, Binkin N. Impact of HIV on tuberculosis in SubSaharan Africa: a regional perspective. Int J Tuberc Lung Dis 1997;1:205–14. 14. Thomas P, Bornschlegel K, Singh T, et al. Tuberculosis in human immunodeficiency virus-infected and human immunodeficiency virus-exposed children in New York City. Pediatr Infect Dis J 2000;19:700–6.