Skip directly to site content Skip directly to page options Skip directly to A-Z link Skip directly to A-Z link Skip directly to A-Z link
Volume 24, Number 3—March 2018
Research

Prospective Observational Study of Incidence and Preventable Burden of Childhood Tuberculosis, Kenya

Andrew J. BrentComments to Author , Christopher Nyundo, Joyce Langat, Caroline Mulunda, Joshua Wambua, Evasius Bauni, Joyce Sande, Kate Park, Thomas N. Williams, Charles R.J. Newton, Michael Levin, J. Anthony G. Scott, on behalf of the KIDS TB Study Group
Author affiliations: KEMRI–Wellcome Trust Research Programme, Kilifi, Kenya (A.J. Brent, C. Nyundo, J. Langat, C. Mulunda, J. Wambua, E. Bauni, T.N. Williams, C.R.J. Newton, J.A.G. Scott); Oxford University Hospitals NHS Foundation Trust, Oxford, UK (A.J. Brent, K. Park); University of Oxford, Oxford (A.J. Brent, C.R.J. Newton, J.A.G. Scott); Imperial College London, London, UK (A.J. Brent, M. Levin); Aga Khan University, Nairobi, Kenya (J. Sande); London School of Hygiene and Tropical Medicine, London (J.A.G. Scott)

Main Article

Table 3

Incidence of childhood TB derived by applying other published clinical definitions, algorithms, and guidelines, in order of increasing incidence, Kilifi Health and Demographic Surveillance Survey, Kenya, August 2009–July 2011*

Author, year (reference) Outcomes defined No. cases Incidence, cases/100,000 children/y (95% CI)†
WHO, 2006 (27) (a) Strongly suggestive of TB‡ 7 2.9 (1.2–6.0)
Stegen (28) (a) Probable TB 18 7.5 (4.5–11.9)
Nair (29) (a) “TB appears unquestionable” 28 11.7 (7.8–17.0)
WHO, 2006 (27) (b) Requires investigation for TB‡ 33 13.8 (9.5–19.4)
Graham (26) Probable TB 42 17.6 (12.7–23.8)
Hawkridge (30) Probable TB 54 22.6 (17.0–29.5)
Nair (29) (b) TB probable or “unquestionable” 55 23.0 (17.4–30.0)
Stoltz (31) Probable TB 73 30.6 (24.0–38.5)
Jeena (32) Probable TB 107 44.8 (36.7–54.2)
Edwards (33) Criteria for TB treatment 110 46.1 (37.9–55.5)
Ghidey (34) (a) Criteria for TB treatment§ 113 47.3 (39.0–56.9)
WHO, 1983 (35) Probable TB 116 48.6 (40.2–58.3)
Ramachandran (36) Criteria for TB treatment 118 49.4 (40.9–59.2)
Ghidey (34) (b) Criteria for TB treatment§ 130 54.5 (45.4–64.7)
Stegen (28) (b) Probable or possible TB 136 57.0 (47.8–67.4)
Graham (26) Probable or possible TB 145 60.7 (51.3–71.5)
Osborne (37) Probable TB 159 66.6 (56.7–77.8)
Fourie (38) High probability of TB¶ 162 67.9 (57.8–79.2)
Cundall (39) Probable TB 207 86.7 (75.3–99.4)
Kiwanuka (40) Probable TB 219 91.7 (80.0–104.7)

*TB, tuberculosis; WHO, World Health Organization.
†Denominator for incidence calculations is the total person-years observation among children age <15 y (N = 238,746).
‡Results shown separately for (a) children whose clinical features “strongly suggest a diagnosis of TB” according to the guidelines, and (b) using broader criteria that included under “physical signs highly suggestive of TB” all the other “suggestive clinical signs” listed as requiring investigation for TB.
§Results for Ghidey and Habte tool (34) shown using both (a) >3 and (b) >2 signs and symptoms to define a “suggestive symptom complex of TB” (online Technical Appendix Table 1, https://wwwnc.cdc.gov/EID/article/24/3/17-0785-Techapp1.pdf).
¶For the purposes of our analyses, we used “score 2” proposed by Fourie et al (38), which was derived in high TB burden settings in South Africa, Madagascar, and Nicaragua.

Main Article

References
  1. World Health Organization. Global tuberculosis report 2016. Geneva: The Organization; 2016.
  2. Uplekar  M, Weil  D, Lonnroth  K, Jaramillo  E, Lienhardt  C, Dias  HM, et al.; for WHO’s Global TB Programme. WHO’s new end TB strategy. Lancet. 2015;385:1799–801. DOIPubMedGoogle Scholar
  3. Brent  AJ. Childhood TB surveillance: bridging the knowledge gap to inform policy. J Trop Med. 2012;2012:865436. PMID: 22518169
  4. Hesseling  AC, Schaaf  HS, Gie  RP, Starke  JR, Beyers  N. A critical review of diagnostic approaches used in the diagnosis of childhood tuberculosis. Int J Tuberc Lung Dis. 2002;6:1038–45.PubMedGoogle Scholar
  5. Dodd  PJ, Gardiner  E, Coghlan  R, Seddon  JA. Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling study. Lancet Glob Health. 2014;2:e453–9. DOIPubMedGoogle Scholar
  6. Jenkins  HE, Tolman  AW, Yuen  CM, Parr  JB, Keshavjee  S, Pérez-Vélez  CM, et al. Incidence of multidrug-resistant tuberculosis disease in children: systematic review and global estimates. Lancet. 2014;383:1572–9. DOIPubMedGoogle Scholar
  7. Murray  CJ, Ortblad  KF, Guinovart  C, Lim  SS, Wolock  TM, Roberts  DA, et al. Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384:1005–70. DOIPubMedGoogle Scholar
  8. World Health Organization. Global tuberculosis report 2014. Geneva: The Organization; 2014.
  9. World Health Organization. Global tuberculosis report 2015. Geneva: The Organization; 2015.
  10. Dodd  PJ, Sismanidis  C, Seddon  JA. Global burden of drug-resistant tuberculosis in children: a mathematical modelling study. Lancet Infect Dis. 2016;16:1193–201. DOIPubMedGoogle Scholar
  11. Seddon  JA, Jenkins  HE, Liu  L, Cohen  T, Black  RE, Vos  T, et al. Counting children with tuberculosis: why numbers matter. Int J Tuberc Lung Dis. 2015;19(Suppl 1):9–16. DOIGoogle Scholar
  12. Donald  P, Maher  D, Qazi  S. A research agenda for childhood tuberculosis. Improving the management of childhood tuberculosis within national tuberculosis programmes: research priorities based on a literature review. Geneva: World Health Organization; 2007.
  13. Scott  JA, Bauni  E, Moisi  JC, Ojal  J, Gatakaa  H, Nyundo  C, et al. Profile: The Kilifi Health and Demographic Surveillance System (KHDSS). Int J Epidemiol. 2012;41:650–7. DOIPubMedGoogle Scholar
  14. World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children. Second edition. Geneva: The Organization; 2014.
  15. Liebeschuetz  S, Bamber  S, Ewer  K, Deeks  J, Pathan  AA, Lalvani  A. Diagnosis of tuberculosis in South African children with a T-cell-based assay: a prospective cohort study. Lancet. 2004;364:2196–203. DOIPubMedGoogle Scholar
  16. Rachow  A, Clowes  P, Saathoff  E, Mtafya  B, Michael  E, Ntinginya  EN, et al. Increased and expedited case detection by Xpert MTB/RIF assay in childhood tuberculosis: a prospective cohort study. Clin Infect Dis. 2012;54:1388–96. DOIPubMedGoogle Scholar
  17. Siddiqi  SH, Ruesch-Gerdes  S. MGIT procedure manual. Geneva: Foundation for Innovative New Diagnostics; 2006.
  18. Moïsi  JC, Nokes  DJ, Gatakaa  H, Williams  TN, Bauni  E, Levine  OS, et al. Sensitivity of hospital-based surveillance for severe disease: a geographic information system analysis of access to care in Kilifi district, Kenya. Bull World Health Organ. 2011;89:102–11. DOIPubMedGoogle Scholar
  19. Chuma  J, Gilson  L, Molyneux  C. Treatment-seeking behaviour, cost burdens and coping strategies among rural and urban households in Coastal Kenya: an equity analysis. Trop Med Int Health. 2007;12:673–86. DOIPubMedGoogle Scholar
  20. Molyneux  CS, Murira  G, Masha  J, Snow  RW. Intra-household relations and treatment decision-making for childhood illness: a Kenyan case study. J Biosoc Sci. 2002;34:109–31.PubMedGoogle Scholar
  21. Bauni  E, Ndila  C, Mochamah  G, Nyutu  G, Matata  L, Ondieki  C, et al. Validating physician-certified verbal autopsy and probabilistic modeling (InterVA) approaches to verbal autopsy interpretation using hospital causes of adult deaths. Popul Health Metr. 2011;9:49. DOIPubMedGoogle Scholar
  22. Molyneux  CS, Mung’Ala-Odera  V, Harpham  T, Snow  RW. Maternal responses to childhood fevers: a comparison of rural and urban residents in coastal Kenya. Trop Med Int Health. 1999;4:836–45. DOIPubMedGoogle Scholar
  23. World Health Organization. Global tuberculosis control 2011: Kenya country profile. Geneva: The Organization; 2011.
  24. Kenya National Bureau of Statistics. Kenya Demographic and Health Survey 2008–09. Nairobi (Kenya): The Bureau; 2010.
  25. Yuen  CM, Jenkins  HE, Chang  R, Mpunga  J, Becerra  MC. Two methods for setting child-focused tuberculosis care targets. Public Health Action. 2016;6:83–96. DOIPubMedGoogle Scholar
  26. Graham  SM, Ahmed  T, Amanullah  F, Browning  R, Cardenas  V, Casenghi  M, et al. Evaluation of tuberculosis diagnostics in children: 1. Proposed clinical case definitions for classification of intrathoracic tuberculosis disease. Consensus from an expert panel. J Infect Dis. 2012;205(Suppl 2):S199–208. DOIPubMedGoogle Scholar
  27. World Health Organization. Guidance for national tuberculosis programmes on the management of tuberculosis in children. Geneva: The Organization; 2006.
  28. Stegen  G, Jones  K, Kaplan  P. Criteria for guidance in the diagnosis of tuberculosis. Pediatrics. 1969;43:260–3.PubMedGoogle Scholar
  29. Nair  PH, Philip  E. A scoring system for the diagnosis of tuberculosis in children. Indian Pediatr. 1981;18:299–303.PubMedGoogle Scholar
  30. Hawkridge  A, Hatherill  M, Little  F, Goetz  MA, Barker  L, Mahomed  H, et al.; South African BCG trial team. Efficacy of percutaneous versus intradermal BCG in the prevention of tuberculosis in South African infants: randomised trial. BMJ. 2008;337(nov13 1):a2052.
  31. Stoltz  AP, Donald  PR, Strebel  PM, Talent  JMT. Criteria for the notification of childhood tuberculosis in a high-incidence area of the western Cape Province. S Afr Med J. 1990;77:385–6.PubMedGoogle Scholar
  32. Jeena  PM, Mitha  T, Bamber  S, Wesley  A, Coutsoudis  A, Coovadia  HM. Effects of the human immunodeficiency virus on tuberculosis in children. Tuber Lung Dis. 1996;77:437–43. DOIPubMedGoogle Scholar
  33. Edwards  K. The diagnosis of childhood tuberculosis. P N G Med J. 1987;30:169–78.PubMedGoogle Scholar
  34. Ghidey  Y, Habte  D. Tuberculosis in childhood: an analysis of 412 cases. Ethiop Med J. 1983;21:161–7.PubMedGoogle Scholar
  35. World Health Organization. Provisional guidelines for the diagnosis and classification of the EPI target diseases for primary health care, surveillance and special studies. Geneva: The Organization; 1983.
  36. Ramachandran  RS. Tuberculosis in children: experience with 1284 cases. Indian Pediatr. 1968;5:564–71.PubMedGoogle Scholar
  37. Osborne  CM. The challenge of diagnosing childhood tuberculosis in a developing country. Arch Dis Child. 1995;72:369–74. DOIPubMedGoogle Scholar
  38. Fourie  PB, Becker  PJ, Festenstein  F, Migliori  GB, Alcaide  J, Antunes  M, et al. Procedures for developing a simple scoring method based on unsophisticated criteria for screening children for tuberculosis. Int J Tuberc Lung Dis. 1998;2:116–23.PubMedGoogle Scholar
  39. Cundall  DB. The diagnosis of pulmonary tuberculosis in malnourished Kenyan children. Ann Trop Paediatr. 1986;6:249–55. DOIPubMedGoogle Scholar
  40. Kiwanuka  J, Graham  SM, Coulter  JB, Gondwe  JS, Chilewani  N, Carty  H, et al. Diagnosis of pulmonary tuberculosis in children in an HIV-endemic area, Malawi. Ann Trop Paediatr. 2001;21:5–14. DOIPubMedGoogle Scholar
  41. World Health Organization. Global tuberculosis control 2011. Geneva: The Organization; 2011.
  42. World Health Organization. Pocket book of hospital care for children: guidelines for the management of common illnesses with limited resources. Geneva: The Organization; 2005.
  43. Harries  AD, Hargreaves  NJ, Graham  SM, Mwansambo  C, Kazembe  P, Broadhead  RL, et al. Childhood tuberculosis in Malawi: nationwide case-finding and treatment outcomes. Int J Tuberc Lung Dis. 2002;6:424–31.PubMedGoogle Scholar
  44. Marais  BJ, Hesseling  AC, Gie  RP, Schaaf  HS, Beyers  N. The burden of childhood tuberculosis and the accuracy of community-based surveillance data. Int J Tuberc Lung Dis. 2006;10:259–63.PubMedGoogle Scholar
  45. Jenkins  HE, Pagano  M, Yuen  CM, Becerra  MC, Cohen  T. The burden of tuberculosis disease in children—Authors’ reply. Lancet. 2014;384:1343–4. DOIPubMedGoogle Scholar
  46. Seddon  JA. Knowing how many children to find is the first step in finding them. Public Health Action. 2016;6:52.PubMedGoogle Scholar
  47. Kwamanga  D, Chakaya  J, Sitienei  J, Kalisvaart  N, L’herminez  R, van der Werf  MJ. Tuberculosis transmission in Kenya: results of the third National Tuberculin Survey. Int J Tuberc Lung Dis. 2010;14:695–700.PubMedGoogle Scholar
  48. Starke  JR. Mortality in childhood tuberculosis: has there been progress? Lancet Infect Dis. 2017;17:239–41. DOIPubMedGoogle Scholar

Main Article

1The following members of the Kilifi Improving Diagnosis and Surveillance of Childhood TB (KIDS TB) Study Group also contributed to patient recruitment, investigation, and management: Victor Bandika, Jay Berkley, Kath Maitland, Susan Morpeth, Daisy Mugo, Robert Musyimi, Agnes Mutiso, John Paul Odhiambo, Monica Toroitich, and Hemed Twahir.

Prospective data on childhood tuberculosis (TB) incidence and case detection rates (CDRs) are scant, and the preventable burden of childhood TB has not been measured in prospective studies. We investigated 2,042 children (<15 years of age) with suspected TB by using enhanced surveillance and linked hospital, demographic, notification, and verbal autopsy data to estimate the incidence, CDR, risk factors, and preventable burden of TB among children in Kenya. Estimated TB incidence was 53 cases/100,000 children/year locally and 95 cases/100,000 children/year nationally. The estimated CDR was 0.20–0.35. Among children <5 years of age, 49% of cases were attributable to a known household contact with TB. This study provides much needed empiric data on TB CDRs in children to inform national and global incidence estimates. Moreover, our findings indicate that nearly half of TB cases in young children might be prevented by implementing existing guidelines for TB contact tracing and chemoprophylaxis.

Page created: February 15, 2018
Page updated: February 15, 2018
Page reviewed: February 15, 2018
The conclusions, findings, and opinions expressed by authors contributing to this journal do not necessarily reflect the official position of the U.S. Department of Health and Human Services, the Public Health Service, the Centers for Disease Control and Prevention, or the authors' affiliated institutions. Use of trade names is for identification only and does not imply endorsement by any of the groups named above.
file_external