What's in a number? Accurate estimates of childhood tuberculosis
Authors: Andrea T Cruz, Jeffrey R Starke
Journal: The Lancet Global Health (2014)

There is growing recognition that children bear a substantial burden of tuberculosis morbidity and mortality. However, in regions where the diagnosis is contingent on smear microscopy, the burden attributable to children, who usually have paucibacillary disease, is grossly underestimated. The downstream ramifications of inaccurate estimates include inadequate attention and funding for childhood tuberculosis surveillance, diagnosis, treatment, prevention, and research. In the absence of microbiologically based diagnoses, estimates of tuberculosis in children have been based on extrapolation from adult data. In this issue of The Lancet Global Health, Peter Dodd and colleagues1Dodd PJ Gardiner E Coghlan R Seddon JA Burden of childhood tuberculosis in the 22 high-burden countries: a mathematical modelling study.Lancet Glob Health. 2014; (published online July 9.)http://dx.doi.org/10.1016/S2214-109X(14)70245-1Google Scholar provide new estimates of the burden of childhood tuberculosis in the 22 high-burden countries. By contrast with standard estimates that are contingent on paediatric case reporting, which varies widely between countries, these estimates used country-specific household-based and population-based data. WHO first disaggregated paediatric data in 2012 and has not included children with HIV infection in the estimates of mortality. The estimates by Dodd and colleagues differ substantially from WHO estimates in terms of incidence rates and the proportion of disease in children. The median number of incident cases in the high-burden countries (650 997, IQR 424 871–983 118), although almost 25% higher than the WHO global estimate of 530 000 paediatric cases in 2012,2WHOGlobal Tuberculosis Report, 2013. World Health Organization, Geneva2013Available online at: http://apps.who.int/iris/bitstream/10665/91355/1/9789241564656_eng.pdfGoogle Scholar is more consistent with other estimates. Jenkins and colleagues3Jenkins HE Tolman AW Yuen CM et al.Incidence of multidrug-resistant tuberculosis disease in children: systematic review and global estimates.Lancet. 2014; 383: 1572-1579Summary Full Text Full Text PDF PubMed Scopus (225) Google Scholar used data from a systematic review to estimate that, in 2010, almost 1 million children developed the disease. These higher estimates seem to reflect global population structure more accurately; roughly 25% of the world population is estimated to be younger than 15 years, with a range of 15–49% (median 31%) in high-burden countries.4World BankPopulation ages 0–14.http://data.worldbank.org/indicator/SP.POP.0014.TO.ZSGoogle Scholar Dodd and colleagues also provided estimates of the burden of tuberculosis in HIV-infected children, which infrequently has been disaggregated from adult tuberculosis and HIV co-infection. The overall estimated case detection rate of 35% was substantially lower than the WHO estimate of 66% case detection in children. This finding has profound implications for resource allocation and, combined with the estimated disparities in the burden of disease borne by children in the high-burden countries, prompts questions about how to make paediatric diagnosis and reporting easier. Although molecular methods such as Xpert MTB/RIF offer improved sensitivity over smear microscopy, their role is restricted to settings in which respiratory specimens can be obtained from younger children and to situations in which tuberculosis is suspected. Findings of a Peruvian study5Drobac PC Shin SS Huamani P et al.Risk factors for in-hospital mortality among children with tuberculosis: the 25-year experience in Peru.Pediatrics. 2012; 130: e373-e379Crossref PubMed Scopus (33) Google Scholar showed that a negative tuberculin skin test strongly predicted death in children admitted to hospital with tuberculosis, possibly because the diagnosis was considered initially but discarded on the basis of this insensitive test. Additionally, Dodd and colleagues modelled tuberculosis infection and estimated a prevalence of 50 million infected children. Because infection is not reportable in most settings, few population-based infection estimates exist. The new estimates allow for future benchmarking of preventable disease cases (eg, young children who are household contacts of cases, who did not receive isoniazid preventive therapy, and who progressed to disease). Although several studies6Van Wyk SS Reid AJ Mandalakas AM et al.Operational challenges in managing isoniazid preventive therapy in child contacts: a high-burden setting perspective.BMC Public Health. 2011; 11: 544Crossref PubMed Scopus (42) Google Scholar have reported poor use of isoniazid preventive therapy as per WHO guidelines in young exposed children,7WHOWHO policy on collaborative TB/HIV activities. Guidelines for national programmes and other stakeholders. World Health Organization, Geneva2012http://www.who.int/tb/publications/2012/tb_hiv_policy_9789241503006/en/Google Scholar broader population-based estimates of infection would encourage countries to alter resource allocation to improve secondary prevention. The study by Dodd and colleagues provides a strong foundation for future studies attempting to model the burden of childhood tuberculosis. The model incorporates both social and epidemiological variables. It would be intriguing to apply the model to low-incidence nations, where more complete paediatric data are available. If the model could be validated in these countries, confidence in its accuracy might be increased. Also of interest would be another sensitivity analysis changing the estimates of adult prevalence to see the effect on estimates in children. Variables that could be included in future models include modelling risk of tuberculosis exposure outside the home, especially in high-incidence settings where up to 40% of exposures stem from non-household contacts.8Middelkoop K Bekker LG Morrow C Lee N Wood R Decreasing household contribution to TB transmission with age: a retrospective geographic analysis of young people in a South African township.BMC Infect Dis. 2014; 14: 221Crossref PubMed Scopus (38) Google Scholar Finally, there is growing evidence that only a minority of adults with culture-confirmed pulmonary tuberculosis produce culturable aerosols, which might be a better marker of infectiousness than smear positivity.9Jones-López EC Namaugga O Mumbowa F et al.Cough aerosols of Mycobacterium tuberculosis predict new infection: a household contact study.Am J Respir Crit Care Med. 2013; 187: 1007-1015Crossref PubMed Scopus (100) Google Scholar Integration of these data into future models could result in more accurate estimates. The estimates of the burden of childhood tuberculosis provided by Dodd and colleagues are substantially higher than previous global estimates in high-burden countries. These findings show that what often has been taken as truth—that control of tuberculosis in adults will inevitably result in improved tuberculosis control for children—is fallacious as a stand-alone control strategy. Until the gap in case-detection and reporting is closed, children will continue to suffer from insufficient access to appropriate resources. The crucial role of childhood infection as a reservoir for future disease cases is ignored in many high-burden countries. Without improved case-detection and prevention strategies for children, it is difficult to envisage the high-burden countries following the same downward trajectory of incidence rates seen by industrialised countries during the past several decades. JRS is a member of a data safety monitoring board for paediatric studies of a tuberculosis drug (delamanid) made by Otsuka Pharmaceuticals. ATC declares no competing interests. Burden of childhood tuberculosis in 22 high-burden countries: a mathematical modelling studyOur model has shown that the incidence of paediatric tuberculosis is higher than the number of notifications, particularly in young children. Estimates of current household exposure and cumulative infection suggest an enormous opportunity for preventive treatment. Full-Text PDF Open Access