Childhood tuberculosis: In Canada and around the world

In North America today, there is a risk that tuberculosis (TB) will become a forgotten disease. Rates of TB are so low in Canada (5.5/100,000 [1]) and in the United States, (5.6/100,000 [2]) that without concerted effort, expertise will be lost, impeding the final push toward elimination. The United States Centers for Disease Control and Prevention (CDC) declared a goal of elimination in 1989 (3) about the time of the resurgence of TB in inner cities linked to human immunodeficiency virus (HIV) and failing public health infrastructure. With vigorous effort and influx of dollars the rise has been reversed, restoring the continued decline of about 7% a year. How to sustain control is the subject of much discussion (4) and will necessitate more aggressive application of treatment of latent infection, education of health professions and risk groups, and a commitment to contribute to controlling the global epidemic. Although Canada did not suffer the same resurgence, there was a plateau from 1988 to 1994 prompting our own declaration of a goal of elimination (5). We need to remind ourselves repeatedly of the clinical presentation of the disease (Clinician's Corner, pages 175–177), the challenges of making the diagnosis in the child, the role for the clinician in control strategies (Tapiéro and Lamarre, pages 139–140) and the need for solidarity with the Global Stop TB partnership goals to reach the targets of finding 70% and curing 85% with the DOTS. DOTS is more than Directly Observed Therapy short-course. It refers to the five essential elements of a National TB Program: simple sputum smear microscopy diagnosis, uninterrupted drug supplies given with supervision, recording, reporting and outcome evaluation, and political commitment to sustain these efforts (Kitai and Malloy, pages 162–172) (6). The inescapable reality is that TB is a disease of poverty that is not only curable for about $10 with DOTS, but is preventable for little more, yet only 27% of the world's cases have access to this life-saving strategy. Globally, the World Health Organization estimates that there are 8.74 million new cases of TB each year, of which 15% are children (1.3 million) resulting in 450,000 childhood deaths annually (7). There is little detail collected about paediatric cases because the focus of global surveillance is on smear-positive patients who are the priority for treatment to stop the transmission of infection. Evidence of the likelihood that these numbers are an underestimation comes from various sources. Even before HIV, in some settings, TB accounted for 10% of childhood admissions and 10% of hospital deaths (8). HIV coinfection in sub-Saharan Africa has increased the already high rates of TB by as much as 500% in some countries. In these settings paediatric rates have also increased (9). The startling report from South Africa (10) of notification rates in children younger than five years of age is 3588/100,000 – 3.5 times higher than the rate in adults at a time (1985 to 1994) when HIV prevalence was relatively low is frightening evidence that the epidemic will be sustained in this population for decades to come. It is time to move rapidly to institute a global policy of treatment for latent infection (prophylaxis) to household contacts of smear-positive cases as a basic part of national TB programs, even in the most impoverished countries. In industrialized countries 3% to 6% of TB patients are younger than 15 years of age. In Canada in 2001 (1), 111 of 1703 (6.5%) patients were younger than 15 years of age. In an unpublished study, Yacoub reviewed paediatric TB cases in Alberta and found that in the years 1989 to 1994, children younger than 15 years of age accounted for 64% of cases among First Nations children compared with 8.1% of all provincial TB childhood cases (personal communication, Wadieh Yacoub). Childhood TB is clear evidence of transmission. Once infected, young children have an increased risk of progression to active disease: 43% in those younger than one year of age, 24% in those one to five years of age and 15% in adolescents (8). Children have been likened to the canary in the coal mine – a sorry allusion to the unheeded warning of ongoing transmission. While supporting global commitment to control TB, we must renew our determination to prevent childhood TB at home. We should follow with interest the research proposal funded by the CDC to apply the notion of ‘zero tolerance’ for childhood TB in marginalized communities where it still exists. This will prompt aggressive contact follow-up of active smear-positive cases, especially in households with small children: tuberculin skin test (TST) within a week and if no disease (normal x-ray and no symptoms), the immediate initiation of isoniazid prophylaxis. Clinicians seem to stall at the skin testing, reluctant to act on a positive interpretation. Once started, prophylaxis must be completed to be protective; thus, the need to consider directly observed prophylaxis. Inherent in all this is the need to partner with the public health system whose mandate is control, with the family and the community who need to understand and support the intervention and the goal. TB in childhood is very difficult to diagnose even in Canada with easy access to culture, radiology and molecular tools. Case #1 (Clinician's Corner), illustrates the prolonged nature of the illness and the need to glean historical information of possible contacts in risk populations of Canada, First Nations and those born in countries with high TB prevalence (1). The diagnosis of TB depends on history of contact with an infectious case, clinical signs and symptoms, chest x-ray and TST. Bacillus Calmette-Guerin vaccination raises uncertainty about the skin test result (Vaudry, pages 141–144), even though tuberculin reactivity is seldom more than 10 mm, and fades 10% per year. In the presence of clear exposure, the Bacillus Calmette-Guerin history should be ignored and the positive result acted upon (11). The gold standard of culture is seldom achieved in more than 40% of paediatric cases and if treatment is delayed until confirmation with culture, the disease is missed, with tragic results. In low income countries where diagnosis rests on sputum smear microscopy, algorithms have been developed to diagnose childhood TB (12). Hesseling et al (12) reviewed 16 diagnostic scoring systems; some were point scores, others used the World Health Organization category of ‘suspect’, ‘probably’ and ‘confirmed’. While all scoring systems used skin test, x-ray and family history, 15 used weight loss, 14 used cough, 14 used bacteriology, 11 used lymph adenopathy, 10 used fever, nine used response to treatment, eight used failed recovery of childhood infections such as measles, eight used duration of symptoms and seven used histology. Because the gold standard of bacteriological confirmation is not reached in most, there is an urgent need for new diagnostic criteria that recognize the limited resources in settings with high levels of malnutrition and HIV infection, where the diagnosis is even more problematic, especially in reliance on TST, response to treatment and fever. TB is the great imitator, and given the setting of a child with failure to thrive, from one of the risk populations, the diagnosis must be vigorously pursued. Extra pulmonary sites account for 25% of TB cases in American children, most commonly miliary, meningitis, bone and lymph node. A scoring system in Canada, where access to highly technical diagnostic tests are readily available, may direct further investigation. When the index of suspicion is high, specimens for culture should be obtained from the site of concern and in the case of hilar adenopathy, miliary lesion, or unresolving pneumonia, a gastric wash buffered for transport and done before rising in the morning will yield good results. The clinician is not finished when the diagnosis is established. There is an obligation to ensure that a case manager is assigned to observe the swallowing of all medications until cure is achieved. Partnership with the family, the social support system, the family doctor and the public health system, as well as the paediatrician, is critical to the completion of treatment (13). Although the possibility of TB resurgence in Canada exists, it is highly unlikely, but the disease will continue to smolder causing sickness and some deaths in marginalized populations of First Nations and inner city residents. Hence the need for a strong national TB program with strengthened surveillance in these groups. There is no evidence that TB in the foreign-born has a significant spillover effect on the Canadian-born population (14). So, while we should continue to screen immigrants and visitors from endemic countries there is little justification for prearrival prophylaxis. Of much greater impact would be a major long term commitment to support the Global Stop TB partnership, to raise awareness and, most importantly, dollars to control the global epidemic. The goal of TB elimination at home is fine, as long as it is not applied in isolation from the imperative to address the global problem. Canada signed the G8 Okinawa accord of 2000 (15), which committed Canada to reduce TB along with other diseases of poverty by 50% by 2010. We have seven years left and a long way to go!

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