Chapter 36. Childhood Tuberculosis

Tuberculosis (TB) is an ancient disease; suggestive spinal changes have been described in Neolithic man, and clear evidence of TB bone lesions have been found in mummified remains from Egypt.1 Hippocrates (460–377 BC) introduced the ancient Greek term for TB, phthisis, better known as consumption.1 Although TB is an ancient disease, it remains one of the major public health challenges of the new millennium. Fuelled mainly by rampant third world poverty and the human immunodeficiency virus (HIV) epidemic, TB affects and kills more people today than ever before. The gravity of the situation is reflected by (1) the fact that the epidemic continues to escalate despite the declaration of a global TB emergency by the World Health Organization (WHO) in 1993 and (2) the increased transmission of drug-resistant TB.

Robert Koch (1843–1910) discovered that Mycobacterium tuberculosis causes TB, but it was soon recognized that infection, as indicated by a positive tuberculin skin test (TST), is not at all uncommon. It remains an intriguing and largely unexplained observation that only a small minority of people infected with M. tuberculosis ever progress to active disease. In endemic countries, TB control programs focus on the diagnosis and treatment of the most infectious cases (adults with sputum smear-positive TB) in an attempt to control the epidemic. Childhood TB receives little public health emphasis, as children tend to have paucibacillary disease and rarely transmit the organism. However, children in endemic areas carry a huge disease burden and experience considerable TB-related morbidity and mortality.2,3 In addition, adolescent children frequently develop cavitary disease4 and contribute to disease transmission within the community, particularly in congregate settings such as schools.5

An estimated 8.3 million new TB cases were diagnosed in 2000, of whom 884, 019 (11%) were <15 years of age.6 Poor countries carry the bulk of the TB disease burden, as exposure to both the organism and the vulnerability to progress to disease following infection are increased in these settings (Figure 36–1).7 HIV-related immune compromise is the most important factor that increases the vulnerability of individuals to develop TB following exposure and infection, which explains why Sub-Saharan Africa, the region worst affected by HIV, reports the highest TB incidence rates in the world.8

The risk to develop active TB following infection is mainly determined by the age and immune status of the child.9 The highest risk occurs in very young (immune immature) and/or immune-compromised children (Table 36–1).9 If children do progress to active TB, it usually occurs within 12 months of primary infection.9 Therefore, the burden of childhood TB provides a valuable epidemiologic perspective, as it reflects ongoing transmission within the community it serves as an important indicator of epidemic control.

TB is spread via tiny aerosol droplets, predominantly produced by adults with cavitary TB. The risk of infection following TB exposure depends on the infectiousness of the index case, as well as the proximity and duration of contact. In highly endemic areas, the majority of transmission occurs outside the household,10 but this does not reduce the importance of household exposure, especially in young and vulnerable children. In nonendemic countries like the United States, household exposure remains the most likely source of infection. In general, known household exposure to an adult index case presents an important opportunity for intervention, providing appropriate health education and preventive chemotherapy.

Both intra- and extrathoracic manifestations of TB will be discussed below. Intrathoracic manifestations include mediastinal lymph node disease, pleural and pericardial effusion, disseminated or miliary disease, and adult-type intrathoracic disease. Extrathoracic manifestations include cervical lymphadenitis, tuberculous meningitis, other organ involvement, and, in patients with HIV, immune reconstitution.

Intrathoracic Disease

The TB bacillus usually enters its human host via the lungs; inhalation of an infectious droplet with the right size to penetrate into the periphery of the lung results in a localized area of pneumonic consolidation at the site of organism deposition. This is referred to as the primary (Ghon) focus, from where TB bacilli drain via local lymphatics to the regional lymph nodes. The combination of the Ghon focus and enlarged regional lymph nodes, usually involving the perihilar area, is referred to as the primary complex.11 Active disease may present with a diverse spectrum of pathology. Figure 36–2 provides a schematic illustration of potential disease progression following primary infection with M. tuberculosis and how the various disease manifestations develop.11 The different disease manifestations show clear patterns related to (1) the time since infection occurred (Figure 36–3)9 and (2) the age at the time of primary infection (Figure 36–4).12 The disease manifestations observed in immune-compromised children seem to correlate with those seen in very young (<3 years of age) children.12,13

Lymph Node Disease

Involvement of the intrathoracic lymph nodes (perihilar and/or paratracheal) is considered the radiological hallmark of primary infection.14 Both anteroposterior and lateral views are required for optimal lymph node visualization (Figures 36–5 and 36–6). However, transient hilar adenopathy is not uncommon following recent primary infection, and particular care should be exercised when interpreting results of very sensitive tests such as high-resolution computed tomography of the lung, in the absence of clinical data.13

Lymph node disease may be complicated by airway involvement and/or penetration into adjacent anatomical structures.11 Complicated lymph node disease occurs most commonly in children <5 years of age, probably because of exuberant lymph node responses and the small caliber of their airways. Airway compression results when an airway is surrounded and fixated by diseased lymph nodes and associated inflammation, and this may be best visualized on a high-kilovolt chest radiograph (CXR). Various disease presentations include partial airway obstruction with a check-valve effect and alveolar hyperinflation, or total airway obstruction with alveolar collapse. When a diseased lymph node erupts into an airway, caseous material may be aspirated and the resulting pathology may range from pure hypersensitivity-induced inflammation (dead bacilli and/or “toxins”) to destructive caseating pneumonia (virulent bacilli), depending on the bacterial load and viability of the bacilli aspirated. Caseating pneumonia often causes an expansile (bulging against their anatomical boundaries) pneumonic process with visible parenchymal breakdown (Figure 36–7).15 Penetration into adjacent anatomical structures may involve the phrenic nerve with unilateral diaphragmatic palsy, the esophagus with the formation of a broncho- or tracheoesophageal fistula, and/or the thoracic duct with the formation of a unilateral chylothorax.11

Pleural and Pericardial Effusion

The accumulation of the typical lymphocyte-rich, straw-colored fluid represents a hypersensitivity response. The pleural fluid typically obliterates 30–60% of the affected hemithorax (Figure 36–8), although massive fluid collections may cause mediastinal shift and cardiovascular compromise.11 In general, isolated pleural effusions are unusual in children <3 years of age and tend to develop soon (within the first 3–9 months) after primary infection.9

A loculated fluid collection may indicate TB empyema that results when bacilli actively multiply within the pleural space. This is not common, but immune-compromised individuals seem to be at increased risk.

Pericardial effusion usually develops when a subcarinal lymph node erupts into the pericardial space.9 On CXR the heart shadow may be enlarged with a suggestive globular appearance, but cardiac ultrasound is the most sensitive test to confirm or exclude the presence of a pericardial effusion. Long-term sequelae include constrictive pericarditis, and this is an indication for the use of corticosteroids together with anti-TB treatment.11

Disseminated (Miliary) Disease

Dissemination represents a condition of infinite gradation. Occult dissemination is common following primary infection; however, it rarely progresses to disseminated disease except in very young (<2–3 years of age) and immune-compromised children.9,13 Typical radiologic signs include the presence of even-sized miliary lesions (<2 mm), which are distributed bilaterally into the very periphery of the lung (Figure 36–9).11 Diagnostic confusion often exists in HIV-infected children in whom lymphocytic interstitial pneumonitis, malignancies, and opportunistic infections such as Pneumocystis jeroveci may present with a similar radiological picture.16 In these instances, response to treatment and/or bacteriologic confirmation may be the only way to establish a definitive diagnosis.

Adult-Type Disease

Adult-type disease first appears around puberty (from 8 to 10 years of age) and becomes the dominant disease manifestation during adolescence.9 As with pulmonary TB in adults, the apical and posterior segments of the upper lobe and the apical segment of the lower lobe are most commonly affected (Figure 36–10). Complications include progressive cavity formation and bronchial spread.11

Extrathoracic Disease

Cervical Lymphadenitis

The most common extrathoracic manifestation of TB in children is cervical lymphadenitis (Table 36–2). Disease pathology within the lymph node is similar to that seen in other organs, with initial tubercle formation and lymphoid hyperplasia that may progress to caseation and necrosis. Isolated involvement of a single node is rare, and nodes are usually matted because of considerable periadenitis. A cold abscess results when the caseous material liquefies, and this is signified by a soft fluctuant node with violaceous discoloration of the overlying skin; spontaneous drainage and sinus formation may follow. Untreated, the natural course of TB lymphadenitis in an immune-competent host follows a prolonged and relapsing course, often interrupted by transient lymph node enlargement, fluctuation, and/or sinus formation.

Table 36–3 reflects the clinical characteristics of children diagnosed with TB lymphadenitis.17 A simple clinical algorithm that identifies children with persistent (>4 weeks) cervical adenopathy, without a visible local cause or response to first-line antibiotics, and a cervical mass ≥2 × 2 cm showed excellent diagnostic accuracy in this highly endemic area. However, a clinical diagnostic approach would be far less accurate in nonendemic areas and in areas where alternative diagnoses, such as Burkitt's lymphoma, are more common. In these settings, a positive TST result may have additional value to indicate mycobacterial disease,17 although it may not differentiate TB lymph adenitis from disease caused by non-TB mycobacteria.18 Establishing a definitive tissue and/or culture diagnosis remains preferable, and this can be done in a minimally invasive fashion using fine needle aspiration biopsy.17

The mycobacteria that cause cervical lymphadenitis are highly variable in different settings. In areas where the control of bovine TB is poor and milk is not routinely pasteurized, Mycobacterium bovis may be a frequent cause, but in areas where TB is endemic and bovine TB is well controlled, M. tuberculosis would be the most common causative organism. In developed countries with low rates of TB transmission, non-TB (environmental) mycobacteria and, in particular, M. avium-intracellulare are most frequently responsible.18

Tuberculous Meningitis

Tuberculous meningitis is the most severe manifestation of childhood TB. Bacille Calmette Geurin (BCG) vaccination provides some degree of protection against the severe forms of TB (miliary disease and tuberculous meningitis), but despite universal BCG vaccination severe disease manifestations still occur, mainly affecting very young (immune immature) and/or immuno-compromised children in endemic areas.

Other TB Manifestations

TB can affect nearly every organ system (Table 36–2), and this is mostly the result of disease progression, which occurs at sites where the TB bacillus was deposited during the initial phase of occult dissemination. In addition, newborn babies may acquire congenital TB via the placenta, in which case the primary (Ghon) focus is usually located in the liver, if the mother develops active TB or M. tuberculosis infection with hematogenous dissemination during pregnancy. The experience is that cases of congenital TB are on the rise in countries where TB/HIV coinfection rates among expectant mothers are high.

Immune Reconstitution

The clinical syndrome was first documented in the prechemotherapy era, following nutritional rehabilitation and/or the termination of high-dose steroid treatment.9 Recently, immune reconstitution inflammatory syndrome (IRIS) has emerged as an important complication to consider after the introduction of highly active antiretroviral therapy in HIV-infected, immune-compromised patients.19 Radiologic signs may include airway compression as a result of increased inflammation surrounding diseased lymph nodes, or dense alveolar consolidation caused by excessive inflammation in areas of previous “subclinical” TB infiltration. This temporary exacerbation of TB symptoms and signs is mainly ascribed to the effects of improved immune function, although a “hypersensitivity” reaction to antigens released by killed TB bacilli may also contribute. It does not indicate treatment failure and should subside spontaneously, although severe cases may require treatment with corticosteroids. In a recent prospective survey of 152 Thai children with low CD4 percentages (<15%), IRIS was documented in 14 (19%), usually within 4 weeks of highly active antiretroviral therapy initiation.20 The majority of IRIS cases (nine) were caused by atypical mycobacteria, three because of M. tuberculosis, and two because of M. bovis BCG.

Establishing a definitive diagnosis of childhood TB remains a challenge. Sputum smear microscopy is positive in <10–15% of children with TB, and culture yields are generally low (30–40%),21 although it may be considerably higher in children with advanced disease.22 In low-burden countries the triad of (1) known contact with an infectious source case, (2) a positive TST, and (3) a CXR is frequently used to establish a diagnosis of childhood TB. This provides a reasonably accurate diagnosis in nonendemic settings where exposure to M. tuberculosis is rare and usually well documented. However, it has limited value in endemic areas where exposure to, and/or infection with, M. tuberculosis is common.13 Consequently, the diagnosis of TB in endemic areas depends predominantly on the subjective interpretation of the CXR, which provides a fairly accurate diagnosis in experienced hands, despite its many limitations.23,24 An important concept derived from the natural history of disease is risk stratification, which determines the diagnostic emphasis and guides therapeutic decision making.13 Exposure and/or infection warrants preventive chemotherapy in all children who are at high risk of developing active TB but are less relevant in low-risk children from endemic areas where infection is a common event.

Symptom-Based Diagnosis

WHO guidelines advise that all children <5 years of age in close contact with a sputum smear-positive index case should be actively traced, screened for TB, and provided preventive chemotherapy once active TB has been excluded.25 National guidelines frequently regard the TST and CXR as prerequisite tests for adequate screening of household contacts, but these tests are rarely available in endemic areas with limited resources. In these settings, symptom-based screening may have considerable value to improve access to preventive therapy,26 and this is acknowledged by the most recent WHO guidelines.25 In low-burden countries where TB eradication is an achievable goal and the risk of reinfection is low, preventive chemotherapy may be provided to everyone with documented TB infection to try and eradicate the pool of latent TB infection, from which future reactivation disease may result.13

As a result of the diagnostic limitations mentioned and the difficulty of obtaining a CXR in many endemic areas, a variety of clinical scoring systems have been developed to diagnose active TB. A critical review of these scoring systems concluded that these are severely limited by the absence of standard symptom definitions and inadequate validation.27 Accurate symptom definition is important to differentiate TB from other common conditions, as poorly defined symptoms (such as a cough of >3 weeks’ duration) have poor discriminatory power.28 However, the diagnostic use of well-defined symptoms with a persistent, nonremitting character holds definite promise in low-risk children (immune-competent children >3 years) in whom TB is usually a slowly progressive disease.29,30 The most helpful symptoms include (1) persistent, nonremittent coughing or wheezing, (2) documented failure to thrive despite food supplementation (if food security is a concern), and (3) fatigue or reduced playfulness.29 Clinical follow-up is also a valuable diagnostic tool. In young children (<3 years), who are at greatest risk of developing disseminated (miliary) disease and tuberculous meningitis, persistent or intermittent unexplained fever (>5–7 days) and lethargy are of great importance as well.

In HIV-infected (immune-compromised) children, the diagnostic challenge is most pronounced because of the following factors.31

HIV-infected children who live with HIV-infected adults are more likely to be exposed to an adult index case at home. However, HIV-infected adults often have sputum smear-negative TB, and therefore the infection risk posed by this exposure is less appreciated.

The TST has low sensitivity in HIV-infected children and is positive in the minority of HIV-infected children with bacteriologically confirmed TB despite using a reduced induration size cutoff of ≥5 mm.32

Chronic pulmonary symptoms from other HIV-related conditions such as gastroesophageal reflux and bronchiectasis are not uncommon, while failure to thrive is a typical feature of both TB and HIV, reducing the specificity of symptom-based diagnostic approaches.

Rapid disease progression may occur, reducing the sensitivity of diagnostic approaches that focus on persistent, nonremitting symptoms.

CXR interpretation is complicated by HIV-related comorbidity such as bacterial pneumonia, lymphocytic interstitial pneumonitis, bronchiectasis, pulmonary Kaposi sarcoma, and the atypical presentation of TB in immune-compromised children.16

Immune-Based Diagnosis

Although commercial kits for antibody detection are marketed widely in the developing world, no serological assay is currently accurate enough to replace microscopy and culture.33 Immune-based diagnosis is complicated by the wide clinical disease spectrum (ranging from subclinical latent infection to various manifestations of active disease) and other factors that influence the immune response such as BCG vaccination, exposure to environmental mycobacteria, and HIV coinfection, all of which are particularly prevalent in endemic areas.33

Novel T-cell assays measure interferon-gamma released after stimulation by M. tuberculosis-specific antigens. Two assays are currently available as commercial kits: the T-SPOT.TB® test (Oxford Immunotec, Oxford, UK), and the QuantiFERON®-TB Gold® assay (Cellestis Ltd, Carnegie, Australia). In general, these tests are regarded as more specific and potentially more sensitive than the traditional TST.33 However, like the TST, these novel T-cell assays fail to differentiate M. tuberculosis infection from active disease.33 Identifying the correct application of these novel T-cell-based assays in endemic and nonendemic areas remains a priority for future research.

Bacteriology-Based Diagnosis

A positive culture is still regarded as the “gold standard test” to establish a definitive diagnosis of TB in a symptomatic child. Traditional culture methods are limited by suboptimal sensitivity, slow turnaround times, excessive cost (automated liquid broth systems), and the fact that bacteriologic yields in children are low. However, the yield in children with complicated intrathoracic disease is significantly higher than in those with uncomplicated hilar adenopathy (77% vs. 35%),22 and adolescent children frequently develop sputum smear-positive adult-type disease.4

Novel culture-based approaches include TK Medium® (Salubris Inc., Cambridge, MA, USA), a simple colorimetric system that rapidly indicates mycobacterial growth, but its accuracy and robustness in field conditions are still being evaluated.33 The phage amplification assay uses bacteriophages to infect live M. tuberculosis and is commercially available as FASTPlaque-TB® (Biotec Laboratories Ltd, Ipswich, Suffolk, UK); a variant (FASTPlaque-TB Response®) was designed to rapidly detect rifampin resistance. The test has a turn around time of only 2–3 days but is less sensitive than traditional culture methods, and no information exists on its utility in children.33 Another novel test is the microscopic observation drug susceptibility assay, which uses an inverted light microscope to rapidly detect mycobacterial growth in liquid growth media. Microscopic observation drug susceptibility is an inexpensive method, which has shown excellent performance under field conditions34 and may significantly improve the capability to detect pediatric TB in resource-limited settings.35

Polymerase chain reaction-based tests amplify nucleic acid regions specific to the M. tuberculosis complex but have shown highly variable results and limited utility in children.33 Detecting antigens instead of antibodies offers another innovative approach, and novel antigen-capture assays that detect lipoarabinomannan in sputum and/or urine samples look promising, but results from field trials are awaited Table 36–4.36

Sample Collection

Even before various bacteriologic detection methods can be applied, sample collection presents a significant challenge, particularly in small children who cannot produce an adequate sputum specimen. Table 36–5 provides an overview of the various sampling methods and the perceived problems and/or benefits of each. Routine specimen collection includes two to three fasting gastric aspirates, collected on consecutive days and usually requiring hospitalization. The collection of a single specimen using hypertonic-saline-induced sputum collection may provide the same yield as three gastric aspirate specimens.37 The string test (HDC Corporation, CA, USA) has been used successfully to retrieve M. tuberculosis from sputum smear-negative HIV-infected adults and demonstrated superior sensitivity compared to induced sputum38; the test is also well tolerated by children as young as 4 years of age.39 Fine needle aspiration biopsy is a robust and simple technique that provides a rapid and definitive diagnosis in children with superficial TB lymph adenitis; the use of a small 23-gauge needle is well tolerated and associated with minimal side effects.17Table 36–5 provides a summary of various bacteriologic specimen collection methods and the perceived problems and/or benefits of each.

The two principles of anti-TB treatment are to (1) reduce the organism load as rapidly as possible and (2) ensure effective eradication of all persistent bacilli.13,40 This provides the rationale behind the intensive and continuation phases of current anti-TB treatment regimens. Rapid reduction of the organism load is important to reduce clinical symptoms, limit disease progression, terminate transmission, and reduce the risk of acquired drug resistance. Eradication of persistent (dormant or intermittently metabolizing) bacilli is essential to prevent future disease relapse.13

Preventive Chemotherapy

Isoniazid (INH) monotherapy for 6–9 months is the best-studied prophylactic regimen,40 but poor adherence with unsupervised treatment is a serious concern and alternative prophylactic regimens with improved adherence require consideration.41 The addition of rifampicin (RMP) to prophylactic regimens has numerous advantages: reducing the risk of INH monoresistance, improving organism eradication, shortening the duration of treatment, and improving adherence.42 INH and RMP for a duration of 3 months are a well-established prophylactic regimen, which provides equivalent protection to 6–9 months of INH monotherapy, although it is important to remember that RMP interacts with highly active anti-retroviral therapy (HAART).42 In theory, the addition of pyrazinamide (PZA), another drug with strong sterilizing activity, should further improve the sterilizing ability of preventive therapy regimens and shorten the required treatment duration, but this requires further evaluation.13

Standard Treatment

The main variables that influence the success of chemotherapy, apart from primary drug resistance, are the bacterial load and the anatomical distribution of bacilli.13 From a public health perspective, children with TB can be categorized into three groups: (1) sputum smear-negative disease, (2) sputum smear-positive (often cavitary) disease, and 3) disseminated (miliary) disease or TB meningitis.

Sputum smear-negative disease is usually paucibacillary, and therefore the risk of acquired drug resistance is low. Drug penetration into the anatomical sites involved is good, and the successes of three drugs (INH, RMP, and PZA) during the 2-month intensive phase and two drugs (INH and RMP) during the 4-month continuation phase are well established.13 In the presence of extensive radiographic disease with or without cavitation, and/or suspicion of INH resistance, the use of ethambutol in addition to the three drugs during intensive phase should be contemplated. After completion of the intensive phase, successful organism eradication may be achieved with intermittent (2–3×/week) therapy during the continuation phase.13

Sputum smear-positive disease implies a high organism load and an increased risk for random drug resistance.13 Selecting drug-resistant mutants is a particular concern where INH monoresistance is prevalent, as this increases the likelihood of selecting multi-drug-resistant (MDR) organisms. The use of four drugs (INH, RMP, PZA, and ethambutol) during the 2-month intensive phase should reduce this risk. Once the organism load is sufficiently reduced, intermittent (2–3×/week) therapy with INH and RMP during the 4-month continuation phase is sufficient to ensure organism eradication. However, caution should be exercised when initial treatment response has not been optimal and in patients with HIV.13

Disseminated (miliary) disease is frequently associated with central nervous system involvement.13 It is therefore essential to consider the cerebrospinal fluid (CSF) penetration of drugs used in the treatment of disseminated (miliary) disease. INH and PZA penetrate the CSF well.43 RMP and streptomycin (S) penetrate the CSF poorly but may achieve therapeutic levels in the presence of meningeal inflammation.43 The value of streptomycin is limited by poor CSF penetration and intramuscular administration. Ethambutol hardly penetrates the CSF, even in the presence of meningeal inflammation, and has no demonstrated efficacy in the treatment of tuberculous meningitis.13,43

A flow diagram has been developed (Figure 36–11) to guide individual patient classification and management.13 It is based on answering five simple questions: (1) Is the child exposed to or infected with M. tuberculosis? (2) Does the child have active TB? (3) If the child is exposed or infected but does not have active TB, is preventive chemotherapy indicated? (4) If the child has active TB, what is the appropriate treatment regimen? (5) Are there any special circumstances such as HIV infection, retreatment, or exposure to a drug-resistant source case to consider?

The recommended treatment for intrathoracic TB in children is 6 months of directly observed therapy (DOT) and 2 months of three drugs (INH, RMP, and PZA), followed by 4 months of two drugs (INH and RMP).26,40Table 36–6 summarizes current treatment guidelines. RMP-based regimens are effective and cheap, and child-friendly formulations are available; from 2007, child friendly formulations will also be made available via the Global Drug Facility. The cellular immune response assists with organism containment and eradication. Because immune-compromised children lack this important immune contribution, they are at increased risk of disease relapse following standard short-course therapy.44 It seems prudent to prolong the treatment duration in immune-compromised children, although this has not been verified in placebo-controlled trials. In the absence of sufficient evidence, the current recommendation is to consider prolonging the treatment duration to 9 months.13,40

Drug Resistance

The selection of drug-resistant organisms occurs primarily in patients with high organism loads. Because of the paucibacillary nature of childhood TB in general, children contribute little to the creation of the drug resistance problem, but they are severely affected by it. A recent survey from Cape Town recorded INH resistance in 12.4% of child isolates, and MDR (INH and RMP resistance) in 5.3%.45 This is alarming, as drug resistance patterns among children provide an accurate indication of transmitted drug resistance within the community. The transmission of drug-resistant disease poses a major new challenge to TB control programs globally. However, the principles of diagnosis and treatment remain exactly the same as those outlined for drug-sensitive TB. Following MDR exposure, high-risk children should be protected with appropriate chemoprophylaxis. Table 36–7 provides a list of the first second-line drugs currently available for treatment. The management of drug-resistant TB should be discussed with an expert in the field, as second-line drugs are less potent, have poor sterilizing capability, and are associated with more side effects.

Improving the access of (1) high-risk exposed and/or infected children to preventive therapy and (2) all children with active disease to anti-TB treatment will drastically reduce the severe TB-related morbidity and mortality suffered by children in endemic areas. However, the burden of childhood TB is ultimately only a reflection of the level of epidemic control achieved within communities.7 Current TB control efforts are mainly directed toward reducing transmission by treating sputum smear-positive adults, but little emphasis is placed on reducing the vulnerability of communities. The formulation of the United Nations Millennium Developmental Goals46 is an important step in this direction, but global political commitment and sufficient funding are required to support this key initiative.