Chapter 16: Tuberculosis in Children
by Nora Morcillo
The incidence and prevalence of pediatric tuberculosis (TB) worldwide varies significantly according to the burden of the disease in different countries. It has been estimated that 3.1 million children under 15 years of age are infected with TB worldwide. According to the World Health Organization (WHO), children with TB represent 10 % to 20 % of all TB cases. The majority of these cases occur in low-income countries where the prevalence of Human Immunodeficiency Virus/Acquired Immunodeficiency Syndrome (HIV/AIDS) is high. TB occurs frequently among disadvantaged populations, such as malnourished individuals, and those living in crowded areas. According to WHO reports, India, China, Pakistan, the Philippines, Thailand, Indonesia, Bangladesh, and the Democratic Republic of the Congo account for nearly 75 % of all cases of pediatric TB (World Health Organization 2006, Dye 1990). Furthermore, it has also been reported that TB is responsible in Sub-Saharan countries for between 7 % and 16 % of all episodes of acute pneumonia in HIV-infected children, and for approximately one fifth of all deaths in children presenting with acute pneumonia (Chintu 2002, Jeena 2002).
On the other hand, in developed countries such as the United States (US), while an increase in the incidence of TB of approximately 13 % was reported in all ages from 1985-1994, the rate among children younger than 15 years old increased by 33 %. This was mainly attributed to the HIV epidemic, which increased the risk of developing active TB among persons with latent TB infection and HIV co-infection (American Thoracic Society/Centers for Disease Control and Prevention 2001, Taylor 2005). As in adults, TB equally affects children of both genders (males and females), but an increased risk of mortality exists at the extremes of age. Therefore, young children and especially newborns are at a high life risk when they are exposed to a contagious source (Dye 1999). Since most pediatric cases occur due to a rapid progression of a recent infection with a short incubation period, this implies a high rate of recent transmission in the community. Therefore, the infected and ill children in the community are an indirect, useful parameter for assessing the impact of Tuberculosis Control Program activities.
Pulmonary TB in children has a low bacillary load and cavities are also rarely present. Children also lack the forceful cough mechanism seen in adults. Adolescents and older children are important exceptions since their disease closely resembles that of adults. In these cases, the disease is frequently associated with unfavorable conditions, such as bad nutrition (Correa 1997).
Most risk factors for the acquisition of TB are usually exogenous to the patient. Thus, the likelihood of being infected depends on the environment and characteristics of the index case. However, the development of active disease also depends on the inherent immunologic status of the host (Alcaiis 2006, Alet 2003).
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16.2. Etiology, transmission and pathogenesis In about 95 % of cases, TB is an airborne disease, transmitted by particles, or droplet nuclei that are expelled when persons who have pulmonary or laryngeal TB sneeze, cough, speak or sing (Feja 1999). When the recipients are persons without previous natural contact with M. tuberculosis, the infectious process is denominated primary infection. When this infection evolves to the disease, it is called primary TB (Vallejo 1994). Droplet nuclei containing between one to 10 bacilli and a diameter close to 10 µm are expelled with the cough, suspended in the air and transported by air currents. Normal air currents can keep them airborne for prolonged periods of time and spread them throughout rooms or building. Some of these droplet nuclei, usually larger than 10 µm, are inhaled and anchored in the upper respiratory tract (Wells 1995). The mucus and the ciliary system of the respiratory tract avoid further progression of mycobacteria. The effective infective droplet nucleus is very small; measuring 5 µm or less, it is able to avoid the mucus and ciliary system action and produce the anchorage in bronchioles and respiratory alveoli. The small size of the droplets allows them to remain suspended in the air for prolonged periods of time. Although theoretically a single organism may cause disease, it is generally accepted that about five to 200 inhaled bacilli are necessary for a successful infection. After inhalation, the bacilli are usually installed in the midlung zone, into the distal and subpleural respiratory bronchioles or alveoli. Subsequently, alveolar macrophages phagocytose the inhaled bacilli. However, these first macrophages are unable to kill mycobacteria and the bacilli continue their replication inside these cells. Logarithmic multiplication of the mycobacteria takes place within the macrophage at the primary infection site. Thereafter, transportation of the infected macrophages to the regional lymph nodes occurs leading to the lymphohematogenous dissemination of the mycobacteria to other lymph nodes and organs such as kidneys, epiphyses of long bones, vertebral bodies, juxtaependymal meninges adjacent to the subarachnoid space, and, occasionally, to the apical posterior areas of the lungs. In addition, chemotactic factors released by the macrophages attract circulating monocytes to the infection site, leading to their differentiation into mature macrophages with increased capacity to ingest and kill free bacteria (Correa 1997, Starke 1996, Vallejo 1994). Two or three weeks after the initial M. tuberculosis infection, a cell-mediated immune response is fully established. While CD4+ T helper cells activate the macrophages to kill the intracellular bacteria and finally cause epithelioid granuloma formation, CD8+ suppressor T cells lyse the infected macrophages, resulting in the formation of caseous granulomas with central necrosis. Due to the fact that mycobacteria are not able to grow under the adverse conditions of the extracellular environment, most infections are controlled by the host immune system. The only evidence of a real and effective infection is a positive TST (Correa 1997, Seibert 1932, Seibert 1934). However, the initial pulmonary infection site, which is denominated “primary complex or Ghon focus” and its adjacent lymph nodes, sometimes reach sufficient size to develop necrosis and calcification demonstrable by radiographs (Feja 2005, Schluger 1994). As in adults, childhood TB is mostly due to M. tuberculosis. The proportion of both pediatric and adults TB cases caused by M. bovis is very low. It is generally associated with close contact with cattle, and is variable from one country to another and even from region to region inside the same country (see Chapter 8). Bacille Calmette-Guérin (BCG) vaccination applied to newborns reproduces a natural infection under controlled conditions in an attempt to avoid a first productive contact – leading to a severe disease – between children and virulent M. tuberculosis strains spread in the community. During further contacts with M. tuberculosis from a natural infectious source, a child’s immune system, already prepared by BCG vaccination, will be more capable of controlling this new infection. BCG vaccination can sometimes cause a disease clinically indistinguishable from TB, but this usually occurs in patients with severe impairment of their immune system (Jacobs 1993, Vallejo 1994, see Chapters 8 and 10). 16.2.1. Infection acquisition Most pediatric TB cases can be traced to a household relative contact. In general, it is believed that the younger the child with a positive tuberculin skin test (TST), the higher the probability of an infectious source within the home. This situation occurs when repetitive or constant contact with the infectious source – generally family members – takes place. Therefore, when a child is diagnosed, a search should be performed for an adult case with a high bacillary load in the respiratory tract (Alet 1986). On the other hand, older children may become infected from an external source, such as schoolmates, team leaders or young adults outside the home. The presence of extensive pulmonary lesions, such as cavities, is the most important individual human factor in determining the infectious power, since these lesions are associated not only with an important concentration of oxygen that allows active bacillary multiplication, but also with a rapid pathway to the external environment. The amount of bacilli released into the atmosphere under these conditions is enough to produce the transmission from person to person (Correa 1997, Schluger 1994). The degree of pulmonary involvement is another important factor, since the extension of the lesions is related to the bacillary load, the intensity and frequency of coughing, and the number of cavities that may propagate these bacilli. Rarely, non-pulmonary localization of the disease with high infectious power, such as the laryngeal form, becomes an infectious source. In this case, simple actions such as talking can cause the elimination of an important amount of mycobacteria (Correa 1997). Socioeconomic factors as well as the overcrowded living places in urban areas increase the risk of infection allowing larger contacts with infected persons. Race may not be considered an independent risk factor (Brailey 1996). The infectious capacity of the source case is also associated with the virulence of the bacilli. Environmental factors also contribute to the likelihood of acquiring the infection. The concentration of bacilli depends on ventilation of the surroundings and exposure to ultraviolet light. Thus, overcrowding, congregation in schools, poor housing and inadequate ventilation predispose individuals to infection and development of TB (American Academy of Pediatrics 2003). 16.2.2. Infection development Defects in the level of immunocompetence, especially in cell-mediated immunity, such as HIV infection, are major determinants for development of TB. In general, TB case rates for persons who are co-infected with HIV and M. tuberculosis exceed the lifetime risk of persons without HIV co-infection. It has been estimated that for patients with HIV infection, the risk of developing TB is 7 % to 10 % per year (American Thoracic Society 2000, see Chapter 17). Children under steroid therapy, cancer chemotherapy, and hematological malignancies have an increased risk of developing TB. Something similar happens with malnutrition, which interferes with cell-mediated immune response and therefore accounts for much of the increased frequency of TB in impoverished patients. Other infections, such as measles, varicella, and pertussis, may activate quiescent bacilli with subsequent TB development. Individuals with certain human leukocyte antigen types and hereditary factors, including the presence of a bcg gene, seem to have a predisposition for TB acquisition (American Thoracic Society 2000, Caminero 2003, see Chapter 6). In pediatric TB, it is possible to clearly distinguish among three basic stages: exposure, infection, and disease. From a public health point of view, these stages have absolutely different transmission implications and epidemiologic consequences. Exposure is related to the fact that the child has been in contact with adolescents or adults with suspected or confirmed contagious pulmonary TB. Household is the most frequent setting for exposure although several places that allow a close contact with potentially contagious adults such as school, day care centers and other environments become occasional exposure places. During the 18th century, the “familial hypothesis” raised by the occurrence of familial clustering, dominated medical thinking. However, it was not until the ’30s that rigorous epidemiological studies provided solid evidence for the contribution of genetic factors in addition to exposure in the development of TB (Alcaiis 2006). In populations that do not include BCG vaccination as part of the infant vaccination scheme, the TST is negative during the exposure period, the chest radiograph is normal, and there are neither signs nor symptoms of disease (World Health Organization 1982). Since a positive TST may take up to three or four months to develop from the time of infection, it is not possible to be precise about whether the child is truly infected during this period. The hallmark of TB infection is a reactive TST in the absence of signs or symptoms of the disease, and in the presence of a chest radiograph that could be either normal or showing only a granuloma-compatible image (Correa 1997, Starke 1993). Infection is then clinically different from disease. Disease is the presence of signs and symptoms or radiographic abnormalities after the infection. In adults, the distinction between infection and disease becomes less difficult because the latter may be the result of dormant bacilli acquired during a past infection. In children, the distinction may not be so clear because the disease more often progresses from an initial or primary infection. From a practical point of view, adults with TB almost always manifest significant radiographic abnormalities and/or clinical symptoms, whereas up to 50 % of pediatric patients may remain asymptomatic with subtle abnormalities on the chest radiograph. Sometimes, erythema nodosum may be the only clinical finding in a child recently infected with M. tuberculosis (Jacobs 1993, Centers for Disease Control and Prevention 1999). 16.3. Primary pulmonary tuberculosis Unfortunately, children younger than five years old may develop disseminated TB in the form of miliary disease or tuberculous meningoencephalitis before the TST result becomes positive. Thus, a very high index of suspicion must be adopted when pediatric patients have a contact history. Children with asymptomatic infection usually have a positive TST result but do not have any clinical or radiographic manifestations. These children may be identified on a routine medical examination, as children who have recently emigrated from a high prevalence country, or adopted children, or they may be identified subsequent to TB diagnosis in household or other contacts (Centers for Disease Control and Prevention 1999, Saltik 1991). Pulmonary TB in children can range from an asymptomatic primary infection to a progressive primary TB. Primary TB is very often characterized by the absence of signs on clinical evaluation. Asymptomatic presentations are more common among school-age children (80-90 %) than in infants less than one year old (40-50 %) (Correa 1997, Vallejo 1996). Disease should be suspected if the child has been exposed to a contagious source and if the TST is positive. In contrast to pulmonary TB in adults, the TST following standard procedures is an important element for TB diagnosis in children. Sometimes these patients are identified by a positive TST that may be associated with allergic manifestations such as erythema nodosum and phlyctenular conjunctivitis. Erythema nodosum is a toxic allergic erythema with nodular lesions in the skin or under it, 2 to 3 cm large. These lesions are spontaneously painful and very painful under pressure, and are usually located bilaterally in feet and legs. The erythema nodosum is usually accompanied by pharyngitis, fever and joint inflammation and is more frequent in girls over six years. Phlyctenular conjunctivitis is an allergic keratoconjunctivitis characterized by the presence of small vesicles that usually evolve to ulcers and resolve without scars. The more frequent symptoms associated to the phlyctenular conjunctivitis are photophobia and an excessive lacrimation (Peroncini 1977). Progression of the primary infectious complex may lead to enlargement of hilar and mediastinal lymph nodes with resultant bronchial collapse. Progressive primary TB, which is considered to be a serious form of the disease, may develop when the primary focus cavitates and bacteria spread through contiguous bronchi. Lymphohematogenous dissemination, especially in young patients, may lead to miliary TB when caseous material reaches the bloodstream from a primary focus or a caseating metastatic focus in the wall of a pulmonary vein (Weigert focus). Tubercular meningoencephalitis may also result from hematogenous dissemination (Newton 1994, Smith 1992). When the disease is controlled by the host immune system, those bacilli spread by the bloodstream may remain dormant in all areas of the lung or other organs for several months or years. Afterwards, in adult life, a progression to the disease may occur from an endogenous reactivation. Primary TB includes various presentations of the disease as described in the following sections. 16.3.1. Endobronchial tuberculosis This form of pulmonary TB occurs when the infected lymph nodes erode into a bronchus. Enlargement of lymph nodes may result in signs suggestive of bronchial obstruction or hemidiaphragmatic paralysis. Dysphagia due to esophageal compression may be observed. Vocal cord paralysis may also occur as a result of local nerve compression. A partial or complete bronchial obstruction can also occur. Usually it is the result of deposition of caseous material within the lumen. Obstructive hyperaeration of a lobar segment or a complete lobe is less common in pediatric patients while cavities, bronchiectasis and bullous emphysema are occasionally seen. Even in the presence of extensive pulmonary disease, many older children are asymptomatic at the time of diagnosis. In general, however, children are more likely to present with wheezing, cough, fever, and anorexia as part of the symptoms (Lincoln 1958, Starke 1996, Vallejo 1995). Persistent cough may be indicative of bronchial obstruction, while difficulty in swallowing may result from esophageal compression. Hoarseness or difficult breathing may suggest vocal cord paralysis. 16.3.2. Progressive primary pulmonary tuberculosis Progression of the pulmonary parenchymal component leads to enlargement of the caseous area and may lead to pneumonia, atelectasis, and air trapping. This is more likely to occur in young children than in adolescents. The child usually appears ill with symptoms of fever, cough, malaise, and weight loss. This form presents classic signs of pneumonia, including tachypnea, dullness to percussion, nasal flaring, grunting, egophony, decreased breath sounds, and crackles. 16.3.3. Pleural involvement Pleural effusion due to TB usually occurs in older children and is rarely associated with miliary disease. Typical history reveals an acute onset of fever, chest pain that increases in intensity on deep inspiration, and shortness of breath. The pain accompanies the onset of the pleural effusion, but after that the pleural involvement is painless. Fever usually persists for 14-21 days. The signs of pleural effusion include tachypnea, respiratory distress, decreased breath sounds, dullness to percussion, and occasionally, features of mediastinal shift. 16.3.4. Reactivated pulmonary disease Chronic pulmonary or adult-type TB is rare in children. This condition generally occurs in children who are at least seven years old when they develop TB, but is more common in older children and adolescents. Usually, it has a subacute presentation with weight loss, fever, cough, and, rarely, hemoptysis. When the primary infection has not been treated properly, the lesion can reactivate from dormant bacilli in either lymph nodes or parenchymal nodules. In contrast to primary disease, the characteristic feature of reactivation is the parenchymal involvement, which usually evolves to cavities or diffuse infiltrates, without significant radiograph changes in pulmonary adenopathies (Peroncini 1979). Physical examination may show no abnormalities or may reveal posttussive crackles. 16.3.5. Primary tuberculosis complications TB complications are dependent on the delay in diagnosis and start of treatment. Miliary disease and tubercular meningoencephalitis are the earliest and most deadly complications of primary TB. Pulmonary complications of TB include the development of pleural effusions and pneumothorax. Complete obstruction of a bronchus can result if caseous material extrudes into the lumen. Bronchiectasis, stenosis of the airways, bronchoesophageal fistula, and endobronchial disease caused by penetration through an airway wall are other complications that may occur in primary TB. When dissemination of the disease occurs, perforation of the small bowel, obstruction, enterocutaneous fistula, and the development of severe malabsorption may complicate TB of the small intestine. Pericardial effusion can be an acute complication or can resemble chronic constrictive pericarditis. Renal complications, including hydronephrosis and autonephrectomy usually do not occur in children. Paraplegia may arise as a complication of TB located in the spine (i.e. tubercular spondylitis) (American Academy of Pediatrics 2003, Correa 1997, Jacobs 1993, Lincoln 1958). 16.4. Non-respiratory disease Non-respiratory disease implies the dissemination of the bacilli through the circulatory and lymphatic systems. Localizations other than pulmonary are more frequent in children than in adults. Extrapulmonary TB includes peripheral lymphadenopathy, miliary TB, tubercular meningitis, skeletal TB, and other organ involvement (Caminero 2003, American Academy of Pediatrics 2003, American Thoracic Society 2000). 16.4.1. Peripheral lymphadenopathy In fact, the high tropism that M. tuberculosis shows to lymph nodes in children under five years old is remarkable. In the majority of these cases, the localization is intrathoracic affecting mainly the mediastinal lymph nodes. Close to 25-35 % of these forms have extrathoracic localizations, such as on the neck lymph nodes called scrofula. However, it is important to remark that when scrofula affects children under five years old, it is caused by non-tuberculous mycobacteria (NTM) in 75 % to 80 % of cases. In different geographic areas, the prevalence of NTM varies greatly, being more prevalent in hot climate regions. It has been estimated that 65 % to 80 % of children under 12 years old may be infected with Mycobacterium avium complex; 10 % to 20 % with Mycobacterium scrofulaceum; and 10 % with M. tuberculosis. In contrast, more than 90 % of culture-proven mycobacterial lymphadenitis in adults and children older than 12 years are caused by M. tuberculosis (Johnson 1998, Saltik 1991). Although in developed countries the scrofula presentation is mostly caused by M. avium and M. scrofulaceum, the real situation in low-income countries still remains to be elucidated. To distinguish between NTM and M. tuberculosis infected lymph nodes is frequently difficult; therefore, surgical dissection and culture of the biopsy material is usually necessary for both diagnostic and therapeutic reasons (Smith 1992, Starke 1995). Patients with scrofula may complain of enlarged nodes. Fever, weight loss, fatigue, and malaise are usually absent or minimal. Lymph node involvement typically occurs between six to nine months following the initial infection. Lymphadenopathy usually involves the anterior or posterior cervical and supraclavicular nodes. Less commonly involved are the submandibular, submental, axillary, and inguinal lymph nodes. The infected lymph nodes are typically firm, non-tender, and painless, with non-erythematous overlying skin. The nodes are initially non-fluctuant. Lymph node suppuration and spontaneous drainage may occur after caseation and necrosis development (Freixinet 1995, Starke 1995). 16.4.2. Miliary tuberculosis As was mentioned before, miliary TB can be a complication of primary TB in young children. A rapid onset of fever and associated symptoms may be observed. When the lungs are involved, respiratory signs may evolve to include tachypnea, cyanosis, and respiratory distress, so miliary TB should be considered in a child with a history of cough and respiratory distress. Miliary TB can also develop from an extrapulmonary form, leading to a disease in two or more organs, usually the brain and liver. Infants are particularly prone to the bacilli spreading throughout their body and development of the miliary form of the disease. Both pulmonary and extrapulmonary miliary forms are particularly severe diseases (Correa 1997, Rodrigues 1993). 16.4.3. Tuberculous meningitis This is one of the most dangerous complications of TB. Between 30 % and 50 % of children with miliary TB have meningitis at the time of diagnosis. It occurs in up to 5 % to 10 % of cases of TB in children younger than two years old. Thereafter, the frequency drops to less than 1 %. Because of the frequent insidious onset of the disease, a very high index of suspicion is required to make a timely diagnosis. A subacute presentation can also occur within three to six months after the initial infection. The clinical presentation comprises a variety of signs and symptoms with an insidious or acute start. The signs and symptoms include low-grade persistent fever, malaise, anorexia, weight loss, fatigue, hepatomegaly, splenomegaly and generalized lymphadenopathy, alteration in consciousness and sensorium, stupor and the emergence of focal neurological signs. As the disease progresses, a deterioration of mental status is accompanied by headache and neck stiffness, photophobia, seizures, coma, and death may occur if a proper diagnosis and early intervention are not promptly started. Typical cerebrospinal fluid findings include a moderate lymphocytic pleocytosis, low glucose level and an elevated protein concentration. Hyponatremia caused by inappropriate excretion of antidiuretic hormone is frequently seen. Abnormal chest radiographs are seen in 50 % of children with meningitis, but TST can be negative in 40 % of children at the time of diagnosis. Three stages of tubercular meningitis have been identified: · in the first stage, no focal or generalized neurological signs are present. Possibly, only nonspecific behavioral abnormalities are found. · the second stage is characterized by the presence of nuchal rigidity, altered deep tendon reflexes, lethargy, and/or cranial nerve palsies. TB meningitis most often affects the sixth cranial nerve, resulting in lateral rectus palsy. This is due to the pressure of the thick basilar inflammatory exudates on the cranial nerves or to hydrocephalus. The third, fourth, and seventh cranial nerves may also be affected. Fundoscopic changes may include papilledema and the presence of choroid tubercles, which should be carefully sought. · the final stage comprises major neurological defects, including coma, seizures, and abnormal movements (e.g. choreoathetosis, paresis, paralysis of one or more extremities). In the terminal phase, decerebrated or decorticated posturing, opisthotonus, and death may occur. Patients with tuberculomas or tubercular brain abscesses may present with focal neurological signs. Spinal cord disease may result in the acute development of spinal block or a transverse myelitis-like syndrome. A slowly ascending paralysis may develop over several months to years (Correa 1997, Vallejo 1994). 16.4.4. Skeletal tuberculosis Osteoarticular TB complications appear in 1 % to 6 % of untreated primary infections. Clinical and radiographic presentations vary widely and depend upon the stage of the disease at the time of diagnosis. Skeletal TB may remain unrecognized for months to years because of its lack of specific signs and symptoms and indolent nature. Bone or joint TB may present acutely or subacutely. Sites commonly involved are the large weight-bearing bones or joints including the vertebrae (50 %), hips (15 %), and knees (15 %). Less common skeletal sites are the femur, tibia, and fibula. Destruction of the bones with deformity is a late sign of TB. Manifestations may include angulation of the spine or “gibbus deformity” and/or the severe kyphosis with destruction of the vertebral bodies or “Pott’s disease”. Cervical spine involvement may result in atlantoaxial subluxation, which may lead to paraplegia or quadriplegia. TB of the skeletal system may also lead to involvement of the inguinal, epitrochlear, or axillary lymph nodes. (Correa 1997, Vallejo 1995). 16.5. Congenital tuberculosis Congenital TB is considered a rare event in the whole spectrum of TB presentations. This infection is caused by lymphohematogenous spread during pregnancy from an infected placenta or aspiration of contaminated amniotic fluid. Symptoms typically develop during the second or third week of life and include poor feeding, poor weight gain, cough, lethargy, and irritability. Other symptoms include fever, ear discharge, and skin lesions, failure to thrive, icterus, hepatosplenomegaly, tachypnea, and lymphadenopathy. Congenital TB diagnosis is based on clinical features and the infant should have at least one of the following proven TB lesions (Correa 1997, Cantwell 1994): · skin lesions during the first week of life, including papular lesions or petechiae, necrotic or purpuric lesions · choroidal tubercles in the retina · documentation of TB infection of the placenta or the maternal genital tract · presence of a primary hepatic complex (liver and regional lymph-node involvement) · exclusion of the possibility of postnatal transmission 16.6. Diagnosis 16.6.1. Clinical disease evaluation Pediatric patients with pneumonia, pleural effusion, or a cavitary or mass lesion in the lung that does not improve with standard antibacterial therapy should be evaluated for TB. This evaluation is also indicated for children with fever of unknown origin, failure to thrive, significant weight loss (more than 10 % of normal weight), or unexplained lymphadenopathy. An adequate clinical history should look for household or adult infectious cases, immigration from high prevalence countries, living in shelters or other risk factors (American Academy of Pediatrics 2003, American Thoracic Society 2000, American Thoracic Society /Centers for Disease Control and Prevention 2001, Correa 1997, Feja 2005, Jacobs 1993, Taylor 2005, Vallejo 1994). 16.6.2. Diagnostic laboratory tests in pediatric tuberculosis The cornerstone of the diagnosis of pulmonary TB in adults is based on the demonstration of M. tuberculosis by means of microbiological and/or molecular methods. Pediatric TB is usually considered a paucibacillary disease, which makes bacteriological diagnosis of TB extremely challenging because of the difficulty in isolating M. tuberculosis from clinical specimens. This difficulty decreases as the age of the child increases. Therefore, all tools available in laboratories must be used to diagnose pediatric cases, especially in the very young. Despite innovations in rapid diagnosis, many of the classic diagnostic tools continue to be useful in the evaluation of TB patients (Caminero 2003). Specimen collection The first step in detecting and isolating mycobacteria is to obtain appropriate specimens for bacteriological examination. These specimens are: sputum, gastric lavage, bronchoalveolar lavage, lung tissue, lymph node tissue, pleural fluid, bone marrow, blood, liver, cerebrospinal fluid, urine, and stool, depending on the location of the disease. Children under 12 years old are rarely able to produce sputum and voluntarily expectorate, and therefore gastric lavage is often used to obtain a specimen in very young children (< 6 years old). The rationale for this presumes that the child has coughed up and swallowed their bronchial secretions. The use of the correct technique for obtaining the gastric lavage is important because of the scarcity of bacilli in children compared to adults. The technique requires a nasogastric tube inserted in an inpatient setting, because the sensitivity of outpatient gastric lavages has not been evaluated. Early morning samples, optimally from three consecutive days, should be obtained before the child has had a chance to eat or move, as these activities dilute the bronchial secretions accumulated during the night. Initially, the stomach contents should be aspirated, and then a small amount of sterile water injected through the nasogastric tube. This aspirate also should be added to the specimen. Since gastric acidity is poorly tolerated by t