Diagnosing Tuberculosis in Children

Diagnosing Tuberculosis in Children
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Module 10A Version Module 10A - March 2010 Diagnosing Tuberculosis in Children Instructor’s Notes Module 10A: Diagnosing Tuberculosis in Children ISTC Standards covered: Standards 2, 3, and 6 Module Time: Approximately 60 minutes This module has been divided into the following sections: Introduction to TB in Children (slides 3-6) – 5 min. Clinical Presentations of TB in Children (slides 7-22) – 20 min. Diagnosing TB in Children (slides 23-43) – 30 min. Summary (slide 44-46) – 5 min. Resource documents: Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV (CTBG) Chapter 10 Interactive options: Ideas for interactive discussions are offered on many of the slides in this module. Participant discussion can enhance active learning, but will add more time to the lecture and must be planned for. Additional Material: Slides containing related material may be found in the following modules: 5, 7A, 7B, 9A, 9B, 10B, 15.

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Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Project Partners Module 10A Version Funded by the Health Resources and Services Administration (HRSA)

International Standards 2, 3, and 6
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Module Overview Module 10A Version Clinical presentations of TB in children Diagnosing TB in children Introduction to TB in Children (Slides 3 - 6) – 5 minutes [Review the slide content] The International Standards for Tuberculosis Care (ISTC), published in 2009 presents a set of widely accepted, evidence-based standards describing a level of care that all practitioners, public and private, should seek to achieve in managing patients with, or suspected of having, tuberculosis. These international standards differ from existing guidelines in that standards present what should be done, whereas guidelines describe how the action is to be accomplished. Five of the 21 standards include care of children specifically in their content. Since children are rarely contagious with tuberculosis, they have not always received as much attention from TB control programs as smear positive, contagious adults. Their inclusion in 5 of the International Standards is a much welcome addition for pediatric providers [Image credit (right): Lung Health Image Library/Gary Hampton] [Image credit (CXR): Francis J. Curry National Tuberculosis Center] International Standards 2, 3, and 6

Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV
Learning Objectives Module 10A Version Upon completion of this session, participants will be able to: Name several common presentations of childhood tuberculosis Accurately classify different presentations of pediatric TB Describe the 7 recommended steps involved in diagnosing TB in children [Review learning objectives]

Introduction Module 10A Version The WHO estimates 1 million cases of childhood TB (<15 years of age) annually Children can present with TB at any age The frequency of childhood TB is influenced by: The intensity of the TB epidemic locally, The age structure of the population, The availability of diagnostic tools, and Whether TB contact investigation is routinely conducted Pediatric tuberculosis is under diagnosed globally in part because children can not easily produce sputum for diagnostic microscopy and are rarely smear positive due to their paucibacillary disease (their lung disease and intrathoracic adenopathy primarily represents visualization of the immune response and contains relatively few M. tuberculosis organisms). The WHO estimates that each year approximately 1 million cases of tuberculosis occur in children <15 years of age, accounting for 11% of the annual burden of cases diagnosed worldwide. This may be an underestimate and in some areas of the world, the percent of annual burden contributed by children might be much higher Children can present with TB at any age, but infants and toddlers are more likely to develop disease once infected than are school-aged children or adults There are many factors that influence the frequency of childhood TB such as: [Review remaining slide content]

Introduction (2) Module 10A Version TB transmission to a child usually results from exposure to an infectious adult or adolescent, often within the household Very young children (<3 years of age) and those with weakened immune systems are at great risk for disease progression For infants, the time span between infection and disease can be as short as several weeks Transmission of TB to a child is usually from exposure to an infectious adult or adolescent in their close environment, often within the household. Young children are rarely contagious as they have fewer organisms and less forceful coughs than adults and adolescents On acquiring TB infection, children frequently develop a primary parenchymal lesion, or a Ghon focus, in the lungs with subsequent spread to the regional lymph node(s) The cell-mediated immune response halts further progression in most situations; however, very young children, particularly those < 3 years of age, and those with weakened immune systems are at great risk for disease progression due to the immaturity of their immune response For infants, their immune system may fail to even slow the progression of the infection and the time span between infection and disease can be as short as several weeks. This is why any TB exposure involving small children should be quickly acted upon and those children prioritized for evaluation

Clinical Presentations of TB in Children
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Module 10A Version Clinical Presentations of TB in Children Clinical Presentations of TB in Children (Slides ) – 20 minutes The clinical presentation of TB in children varies widely globally. Factors such as TB prevalence in the population, access to health care, and HIV prevalence may all impact the severity of disease presentation in the pediatric population These next few slides will cover some of the most common presentations [Image credit: Francis J. Curry National TB Center, Kelly Smith]

Clinical Presentations of TB in Children
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Module 10A Version Pulmonary (PTB) or extra-pulmonary TB (EPTB) Most children with TB have PTB, but they are more likely than adults to have EPTB Many children with EPTB also have PTB [Emphasize abbreviations and review slide content] Most children with TB have PTB; however, PTB is more difficult to recognize in children because they present with primary rather than reactivation (cavitary) TB and the majority are too young to produce sputum for smear microscopy Although extrapulmonary sites of tuberculosis frequently are the sites first recognized in children being evaluated for TB, it’s important to remember that many children with EPTB also have PTB. For example, children with intrathoracic lymphadenopathy frequently have parenchymal changes and children with meningitis frequently have lung disease, etc. The WHO notes that the ratio of reported PTB to EPTB in children is usually around 1:3; however, the ratio varies depending on factors such as age, ability to conduct contact investigations, and also possibly genetic factors. Smear-positive PTB is more commonly seen in school-aged children, particularly in adolescents when PTB presents more as it does in adults [Image credit: Francis J. Curry National TB Center, Kelly Smith]

EPTB in Children Module 10A Version The most common type of EPTB seen in children is intrathoracic Other forms of EPTB seen in children include: TB lymphadenopathy (e.g., cervical lymph-adenitis) Central nervous system TB (e.g., meningitis) Disseminated TB (e.g., miliary TB) TB effusions (pleural, pericardial, peritoneal) Spinal TB (Pott’s disease) [Review the slide content] TB can present anywhere in the body so make sure to engage the parents when examining the child. They may give you important information regarding a sign or symptom that could aide in the diagnosis

Uncomplicated Primary TB
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Uncomplicated Primary TB Module 10A Version Primary TB Disease: Often unilateral lymphadenopathy, hilar or mediastinal, without obvious parenchymal involvement Most frequent presentation in children (70-80%) Classify as EPTB The next few slides cover the different common presentations of TB in children Let’s start with the most common, primary TB disease. There are different presentations of primary TB seen in children [Review the slide content] This radiograph shows a generous right hilar lymph node (arrow). The lateral view is very helpful in confirming the presence of hilar lymph nodes. The right side is the most common location for intrathoracic TB lymphadenopathy. These children are frequently not very symptomatic unless the lymph node causes significant compression or erosion of the adjacent airway [Image credit: Francis J. Curry National Tuberculosis Center, Ann M. Loeffler, MD]

Uncomplicated Primary TB (2)
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Uncomplicated Primary TB (2) Module 10A Version Primary TB Disease: Sometimes typical “primary complex”, combining hilar and mediastinal lymphadenopathy and a small opacity in the lung, 3-10 mm in diameter (“primary lesion”) It is less frequent (20%, usually children < 5 years) Classify as PTB [Review the slide content]

Complicated Primary Disease
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Complicated Primary Disease Module 10A Version Primary TB Disease: Lobar or segmental opacity in the lung, combined with unilateral lymphadenopathy on the same side Classify as PTB Occasionally you may see, lobar or segmental opacity in the lung, combined with unilateral lymphadenopathy on the same side and this should be classified as PTB When bronchial compression has resulted in atelectasis or hyperaeration due to a ball-valve phenomenon (air gets in with inspiration, but can not escape due to the airway compression), corticosteroids in addition to chemotherapy may be helpful. If there is a new pneumonia distal to the airway obstruction, antibiotics to treat trapped bacteria are sometimes helpful along with the corticosteroid This radiograph shows right-sided lymphadenopathy (top arrow) and segmental opacity (lower arrow). This child had multi-drug resistant tuberculosis which resolved with 18 months of therapy including one year of an injectable agent Other presentations of complicated primary TB disease that may be encountered include: Unilateral hyperinflation Cavitation of the primary lesion in the lung (exceptional in children, and is classified as PTB), often sputum will be smear-positive Tuberculous bronchopneumonia and expansile pneumonia [Image credit: Francis J. Curry National Tuberculosis Center, Ann M. Loeffler, MD]

Acute Disseminated Primary TB
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Acute Disseminated Primary TB Module 10A Version Acute Disseminated Primary TB (often in children aged under 5 years) Miliary with or without meningitis Classify as PTB [Review the slide content] Acute disseminated primary TB or “miliary” TB results from the hematogenous dissemination of the M. tuberculosis organism throughout the lungs and elsewhere throughout the body The organism enters the blood stream as the proximal intrathoracic lymph node empties its contents into the thoracic duct. In adults, disseminated TB is sometimes caused by an erosion of a lung focus into a blood vessel The symptoms may precede any radiographic changes by several weeks The radiographic lesions may appear small and round like millet seeds, but may be larger and more irregular 20% of cases are associated with meningitis This radiograph shows extensive miliary disease which predominates in the upper lung zones. She also has impressive right-sided paratracheal adenopathy (arrow) [Image credit: Francis J. Curry National Tuberculosis Center, Ann M. Loeffler, MD]

Post-primary PTB Module 10A Version Post-primary PTB (usually in children aged over 10 years) is: Without cavitation, smear-negative classified as PTB With cavitation, smear-positive is also classified as PTB [Review slide content] Post-primary or reactivation disease occurs in older children some period of time after their initial infection and its initial containment by the immune response. Like adults, the disease is more often in the lung apices and more likely to be cavitary, smear-positive and associated with contagion This radiograph shows several small cavities (3 arrows) in the right apex of a teen’s lung. He became smear-positive during a delay in therapy [Image credit: Francis J. Curry National Tuberculosis Center, Ann M. Loeffler, MD] 14

Post-primary EPTB Post-primary EPTB examples include:
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Post-primary EPTB Module 10A Version Post-primary EPTB examples include: Most TB bone and joint disease Renal tuberculosis Some cervical lymph node TB (scrofula) While meningitis, miliary TB and intrathoracic lymphadenopathy frequently present during the primary infection process, other extrapulmonary manifestations occur after a period of initial disease control by the immune system. This phenomenon represents a reactivation of a focus which was seeded during the original primary bacillemia Some examples include: [review the slide content] [Image credit: Francis J. Curry National Tuberculosis Center, Ann M. Loeffler, MD] 15

Presentations of HIV/TB
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Presentations of HIV/TB Module 10A Version The natural history of TB in a child with HIV depends on the stage of HIV disease In early HIV infection, the signs of TB are similar to those of an HIV-uninfected child As HIV infection progresses, dissemination of TB becomes more common Meningitis Miliary TB Widespread tuberculous lymphadenopathy The natural history of TB in a child with HIV depends on the stage of HIV disease [Review remainder of slide content]

Presentations of HIV/TB (2)
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Presentations of HIV/TB (2) Module 10A Version Older HIV-infected children with TB may have clinical presentations similar to that seen in HIV-infected adults Children with TB/HIV co-infection have: Longer hospital stays, and higher mortality despite initiation of appropriate anti-TB medications [Review the slide content] [Click: Slide Animation. Last bullet will appear with click of the mouse or by pressing down arrow key]  It is essential to have a high index of suspicion for TB disease in HIV-infected children

TB Diagnostic Gold Standard
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV TB Diagnostic Gold Standard Module 10A Version A definitive diagnosis of TB disease requires isolation of M. tuberculosis from any of the following: Expectorated or induced sputum Bronchoalveolar lavage fluid, aspirated gastric fluid, or pleural fluid Biopsied lung, peripheral lymph node, or other tissue [Review the slide content] Whenever possible, attempts should always be made to get a specimen for AFB smear and culture While culture confirmation is highly desired, it is frequently not possible in children Resources and facilities may not be available to collect specimens AFB smears are rarely positive in children as they have few organisms in their tissue (paucibacillary) AFB cultures from children have much lower yields than those in adults, in part due to technical limitations and in part due to the paucibacillary disease Bronchoalveolar lavage fluid, aspirated gastric fluid, or pleural fluid may yield AFB. A gastric aspirate should be obtained in the early morning after overnight fast [Can refer participants to Appendix E in the Caribbean TB guidelines which covers the patient preparation and procedure for obtaining gastric aspirate]

ISTC Standard 2 Module 10A Version All patients (adults, adolescents, and children who are capable of producing sputum) suspected of having pulmonary TB should have at least two sputum specimens submitted for microscopic examination in a quality-assured laboratory. There are several International Standards for Tuberculosis Care that relate to diagnosis, treatment and management of TB in Children [Standard 2, is also covered in Case Finding and Diagnosis, Module 5] Quickly review standard 2, or [Interactive option: Ask a volunteer to summarize what this standard holds us accountable to do in the care of children in whom TB is suspected] [Image credit: CDC Public Health Image Library / Dr. George P. Kubica] When possible, at least one early morning specimen should be obtained. 19

ISTC Standard 3 Module 10A Version For all patients (adults, adolescents, and children) suspected of having EPTB, appropriate specimens from the suspected sites of involvement should be obtained for microscopy, culture and histopathological examination. Standard 3, was also covered in the presentation on Case Finding and Diagnosis, Module 5 Quickly review standard 3, or [Interactive option:] Ask a volunteer to summarize what this standard holds us accountable to do in the care of children in whom TB is suspected Ask: What do you think the health care provider is going for in this picture? Answer: lumbar puncture - collection of spinal fluid to diagnose TB meningitis [Image credit: Francis J. Curry National Tuberculosis Center, Ann M. Loeffler, MD] 20

ISTC Standard 6 Module 10A Version In all children suspected of having intrathoracic (i.e., pulmonary, pleural, and mediastinal or hilar lymph node) TB, bacteriological confirmation should be sought through examination of sputum (by expectoration, gastric washings, or induced sputum) for smear microscopy and culture. While Standards 2 & 3 pertain to children as well as adults, there are several that specifically relate to children to guide clinicians in the care of TB in Children We’re now going to cover material related to ISTC Standard 6 and the diagnosis of TB: [Review the slide content] [Interactive option: Ask for a volunteer to read Standard 6]

ISTC Standard 6 (2) Module 10A Version In the event of negative bacteriological results, a diagnosis of TB should be based on: The presence of abnormalities consistent with TB on chest radiography A history of exposure to an infectious case Evidence of TB infection (positive tuberculin skin test or interferon gamma-release assay), and Clinical findings suggestive of TB [Review the slide content] [Interactive option: Ask for a volunteer to read Standard 6] The last part of Standard 6 reiterates what Standard 3 covers which is that in children suspected of having EPTB, appropriate specimens from the suspected sites of involvement should be obtained for microscopy and for culture and histopathological examination

Diagnosing TB in Children
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Module 10A Version Diagnosing TB in Children Diagnosing TB in Children (Slides ) – 30 minutes Like adults, the elements which are helpful in diagnosing TB in children include TB exposure history, clinical signs and symptoms, radiographic findings, tuberculin skin test results and bacteriologic findings [Image credit: Francis J. Curry National TB Center, Kelly Smith]

Diagnosing TB in Children
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Diagnosing TB in Children Module 10A Version Diagnosing tuberculosis in children is particularly problematic Children <5 years of age rarely expectorate sputum for evaluation Even when specimens are obtained they are rarely smear-positive for AFB on routine microscopy However, making the diagnosis of pediatric TB is challenging: Clinical signs and symptoms of TB in children might be quite indolent and subtle. Occasionally the children are acutely and severely ill Pediatric TB radiographic findings are different from those of adults The tuberculin skin test may be falsely negative, especially in infancy, early in the disease, or in the case of disseminated or widespread disease Children can not easily produce sputum for analysis and their sputum is frequently smear-negative due to the paucibacillary nature of their disease In very young children, gastric aspirate specimens can be collected; however, the yield of positive smear is also fairly low (less than 20%) and the procedure is often not practical outside of urban centers. Even culture yield for three gastric aspirates is only about 50% positive (somewhat higher in extensive disease) in cases of pulmonary TB

Diagnostic Approach Module 10A Version The diagnostic TB workup in a child should include all of the following: Symptom and contact history Clinical exam (including growth assessment) Mantoux tuberculin skin test (TST) result Bacteriological confirmation (when possible) Chest radiograph Other specific evaluation indicated by disease site or co-morbidity HIV testing Symptoms can vary from acute and fulminating to subtle / indolent and even absent. In general, symptomatic children with TB have modest symptoms which have been evolving over time Many families will not be aware of exposure to an active TB case. It may be necessary to ask about exposure to someone with chronic cough, weight loss, night sweats, fever, hemoptysis etc. The physical exam may be completely normal for children with TB disease. Weight loss or failure to gain weight might be the only evident finding. A good exam looking for any of the many sites of extrapulmonary TB is paramount The tuberculin skin test (TST) is an adjunct to TB diagnosis. A positive TST suggests TB infection, but can not distinguish infection from disease. Conversely, a negative TST never rules out active TB disease The importance and role of bacteriologic specimens and radiographic findings have been previously discussed Other specific evaluation indicated by disease site (e.g., lumbar puncture to diagnose meningitis, fine needle aspirates of lymph node tissue) or as indicated by concurrent co-morbidity (e.g., diabetes, kidney or liver disease) Of equal importance to all those listed is HIV testing The following slides will review these seven important elements in the diagnosis of pediatric TB in more detail

1. Careful History: Contact
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV 1. Careful History: Contact Module 10A Version Contact History A close contact is defined as living in the same household or in frequent contact with someone with sputum smear-positive TB Persons with TB who are sputum smear-negative but culture-positive are also infectious, but to a much lesser degree The first step in diagnosing TB in children is the identification of an adolescent or adult in the child’s life who might have contagious TB disease The careful history should include the history of TB contact and symptoms consistent with TB Since children may have more rapidly progressive disease than adults, it is not uncommon to identify a source case after a child with TB has been identified While close and household contacts most often infect children, other adolescent and adult contacts should be sought…Review the slide content Related content can also be found in Module 15 on TB Contact Investigation and in Module 10C

1. Careful History: Contact (2)
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV 1. Careful History: Contact (2) Module 10A Version Children (especially <5 years of age) who have been in close contact with a smear-positive TB case must be screened for TB After TB is diagnosed in a child or adolescent, an effort should be made to detect the adult source case(s), especially within the household Children whose sputum is smear-positive or with a visible cavity on CXR should be considered infectious In areas with TB control programs sufficiently staffed and funded, contacts to individuals with TB disease should be evaluated and treated for TB disease and infection. The highest priority contacts are children and immunodeficient individuals (most likely to progress on to TB disease). Children less than five years of age are at highest risk Another high priority TB control activity is to evaluate close contacts to children and adolescents with TB disease in order to identify the source of their infection. Identifying and treating that individual for TB will not only benefit the individual, but will stop the ongoing spread of TB in that environment Children are rarely contagious with TB – but if a child is found to have smear positive sputum or to have a cavity on chest radiograph, they should be considered to be contagious and their contacts should be evaluated just as any other individual with contagious TB disease [Reference also Appendix C of the CTBG: Implementing TB Contact Investigation and Module 15]

1. Careful History: Symptoms
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV 1. Careful History: Symptoms Module 10A Version Children with symptomatic disease develop chronic symptoms in most cases The most frequent symptoms are chronic and unremitting cough, fever, and weight loss [Review the slide content] When children have symptoms, they are usually indolent and chronic and include cough, fever and weight loss or failure to gain weight [Image source: World Lung Foundation Image Library, Jad Davenport]

1. Careful History: Symptoms (2)
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV 1. Careful History: Symptoms (2) Module 10A Version The specificity of symptoms for the diagnosis of TB depends on how strict the definitions of the symptoms are: Chronic cough: an unremitting cough that is not improving and has been present for 2-3 weeks Fever: of 38°C for 14 days after common causes such as malaria or pneumonia have been excluded Weight loss or failure to thrive: always ask and look at the child’s growth chart [Review the slide content] Always ask the parent or guardian about weight loss or failure to thrive

2. Clinical Exam Module 10A Version There are no specific features on clinical examination that can confirm that the presenting illness is due to PTB Some less common signs are highly suggestive of EPTB and the threshold to initiate treatment should be lower Other signs are common and should initiate investigation as to the possibility of childhood TB The second of the seven elements of diagnosing TB disease in children is the physical exam Unfortunately, there are no specific features on clinical exam that can confirm that the presenting illness is due to tuberculosis. In the case of pulmonary and intrathoracic disease, children tend to have fewer physical findings than do children with an acute bacterial pneumonia Some less common signs are highly suggestive of EPTB and the threshold to initiate treatment should be lower. These might include things like swollen and enlarging peripheral lymph nodes which are not particularly painful and which do not respond to treatment for bacterial lymphadenitis (possible scrofula), altered mental status (possible TB meningitis) although TB is not the only condition on the differential list for these types of signs and symptoms Common signs such as cough, fever, weight loss or failure to thrive should prompt an evaluation for TB and therefore, the clinical exam should always include temperature and growth assessment

2. Clinical Exam (2) Physical signs highly suggestive of EPTB:
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV 2. Clinical Exam (2) Module 10A Version Physical signs highly suggestive of EPTB: Gibbus, especially of recent onset (vertebral TB) Non-painful enlarged cervical lymphadenopathy with ﬁstula formation [Review the slide content] In advanced disease, there may not only be gibbus (angulation of the spine). Weakness of the lower limbs and paralysis can also occur due to pressure on the spinal cord or its blood vessels The physical exam then should be geared toward evaluating for sites of TB outside the chest as these are the areas the chest X-ray will not be able to evaluate Scrofula – or peripheral mycobacterial lymphadenitis is most common in the cervical area, but can happen anywhere in the body. These are usually solitary cervical lymph nodes that enlarge gradually over time, develop some pinkish or dusky discoloration in the overlying skin and which, untreated, will adhere to the overlying skin and develop a fistula with resultant drainage of purulent material Again, it is really important to talk with the parents and involve them in the exam as they may point out something that has been overlooked [Image source: World Lung Foundation Image Library, Jad Davenport]

2. Clinical Exam (3) Module 10A Version Physical signs requiring investigation to exclude EPTB: Meningitis not responding to antibiotic treatment, with sub-acute onset or  intracranial pressure Pleural or pericardial effusion Distended abdomen with ascites Non-painful enlarged lymph nodes without ﬁstula formation Non-painful enlarged joint Signs of tuberculin hypersensitivity: phlyctenular conjunctivitis, erythema nodosum As mentioned earlier, TB can present anywhere in the body so any of these signs should prompt an evaluation for TB. [Review slide content] Refer participants to the 2010 Caribbean TB guidelines, Chapter 10, Table 17 (page 103) which provides a nice summary of the history and physical exam findings that would suggest a diagnosis of TB in a child Documented weight loss or failure to gain weight, especially after being treated in a nutritional rehabilitation program, is a good indicator of chronic disease in children, and TB may be the cause

3. Mantoux TST Module 10A Version Using the test: The Mantoux TST should be standardized for each country using either: 5 tuberculin units (TU) of tuberculin puriﬁed protein derivative (PPD) S, or 2 TU of tuberculin PPD RT23 A positive Mantoux TST occurs when a child is infected with M. tuberculosis In children, the TST can also be used as an adjunct in diagnosing TB when used in conjunction with history, physical exam and other diagnostic tests The third of the seven elements in diagnosis of pediatric TB is the use of the tuberculin skin test or TST The TST should be standardized for each country using either 5 tuberculin units (TU) of tuberculin puriﬁed protein derivative (PPD) S or 2TU of tuberculin PPD RT23, as these give similar reactions in infected children A positive Mantoux TST occurs when a child is infected with M. tuberculosis and does not necessarily indicate disease However, in children, the Mantoux TST can also be used as an adjunct in diagnosing TB disease, when it is used in conjunction with signs and symptoms of TB and other diagnostic tests. For example, when used in a child with symptoms and other evidence of TB disease (such as an abnormal CXR), it is a useful tool in making the diagnosis of TB in a child There are a number of TSTs available (e.g., Mantoux, multipunture, Tine and Heaf), but the Mantoux TST is the recommended test Health care workers (HCWs) must be trained in performing and reading a TST (see also Appendix A of the 2010 Caribbean TB guidelines) HCWs performing TST on children should seek help holding the child as still as possible and be prepared to repeat the placement of the test at least 2 cm away from the original site if the first skin test is placed too deeply and fails to generate a 6 – 10 mm distinct, pale wheel which doesn’t drop down immediately

3. Mantoux TST (2) A TST should be regarded as “positive” as follows:
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV 3. Mantoux TST (2) Module 10A Version A TST should be regarded as “positive” as follows: High-risk children: TST ≥5mm induration Close contact to person with active PTB HIV-infected children severely malnourished children, i.e., those with clinical evidence of marasmus or kwashiorkor) Chest X-ray consistent with TB disease All other children: TST ≥10mm induration is regarded as positive (whether or not they have been BCG vaccinated) [Review the slide content] A TST should be regarded as positive as follows: High-risk children: TST >5mm induration (high risk includes HIV-infected children, close contacts to a person with active PTB, severely malnourished children (i.e., those with clinical evidence of marasmus or kwashiorkor), and those with CXR abnormalities consistent with TB disease All other children: TST >10mm induration is regarded as positive (whether or not they have been BCG vaccinated). As the BCG vaccine may confound the interpretation of the TST, if a child is <4 years of age or if child or adolescent has known exposure to an adult considered high risk for TB infection and/or disease, the weight for considering the TST positive with 10mm induration is increased Refer participants to Table 29 in Appendix A of the Caribbean TB guidelines on page 148, which describes the induration cut points for interpreting the Mantoux TST

3. Mantoux TST (3) Module 10A Version The TST is useful in HIV-infected children to identify those with dual TB/HIV infection and as an aid in the diagnosis of TB There can be false-positive TST results as well as false-negative TST tests  A negative Mantoux TST never rules out a diagnosis of TB in a child The TST is useful in HIV-infected children to identify those with dual TB/HIV infection and as an aid in the diagnosis of TB, although fewer HIV-infected children will have a positive test, as a normal immune response is required to produce a positive TST, and many HIV-infected children have immune suppression There can be false-positive as well as false-negative TST tests (see also Appendix A of the 2010 Caribbean TB guidelines). A negative TST never rules out a diagnosis of TB disease in a child. A false negative TST may be seen early in disease, in children with TB meningitis or disseminated disease and in children with weakened immune systems (immunocompromised) or infants. [This is covered in more detail in Module 14: Diagnosing and Treating Latent TB Infection] It is sometimes useful to repeat the TST in children once their malnutrition has been addressed or their severe illness (including TB) has resolved, as they may be initially TST negative, but positive after 2–3 months on treatment [Click: Slide Animation. Last bullet will appear with click of mouse to advance or by pressing the down arrow]

4. Bacteriological Confirmation
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV 4. Bacteriological Confirmation Module 10A Version It is always preferable to make a diagnosis of TB based on bacteriology using whatever specimens and laboratory methods are available Samples might include sputum, gastric aspirate and other material (e.g., lymph node biopsy) Fine needle aspiration of enlarged lymph glands for both histology and staining for AFB has been shown to be a useful test with a high bacteriological yield Bacteriological confirmation should be completed whenever possible, this is step 4 in diagnosing TB in children [Review the slide content]

4. Bacteriological Confirmation (2)
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV 4. Bacteriological Confirmation (2) Module 10A Version All specimens that are obtained should be sent for mycobacterial culture whenever possible A bacteriological diagnosis is especially important for children who have one or more of the following: Suspected drug resistance HIV infection Complicated or severe cases of disease An uncertain diagnosis [Review the slide content] Sending all specimens for culture will improve the yield of the test (i.e., it is more sensitive), but it is also the only way to differentiate M. tuberculosis from other non-tuberculous mycobacteria

4. Bacteriological Confirmation (3)
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV 4. Bacteriological Confirmation (3) Module 10A Version The more common ways of obtaining sputum for microscopy include: Expectoration Gastric aspirates Sputum induction Expectoration: Sputum for smear microscopy is a useful test and should always be obtained in adults and older children ( >10 years of age) who are pulmonary TB suspects. Among younger children, especially children <5 years of age, sputum is difficult to obtain and most children are ‘sputum smear-negative.’ However, in children who are able to produce a specimen, it is worth sending for smear microscopy (and culture if available). Yields are higher in older children (>5 years of age) and adolescents, and in children of all ages with severe disease. As with adult TB suspects, three sputum specimens should be obtained: spot specimen (at first evaluation), early morning, and spot specimen (at the follow-up visit) Gastric aspirates: Gastric aspiration using a nasogastric feeding tube can be performed in young children who are unable or unwilling to expectorate sputum. If performed, gastric aspirates should be sent for smear microscopy and mycobacterial culture. Ideally three specimens should be collected first thing in the morning after an overnight fast. The yield for these samples in culture is around 50% and the results are only helpful if they are positive Sputum induction: Several recent studies have found that sputum induction can be performed safely and effectively in children of all ages, and the bacteriological yield may be as good as or better than for gastric aspirates. However, training and specialized equipment are required to perform this test properly. Your center should use the test which yields the highest results in your experience [Image credit: Francis J. Curry National TB Center, Ann Loeffler]

5. Chest Radiograph Investigations Relevant for Suspected PTB
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV 5. Chest Radiograph Module 10A Version Investigations Relevant for Suspected PTB Children with PTB frequently have CXR changes suggestive of TB Persistent opacification in the lung with enlarged hilar or subcarinal lymph node is common Adolescent with TB often have CXR changes similar to adults (large pleural effusions and apical infiltrates with cavity formation being the most common) Adolescents may also develop primary disease, with hilar adenopathy and collapse lesions visible on CXR The chest radiograph is the next step in the diagnosis of pediatric TB Chest radiography is useful in the diagnosis of TB in children and ideally should be read by a radiologist or other health care worker trained in their reading. Good quality CXRs are essential for proper evaluation Earlier in this talk, we reviewed the most common patterns of intrathoracic TB in children, lymphadenopathy with or without parenchymal disease, atelectasis, etc. [Review remaining the slide content] A miliary pattern of opacification in non-HIV infected children is highly suggestive of TB. Patients with persistent opacification that does not improve after a course of antibiotics should be investigated for TB [Image source: Ann Raftery, Francis J. Curry National Tuberculosis Center]

5. Chest Radiograph (2) Investigations Relevant for Suspected EPTB
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV 5. Chest Radiograph (2) Module 10A Version Investigations Relevant for Suspected EPTB Most useful EPTB application is for diagnosing intrathoracic lymphadenopathy Lateral view may be helpful in diagnosing if frontal view is difficult to interpret In most other cases, TB will be suspected from the clinical picture and confirmed by histology or other special investigations [Review the slide content] Where resources permit, a lateral view can be helpful in identifying intrathoracic lymph nodes which are frequently seen in children with TB Good quality CXRs are essential for proper evaluation Can refer to Chapter 5 of the 2010 Caribbean TB guidelines and Module 5 for more information on evaluations specific to other EPTB sites

6. Other Tests Module 10A Version Serological and nucleic acid amplification (e.g., polymerase chain reaction [PCR]) tests are not currently recommended for the routine diagnosis of childhood TB They have been inadequately studied in children and they have performed poorly in the few studies that have been done This is an area that requires further research, as they may prove to be useful in the future [Review the slide content] These tests are not widely available or readily accessible in many CMCs (CAREC Member Countries)

6. Other Tests (2) Module 10A Version Many experts recommend that all children with miliary TB (or suspected of having miliary TB) should undergo lumbar puncture to evaluate for the presence of meningitis Note: Other specialised tests, such as computerized chest tomography and bronchoscopy, are not recommended for the routine diagnosis of TB in children Miliary TB has a high risk (60–70%) of meningeal involvement and should therefore be managed similarly to TB meningitis; therefore, many experts recommend that all children with miliary TB (or suspected of having miliary TB) should undergo lumbar puncture to evaluate for the presence of meningitis

7. HIV Testing Module 10A Version In areas with a high prevalence of HIV infection in the general population, counseling and testing for HIV should be included as part of routine care and management of children in which TB is diagnosed In areas with lower prevalence rates of HIV, HIV counseling and testing is indicated when: a TB patient has symptoms and/or signs of HIV-related conditions, and a TB patient has history suggestive of high risk of HIV exposure In settings where HIV prevalence in the general population is high (where TB and HIV infection are likely to co-exist) HIV counseling and testing should be included as part of routine care and management of children in which TB is diagnosed. It goes without saying that the parents or guardians are crucial to include as recipients of HIV counseling in such situations where a child is diagnosed with TB [Review remaining bullet]

Summary TB infection in a child can progress rapidly to TB disease
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Summary Module 10A Version TB infection in a child can progress rapidly to TB disease Diagnosing TB, particularly PTB, in children is difficult and should include the 7 diagnostic elements discussed Not all children with TB disease have a positive TST and not all children with a positive TST and radiographic abnormalities have TB disease Attempts should be made to obtain and send sputum and/or other sample for AFB smear and TB culture on children with suspect TB Summary (Slide ) – 5 minutes [Review slide summary points] [Interactive option: Could ask for volunteers to name the 7 diagnostic elements involved in the evaluation of a child for tuberculosis] Check if there are any remaining questions

Summary: ISTC Standards Covered*
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Summary: ISTC Standards Covered* Module 10A Version Standard 2: All TB suspects should have at least 2 sputum specimens obtained for microscopic examination (at least one early morning specimen if possible). Standard 3: Specimens from suspected extrapulmonary TB sites should be obtained for microscopy, culture, and histopathological exam. [Review the slide content] * Abbreviated versions

Summary: ISTC Standards Covered* (2)
Caribbean Guidelines for the Prevention, Treatment, Care, and Control of Tuberculosis and TB/HIV Summary: ISTC Standards Covered* (2) Module 10A Version Standard 6: The diagnosis of intrathoracic TB in symptomatic children with negative sputum smears should be based on: The presence of abnormalities consistent with TB on chest radiography A history of exposure to an infectious case Evidence of TB infection (positive tuberculin skin test or interferon gamma-release assay), and Clinical findings suggestive of TB Specimens should be obtained for microscopy and for culture and histopathological examination [Review the slide content] * Abbreviated versions

Diagnosing Tuberculosis in Children

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