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ISTC Training Modules 2008 Slide 1 Clinical Presentation and Diagnosis of TB (animated version) Instructor’s Guide Module: Clinical Presentation and Diagnosis of Tuberculosis ISTC Standards covered: 1 – 5 Module Time: Approximately 60 minutes Alternate slides: Introductory ISTC slides 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. Slide-show Animation: A second version of this talk is available with slide animations: Clinical Presentation and Diagnosis of TB (Animated). Additional Material: Slides containing related material may be found in the following modules: Microbiological diagnosis of Tuberculosis, TB and HIV Infection: Introduction and Diagnosis. Test Questions: May be attached or inserted within presentation for discussion purposes, or alternatively, combined with questions from other modules to produce evaluation tool. The full text of the ISTC and all supporting references are available at www.istcweb.org Other useful Resources/References: • Management of tuberculosis training for health facility staff. World Health Organization, 2003. www.who.int/tb • Radiographic Manifestations of Tuberculosis: A Primer for Clinicians, Second Edition. Francis J. Curry National Tuberculosis Center. www.nationaltbcenter.edu • Toman’s tuberculosis. Case detection, treatment and monitoring, 2nd Edition. Freiden TR ed., World Health Organization, 2004. www.who.int/tb • A Tuberculosis Guide for Specialist Physicians. Jose A. Caminero Luna, IUATLD, Sept. 2004. www.tbrieder.org [Image Credit: Lung Health Image Library/Jad Davenport] Clinical_diagnosis_animated_2008.ppt Page 1 of 22 Slide 3 Slide 2 ISTC Training Modules 2008 • It is intended that after completion of this module the student will be able to describe the approach to diagnosis of TB and the proper role of diagnostic testing, particularly sputum microscopy, in that process. • [Review objectives from slide] • Overview of Clinical Presentation and Diagnosis of TB [Review overview from slide] • Lecture/module includes International Standards 1 –5 • [Image of sputum smear photomicrograph reveals Mycobacterium tuberculosis bacteria using acidfast Ziehl-Neelsen stain] Slide 4 [Image credits: Lung Health Image Library/Jad Davenport (top); CDC Public Health Image Library/Dr. George P. Kubica (bottom)] • In introducing the Standards for Diagnosis of TB, it is important to recognize: [Review content of slide] [Image credit: Lung Health Image Library/Virginia Arnold] Clinical_diagnosis_animated_2008.ppt Page 2 of 22 Slide 5 Animation Clicks: 3 ISTC Training Modules 2008 • Therefore, two fundamental points that should be stressed are: [Review content of slide] • [Click: Slide-show Animation]. • To diagnose TB, we must Think TB. Slide 6 [Image credit: Lung Health Image Library/Pierre Virot] Begin with: Classic TB clinical presentation. • Slide 7 Animation Clicks: 1 • Clinical_diagnosis_animated_2008.ppt The most common symptom of pulmonary TB is persistent productive cough, often accompanied by nonspecific constitutional symptoms, such as fever, night sweats, and weight loss. Extra-pulmonary TB, such as lymphadenopathy, may be noted, especially in patients with HIV infection. • Nonspecific systemic, constitutional symptoms may include: [Review content of slide] • [Click: Slide-show Animation]. It is important to also recognize that there are many cases of TB, up to 10-20%, that may present without any symptoms at all. Page 3 of 22 Slide 8 ISTC Training Modules 2008 Slide 9 The diagnosis of TB with HIV co-infection can be more difficult. • Symptoms may be more nonspecific, but fever and weight loss may be more prominent at presentation. • Cough and hemoptysis are less common because there may be less cavitation, inflammation and endobronchial irritation in HIV patients. • CXR findings can be more variable, with both “typical, post-primary or reactivation TB” and “atypical, primary TB” CXR patterns commonly seen. In people infected with HIV, obtaining a timely CXR plays an important role in shortening delays in diagnosis and should be performed early in the investigation of a TB suspect. • The diagnosis of TB may be further complicated by the broader range of possible alternative diagnoses. The physical signs of respiratory infection in patients with pulmonary TB (PTB) do not readily distinguish PTB from other chest diseases and chest examination may even be normal. Because of the broader differential diagnosis, access to and utilization of culture and more invasive diagnostic become more important issues. • An accurate TB diagnosis may be further complicated due to the higher rate of extrapulmonary and disseminated disease in HIVinfected individuals. • So what guidance do the International Standards for TB Care offer for prioritizing who to evaluate for the diagnosis of TB? • Standard 1: [Read Standard] [Image credit: Lung Health Image Library] Clinical_diagnosis_animated_2008.ppt Page 4 of 22 Slide 10 Animation Clicks: 1 ISTC Training Modules 2008 • • • • Although most patients with pulmonary TB have cough, the symptom is not specific to TB; it can occur in a wide range of respiratory conditions, including acute respiratory tract infections, asthma, and chronic obstructive pulmonary disease. While the presence of cough for 2-3 weeks is nonspecific, traditionally, having cough of this duration has served as the criterion for defining suspected TB and is used in most national and international guidelines, particularly in areas of moderate- to high-prevalence of TB. Data from India, Algeria, and Chile generally show that the percentage of patients with positive sputum smears increases with increasing duration of cough, and a more recent assessment from India demonstrated that by using a threshold of >2weeks to prompt collection of sputum specimens, the number of TB cases identified increased by 46%. Certainly, duration of cough is not the only criterion that should raise suspicion for tuberculosis, other features of the presentation may raise your concern for TB in patients with a shorter duration or even absence of cough, therefore [Click: Slide-show Animation] clinical intuition plays an important role in the evaluation for TB. This is particularly true with HIV coinfection where TB presentation may be more atypical and lack of cough more common. [Reference: Santha T., et al. Comparison of cough 2 and 3 weeks to improve detection of smear-positive tuberculosis cases among out-patients in India. Int J Lung Dis 2005;9(1):61-8] Clinical_diagnosis_animated_2008.ppt Page 5 of 22 Slide 11 ISTC Training Modules 2008 Slide 13 Animation Clicks: 1 Slide 12 In evaluating persons who have symptoms that my be caused by TB it is important to identify risk factors for either: • Recent infection with M. TB due to transmission risks and/or factors that may increase the likelihood of progression to active TB once an individual is infected. Clinical_diagnosis_animated_2008.ppt • The presence of any of these factors should raise the clinician’s suspicion for TB. • Significant risk factors for possible recent infection include: [Review content of slide]. • Significant risk factors that may increase the likelihood of progression to active TB once an individual is infected include: [Review content of slide] • [Interactive option – ask participants what risk factors are most prevalent in their local areas and practices? Are there any other special groups or settings not listed here that are important to their region?] • The physical examination is non-specific in TB but useful to identify sites of TB: [Review content of slide] [Click: Slide-show Animation] Page 6 of 22 Slide 14 ISTC Training Modules 2008 • • • • In persons who are suspected of having TB based on symptoms and/or physical findings, every effort must be made to identify the causative agent. The first important step is highlighted by the International Standard 2: [Read Standard] [Note: Guidelines have recently changed from three sputum smears to at least two sputum smears. The change is reflected above and differs from the wording in the original published ISTC.] [Image shows sputum smear with carbolfuchsinbased stain demonstrating typical acid-fast bacilli morphology] Slide 15 [Image credit: CDC Public Health Image Library / Dr. George P. Kubica] • • • • While a definitive microbiological diagnosis can only be confirmed by culturing M. tuberculosis complex (or, under appropriate circumstances, identifying specific nucleic acid sequences) from clinical specimens, in practice, there are many settings where these tests are not currently feasible (due to resource limitations). Fortunately, microscopic examination of stained sputum, i.e. an AFB smear, is feasible in nearly all settings. In almost all clinical circumstances in high prevalence areas, finding acid-fast bacilli in stained sputum is highly specific and, thus, is the equivalent of a confirmed diagnosis. In addition to being highly specific for M.tb, identification of AFB by smear is particularly important for three reasons: • It is the most rapid method for determining if a person has TB • It identifies persons who are at greatest risk of dying from the disease* • And it identifies the most likely transmitters of infection *[Note that in persons with HIV infection, mortality rates are greater in patients with clinically-diagnosed TB who have negative sputum smears than among HIV-infected patients who have positive sputum smears.] Clinical_diagnosis_animated_2008.ppt Page 7 of 22 Slide 16 ISTC Training Modules 2008 • The limitation of sputum smear microscopy is its sensitivity. • As illustrated in the table: compared with culture, sputum smear microscopy is 68% sensitive in detecting M. tuberculosis. • Of all specimens that are AFB positive nearly 86% are detected by examining one specimen and an additional 12% are found on the 2nd specimen; thus, the incremental yield of the 3rd specimen is very low. A similar increment is found for the sensitivity of the 2nd and 3rd specimens. • The yield is better with a single early morning specimen than with a spot specimen obtained at other times during the day. [Reference: Mase SR, et al. Yield of serial sputum specimen examinations in the diagnosis of pulmonary tuberculosis: a systematic review. Int J tuberc Lung Dis 2007;11(5): 485-95] Clinical_diagnosis_animated_2008.ppt Page 8 of 22 Slide 17 Animation Clicks: 1 ISTC Training Modules 2008 While we often focus on the pulmonary presentation and evaluation for TB, it is important to remember that TB may present in many ways. Can this case be TB? “A 54 year-old man with three months of focal low back pain” presents with this radiographic finding. [Click: Slide-show Animation] • Yes, this is a patient presenting with spinal tuberculosis, or “Pott’s disease”, with radiographic evidence of vertebral destruction. • Site specific symptoms are often the catalyst for discovery of extrapulmonary sites of involvement. • While the radiographic findings in this case may easily bring TB into the differential diagnosis for this patient, often with extrapulmonary disease, pertinent TB risk factors must be recognized by the astute clinician for TB to be considered and proper diagnostic testing (which include both culture and histopathologic sampling if available) be initiated. [Interactive option – Ask participants for their experiences with cases of extrapulmonary TB where the diagnosis was a surprise. What kind of sampling/testing for extrapulmonary disease is available to them in their practice? Any creative solutions to difficulties encountered in obtaining diagnostic samples or possibilities for shared resources?] [Image credit: Francis J. Curry National Tuberculosis Center, University of California, San Francisco] Clinical_diagnosis_animated_2008.ppt Page 9 of 22 Slide 18 ISTC Training Modules 2008 Standard 3 reinforces these points: [Read Standard 3] • • • • Clearly, appropriate specimens may be difficult to obtain from some extrapulmonary sites. In spite of the difficulties, however, the basic principle that bacteriological confirmation of the diagnosis should be sought still holds. Generally, there are fewer M.tb organisms present in extrapulmonary sites, so identification of acidfast bacilli by microscopy in specimens from these sites is less frequent and culture is more important. If tissue biopsy material is obtained, diagnosis of TB may also be suggested by histopathologic demonstration of appropriate granulomatous lesions. [Instructor Notes: If the Microscopic Diagnosis module will not be covered in your curriculum, consider reviewing the Microscopic Diagnosis module for additional speaking points or slides that would be of interest for this topic.] Slide 19 Animation Clicks: 1 [Image credit: IUATLD www.tbreider.org] • • Extrapulmonary TB (without lung involvement) accounts for 15-20% of TB in populations with a low prevalence of HIV infection. In populations with a high prevalence of HIV infection, the proportion of cases with extrapulmonary TB is higher. [Click: Slide-show Animation] • Clinical_diagnosis_animated_2008.ppt Here, as a general example, is the breakdown of extrapulmonary involvement by site as reported in the United States. [Review content of slide] Page 10 of 22 Slide 20 ISTC Training Modules 2008 Other examples of extrapulmonary presentations: • Tuberculous pleural effusion • CNS tuberculomas (two enhancing lesions seen on CT scan of head). • Tuberculous adenitis (sometimes referred to as “scrofula”). Patient had both an enlarged anterior cervical node as well as a draining cutaneous fistula from supraclavicular nodes. Slide 21 [Image credits: Francis J. Curry National TB Center (left and top right); Austin Brewin, MD (bottom right)] Slide 22 [Image credit: Francis J. Curry National Tuberculosis Center, University of California, San Francisco] • • • While CXR examination can be a useful tool in the diagnosis of TB, remember that it is a sensitive, but not specific test for detecting TB. Key point: A diagnosis of TB cannot be established by radiography alone. Reliance on the chest radiograph as the only diagnostic test for TB will result in both over-diagnosis of TB and missed diagnosis of TB and other diseases. Thus, the importance of Standard 4: [Read Standard] [Image credit: Francis J. Curry National Tuberculosis Center, University of California, San Francisco] Clinical_diagnosis_animated_2008.ppt Page 11 of 22 Slide 23 Animation Clicks: 1 ISTC Training Modules 2008 Can this case be TB? [Click: Slide-show Animation] • Yes - This is an example of a classic CXR pattern many would describe as a “typical pattern” or a reactivation/post-primary TB pattern. • The distribution of disease is often cited as: [Review content of slide] • Note that the presentation of an isolated upper lobe anterior segment infiltrate on CXR is unusual for M.tb, and may hint at another etiologic organism, perhaps a non-tuberculous mycobacterium (e.g. M. avium complex). The anterior segment of the upper lobe in this CXR is clear. [Interactive option – ask participants to respond to the question (this will likely illicit a quick “yes” response and will confirm what they know)] Slide 24 [Image credit: Francis J. Curry National Tuberculosis Center, University of California, San Francisco] • Specific radiographic patterns seen on CXR that may be associated with reactivation/post-primary TB include: [Review content of slide] • This radiograph shows a small area of opacity with cavitation in the left upper lobe. [Image credit: Francis J. Curry National Tuberculosis Center, University of California, San Francisco] Clinical_diagnosis_animated_2008.ppt Page 12 of 22 Slide 25 Animation Clicks: 1 ISTC Training Modules 2008 Can this case be TB? • [Top CXR: Focal right mid-lung infiltrate with hilar adenopathy] • [Bottom CXR: Focal left lower lobe infiltrate] [Click: Slide-show Animation] • Yes, both of these patients had TB and represent examples of “atypical” patterns” of CXR presentation [Review content of slide]. • An “atypical pattern” may often be associated with Primary TB and also be commonly seen in patients with TB and HIV/AIDS co-infection. [Interactive option – ask participants to respond to question. There may be less certainty in participant response because these CXR findings are common for other infectious pneumonias.] [Image credit: Francis J. Curry National Tuberculosis Center, University of California, San Francisco] Slide 26 Can this case be TB? [Automatic Slide-show Animation] Yes, these are all examples of the fine, stippled pattern of small nodules seen in miliary TB by chest radiograph (which correspond to the gross pathology demonstrating scattered granulomatous lesions seen on the right). • • This pattern of nodules, which reflects the hematogenous spread of disease, can also be appreciated well by chest CT imaging. Note that a miliary pattern may be seen in either primary or reactivation/post-primary disease. [Image credit: Francis J. Curry National Tuberculosis Center, University of California, San Francisco (left and center); University of California, San Francisco/Walter Finkbeiner, MD (right)] Clinical_diagnosis_animated_2008.ppt Page 13 of 22 Slide 27 Animation Clicks: 1 ISTC Training Modules 2008 Can this case be TB? [Click: Slide-show Animation] • Yes, these are examples of residual radiographic findings that can be found as the sequelae of prior active TB [Review content of slide] • [Top: Ca+ granuloma and hilar node calcification - Ranke complex] [Left: Apical pleural thickening] [Right: Apical fibrosis with volume loss] • • [Interactive option – ask participants to respond to question.] Slide 28 [Image credit: Francis J. Curry National Tuberculosis Center, University of California, San Francisco] • • • Over-reliance on CXR without the use of sputum microscopy is a common practice in some areas. Data from a study done in a high-incidence country demonstrates just how misleading reliance on the CXR alone can be. [Review content of slide] Overall, radiographic examination for the evaluation of TB is most useful when applied as part of a systematic approach -- particularly, as we will discuss next, in the evaluation of persons whose symptoms and/or findings suggest TB, but who have negative sputum smears. [Reference: Nagpaul DR, Proceedings of the 9th Eastern Region Tuberculosis Conference and 29th National Conference on Tuberculosis and Chest Diseases. 1974 Delhi, as cited in Toman’s tuberculosis. Case detection, treatment and monitoring, 2 nd Edition. Freiden TR ed. Geneva: World Health Organization, 2004] Clinical_diagnosis_animated_2008.ppt Page 14 of 22 Slide 29 ISTC Training Modules 2008 • • • • The designation of “sputum smear-negative tuberculosis” presents a difficult diagnostic dilemma. On average, sputum smear microscopy is only about 50-70% sensitive when compared with culture. When clinical judgment suggests a high suspicion for TB, it is important that a rigorous approach be taken to evaluate fully for this diagnosis, despite the finding of three negative sputum smears. Standard 5 addresses the diagnosis of smearnegative TB. To diagnose smear negative TB, the following criteria should be met: [Read Standard] Slide 30 [Note: Guidelines (WHO – pending publication) have recently changed from three sputum smears to at least two sputum smears. The change is reflected above and differs from the wording in the original published ISTC.] Continued: Clinical_diagnosis_animated_2008.ppt [Read Standard] Page 15 of 22 Slide 31 Animation Clicks: 3 ISTC Training Modules 2008 Clinical_diagnosis_animated_2008.ppt A number of algorithms have been developed as a means to systematize the diagnosis of smear-negative TB, although none has been adequately validated under field conditions. Here, as an example of a systematic approach, is a modified algorithm developed by WHO for use in HIVnegative patients or low HIV prevalence settings. The difference in approach to the evaluation based on HIV status illustrates the desirability to have HIV testing on all TB suspects. • Begin with the clinical suspicion for TB (TB Suspect). • [Click: Slide-show Animation]. The most important first step toward making a diagnosis would be to obtain sputum for AFB microscopy. • [Click: Slide-show Animation]. If at least two smears are negative, the WHO offers one practical step-wise approach that incorporates the criteria in Standard 5. [Review as above: down right side of flowchart] • [Click: Slide-show Animation]. And if the smear results are positive initially, treat as TB. [Review as above: down left side of flowchart] • Note: This is one example of an algorithm that incorporates the fundamental principles recommended for diagnosing TB, and in practice, some local or national programs may follow a different sequence. • Caution: it should be emphasized that the completion of all of the steps requires a substantial amount of time; thus, the algorithm should not be used for patients with an illness that is worsening rapidly. This is especially true in patients with HIV infection in whom TB may be rapidly progressive (as will be outlined on next slide). • As noted in Standard 5, the use of fluoroquinolones as empiric treatment for respiratory track infections may confuse the picture by causing a transient improvement of TB, thus delaying both the diagnosis of TB and the institution of proper treatment. • And finally, following the above approach may be quite costly to the patient and deter her/him from continuing with the diagnostic evaluation. • Given these concerns, application of such an algorithm in patients with at least two negative sputum smears must be done in a flexible. • Page 16 of 22 • manner. [Note: Guidelines (WHO – pending publication) have recently changed from three sputum smears to at least Slide 32 ISTC Training Modules 2008 Because of the increased frequency of AFB smear negative TB among persons with HIV infection a separate set of algorithms has been developed for use in high HIV prevalence settings. [Automatic animation will highlight “Seriously ill TB suspects”]. • • • Clinical assessment of the severity of illness determines the recommended course of action, and two diagnostic algorithms based on severity of illness are offered. In seriously ill patients the tempo of the evaluation and initiation of treatment must be accelerated. Empiric broad spectrum antibiotic treatment is recommended in seriously ill patients and empiric treatment for P. jiroveci pneumonia (PCP) should be considered. One or more of the following danger signs would suggest that a patient is seriously ill: inability to walk unaided, respiratory rate over 30 breaths per minute, fever of more than 39 C, or pulse rate of over 120 beats per minute. It should be noted that even when the diagnosis is TB, patients may respond to a course of antibiotic treatment. Slide 33 [Reference: World Health Organization. Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents. Recommendations for HIV-prevalent and resource-constrained settings. Geneva: WHO 2007] • • • In patients who do not present with signs/symptoms of a serious level of illness, i.e. those considered ambulatory, but still with known HIV or at high risk due to high HIV prevalence, the evaluation may be managed along a somewhat different path. Obtaining cultures, if available, remains of key importance in these smear-negative suspects. If the smears are negative and the initial clinical evaluation deems a diagnosis of TB unlikely, it is reasonable to give treatment for alternative diagnoses more time and fully assess the response before considering a re-evaluation for TB. [World Health Organization. Improving the diagnosis and treatment of smear-negative pulmonary and extrapulmonary tuberculosis among adults and adolescents. Recommendations for HIV-prevalent and resource-constrained settings. Geneva: WHO 2007] Clinical_diagnosis_animated_2008.ppt Page 17 of 22 Slide 34 Animation Clicks: 1 ISTC Training Modules 2008 • Slide 35 Animation Clicks: 4 • • • While this lecture has reviewed many of the classic features of the clinical presentation of TB, it is worth repeating that it is a disease that may attempt to fool even the most astute clinician. A great range in presentation exists, especially if HIV is present (where atypical presentations are more common). One should remember: [Review content of slide] [Click: Slide-show Animation]. Therefore it is important to realize that TB can present in many ways beyond the classic description. The ISTC offer guidelines to help prioritize our investigations in the initial recognition and diagnostic workup for TB. To summarize, the key points of this presentation were: [Review content of slide] Slide 36 Animation Clicks: 2 [Click: Slide-show Animation]. • And in summary, the International Standards reviewed: (abbreviated) [Review content of slide] [Click: Slide-show Animation]. Clinical_diagnosis_animated_2008.ppt Page 18 of 22 Slide 37 Animation Clicks: 1 ISTC Training Modules 2008 • [Continued - Review content of slide] [Click: Slide-show Animation]. And above all, Think TB. Slide 39 Slide 38 [End] • Alternate Slides: Offer additional options that may be added or substituted into module. • See Facilitator’s Guide for further information. The International Standards for Tuberculosis Care (ISTC): • Are intended to unite public and private sectors in providing a uniformly accepted level of care for all patients with, or suspected of having, TB. • Describes the essential elements of TB care that should be available everywhere. • Provides a vehicle for mobilizing professional societies globally in support of TB programs. • Serves as a powerful advocacy tool to ensure that the essential elements are available. [Image Credit: Lung Health Image Library/Gary Hampton] Clinical_diagnosis_animated_2008.ppt Page 19 of 22 Slide 40 ISTC Training Modules 2008 • • • • • • • The ISTC consist of 17 evidence-based standards. Standards differ from existing guidelines in that standards present what should be done, whereas, guidelines describe how the action is to be accomplished. To meet the requirements of the Standards, approaches and strategies, determined by local circumstances and practices and developed in collaboration with local and national public health authorities, will be necessary. There are many situations in which the level of care can, and should, go beyond what is specified in the Standards. The Standards should be viewed as a living document that will be revised as technology, resources, and circumstances change. Revisions to the original document released December 2005 are currently underway. Funded (Oct 1, 2004) by USAID via TBCTA, development was supervised by an international steering committee (28 members / 14 countries) chosen to represent perspectives relevant to tuberculosis care and control. The Standards are also intended to serve as a companion to and support for the Patients’ Charter for Tuberculosis Care developed in tandem with the Standards. A Handbook for using the International Standards for Tuberculosis Care is also available (2007). The Handbook presents suggestions and guidance, based mainly on country-level experiences, for using the ISTC as a tool to foster and guide the delivery of high-quality care by all practitioners providing TB care. [Resource: www.istcweb.org] Clinical_diagnosis_animated_2008.ppt Page 20 of 22 Slide 41 ISTC Training Modules 2008 • • The Standards are addressed to all healthcare providers, private and public, who care for persons with proven tuberculosis or with symptoms and signs suggestive of TB. Three categories of activities are addressed by the Standards: diagnosis, treatment, and public health responsibilities of all providers. The ISTC are Slide 43 Slide 42 intended to be complementary to local and national TB control policies that are consistent with the World Health Organization (WHO) recommendations. • In many parts of the world there is great variability in the quality of tuberculosis care, and poor quality care continues to plague global tuberculosis control efforts. Effective engagement of all providers in providing high quality care in collaboration with TB control programs is key to the promotion of sound tuberculosis control. • Questions: May be used for interactive discussion, course evaluation, or continuing medical education purposes. • See Facilitator Guide for further information. Correct Answer: C Clinical_diagnosis_animated_2008.ppt Page 21 of 22 Slide 44 ISTC Training Modules 2008 Slide 45 Correct Answer: D Correct Answer: C Clinical_diagnosis_animated_2008.ppt Page 22 of 22