Test your knowledge

The correct answer is (c). Interferon-gamma release assays (e.g., TB Gold) are meant for the diagnosis of latent TB infection. They should not be used for active TB diagnosis because they cannot distinguish between latent TB and active disease. A 2011 World Health Organization (WHO) policy discourages their use for active TB diagnosis.
Reference: World Health Organization . Policy statement Use of tub erculosis interferon-gamma re lease assays (IGRAs) in lowand middle-income countries. In. Geneva: World Health Organization; 2011.

The correct answer is (b). Liquid culture can be used to grow Mycobacterium tuberculosis and also identify drug resistance (to first and second line drugs). The use of liquid culture is endorsed by the WHO.
Reference: World Health Organization . The use of liquid medium for culture and DSf. URL: http://www.who.int/tb/laboratory/policy_liquid_medium_foc culture_dst/en/index.html. In. Geneva: World Health Organization; 2007.

The correct answer is (d). The Indian Government has banned the use, sale and import of all commercial serological (antibody-detection) TB tests. This includes ELISA as well as rapid antibody tests. The ban applies to domestic as well as imported serodiagnostics kits. The ban is based on a WHO policy that strongly recommends against the use of serological, antibody tests for TB. The International Standards for TB Care also discourages the use of serological TB tests.
References:
World Health Organization. Policy statement Use of tuberculosis interferon-gamma re lease assays (IGRAs) in low and middle-income countries. In. Geneva: World Health Organization; 2011.
World Health Organization. Policy statement Commercial serodiagnostic tests for diagnosis of tuberculosis. In. Geneva: World Health Organization; 2011.

The correct answer is (b). Sputum is the best clinical specimen for diagnosis of pulmonary TB. There are no accurate, validated tests for specimens such as blood, urine and tissue.

The correct answer is (d). Culture is not faster than smear microscopy because even liquid culture needs 10 -14 days for a result to be obtained. Sputum smear results are usually available within 1-2 days.

The correct answer is (c). Chest X-rays alone is NOT sufficient to diagnose pulmonary TB) It needs to be followed by sputum testing. While chest X-rays have fairly high sensitivity for pulmonary TB, its specificity is low. Many lung conditions and infections can cause chest X-ray abnormalities. So, all patients with chest X-ray abnormalities must be investigated with sputum smears, NAAT and/or culture.

The correct answer is (c). Sputum expectoration can release infectious aerosols, which are diluted in the open-air or a well ventilated room and are inactivated by UV light in the outdoors.

The correct answer is (d). There is no approved blood test for the diagnosis of active pulmonary TB) IGRAs are tested on blood but only give information on latent TB infection, not active disease.
Reference: World Health Organization. Policy statement: Use of tuberculosis interferon-gamma release assays (IGRAs) in low- and middle-income countries. In. Geneva: World Health Organization; 2011.

The correct answer is (a). Sputum quality and quantity are essential features of a good specimen for TB testing. Five ml of muco-purulent specimen collected in a sterile laboratory approved container is the ideal specimen for sputum microscopy for TB).

The correct answer is (c). Young children cannot expectorate sputum but it is often swallowed overnight. The best specimen is, therefore, a series of two to three consecutive, fasting gastric aspirates.
Reference: Marais BJ, Pai M. Specimen collection methods in the diagnosis of childhood tuberculosis. Indian J Med Microbiol 2006;24:249-51.

The correct answer is (b). The minimum requirement for sputum testing is two specimens taken one hour apart. Previously three consecutive early morning sputum samples were recommended but research has shown that the 3rd sample does not add much to the overall yield (and can increase the risk of patient drop-out).
Reference: Policy statement. Same-day diagnosis of tuberculosis by microscopy. World Health Organization, 2011. (Accessed 2011, at http://whqlibdoc)who.int/publications/2011/9789241501606_eng.pdf.)
Mase SR, Ramsay A, Ng V, et al. Yield of serial sputum specimen examinations in the diagnosis of pulmonary tuberculosis: a systematic review. Int J Tuberc Lung Dis 2007;11:485-95.

The correct answer is (d). Specimens that are unlabeled or do not have a properly filled out form, are rejected by the laboratory. Fixatives, such as formalin, will inactivate any micro-organisms in a tissue sample, therefore, making it unsuitable for culture.

The correct answer is (c). Endometrial issue for culture and histopathology is critical for diagnosing genito-urinary tract TB) Blood (venous or menstrual) is not the appropriate sample as it is very difficult to isolate M. tuberculosis or detect MTB DNA in such samples.

The correct answer is (a). Chest x-rays are not specific for TB) Many lung infections and conditions can cause radiological abnormalities. This is why all persons with radiographic abnormalities suggestive of TB should have sputum specimens submitted for microbiological examination. Only microbiological examination can confirm the diagnosis of TB).
Reference:
Hopewell PC, Pai M, Maher D, Uplekar M, Raviglione MC) International standards for tuberculosis care. Lancet Infect Dis 2006;6:710-25.
Pai M. Diagnosis of pulmonary tuberculosis: what every GP should know. GP Clinics 2013;3:22-8.

The correct answer is (b). Although TB can cause any of the radiologic findings listed, upper lobe disease with or without cavitation is the most common.
Reference:
Pinto L, Dheda K, Theron G, et al. Development of a Simple Reliable Radiographic Scoring System to Aid the Diagnosis of Pulmonary Tuberculosis. PLoS One 2013;8(1): :e54235.
Pinto LM, Pai M, Dheda K, Schwartzman K, Menzies D, Steingart KR. Scoring systems using chest radiographic features for the diagnosis of pulmonary tuberculosis in adults: a systematic review. Eur Respir J 2012.

The correct answer is (e). Although TB most commonly occurs in the upper lobes it can occur in any part of the lung.

The answer is (c). CXR’s must be interpreted in the clinical context. An acute presentation suggests acute bacterial infection. Sputum specimens should be obtained before starting conventional antibiotics. Fluoroquinolones should be avoided if TB is at all suspected as they will result in temporary improvement because TB is sensitive to this class of drugs, leading to delay in diagnosis.

The answer is (c). Although TB must be suspected in anyone with an upper lobe cavitary mass, in a heavy smoker with a 2 month history of cough and bloody sputum, in the absence of infectious symptoms, lung cancer must be suspected) A bronchoscopy can obtain specimens for AFB but at the same time, can make the diagnosis of cancer.

The correct answer is (c). Injectable drugs are not part of the regimen for newly diagnosed pulmonary tuberculosis. The standard regimen for the treatment of TB lasts 6 months, with 4 drugs (Rifampicin, Isoniazid, Pyrazinamide and Ethambutol) prescribed in the first two months (intensive phase), and Rifampicin and Isoniazid continued for another 4 months (continuation phase). In India, because of high levels of INH resistance, the Standards for TB Care in India recommends the addition of ethambutol to the continuation phase.

The correct answer is (b). Sputum smear examination is recommended at the end of the intensive phase of treatment and at the end of treatment. Investigations for drug resistant TB need to be performed if the smear continues to be positive at 3 months. Treatment is considered to have failed if the smear at end of treatment is positive. Improvements in chest radiographs, while reassuring in the clinical context, are not specific enough to be used to monitor disease. TB IgG and IgM are serological tests that have been banned and have no role in the management of TB) IGRA (e.g., TB Gold) is a test to diagnose latent TB, and has no role in the diagnosis or monitoring of active disease.

The correct answer is (d). Relapse, retreatment and having a close contact with drug-resistant TB are important risk factors for drug-resistant TB, and questions pertaining to these risk factors are very important in the initial assessment of patients with TB)

The correct answer is (c). While intermittent treatment is an accepted modality of treatment, it is recommended only when compliance is ensured through direct supervision, and given for a minimum of three times a week. Twice-weekly regimens are not acceptable. Injectable drugs are not part of a standard intermittent treatment regimen for newly diagnosed pulmonary TB).

The correct answer is (a). Jaundice is a sign of hepatitis and warrants stoppage of all TB medications, and investigations for drug-induced hepatitis. It is more common in the elderly and in patients with pre-existing liver disease.

The correct answer is (a). There is no validated blood test for pleural or any form of extrapulmonary tuberculosis. Other samples listed are useful to collect.

The correct answer is (c). In 2013, WHO endorsed the use of Xpert MTB/RIF for extrapulmonary TB.

The correct answer is (d). The Indian Government has banned the use, sale and import of all commercial serological (antibody-detection) TB tests. This includes ELISA as well as rapid antibody tests. The ban applies to domestic as well as imported serodiagnostics kits. The ban is based on a WHO policy that strongly recommends against the use of serological, antibody tests for TB) The International Standards for TB Care, and Standards for TB Care in India also discourage the use of serological TB tests.

The correct answer is TRUE. Neither Mantoux nor TB Gold can separate latency from active TB disease. Thus, they are discouraged for active TB diagnosis.

The correct answer is (c). Liquid cultures have the highest sensitivity.

The correct answer is (d). Xpert does not have high sensitivity in pleural fluid samples, and therefore should not be used alone. It should be used in combination with other tests such as pleural fluid/tissue cultures and biopsy.

The correct answer is (c). An estimated 40% of the Indian population is estimated to be latently infected, using tuberculin surveys.

The correct answer is (d). The tuberculin skin test, using Mantoux technique, is one of the two accepted tests for latent TB infection screening. The other test is interferon-gamma release assays (e.g., TB Gold)

The correct answer is (e). Latent TB screening should be restricted to high-risk groups. These include people living with HIV and AIDS, adult and child contacts of pulmonary TB cases, patients initiating anti-tumour necrosis factor (TNF-alpha) treatment, patients with end stage renal failure on dialysis, patients preparing for organ or haematologic transplantation, and patients with silicosis.

The correct answer is (a). IGRAs cannot separate latent infection from active TB, and, therefore, not recommended for active TB detection. This is also true for Mantoux skin test. Both IGRAs and TST should be restricted to LTBI screening, and should not be used for active TB diagnosis. In children, Mantoux test may have some value as a test for infection, in addition to chest x-rays, symptoms, history of contact, and other microbiological investigations (e.g., gastric juice acid fast bacilli and Xpert MTB/RIF).

The correct answer is (e). The HRZE drug regimen is meant for treating active tuberculosis. For latent TB infection, treatment options recommended by WHO include 6 to 9 months of isoniazid, 3-month regimen of weekly rifapentine plus isoniazid, or 3–4 months isoniazid plus rifampicin, or 3–4 months rifampicin alone.

The correct answer is (d). The WHO and STCI recommendation is that GeneXpert (Xpert MTB/RIF) be used as the frontline test for PLWH suspected of having active pulmonary TB) This test is more sensitive than sputum smear microscopy. The interferon-gamma release assay is a test for latent TB infection, it should not be used as a diagnostic test for investigating suspected active pulmonary TB) Sputum culture is highly sensitive and specific for the diagnosis of active pulmonary TB; however, GeneXpert is recommended as the frontline test because it provides results within a few hours, whereas sputum culture can take weeks.

The correct answer is (c). The WHO and STCI recommend that all persons diagnosed with active TB should be tested for HIV infection. This is because HIV is more common amongst persons with active TB, and also because the management of active TB will be different among patients that are PLWH.

The correct answer is (e). The WHO and the STCI recommend TB screening for PLWH in high TB burden areas. The WHO recommendation is to use symptom-based screening, and if resources are available, a CXR. The symptom-based screen recommended by the WHO consists of asking about the presence of four symptoms: fevers, coughs, night sweats, and weight loss; if any symptom is present, then active TB should be suspected and the patient will require additional diagnostic work up. A CXR should be used as a supplement to symptom-based screening to increase sensitivity. The CXR should be performed even amongst PLWH that do not have any of the four symptoms asked about in symptom-based screening; this will increase the sensitivity. The presence of any abnormality on a CXR means that further diagnostic testing (e.g., GeneXpert) should be pursued in order to diagnose or exclude active TB).

The correct answer is (d). Antiretroviral therapy and isoniazid preventive therapy both lower the risk of active TB in PLWH. All PLWH should be regularly assessed to determine if they meet criteria for initiating antiretrovirals.

The correct answer is (d). Antiretroviral therapy and co-trimoxazole lower mortality in PLWH who have active TB) Isoniazid preventive therapy is contraindicated when active TB is suspected (or confirmed, of course)—as this will expose the M. tuberculosis to isoniazid monotherapy which will lead to the development of isoniazid resistance. Antiretroviral therapy should be initiated in all PLWH who have active TB, regardless of their CD4 count, within 8 weeks of starting TB treatment.

The correct answer is (b). The preferred regimen for the treatment of active TB in PLWH is 2 months of isoniazid, rifampin, pyrazinamide and ethambutol, followed by 4 months of isoniazid and rifampin, with treatment dosed daily throughout. Regimens that used rifampin only in the intensive phase (question 6. choice “a)”, where rifampin is used for only 2 months) have been associated with worse TB outcomes in PLWH (and also in HIV-uninfected TB patients). Intermittent TB therapy has also been associated with worse TB treatment outcomes in PLWH—hence, all efforts should be made to ensure PLWH who have active TB are treated with regimens in which dosing is daily throughout treatment.

The correct answer is (c). The propensity of the drugs to cause erythroderma (exfoliative dermatitis) are PZA >SM >EMB >RIF >INH with rates for PZA being 2.4 %. All the drugs have to be stopped and reintroduction of the ATT is to be done with INH followed by RIF, EMB and PZA with careful monitoring. To prevent monotherapy, 2 new drugs which were not used previously should be added while introducing individual drugs.

The correct answer is (c). Drug induced thrombocytopenia is because of immune mediated mechanisms because of production of autoantibodies or drug dependent antibodies resulting in rapid destruction of platelets. It is a life threatening complication and is an absolute contraindication to rechallenge as even minute quantities of the drug can trigger immune mediated destruction of platelets leading to severe hemorrhage.

The correct answer is (d). The propensity to produce hepatotoxicity is with PZA> INH> RIF. Ethambutol, streptomycin and moxifloxacin do not have hepatotoxic potential and they can be administered safely in patients with hepatotoxicity while discontinuing those drugs with hepatotoxic potential and to accompany the individual drugs on rechallenge to prevent monotherapy .

The correct answer is (d). Advancing age, female gender, chronic alcohol consumption, pre existing liver diseases, hepatitis B, C and HIV coinfection, malnutrition are some of the important risk factors for drug induced hepatotoxicity. They have to be carefully sought prior to the initiation of ATT and their presence warrant close monitoring of liver function tests every 2-4 weeks on therapy.

The correct answer is (a). Jaundice is a sign of hepatitis and warrants stoppage of all TB medications, and investigations for druginduced hepatitis. However, it can also occur rarely due to drug induced hemolysis which is a life threatening complication. Liver function tests and complete blood counts are to be requested to differentiate drug induced hepatitis and hemolytic jaundice. Drug induced hepatitis is diagnosed when serum aminotransferase level >5 times the upper limit of normal [ULN] without symptoms or >3 times the ULN with symptoms.

The correct answer is (F). Rifampicin often turns body fluids a red-orange color. Alerting patients ahead of time to this benign side effect may help minimize unnecessary concern or interruptions in therapy.

Pyridoxine should be considered for all patients starting TB therapy including isoniazid, but Mohan is at particularly high risk for isoniazid-related peripheral neuropathy due to his diabetes, which can also cause peripheral neuropathy. People living with HIV, malnourished patients, and patients on other medications that can cause peripheral neuropathy (e.g., multidrug resistant TB patients on ethionamide, cycloserine, or linezolid) are also at higher risk for isoniazid-related peripheral neuropathy.

Rifampicin can decrease blood levels of sulfonylureas used to treat diabetes, including glyburide, which can result in worsened blood sugar control in some patients.1,2 As such, patients on sulfonylurea medications should have their diabetes monitored closely, as they may require modifications of their medications while on TB therapy.

There is no specific requirement that patients should take their TB medications only at bedtime. In general, for patients on standard therapy for drug-susceptible TB, it is important that patients take their medications at the same time every day (whether in the morning or at night). TB medications are best absorbed if taken on an empty stomach; however, for patients with significant gastrointestinal side effects, taking medications with food may be considered to reduce these side effects.

The correct answer is (F). Ongoing weight loss after weeks of TB therapy should raise concern for potential drug-resistance, poor medication adherence, and poor quality of the patient’s diet. Per the Standards for TB Care in India, drug susceptibility testing (DST) should be offered to all diagnosed TB patients prior to starting therapy. however, in cases where DST was not done at the initiation of therapy, failure to respond to therapy as evidenced by ongoing weight loss should prompt GPs to send a DST.

Ongoing weight loss may also suggest that a patient is not taking his or her medications, so screening for non-adherence using simple questions (such as the Morisky questions) is important.
Low caloric intake and poor protein intake may blunt replenishment of the patient’s nutritional stores, especially in patients with food insecurity, vegetarian patients with poor protein intake, and patients with a high catabolic state from other comorbidities (e.g., HIV cachexia).

Streptomycin alone should not be added empirically to the patient’s medication regimen. If there is high concern for drug-resistant TB, DST should be performed, and empiric multidrug- resistant TB therapy (which would involve addition of multiple medications) can be considered in some cases pending the DST result.

While a prednisone taper might briefly increase the patient’s weight and temporarily improve symptoms, it would not improve the patient’s long-term response to TB therapy.

The correct answer is (H). Unfortunately, evidence-based data about the best approaches for ensuring adherence to TB medications are lacking. However, some common-sense strategies for improving medication adherence include improving the patient’s treatment literacy (by educating about the consequences of non-adherence), setting daily reminders to facilitate pill-taking, involving close family members in the patient’s TB care, and implementing a “talk back” strategy at each visit, in which the patient repeats back your recommendations to confirm his or her understanding.

Patients should not stop TB medications for acid reflux or mild nausea, though they should get in touch with their GP. GPs can then check LFTs to rule out hepatotoxicity and recommend therapies to reduce these GI side effects, such as antacids.

Maintaining good glycemic control is important during TB therapy, and patients should not be advised to stop their diabetes medications while on TB therapy.

The correct answer is (E). Depression and alcohol use disorder are two common barriers to TB medication adherence. Simple questionnaires—such as the Patient Health Questionnaire- 2 (for depression) and the AUDIT-C (for alcohol use disorder)—can be easily implemented during brief patient visits to screen for these problems. Ideally, patients should be referred to mental health specialists to help with these problems; however, finding a qualified specialist can be difficult in many areas of India. Encouraging compassionate, non-judgmental involvement from a patient’s family members can sometimes provide the social support needed to get through TB therapy.
The patient should not be advised to stop TB therapy, because premature termination of therapy will increase the risk for relapse of TB.

The correct answer is (E). Patients with alcohol use disorder should be reminded about the increased risk of hepatotoxicity from TB medications. Identifying triggers that lead the patient to use alcohol heavily may help patients to reflect upon how they can avoid these triggers and cut down on drinking. For heavy drinkers, eating before drinking may improve nutritional status and blunt the effects of alcohol. It is important to have a non-judgmental approach to patients with substance use disorders. Patients are more likely to have ongoing engagement with healthcare providers who are open and compassionate. Recent studies suggest that supportive engagement of patients with alcohol use disorder can improve their TB treatment outcomes.

The correct answer is (e).

The correct answer is (c). BMI is calculated as weight in kg/(height in metre). The BMI in this patient would be 45/(1.7)2= 15. 57 kg/m2. This is less than 16.0 kg/m2 and indicates severe undernutrition.

The correct answer is (d). The bioavailability and peak serum concentrations of both isoniazid and rifampicin is affected by food.

The correct answer is (c): The commercial protein supplement may contain 40 gm protein in a 200-gm pack, but is costly and inappropriate, as are tonics with amino acids. Mutton and chicken are more expensive than eggs and the labourer is more likely to afford additional pulses or eggs, than eat chicken or mutton on a daily basis. The protein content per 100 gm, does not differ between eggs and chicken.

The correct answer is (b). Isoniazid interferes competitively with pyridoxine metabolism by inhibiting the formation of the active form of the vitamin, and hence often results in peripher¬al neuropathy. This is especially marked in malnutrition, pregnancy, lactation, HIV infection, diabetes and hypertension. This effect can be prevented by giving pyridoxine 10 mg per day.

The correct answer is (a). In a patient with very low BMI and who has probably been eating little for many days, vigorous feeding may result in refeeding syndrome which can be danger¬ous. The feeding should start at 50% of the dietary requirement or even lower in the first few days, along with the other measures mentioned.