Management of HIV and TB: What Every GP Should Know

Authors: Faiz Ahmad Khan, MD, MPH—co-author
Madhukar Pai, MD, PhD—Author and Series Editor
Number of pages: 6
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Overview: Tuberculosis (TB) is the leading cause of morbidity and mortality in people living with HIV (PLWH). The epidemiologic link between HIV and TB is strong even in a low HIV prevalence country such as India
– hence all Indian physicians that see patients with suspected or confirmed TB should understand how to approach TB diagnosis and treatment among PLWH, even if they are not working in a community where HIV infection is common. This article provides general practitioners with a concise and practical overview of TB screening, prevention, diagnosis and treatment, in PLWH.

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Management of Latent Tuberculosis Infection

Authors: Madhukar Pai, MD, PhD—Author and Series Editor; Camila Rodrigues, MD—co-author
Number of pages: 4
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Overview: Most individuals who get exposed to Mycobacterium tuberculosis (MTB) manage to eliminate or contain the infection using host T-cell immune defenses. However, some MTB bacilli may remain viable (latent) and “reactivate” later to cause active TB disease. This state is called Latent TB Infection (LTBI). Identification and treatment (i.e. preventive therapy or prophylaxis) of LTBI can substantially reduce the risk of development of active disease (by as much as 60%). However, because 40% of Indians are latently infected, LTBI screening must be restricted to specific high risk populations in India, where the benefits of LTBI treatment outweigh any risks. These include people living with HIV, 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. While either tuberculin skin test (Mantoux) or interferon-gamma release assays (e.g., TB Gold) can be used for LTBI screening, it is important to make sure that these tests are not used for active TB diagnosis. For persons with symptoms or abnormal chest x-rays, physicians should order smears, cultures, and molecular tests (e.g., Xpert MTB/RIF). If LTBI is diagnosed, then physicians must rule-out TB disease with chest x-rays before starting one of the recommended drug regimens. It is important to ensure adherence, and provide adequate counseling to ensure that patients do not stop therapy prematurely.

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Management of Latent Tuberculosis Infection

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Extrapulmonary TB: New Diagnostics and New Policies

Authors: Ruvandhi Nathavitharana, MD, MPH—Author; Madhukar Pai, MD, PhD—co-author and Series Editor
Number of pages: 6
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Overview: Clinical presentations of extrapulmonary TB (EPTB) is diverse, leading to missed cases and delayed diagnoses. Since the diagnosis of EPTB is often compromised by the paucibacillary nature of the disease, new diagnostic tools and policies have been eagerly awaited. At long last, new tools, and new policies are here. The International Standards for TB Care (ISTC) recommends that all patients, including children, who are suspected of having EPTB, should have appropriate specimens obtained from the suspected sites of involvement for microbiological and histological exam. The World Health Organization (WHO) has endorsed the use of Xpert MTB/RIF assay (Cepheid Inc., Sunnyvale, California), a cartridge based nucleic acid amplification test (NAAT), for EPTB. Xpert MTB/RIF is now considered a central test in the work-up of EPTB, and should be used along with existing tools such as microscopy, liquid cultures (which are the most sensitive technologies for MTB detection), and histopathology (biopsy) to arrive at the final diagnosis. Xpert is particularly useful in cerebrospinal fluid samples and in lymph node and other tissues. Once diagnosed, EPTB must be treated with standardized treatment regimens, as recommended by ISTC.

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Extrapulmonary Tuberculosis: New Diagnostics and New Policies

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Treatment of Pulmonary Tuberculosis: What Every GP Should Know

Authors: Lancelot M. Pinto, MD, MSc—Author; Madhukar Pai, MD, PhD—co-author and Series Editor
Number of pages: 4
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Overview: Nearly 50% of patients with TB in India are treated in the private sector. GPs therefore share the responsibility of TB control in India, and play a major role in preventing the spread of the disease by curing patients and arresting transmission. Every GP will need to consider TB as a differential diagnosis in persons with cough lasting two weeks or more, or with abnormal findings on chest radiography. In such patients, TB must first be microbiologically confirmed, either using sputum smear microscopy, Xpert MTB/RIF (i.e., GeneXpert), or liquid cultures. Once TB is confirmed, the next step is to begin the correct anti-tuberculosis therapy (ATT) regimen, as recommended by Standards for TB Care in India (STCI) and the International Standards for TB Care (ISTC). All patients who have not been treated previously and do not have other risk factors for drug resistance should receive a WHO-approved first-line treatment regimen for a total of 6 months. The initial phase should consist of two months of isoniazid, rifampicin, pyrazinamide and ethambutol. The continuation phase should consist of isoniazid and rifampicin given for 4 months (ethambutol can also be added to the continuation phase in areas with high levels of isoniazid resistance). Treatment can be given daily or as thrice-weekly intermittent dosing. Adherence to the full course of ATT is very important to ensure high cure rates and to prevent the emergence of drug-resistance. If patients have any risk factors for drug-resistance, or do not respond to standard ATT, they must be investigated for MDR-TB using drug-susceptibility tests (DST) like GeneXpert, line probe assays, and liquid cultures. MDR-TB requires long-term and specialized treatment. So, patients should be referred to chest specialists, either in the private sector, or in the public sector where free MDR treatment is available.

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Treatment of Pulmonary Tuberculosis: What Every GP Should Know

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Improving Access to Affordable and Quality TB Tests in India

Authors: Madhukar Pai, MD, PhD—Author and Series Editor
Number of pages: 5
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Overview: This article describes the Initiative for Promoting Affordable, Quality TB tests (IPAQT; www.ipaqt.org), a coalition of private laboratories in India, supported by industry and non-profit groups, that has made several WHO-endorsed TB tests available at more affordable prices to patients in the private sector. General practitioner who manage TB should avoid inaccurate blood-based tests and use WHO-endorsed sputum tests for TB, including LED fluorescence smear microscopy, liquid cultures, line probe assays, and automated, cartridge-based molecular tests (i.e., Xpert MTB/RIF). These tests are validated and backed by strong evidence and WHO policy recommendations. Thanks to IPAQT, their prices have been reduced considerably in the Indian private sector.

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Interpretation of Chest X-rays in Tuberculosis

Authors: Bary Rabinovitch, MD, FRCP(C)—Author; Madhukar Pai, MD, PhD—co-author and Series Editor
Number of pages: 9
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Overview: Every GP in India will need to consider TB as a differential diagnosis in persons with cough lasting two weeks or more, or with unexplained chronic fever and/or weight loss. Chest radiography is very widely used in India. Chest x-rays serve as an invaluable adjunct in the diagnosis and follow-up of TB. However, TB may mimic other diseases on x-rays, and non TB conditions may look like TB. Thus, chest x-rays are neither specific nor sensitive, and so remain a supplement to microbiological tests such as microscopy, PCR and culture. Treatment of TB purely on the basis of x-rays can result in significant over-treatment with adverse consequences for patients. Therefore, all persons with chest radiographic findings suggestive of TB should have sputum specimens submitted for microbiological examination. This article provides a series of x-rays that serve to educate the provider about radiological interpretation of TB and common pitfalls and errors in interpretation.

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Interpretation of Chest X-rays in Tuberculosis

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Diagnosis of Tuberculosis: Specimen Collection

Authors: Madhukar Pai, MD, PhD—Author and Series Editor; Pamela Chedore, MLT—Co-author
Number of pages: 7
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Overview: A good diagnostic approach for TB requires collection of the right clinical specimen(s) of adequate quality and quantity. For pulmonary TB, sputum is the most important sample for laboratory testing. Although blood is a popular sample in the Indian private sector, there is no accurate blood test for active TB. For extra-pulmonary TB, it is critical to obtain specimens from the site of disease, and this usually includes collection of tissue (biopsy) and/or body cavity fluids from the suspected disease site. For childhood TB diagnosis, sputum can be collected from older children. In young children, fasting gastric aspirates are the routinely collected samples. For latent TB infection diagnosis, there are two main options – interferon- gamma release assays which require venous blood samples, or the tuberculin skin test (Mantoux), which is an intra-dermal skin test. In all the above situations, clear instructions on specimen collection should be provided to patients as well as to laboratories and clinics. Quality of specimens can often have a big impact on test results, and every effort should be made to ensure quality in specimen collection, transport and processing.

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Diagnosis of Tuberculosis: Importance of Appropriate Specimen Collection

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Diagnosis of Pulmonary Tuberculosis: What Every GP Should Know

LetsTalkTB_1Authors: Madhukar Pail MD, PhD-Author and Series Editor
Number of pages: 6
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Overview: India has the highest burden of tuberculosis (TB) in the world, and every GP will need to consider TB as a differential diagnosis in persons with cough lasting two weeks or more, or with unexplained chronic fever and/or weight loss. Sputum is the most important sample for laboratory testing. Although blood is a popular sample in theIndian privatesector, there is no accurate blood test for active TB. Blood-based antibody tests (e.g., IgG/lgM ELISA orrapid tests) and interferon-gamma release assays (e.g., TB Gold) are not accurate and should not be used for pulmonary TB diagnosis. In fact, the Government of India has recently banned the use of serodiagnostic tests for TB. There are three internationally accepted sputum tests for active TB:sputum smear microscopy for acid-fast bacilli; nucleic acid amplification test(e.g., GeneXpert); and culture. Chest radiography is useful but cannot provide a conclusive diagnosis on its own, and needs to be followed by sputum testing.

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Diagnosis of Pulmonary Tuberculosis: What Every GP Should Know

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