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Optimal Approach for TB Screening among HIV Infected Indian Children
This study was funded by the Fogarty International Center at the U.S. National Institutes of Health.
Determining TB status (ie, uninfected, latent, and active TB disease) is more difficult among children, particularly HIV-infected children. Diagnosis of TB disease is more difficult among HIV infected children because the signs and symptoms of the disease—such as weight loss, cough, and mild fever—are similar to some manifestations of HIV and opportunistic infections. Identifying children who have TB infection and those who do not is important, as a subset of them may benefit from INH preventive therapy (IPT).
Globally, there is a need to improve TB screening among HIV-infected children and to identify an optimal approach with high case detection to ensure rapid diagnosis and timely treatment initiation. Currently, the World Health Organization (WHO) recommends a standard four-symptom screening tool for HIV infected children: current cough, fever, night sweats, loss of weight or failure to thrive. Some adult studies have found significantly increased yield with addition of Chest X-ray to symptom screen, however this has not been studied well in children, particularly children who have HIV.
There are some tests that have the potential to improve the sensitivity and specificity of symptom screening. These include Interferon-Gamma Release Assays (IGRA) blood tests, Tuberculin Skin Test (TST), Urinary LAM, Xpert MTB/RIF (GeneXpert), MGIT and Chest X-ray.
WHO's 2015 statistics estimate global TB incidence at 9.6 million cases—India accounts for 2.2 million of those cases. The current TB screening tool is based on the WHO recommended four-symptom screening, but symptom-based approaches may have less diagnostic value in HIV-infected children. Despite high TB occurrence in India, including multi-drug resistant (MDR) TB, the sensitivity and specificity of this screening tool has not yet been fully evaluated among HIV infected children in India. The value of additional laboratory tests, including Chest X-ray, IGRA, gastric lavage, Urinary LAM, GeneXpert, MGIT to improve the utility of WHO symptom screening for TB, also have not been fully assessed.
Therefore, we propose to find an optimal approach to determine TB status among HIV-infected children in India using additional laboratory tests along with the WHO symptom screen.
There are scarce data on sensitivity and specificity of WHO TB symptom screen in HIV infected Indian children. There are some tests, which, when used in addition to the WHO symptom screen, improve the sensitivity and specificity of symptom screen. An optimal approach for ascertaining TB status has not been studied in this population.
Research Question: What is the optimal approach to ascertain TB status in HIV infected Indian children?
- To evaluate the sensitivity and specificity of the current TB screening tool (WHO symptom screen) for HIV-infected children against the gold standard of Mycobacterial growth indicator tube (MGIT) sputum culture or XpertMTB/RIF (GeneXpert).
- To assess utility of additional laboratory testing including IGRA, TST and chest radiography, urinary LAM, MGIT, and XpertMTB/RIF (GeneXpert) to ascertain TB status in HIV-infected children.
To evaluate the time taken from initial assessment to starting of anti TB treatment or IPT.