Expanding Xpert Ultra for TB diagnosis among HIV-positive patients admitted to hospitals in Africa

This study intends to find ways to improve TB diagnosis among HIV-positive patients while supporting and accelerating treatment guidance, particularly in the African region. A background study for this investigation confirmed that limitations of existing sputum-based tests for M. tuberculosis (Mtb) diagnosis among PLHIV admitted to hospital imposes the exploring of easy to collect, non-respiratory specimens improving TB diagnosis.

Screening and testing for TB in PLHIV are highly and regularly recommended by The World Health Organization (WHO). Those identified to have any TB-related symptoms are investigated and treated if diagnosed with TB. Confirmation of TB through these tests however can be suboptimal due to sputum collection challenges and few bacillary in sputum resulting in poor diagnostic yield.

The primary objective of this study would be to investigate the effect of an expanded TB screening strategy among HIV-positive patients admitted to hospital (including Ultra on sputum, stool, and urine, and AlereLAM on urine, performed regardless of the presence of TB symptoms) on the proportion of bacteriologically confirmed TB cases starting treatment within 72 hours of enrolment, compared to Ultra testing (on sputum/any tissue) and AlereLAM (on urine) in only those patients who are symptomatic for TB or fulfill WHO testing recommendations.

The primary outcome from the study showed a proportion of participants diagnosed with microbiologically confirmed TB and started on TB treatment within 72 hours of enrolment in whom TB is microbiologically confirmed, separately for control and intervention arms.

TB is an infectious disease caused by the bacteria Mycobacteria tuberculosis which usually attacks the lungs and can affect human beings for a long time without them showing any symptoms. When symptoms do occur, they usually include fever, a cough (sometimes blood-tinged), chest pain, and weight loss. These symptoms however are often atypical among HIV-infected people which makes the diagnosis of TB difficult.

The prevalence of TB among HIV-positive individuals is much higher as it can occur anytime during the period of an HIV infection. This increased risk is 16-27 times higher in PLHIV compared to those who are HIV-negative. This is due to the impaired and lowered innate and passive immunity against TB among HIV-positive individuals, increasing the risk of getting a new TB infection and of progression from latent TB to active TB. Causes of active TB infections are commonly associated with various factors such as malnutrition, smoking, overcrowding, and poverty to name a few.

The study’s duration is 41 months with planning beginning in September 2019. The study is expected to be finalized in August 2024 when the final (EDCPT) report is completed. The study design is a multicenter, parallel, individually randomized, controlled diagnostic trial in consecutively enrolled HIV-positive adults admitted to hospitals in selected sites in Mozambique and Tanzania. Study centers for this study include Instituto Nacional de Saude (INS) and Centro de Investigação em Saúde de Manhiça (CISM) in Mozambique, NIMR – Mbeya and IHI - Ifakara in Tanzania.

Additional supporters for the study are: The European & Developing Countries Clinical Trials Partnership (EDCTP) - the trial funder, Foundation for Innovative Diagnostics (FIND) - the trial coordinator and LING - in charge of contractual and financial management.