A One-stop Shop for the Same Day Diagnosis and Management of TB and HIV
A One-stop Shop for the Same Day Diagnosis and Management of TB and HIV
TB is a major public health problem and the second most common cause of adult death due to
 infection in many low-income countries. Despite major efforts to de-centralise services,
 accessibility to diagnosis is still limited, with one third of the 9 million cases occurring
 each year being missed by national control programmes.

 New TB diagnostics suitable for use at the point-of-care are emerging. Some of these are
 intended for screening purposes, as an initial step to identify individuals who may have TB
 and should undergo further tests for confirmation. These tests may have high sensitivity, but
 also give false-positive results (low specificity). Other tests aim to be the confirmatory
 tests for TB (high specificity), but these tests are often more expensive and complex and are
 only available in hospital laboratories. As these tests have different purposes, it is likely
 they would work better in combination in a step fashion to optimise their impact and to
 develop an efficient diagnostic process. Furthermore, as none of the tests is versatile
 enough to be used in all settings, test combinations will need to consider the health system
 context in which they would be used. Our aim is to develop and evaluate rapid and accurate
 diagnostic approaches for TB that facilitate the initiation of appropriate treatment on the
 same day of the initial consultation in Africa.

 The objectives are to

 1. Evaluate new diagnostics for TB (including among HIV co-infected individuals) that are
 suitable at the point-of-care;

 2. Develop diagnostic algorithms that streamline and accelerate the diagnosis of TB,
 allowing patients to reach clinical management decisions within a single clinic visit;

 3. Determine the impact of using novel point-of-care diagnostic combinations on the
 proportion of patients correctly initiating TB treatment within 24-48 hours of first
 attendance; their potential cost effectiveness

 The investigators conducted studies in 2016-2018 to accomplish the first two objectives and
 have identified diagnostic tests that are suitable for low and middle income countries.

 This document therefore refers to objective 3, which aims to

 1. Assess the performance of two diagnostic schemes for the diagnosis of TB when compared
 to culture.

 2. Assess the yield of two diagnostic schemes for the diagnosis of TB when compared to
 Xpert and

 3. Assess the cost of the two diagnostic schemes compared to Xpert.
The study will enrol patients in TB clinics based in 4 selected district hospitals (two in
 Nigeria and two in Ethiopia) and samples will be processed in a single reference laboratory.
 This diagnostic evaluation trial will comprise two experimental diagnostic schemes which will
 be compared against the standard of care:

 -  One experimental arm (scheme 1) will screen all patients for HIV using two rapid tests
 routinely used by the clinics and a rapid CRP. Selected patients will be further tested
 using ULTRA. Individuals with HIV will undergo an HIV VL using Xpert.

 -  A second experimental arm (scheme 2): will screen individuals for HIV and CRP (as in
 scheme 1) and selected patients will be tested using Molbio Truenat MTB. Individuals
 with HIV will undergo an HIV VL using Molbio Truenat HIV-VL and Truenat RIF.

 -  In addition, all patients will be tested using the standard of care consistent of
 confirmatory HIV and CRP tests, Xpert MTB/RIF and culture.

 -  Randomisation All patients will be randomised at a ratio of 1:1 into schemes 1 and
 2. Random numbers will be generated in LSTM by a statistician independent to the
 study. The scheme allocations will be included in study envelopes assigned to
 individual study numbers. Equal number of participants will be included in Nigeria
 and Ethiopia.

 -  Proposed methods for protecting against source bias

 As this is an open trial, the classification of patients will be based on objective
 quantitative results of laboratory tests. It is expected the test performances will vary
 according to HIV status. Participants will be classified according to their experimental test
 results
Inclusion Criteria:

 1. Adult with presumptive TB

 2. At least one of the following criteria: Cough > 2-week duration, weight loss,
 unexplained fever, night sweats or haemoptysis.

 3. Willing to participate in the study

 Exclusion Criteria:

 1. Age unknown and likely being a minor (looks <18 years old)

 2. Known pregnancy

 3. Has received or is receiving anti-TB treatment

 4. Already diagnosed with TB.