Background The prevalence of diseases other than tuberculosis (TB) detected during chest X‐ray screening is poorly described in sub‐Saharan Africa. Computer‐assisted digital chest X‐ray technology is available for TB screening and has the potential to be a screening tool for non‐communicable diseases as well. Low‐ and middle‐income countries are in a transition period where the burden of non‐communicable diseases is increasing, but health systems are mainly focused on addressing infectious diseases. Methods Participants were adults undergoing computer‐assisted chest X‐ray screening for tuberculosis in a community‐wide tuberculosis prevalence survey in Blantyre, Malawi. Adults with abnormal radiographs by field radiographer interpretation were evaluated by a physician in a community‐based clinic. X‐ray classifications were compared to classifications of a random sample of normal chest X‐rays by radiographer interpretation. Radiographic features were classified using WHO Integrated Management for Adult Illnesses (IMAI) guidelines. All radiographs taken at the screening tent were analysed by the Qure.ai qXR v2.0 software. Results 5% (648/13,490) of adults who underwent chest radiography were identified to have an abnormal chest X‐ray by the radiographer. 387 (59.7%) of the participants attended the X‐ray clinic, and another 387 randomly sampled normal X‐rays were available for comparison. Participants who were referred to the community clinic had a significantly higher HIV prevalence than those who had been identified to have a normal CXR by the field radiographer (90 [23.3%] vs. 43 [11.1%] p‐value < 0.001). The commonest radiographic finding was cardiomegaly (20.7%, 95% CI 18.0–23.7). One in five (81/387) chest X‐rays were misclassified by the radiographer. The overall mean Qure.ai qXR v2.0 score for all reviewed X‐rays was 0.23 (SD 0.20). There was a high concordance of cardiomegaly classification between the physician and the computer‐assisted software (109/118, 92.4%). Conclusion There is a high burden of cardiomegaly on a chest X‐ray at a community level, much of which is in patients with diabetes, heart disease and high blood pressure. Cardiomegaly on chest X‐ray may be a potential tool for screening for cardiovascular NCDs at the primary care level as well as in the community.

Introduction: An estimated 1.2 million children develop tuberculosis (TB) every year with 240,000 dying because of missed diagnosis. Existing tools suffer from lack of accuracy and are often unavailable. Here, we describe the scientific and clinical methodology applied in RaPaed-TB, a diagnostic accuracy study. Methods: This prospective diagnostic accuracy study evaluating several candidate tests for TB was set out to recruit 1000 children <15 years with presumptive TB in 5 countries (Malawi, Mozambique, South Africa, Tanzania, India). Assessments at baseline included documentation of TB signs and symptoms, TB history, radiography, tuberculin skin test, HIV testing and spirometry. Respiratory samples for reference standard testing (culture, Xpert Ultra) included sputum (induced/spontaneous) or gastric aspirate, and nasopharyngeal aspirate (if <5 years). For novel tests, blood, urine and stool were collected. All participants were followed up at months 1 and 3, and month 6 if on TB treatment or unwell. The primary endpoint followed NIH-consensus statements on categorization of TB disease status for each participant. The study was approved by the sponsor’s and all relevant local ethics committees. Discussion: As a diagnostic accuracy study for a disease with an imperfect reference standard, Rapid and Accurate Diagnosis of Pediatric Tuberculosis Disease (RaPaed-TB) was designed following a rigorous and complex methodology. This allows for the determination of diagnostic accuracy of novel assays and combination of testing strategies for optimal care for children, including high-risk groups (ie, very young, malnourished, children living with HIV). Being one of the largest of its kind, RaPaed-TB will inform the development of improved diagnostic approaches to increase case detection in pediatric TB.

Background TB is a leading cause of morbidity among HIV positive individuals. Accurate algorithms are needed to achieve early TB diagnosis and treatment. We investigated the use of Xpert MTB/RIF Ultra in combination with chest radiography for TB diagnosis in ambulatory HIV positive individuals. Methods This was a randomised controlled trial with a 2-by-2 factorial design. Outpatient HIV clinic attendees with cough were randomised to four arms: Arm 1—Standard Xpert/no chest radiography (CXR); Arm 2—Standard Xpert/CXR; Arm 3—Xpert Ultra/no CXR; and Arm 4—Xpert Ultra/CXR. Participants were followed up at days 28 and 56 to assess for TB treatment initiation. Results We randomised 640 participants. Bacteriologically confirmed TB treatment initiation at day 28 were: Arm 1 (8.4% [14/162]), Arm 2 (6.9% [11/159]), Arm 3 (8.2% [13/159]) and Arm 4 (5.6% [9/160]) and between Xpert Ultra group (Arms 3 and 4) (6.9% [22/319]) vs Standard Xpert group (Arms 1 and 2) (7.8% [25/321]), risk ratio 0.89 (95% CI 0.51 to 1.54). By day 56, there were also similar all-TB treatment initiations in the x-ray group (Arms 2 and 4) (16.0% [51/319]) compared with the no x-ray group (Arms 1 and 3) (13.1% [42/321]), risk ratio 1.22 (95% CI 0.84 to 1.78); however, the contribution of clinically diagnosed treatment initiations were higher in x-ray groups (50.9% vs 19.0%). Conclusions Xpert Ultra performed similarly to Xpert MTB/RIF. X-rays are useful for TB screening but further research should investigate how to mitigate false-positive treatment initiations.