A new rapid lipoarabinomannan urine assay for tuberculosis: a two-centre diagnostic accuracy evaluation in outpatients with and without HIV.

Introduction: Non-sputum tests for people attending primary care with symptoms of tuberculosis (TB) are a global priority.

Methods: We performed a cross-sectional two-centre diagnostic accuracy study of a next-generation urine lipoarabinomannan assay (Biopromic TB LAM, BP-LAM) and the lateral flow Determine TB LAM Ag assay (LF-LAM) on urine from 629 adults with presumptive pulmonary TB (315 with TB) attending primary care in South Africa and Uganda. An extended sputum microbiological reference standard (eMRS) was used and, in South Africa, sputum induction done.

Antimycobacterial Activities of the Metabolite Adubangoamide and Non-Natural Fagaramide Analogues.

-Fagaramide () and adubangoamide () are natural products with a cinnamic acid amide skeleton that have recently been isolated from , a medicinal plant used locally in Uganda for the treatment of tuberculosis. Insufficient quantities of material from the natural source originally prevented the antimycobacterial evaluation of the new natural product . Herein, a synthesis of is reported, and its antimycobacterial activity was determined using the synthetic material.

Performance of stool-based molecular tests and processing methods for paediatric tuberculosis diagnosis: a systematic review and meta-analysis.

Background: There has been a global pursuit to improve the diagnosis of tuberculosis in young children by applying diagnostic methods on accessible biospecimens such as stool. We aimed to conduct a systematic review on the accuracy of stool-based molecular tests for tuberculosis diagnosis in children and to assess the impact of the available pre-processing methods and other design characteristics.

Methods: In this systematic review and meta-analysis, we evaluated studies in children younger than 16 years with presumptive tuberculosis that were published in English, Spanish, French, and Portuguese from Jan 1, 2000, to May 3, 2024, in MEDLINE, Embase, and Embase Classic, comparing the molecular detection of Mycobacterium tuberculosis DNA in stool with microbiological tests on other samples or a clinical diagnosis.

Non-sputum-based samples and biomarkers for detection of Mycobacterium tuberculosis: the hope to improve childhood and HIV-associated tuberculosis diagnosis.

In 2014, the World Health Organisation (WHO) published target product profiles (TPP) for development of novel tuberculosis (TB) diagnostics. One of the key highlights is the need for point-of-care non-sputum-based tests capable of detecting all forms of TB through identification of characteristic biomarkers or biosignatures. Compared to the limitations associated with sputum-based TB tests, non-sputum samples are easy to collect, non-invasive, with potential to improve TB diagnosis among children and among people living with HIV/AIDS (PLHIV).

Improved Diagnosis and Treatment Monitoring of Tuberculosis Using Stool and the Tuberculosis Bacterial Load Assay (TB-MBLA).

The diagnosis and monitoring of tuberculosis treatment is difficult as many patients are unable to produce sputum. This means that many patients are treated on the basis of clinical findings and consequently some will be exposed to anti-tuberculosis drugs unnecessarily. Moreover, for those appropriately on treatment and unable to produce a sputum sample, it will be impossible to monitor the response to treatment.

Airway microbiome signature accurately discriminates infection status.

remains one of the deadliest infectious agents globally. Amidst efforts to control TB, long treatment duration, drug toxicity, and resistance underscore the need for novel therapeutic strategies. Despite advances in understanding the interplay between microbiome and disease in humans, the specific role of the microbiome in predicting disease susceptibility and discriminating infection status in tuberculosis still needs to be fully investigated.

Assessment of three antibiotic combination regimens against Gram-negative bacteria causing neonatal sepsis in low- and middle-income countries.

Gram-negative bacteria (GNB) are a major cause of neonatal sepsis in low- and middle-income countries (LMICs). Although the World Health Organization (WHO) reports that over 80% of these sepsis deaths could be prevented through improved treatment, the efficacy of the currently recommended first- and second-line treatment regimens for this condition is increasingly affected by high rates of drug resistance. Here we assess three well known antibiotics, fosfomycin, flomoxef and amikacin, in combination as potential antibiotic treatment regimens by investigating the drug resistance and genetic profiles of commonly isolated GNB causing neonatal sepsis in LMICs.

Accuracy of the tuberculosis molecular bacterial load assay to diagnose and monitor response to anti-tuberculosis therapy: a longitudinal comparative study with standard-of-care smear microscopy, Xpert MTB/RIF Ultra, and culture in Uganda.

Background: In 2018, the tuberculosis molecular bacterial load assay (TB-MBLA), a ribosomal RNA-based test, was acknowledged by WHO as a molecular assay that could replace smear microscopy and culture for monitoring tuberculosis treatment response. In this study, we evaluated the accuracy of TB-MBLA for diagnosis and monitoring of treatment response in comparison with standard-of-care tests.

Methods: For this longitudinal prospective study, patients aged 18 years or older with presumptive tuberculosis (coughing for at least 2 weeks, night sweats, and weight loss) were enrolled at China-Uganda Friendship Hospital Naguru (Kampala, Uganda).

A stool based qPCR for the diagnosis of TB in children and people living with HIV in Uganda, Eswatini and Mozambique (Stool4TB): a protocol for a multicenter diagnostic evaluation.

Background: Tuberculosis (TB) is a major cause of mortality worldwide. Children and people living with HIV (PLHIV) have an increased risk of mortality, particularly in the absence of rapid diagnosis. The main challenges of diagnosing TB in these populations are due to the unspecific and paucibacillary disease presentation and the difficulty of obtaining respiratory samples.

Performance evaluation of Truenat MTB and Truenat MTB-RIF DX assays in comparison to gene XPERT MTB/RIF ultra for the diagnosis of pulmonary tuberculosis in Uganda.

Background: The World Health Organization endorsed Truenat MTB rapid molecular assay in 2020 and recommended additional in-country evaluation studies before uptake. We evaluated the accuracy and operational feasibility of Truenat MTB assay (Truenat) in comparison with GeneXpert Ultra and culture.

Methods: In a cross-sectional study of 250 presumptive TB patients, participants were requested to provide a sputum sample on the day of their visit to the clinic.

Effect of mixed Mycobacterium tuberculosis infection on rapid molecular diagnostics among patients starting MDR-TB treatment in Uganda.

Background: Mixed M. tuberculosis (MTB) infection occurs when one is infected with more than one clonally distinct MTB strain. This form of infection can assist MTB strains to acquire additional mutations, facilitate the spread of drug-resistant strains, and boost the rate of treatment failure.

Effect of mixed Mycobacterium tuberculosis infection on rapid molecular diagnostics among patients starting MDR-TB treatment in Uganda.

Background: We evaluated the effect of mixed-MTB strain infection on the performance of Line Probe Assay (LPA) and GeneXpert MTB/RIF (Xpert) assays among patients initiating MDR-TB treatment in Uganda.

Methods: This was a cross-sectional study using sputum specimens collected from participants screened for STREAM 2 clinical trial between October 2017 and October 2019. Samples from 62 MTB smear-positive patients and rifampicin-resistant patients from the peripheral health facilities were processed for Xpert and LPA as screening tests for eligibility in the trial.

Geographic distribution and predictors of diagnostic delays among possible TB patients in Uganda.

Background: Understanding the geographic distribution and factors associated with delayed TB diagnosis may help target interventions to reduce delays and improve patient outcomes.

Methods: We conducted a secondary analysis of adults undergoing TB evaluation within a public health demonstration project in Uganda. Using Global Moran's I (GMI) and Getis-Ord GI* statistics, we evaluated for residential clustering and hotspots associated with patient-related and health system-related delays.

Evaluation of Xpert MTB/XDR test for susceptibility testing of Mycobacterium tuberculosis to first and second-line drugs in Uganda.

Background: Drug-Resistant Tuberculosis (DR-TB) is one of the major challenges to TB control.

Design And Methods: This was a blinded, laboratory-based cross-sectional study using sputum samples or culture isolates. Samples were from patients with rifampicin-resistant-TB and/or with high risk for isoniazid (INH) resistance and/or 2nd line fluoroquinolones (FQ) and injectable agents (IAs).

Evaluation of Xpert MTB/XDR test for susceptibility testing of to first and second-line drugs in Uganda.

Background: Drug-Resistant Tuberculosis (DR-TB) is one of the key challenges toward TB control. There is an urgent need for rapid and accurate drug susceptibility tests (DST) for the most commonly used 1 and 2 line TB drugs.

Design And Methods: In a blinded, laboratory-based cross-sectional study, we set out to validate the performance of the Xpert MTB/XDR test for DST of .

Prevalence and antimicrobial resistance profiles of Neisseria gonorrhea and Chlamydia trachomatis isolated from individuals attending STD clinics in Kampala, Uganda.

Background: Sexually transmitted diseases (STDs) management in sub-Saharan Africa is syndromic but molecular diagnostics provide quicker, sensitive diagnosis and treatment. Effective STD control hinges on identification and treatment of infected persons and sexual partner contact tracing.

Objectives: This study assessed feasibility of using the Xpert CT/NG test to identify prevalent Chlamydia trachomatis (CT) and Neisseria gonorrhea (NG) infections among STD clinic attendees and their sexual partners and tested for antimicrobial resistance for N.

Cardiovascular risk factors among people with drug-resistant tuberculosis in Uganda.

Background: Tuberculosis (TB) and its risk factors are independently associated with cardiovascular disease (CVD). We determined the prevalence and associations of CVD risk factors among people with drug-resistant tuberculosis (DRTB) in Uganda.

Methods: In this cross-sectional study, we enrolled people with microbiologically confirmed DRTB at four treatment sites in Uganda between July to December 2021.

Quantification of multidrug-resistant bacilli in sputum during the first 8 weeks of treatment.

Mulago Hospital, Kampala, Uganda. To quantify in sputum during the first 8 weeks of pulmonary multidrug-resistant TB (MDR-TB) treatment. We enrolled consecutive adults with pulmonary MDR-TB treated according to national guidelines.

Strategies to Reduce Mortality Among Children Living With HIV and Children Exposed to HIV but Are Uninfected, Admitted With Severe Acute Malnutrition at Mulago Hospital, Uganda (REDMOTHIV): A Mixed Methods Study.

Background: Children living with HIV (CLHIV) and children who are exposed to HIV but uninfected (CHEU) are at increased risk of developing malnutrition. Severely malnourished children have high mortality rates, but mortality is higher in CLHIV/CHEU. This study aims to investigate whether empiric use of an antibiotic with greater antimicrobial sensitivity (ceftriaxone) than standard-of-care (ampicillin plus gentamicin) will reduce mortality among CLHIV/CHEU admitted with severe acute malnutrition.

Recurrent pneumothorax in a human immunodeficiency virus-positive patient with multidrug-resistant tuberculosis: a rare case of bronchopleural fistula: a case report.

Background: Human immunodeficiency virus/tuberculosis coinfections have amplified the multidrug-resistant tuberculosis pandemic in many countries in Sub-Saharan Africa, and multidrug-resistant tuberculosis has become a major public health threat. There is a paucity of data on severe complications of multidrug-resistant tuberculosis in the context of human immunodeficiency virus coinfection despite the increasing prevalence of multidrug-resistant tuberculosis/human immunodeficiency virus coinfection and the complexity of multidrug-resistant tuberculosis treatment. This report describes a rare case of complicated multidrug-resistant tuberculosis in a human immunodeficiency virus-positive individual.

Molecular characterisation of second-line drug resistance among drug resistant tuberculosis patients tested in Uganda: a two and a half-year's review.

Background: Second-line drug resistance (SLD) among tuberculosis (TB) patients is a serious emerging challenge towards global control of the disease. We characterized SLD-resistance conferring-mutations among TB patients with rifampicin and/or isoniazid (RIF and/or INH) drug-resistance tested at the Uganda National TB Reference Laboratory (NTRL) between June 2017 and December 2019.

Methods: This was a descriptive cross-sectional secondary data analysis of 20,508 M.

Phytochemical screening, antimycobacterial activity and acute toxicity of crude extracts of selected medicinal plant species used locally in the treatment of tuberculosis in Uganda.

Background: Tuberculosis (TB) is one of the leading causes of death globally, and the rise in drug-resistant forms of TB has become a significant threat. Subsequently, it is crucial to explore new, effective and safe anti-TB agents. This study aimed at conducting phytochemical screening, antimycobacterial activity, and acute toxicity of the selected plant species' crude extracts to assess their toxicological potentials and efficacies against TB.