Urine-Xpert Ultra for the diagnosis of tuberculosis in people living with HIV: a prospective, multicentre, diagnostic accuracy study.

Background: Diagnostic delays for tuberculosis are common, with high resultant mortality. Urine-Xpert Ultra (Cepheid) could improve time to diagnosis of tuberculosis disease and rifampicin resistance. We previously reported on lot-to-lot variation of the Fujifilm SILVAMP TB LAM.

A prospective evaluation of the diagnostic accuracy of the point-of-care VISITECT CD4 Advanced Disease test in seven countries.

Background: CD4 measurement is pivotal in the management of advanced HIV disease. VISITECT® CD4 Advanced Disease (AccuBio Limited, Alva, UK; VISITECT) is an instrument-free, point-of-care, semi-quantitative test allowing visual identification of a CD4 ≤200 cells/µl, or >200 cells/µl from finger-prick or venous blood.

Methods: As part of a diagnostic accuracy study of FUJIFILM SILVAMP TB LAM (clinicaltrials.

Diagnostic Yield of Urine Xpert MTB/RIF Ultra in Adults With Suspected Extrapulmonary Tuberculosis.

We assessed the diagnostic yield of urine GeneXpert MTB/RIF Ultra and factors associated with a positive test among adult patients suspected to have extrapulmonary tuberculosis. Urine Ultra was positive in 14% of participants with definite or probable tuberculosis. Hospitalization, disseminated tuberculosis, and human immunodeficiency virus infection were associated with a positive result.

Prospective multicentre accuracy evaluation of the FUJIFILM SILVAMP TB LAM test for the diagnosis of tuberculosis in people living with HIV demonstrates lot-to-lot variability.

There is an urgent need for rapid, non-sputum point-of-care diagnostics to detect tuberculosis. This prospective trial in seven high tuberculosis burden countries evaluated the diagnostic accuracy of the point-of-care urine-based lipoarabinomannan assay FUJIFILM SILVAMP TB LAM (FujiLAM) among inpatients and outpatients living with HIV. Diagnostic performance of FujiLAM was assessed against a mycobacterial reference standard (sputum culture, blood culture, and Xpert Ultra from urine and sputum at enrollment, and additional sputum culture ≤7 days from enrollment), an extended mycobacterial reference standard (eMRS), and a composite reference standard including clinical evaluation.

Diagnostic accuracy of a sequence-specific -DNA hybridization assay in urine: a case-control study including subclinical TB cases.

Unlabelled: Tuberculosis (TB) caused by () remains one of the deadliest infectious diseases globally. Timely diagnosis is a key step in the management of TB patients and in the prevention of further transmission events. Current diagnostic tools are limited in these regards.

Bacterial diversity dominates variable macrophage responses of tuberculosis patients in Tanzania.

The Mycobacterium tuberculosis complex (MTBC) comprises nine human-adapted lineages that differ in their geographical distribution. Local adaptation of specific MTBC genotypes to the respective human host population has been invoked in this context. We aimed to assess if bacterial genetics governs MTBC pathogenesis or if local co-adaptation translates into differential susceptibility of human macrophages to infection by different MTBC genotypes.

Study protocol: a pragmatic, cluster-randomized controlled trial to evaluate the effect of implementation of the Truenat platform/MTB assays at primary health care clinics in Mozambique and Tanzania (TB-CAPT CORE).

Background: In 2020, the WHO-approved Molbio Truenat platform and MTB assays to detect Mycobacterium tuberculosis complex (MTB) and resistance to rifampicin directly on sputum specimens. This primary health care center-based trial in Mozambique and Tanzania investigates the effect of Truenat platform/MTB assays (intervention arm) combined with rapid communication of results compared to standard of care on TB diagnosis and treatment initiation for microbiologically confirmed TB at 7 days from enrolment.

Methods: The Tuberculosis Close the Gap, Increase Access, and Provide Adequate Therapy (TB-CAPT) CORE trial employs a pragmatic cluster randomized controlled design to evaluate the impact of a streamlined strategy for delivery of Truenat platform/MTB assays testing at primary health centers.

Back-to-Africa introductions of Mycobacterium tuberculosis as the main cause of tuberculosis in Dar es Salaam, Tanzania.

In settings with high tuberculosis (TB) endemicity, distinct genotypes of the Mycobacterium tuberculosis complex (MTBC) often differ in prevalence. However, the factors leading to these differences remain poorly understood. Here we studied the MTBC population in Dar es Salaam, Tanzania over a six-year period, using 1,082 unique patient-derived MTBC whole-genome sequences (WGS) and associated clinical data.

Ultrasononography in Managing Extrapulmonary Tuberculosis: A Randomized, Controlled, Parallel, Superiority, Open-Label Trial.

Background: Patients with suspected extrapulmonary tuberculosis are often treated empirically. We hypothesized that extended focused assessment with sonography for human immunodeficiency virus (HIV) and tuberculosis (eFASH), in combination with other tests, would increase the proportion of correctly managed patients with suspected extrapulmonary tuberculosis.

Methods: This trial in adults with suspected extrapulmonary tuberculosis was performed in a rural and an urban hospital in Tanzania.

CD38 Expression by Antigen-Specific CD4 T Cells Is Significantly Restored 5 Months After Treatment Initiation Independently of Sputum Bacterial Load at the Time of Tuberculosis Diagnosis.

T cell activation markers (TAM) expressed by antigen-specific T cells constitute promising candidates to attest the presence of an active infection by (). Reciprocally, their modulation may be used to assess antibiotic treatment efficacy and eventually attest disease resolution. We hypothesized that the phenotype of -specific T cells may be quantitatively impacted by the load of bacteria present in a patient.

The Sputum Microbiome in Pulmonary Tuberculosis and Its Association With Disease Manifestations: A Cross-Sectional Study.

Each day, approximately 27,000 people become ill with tuberculosis (TB), and 4,000 die from this disease. Pulmonary TB is the main clinical form of TB, and affects the lungs with a considerably heterogeneous manifestation among patients. Immunomodulation by an interplay of host-, environment-, and pathogen-associated factors partially explains such heterogeneity.

Case-control diagnostic accuracy study of a non-sputum CD38-based TAM-TB test from a single milliliter of blood.

CD4 T cell phenotyping-based blood assays have the potential to meet WHO target product profiles (TPP) of non-sputum-biomarker-based tests to diagnose tuberculosis (TB). Yet, substantial refinements are required to allow their implementation in clinical settings. This study assessed the real time performance of a simplified T cell activation marker (TAM)-TB assay to detect TB in adults from one millilitre of blood with a 24 h turnaround time.

Local adaptation in populations of endemic to the Indian Ocean Rim.

Lineage 1 (L1) and 3 (L3) are two lineages of the complex (MTBC) causing tuberculosis (TB) in humans. L1 and L3 are prevalent around the rim of the Indian Ocean, the region that accounts for most of the world's new TB cases. Despite their relevance for this region, L1 and L3 remain understudied.

Ultrasound in managing extrapulmonary tuberculosis: a randomized controlled two-center study.

Background: Patients with clinically suspected tuberculosis are often treated empirically, as diagnosis - especially of extrapulmonary tuberculosis - remains challenging. This leads to an overtreatment of tuberculosis and to underdiagnosis of possible differential diagnoses.

Methods: This open-label, parallel-group, superiority randomized controlled trial is done in a rural and an urban center in Tanzania.

Insights into the genetic diversity of Mycobacterium tuberculosis in Tanzania.

Background: Human tuberculosis (TB) is caused by seven phylogenetic lineages of the Mycobacterium tuberculosis complex (MTBC), Lineage 1-7. Recent advances in rapid genotyping of MTBC based on single nucleotide polymorphisms (SNP), allow for phylogenetically robust strain classification, paving the way for defining genotype-phenotype relationships in clinical settings. Such studies have revealed that, in addition to host and environmental factors, strain variation in the MTBC influences the outcome of TB infection and disease.

Boosting effect of IL-7 in interferon gamma release assays to diagnose Mycobacterium tuberculosis infection.

Background: A quarter of the world's population is estimated to be infected with Myobacterium tuberculosis (Mtb). Infection is detected by immune response to M. tuberculosis antigens using either tuberculin skin test (TST) and interferon gamma release (IGRA's), tests which have low sensitivity in immunocompromised.

Xpert MTB/RIF Ultra assay for the diagnosis of pulmonary tuberculosis in children: a multicentre comparative accuracy study.

Objectives: We evaluated the diagnostic performance of the novel next-generation Xpert MTB/RIF Ultra (Xpert Ultra) in comparison to Xpert MTB/RIF (Xpert) assay for the detection of paediatric pulmonary tuberculosis in high burden settings.

Methods: From May 2011 to September 2012, children with suspected pulmonary tuberculosis were enrolled at two Tanzanian sites and sputum samples were examined using sputum smear, Xpert and culture. Xpert Ultra was tested between January and June 2017 using sputum pellets, which had been stored at -80°C.

Anemia in tuberculosis cases and household controls from Tanzania: Contribution of disease, coinfections, and the role of hepcidin.

Background: Tuberculosis (TB) induces a systemic inflammatory state affecting iron homeostasis. Patients with TB often have additional comorbidities such as anemia which can result in poorer treat outcomes. We studied the contribution of anemia and the role of the iron regulatory hormone hepcidin among TB patients and household contacts.

Prevalence and clinical significance of respiratory viruses and bacteria detected in tuberculosis patients compared to household contact controls in Tanzania: a cohort study.

Objectives: To describe the prevalence of respiratory pathogens in tuberculosis (TB) patients and in their household contact controls, and to determine the clinical significance of respiratory pathogens in TB patients.

Methods: We studied 489 smear-positive adult TB patients and 305 household contact controls without TB with nasopharyngeal swab samples within an ongoing prospective cohort study in Dar es Salaam, Tanzania, between 2013 and 2015. We used multiplex real-time PCR to detect 16 respiratory viruses and seven bacterial pathogens from nasopharyngeal swabs.

Distinct clinical characteristics and helminth co-infections in adult tuberculosis patients from urban compared to rural Tanzania.

Background: Differences in rural and urban settings could account for distinct characteristics in the epidemiology of tuberculosis (TB). We comparatively studied epidemiological features of TB and helminth co-infections in adult patients from rural and urban settings of Tanzania.

Methods: Adult patients (≥ 18 years) with microbiologically confirmed pulmonary TB were consecutively enrolled into two cohorts in Dar es Salaam, with ~ 4.

Preservation of sputum samples with cetylpyridinium chloride (CPC) for tuberculosis cultures and Xpert MTB/RIF in a low-income country.

Background: Culture contamination with environmental bacteria is a major challenge in tuberculosis (TB) laboratories in hot and humid climate zones. We studied the effect of cetylpyridinium chloride (CPC) preservation on culture results and performance of Xpert MTB/RIF.

Methods: Consecutive sputum samples from microscopy smear-positive TB patients were collected.

Prevalence and clinical relevance of helminth co-infections among tuberculosis patients in urban Tanzania.

Background: Helminth infections can negatively affect the immunologic host control, which may increase the risk of progression from latent Mycobacterium tuberculosis infection to tuberculosis (TB) disease and alter the clinical presentation of TB. We assessed the prevalence and determined the clinical relevance of helminth co-infection among TB patients and household contact controls in urban Tanzania.

Methodology: Between November 2013 and October 2015, we enrolled adult (≥18 years) sputum smear-positive TB patients and household contact controls without TB during an ongoing TB cohort study in Dar es Salaam, Tanzania.

Evaluation of Xpert® MTB/RIF and Ustar EasyNAT™ TB IAD for diagnosis of tuberculous lymphadenitis of children in Tanzania: a prospective descriptive study.

Background: Fine needle aspiration biopsy has become a standard approach for diagnosis of peripheral tuberculous lymphadenitis. The aim of this study was to compare the performance of Xpert MTB/RIF and Ustar EasyNAT TB IAD nucleic acid amplification assays, against acid-fast bacilli microscopy, cytology and mycobacterial culture for the diagnosis of TB lymphadenitis in children from a TB-endemic setting in Tanzania.

Methods: Children of 8 weeks to 16 years of age, suspected of having TB lymphadenitis, were recruited at a district hospital in Tanzania.

Direct Susceptibility Testing of Mycobacterium tuberculosis for Pyrazinamide by Use of the Bactec MGIT 960 System.

Pyrazinamide (PZA) is a key antituberculosis drug, yet no rapid susceptibility test is commercially available. PZA drug susceptibility testing (DST) was performed directly on sputum samples from 327 patients and compared with the indirect method by using the Bactec MGIT 960 system in the context of patient screening for participation in a drug trial. Compared to standard indirect PZA DST, direct DST was successful in only 59% of cases, but results obtained were highly accurate and available faster.