Diagnosing tuberculosis (TB) in people with advanced HIV disease (AHD) remains challenging, particularly in the absence of typical symptoms or obtainable sputum. We evaluated the diagnostic yield and incremental case detection of urine lateral-flow lipoarabinomannan (LF-LAM) testing within routine AHD care in Nigeria. This prospective programmatic evaluation included adults and children with AHD across 334 HIV treatment facilities between July 2022 and July 2025. Participants underwent Determine TB-LAM Ag testing at presentation, with sputum GeneXpert MTB/RIF performed according to the programme diagnostic algorithm. Of 17,155 participants tested, 5212 were LF-LAM positive, yielding an overall diagnostic yield of 30.4% (95% CI 29.7–31.1%). Among these, 2074 (39.8%) had no WHO-defined presumptive TB symptoms, while 283 presumptive TB participants who were unable to produce sputum tested LF-LAM positive. Among 7603 participants with paired LF-LAM and GeneXpert results, 4323 were positive by at least one assay, including 941 LF-LAM-positive/GeneXpert-negative participants, representing an incremental detection proportion of 21.8% (95% CI 20.6–23.0%). Across the entire cohort, 6680 participants tested positive by either assay. Urine LF-LAM complemented sputum GeneXpert by identifying additional test-positive participants particularly among individuals without presumptive symptoms or obtainable sputum. Integrating LF-LAM into routine AHD care may help close important diagnostic gaps in high TB/HIV-burden settings.
Background & aims Globally, the proportion of new multidrug-resistant tuberculosis (MDR-TB) accounts for an estimated 440,000 new cases and 150,000 deaths annually. Pyrazinamide (PZA) plays an important role in treating drug-sensitive TB (DS-TB) and drug-resistant TB (DR-TB) for its ability to target semi-dormant bacilli. This study investigates the association between PZA resistance status and treatment outcomes in adult DR-TB patients. Methods A systematic review and meta-analysis were conducted following PRISMA guidelines. Literature searches on treatment outcomes and sputum culture conversion (SCC) in patients with PZA-sensitive and PZA-resistant TB were performed across seven databases. Risk of bias was assessed using the Newcastle-Ottawa Scale; certainty of evidence using the GRADE approach; and data analysis using RevMan 5.4 with a random-effects model. Results Seven cohort studies were included, with five eligible for meta-analysis. Pooled analysis of phenotypic drug susceptibility testing (DST) showed no significant association between PZA resistance and overall treatment outcome (OR 0.77; 95% CI 0.38–1.53; p = 0.45). However, PZA resistance was significantly associated with delayed SCC. In phenotypic DST studies, the pooled crude hazard ratio (HR) for SCC was 0.50 (95% CI 0.39–0.71; p < 0.0001). Genotypic DST studies also showed a significant association with delayed SCC (HR 0.51; 95% CI 0.35–0.75; p = 0.0007), which remained significant after adjustment (adjusted HR 0.44; 95% CI 0.29–0.68; p = 0.0002). Conclusion PZA resistance was not associated with overall treatment outcomes but was consistently linked to delayed SCC.
Background Tuberculosis (TB) remains a major public health challenge, particularly among displaced populations (DPs) who are at increased risk of infection, delayed diagnosis, treatment interruption, and poor treatment outcomes. However, evidence on GeneXpert negativity during treatment and drug susceptibility patterns among displaced populations in Ethiopia remains limited. Hence, the aim of this study is to assess the longitudinal pattern of GeneXpert negativity during anti-tuberculosis treatment, factors associated with GeneXpert negativity, and drug susceptibility patterns among tuberculosis patients in DPs in Northwest Ethiopia. Methods A prospective longitudinal study was conducted from July 2024 to March 2025 among DPs in Northwest Ethiopia. A total of 1350 presumptive TB patients were screened using the GeneXpert MTB/RIF assay, and 102 GeneXpert-confirmed PTB patients were enrolled and followed for six months. Follow-up GeneXpert testing was performed at the 2nd, 5th, and 6th months of treatment to assess the longitudinal pattern of GeneXpert negativity. The MGIT 960 system was employed to conduct first-line drug susceptibility testing on baseline isolates. Multivariable logistic regression analysis was used to identify factors associated with GeneXpert negativity. Statistical significance was declared at p < 0.05. Results Among the 1350 presumptive TB patients screened, 102 (7.6%) were GeneXpert-positive for M. tuberculosis. Among these, 80(78.4%) were culture-positive. GeneXpert negativity was documented in 73(71.6%) patients at the 2nd month, 92(90.2%) at the 5th month, and all patients by the 6th month of treatment. No resistance to first-line anti-TB drugs was detected among culture-tested isolates. Younger age (<45 years) (AOR = 16.38, 95% CI: 2.32–115.60), unmarried status (AOR = 3.12, 95% CI: 1.18–8.27), absence of weight loss (AOR = 3.51, 95% CI: 1.08–11.43), cough duration <2 weeks (AOR = 3.55, 95% CI: 1.88–14.33), lower baseline bacillary load (AOR = 2.65, 95% CI: 1.99–7.10), HIV-negative status (AOR = 2.91, 95% CI: 1.88–9.66), and non-alcohol use (AOR = 3.06, 95% CI: 1.02–9.21) were significantly associated with GeneXpert negativity. Conclusion The study demonstrated a favorable pattern of GeneXpert negativity during anti-TB treatment and complete susceptibility of culture-positive M. tuberculosis isolates to the first-line anti-TB drugs tested among DPs in Northwest Ethiopia. However, GeneXpert negativity should not be equated with culture-confirmed microbiological cure. Age, nutritional status, cough duration, bacillary load, HIV status, and alcohol consumption significantly influenced GeneXpert negativity. Strengthening early diagnosis, nutritional support, TB/HIV collaborative care, and adherence-focused interventions may improve molecular treatment response among DPs.
Background Timely treatment initiation is central to drug-resistant tuberculosis (DR-TB) control. Uganda's National TB and Leprosy Programme recommends DR-TB treatment initiation within seven (Okethwangu et al., 2019 (7)) days of rifampicin-resistant TB (RR-TB) diagnosis, but the extent of delay and its drivers are poorly documented at tertiary hospitals in Uganda. This study aimed to determine the prevalence and drivers of DR-TB treatment initiation delay at three tertiary hospitals in Uganda. Methods A mixed-methods cross-sectional study conducted at Mulago National Referral Hospital (NRH), Hoima Regional Referral Hospital (RRH), and Arua RRH (December 2018–March 2019), enrolling 203 patients with Xpert MTB/RIF-confirmed RR-TB who had started DR-TB treatment. Data was from MDR-TB registers, patient charts, structured questionnaires, and 15 key informant interviews with healthcare workers. Delay was defined as treatment initiation more than seven (Okethwangu et al., 2019 (7)) days after diagnosis. Poisson regression with robust standard errors identified associated factors for delay. Results DR-TB treatment delay occurred in 65.5% (133/203) of patients overall (73.6% Mulago, 53.9% Hoima, 48.6% Arua), with median diagnosis-to-treatment time of ten (Tefera et al., 2019 (10)) days (IQR 6–20). HIV-positive status (aRR 1.48), female sex (aRR 1.31), and age ≥ 35 years (aRR 1.32) were independently associated with delay at the diagnostic level, while MDR-TB awareness was protective (aRR 0.71) and care at Mulago NRH increased delay risk (aRR 1.65). Qualitative findings pointed to delayed result notification, incomplete laboratory forms, missing baseline investigation equipment, and lack of transport funds as delay drivers. Conclusions Nearly two-thirds of DR-TB patients exceed the national seven (7)-day treatment initiation target, mainly affecting HIV-positives, women, older adults, and those at the NRH. Improved result notification, patient tracing, decentralised diagnostics, and community awareness campaigns are needed to reduce delays.
