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Disseminated tuberculosis TB (DTB) is a rare and immediately life-threatening form of tuberculosis (TB) characterized by spread of infection via the lymphatic and/or cardiovascular systems to multiple organ sites [1]. HIV infection, transplant medicine and expanded use of immunosuppressive drugs increase the probability of dissemination. Believed to account for at least 1-3% of all TB cases, the true prevalence of DTB remains uncertain due to variations in definition, diagnostic workup and reporting requirements [2-7].

Abstract Background An accurate, rapid, non-sputum-based triage test for diagnosing tuberculosis (TB) is needed.Methods A prospective evaluation of the Xpert-MTB-HR cartridge, a prototype blood-based host-response mRNA signature assay, among individuals presenting with TB-like symptoms was performed in Pakistan and results were compared to three reference standards: Xpert MTB/RIF Ultra, bacteriological confirmation (Xpert MTB/RIF Ultra and/or culture positivity), and composite clinical diagnosis (clinician diagnosis, treatment initiation, Xpert MTB/RIF Ultra, and/or culture positivity). Analyses were conducted both for the entire study cohort and separately in the adolescent and young adult cohort (ages 10-24).Results A total of 497 participants, ages 6-83, returned valid Xpert-MTB-HR results. When a diagnostic threshold was set for a sensitivity of >90%, specificity was 32% (95%CI 28–37) when compared to Xpert MTB/RIF Ultra, 29% (95%CI 25–34) when compared to a bacteriological confirmation, and 22% (95%CI 18–26) when compared to a composite clinical diagnosis. However, when evaluating only the adolescent and young adult cohort with a diagnostic threshold set for sensitivity of >90%, specificity was 82% (95%CI 74–89) when compared to Xpert MTB/RIF Ultra, 84% (95%CI 75–90) when compared to a bacteriological confirmation, and 54% (95%CI 44–64) when compared to a composite clinical diagnosis.Conclusions While the Xpert-MTB-HR does not meet World Health Organization minimum criteria in the general population, in our study it does meet the minimum sensitivity and specificity requirements for a non-sputum-based triage test among adolescents and young adults when compared to Xpert MTB/RIF Ultra or bacteriological confirmation.

Tropical Medicine &International Health, EarlyView.

Volume 13, Issue 1, December 2024 .

Volume 13, Issue 1, December 2024 .

Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 111 Issue: 3 Pages: 529-534 …

Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 111 Issue: 3 Pages: 535-539 …

Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 111 Issue: 3 Pages: 540-545 …

Abstract Background This study aimed to investigate the differential expression levels of the cGAS-STING pathway in peripheral blood mononuclear cells (PBMCs) of spinal tuberculosis (TB) patients with different progression and its feasibility as a diagnostic marker. Methods Peripheral blood and medical records of 25 patients with spinal TB and 10 healthy individuals, were prospectively collected and analyzed. PBMCs and serum were extracted from peripheral blood and the expression levels of the cGAS-STING pathway in PBMCs were measured by real-time PCR (RT-PCR) and serum interferon β (IFN-β) expression levels were measured by enzyme-linked immunosorbent assay (ELISA). The expression of Interferon regulatory Factor 3 (IRF3) in PBMCs was measured using western blot. Statistical analysis was performed using the SPSS 26.0 statistical package. Results The results showed that the expression level of the TANK-binding kinase 1 (TBK1) and IRF3 was significantly higher in PBMCs (P 

Drug-resistant tuberculosis poses a significant public health challenge worldwide, threatening global tuberculosis (TB) control efforts. In 2022, an estimated 410,000 new cases of rifampicin-resistant tuberculosis (RR-TB) were reported, presenting considerable treatment difficulties [1]. Historically, the treatment for RR-TB has been lengthy and arduous, involving a higher pill burden and increased risk of adverse effects compared to treatments for drug-susceptible tuberculosis [2]. The last decade, however, has seen considerable progress in shortening treatment durations, which has simplified the management of RR-TB [3].

Abstract Mortality from human immunodeficiency virus (HIV)–associated tuberculosis (TB) is high, particularly among hospitalized patients. In 433 people with HIV hospitalized with symptoms of TB, we investigated plasma matrix metalloproteinases (MMP) and matrix-derived biomarkers in relation to TB diagnosis, mortality, and Mycobacterium tuberculosis (Mtb) bloodstream infection (BSI). Compared to other diagnoses, MMP-8 was elevated in confirmed TB and in Mtb-BSI, positively correlating with extracellular matrix breakdown products. Baseline MMP-3, -7, -8, -10, and PIIINP were associated with Mtb-BSI and 12-week mortality. These findings implicate MMP dysregulation in pathophysiology of advanced HIV-TB and support MMP inhibition as a host-directed therapeutic strategy for HIV-TB.

The chest radiograph (CXR) remains a valuable tool in the diagnostic evaluation of individuals for pulmonary tuberculosis [1, 2]. Advances in artificial intelligence have enabled automated CXR interpretation, also known as computer-aided detection (CAD), for pulmonary tuberculosis. CAD provides objective interpretations and has the potential to facilitate broader use of CXR in resource-limited settings. In 2021, the World Health Organization approved the use of CAD technology as an alternative to human readers for pulmonary tuberculosis screening and triage use-cases, the latter referring to application of CXR in the medical evaluation of symptomatic individuals [3].

by Melese Abate Reta, Zelalem Asmare, Assefa Sisay, Yalewayker Gashaw, Ermias Getachew, Muluken Gashaw, Zelalem Dejazmach, Abdu Jemal, Solomon Gedfie, Getinet Kumie, Marye Nigatie, Wagaw Abebe, Agenagnew Ashagre, Tadesse Misganaw, Woldeteklehaymanot Kassahun, Selamyhun Tadesse, Alene Geteneh, Atitegeb Abera Kidie, Biruk Beletew Abate, Nontuthuko Excellent Maningi, P. Bernard Fourie Background Despite the decline in tuberculosis (TB) incidence across many regions worldwide, including Ethiopia, the disease remains highly concentrated among vulnerable or socially marginalized populations and in high-risk settings. This systematic review and meta-analysis aims to estimate the pooled prevalence of pulmonary tuberculosis (PTB) among key and vulnerable populations (KVPs) residing in hotspot settings in Ethiopia. Methods Potential papers were searched systematically in PubMed, Scopus, ScienceDirect databases, Google Scholar search engine, and institutional electronic repositories/registrars. A total of 34 potential articles that provide necessary information on the prevalence of PTB were reviewed and data were analyzed to determine the pooled prevalence of PTB among KVPs. The relevant data were recorded and analyzed using STATA 17.0. Cohen’s kappa was computed to determine the agreement between reviewers, the Inverse of variance (I2) to evaluate heterogeneity across studies, and Egger’s test to identify publication bias. A random effect model was used to determine the pooled prevalence of PTB, subgroup analysis was computed by types of hotspot settings and year of publication. Results This meta-analysis demonstrates that the pooled prevalence of PTB among populations residing in hotspot settings in Ethiopia was 11.7% (95% confidence interval (95CI): 7.97–15.43) with an I2 of 99.91% and a p< 0.001. Furthermore, the subgroup analysis unveiled the pooled prevalence of PTB among KVPs residing in different hotspot settings as follows: Prison inmates 8.8% (95CI: 5.00–12.55%), University students 23.1% (95CI: 15.81–30.37%), Refugees 28.4% (95CI: -1.27–58.15%), Homeless peoples 5.8% (95CI: -0.67–12.35%), Healthcare settings 11.1% (95CI: 0.58–21.63%), Spiritual holy water sites attendees 12.3% (95CI: -6.26–30.80%), and other high-risk settings 4.3% (95CI: 0.47–8.09%). Besides, the subgroup analysis revealed that the pooled prevalence of PTB post-2015 was 10.79% (95CI: 5.94–15.64%), whereas it stood at 14.04% (95CI: 10.27–17.82%) before 2015. Conclusion The prevalence of PTB among KVPs residing in the hotspot settings in Ethiopia remains significant, with a weighted pooled prevalence of 11.7%. Thus, the national TB control programs should give due attention and appropriate control measures should be instituted that include regular systematic TB screening, compulsory TB testing for presumptive TB cases among KVPs, and tightened infection control at hotspot settings. …

Abstract Background Pulmonary tuberculosis (PTB) is a prevalent chronic disease associated with a significant economic burden on patients. Using machine learning to predict hospitalization costs can allocate medical resources effectively and optimize the cost structure rationally, so as to control the hospitalization costs of patients better. Methods This research analyzed data (2020–2022) from a Kashgar pulmonary hospital’s information system, involving 9570 eligible PTB patients. SPSS 26.0 was used for multiple regression analysis, while Python 3.7 was used for random forest regression (RFR) and MLP. The training set included data from 2020 and 2021, while the test set included data from 2022. The models predicted seven various costs related to PTB patients, including diagnostic cost, medical service cost, material cost, treatment cost, drug cost, other cost, and total hospitalization cost. The model’s predictive performance was evaluated using R-square (R2), Root Mean Squared Error (RMSE), and Mean Absolute Error (MAE) metrics. Results Among the 9570 PTB patients included in the study, the median and quartile of total hospitalization cost were 13,150.45 (9891.34, 19,648.48) yuan. Nine factors, including age, marital status, admission condition, length of hospital stay, initial treatment, presence of other diseases, transfer, drug resistance, and admission department, significantly influenced hospitalization costs for PTB patients. Overall, MLP demonstrated superior performance in most cost predictions, outperforming RFR and multiple regression; The performance of RFR is between MLP and multiple regression; The predictive performance of multiple regression is the lowest, but it shows the best results for Other costs. Conclusion The MLP can effectively leverage patient information and accurately predict various hospitalization costs, achieving a rationalized structure of hospitalization costs by adjusting higher-cost inpatient items and balancing different cost categories. The insights of this predictive model also hold relevance for research in other medical conditions. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Scaling up treatment for latent tuberculosis (TB) infection (LTBI) is essential in order to move toward the ambitious End TB strategy goals for 2035 [1]. Options for LTBI treatment regimens have expanded over the last several decades, with a trend toward shorter treatment durations and rifamycin-containing regimens with or without isoniazid. Clinical trials comparing these shorter regimens have reported improved completion rates compared to treatment with 6 to 9 months of isoniazid alone, but drug tolerability continues to be a limiting factor for treatment completion, and the management of adverse effects can be resource intensive [2–5].

Abstract Background In 2012, the World Health Organization recommended screening and investigation of contacts of index tuberculosis patients as a strategy to accelerate detection of tuberculosis (TB) cases. Nine years after the adoption of this recommendation, coverage of TB contact investigations in Uganda remains low. The objective of this study was to examine health care providers’ perceptions of factors influencing coverage of TB contact investigations in three selected rural health facilities in Mbarara district, southwestern Uganda. Methods This study identified provider opinions on the barriers and facilitators to implementation of TB contact investigation using the Consolidated Framework for Implementation Research. Using an exploratory qualitative study design, semi-structured interviews with 19 health workers involved in the TB program at district, health facility and community levels were conducted from April 2020 and July 2020. Analysis was conducted inductively using reflexive thematic analysis in six iterative steps: familiarizing with the data, creating initial codes, searching for themes, reviewing themes, developing theme definitions, and writing the report. Results Nineteen health care workers participated in this study which translates to a 100% response rate. These included two district TB and leprosy supervisors, five nurses, five clinical officers, six village health team members and one laboratory technician. The three themes that emerged from the analysis were intervention-related, health system and contextual factors. Health system-related barriers included inadequate or delayed government funding for the TB program, shortage of human resources, insufficient personal protective equipment, and a stock-out of supplies such as Xpert MTB cartridges. Contextual barriers included steep terrain, poverty or low income, and the stigma associated with TB and COVID-19. Facilitators comprised increased knowledge and understanding of the intervention, performance review and on-the-job training of health workers. Conclusions This study found that most of the factors affecting TB contact investigations in this rural community were related to health system constraints such as inadequate or delayed funding and human resource shortages. This can be addressed by strengthening the foundational elements of the health system - health financing and human resources - to establish a comprehensive TB control program that will enable the efficient identification of missing TB patients. …

by Md. Abdur Rafi, Senjuti Semanta, Tasnim Shahriar, Mohammad Jahid Hasan, Md. Golam Hossain Background Comorbidity of diabetes mellitus and tuberculosis (TB) is a major public health concern in low- and middle-income countries including Bangladesh. An integrated approach is required for adequate management of diabetes mellitus and TB. The objective of the present study was to investigate the availability and readiness of the TB care centers of Bangladesh toward diabetic patients’ management. Methods The present study was conducted based on existing data obtained from the Bangladesh Health Facility Survey (BHFS) 2017. Data collected from a total of 303 facilities providing TB services were retrieved. The outcome variables of the present study were availability and readiness of the TB health facilities for providing diabetes mellitus service. Readiness was measured for four domains: staff and guidelines, equipment, diagnostic facility and basic medicine. The independent variables were: facility level, management authority and location of the facility. Binary and multiple logistic regression models were constructed for both the outcome variables (availability and readiness) to find out their predictors. Results Services for diabetes mellitus were available in 68% of the TB facilities while high readiness was present in 36% of the facilities. For domain-specific readiness index, readiness for the domains of staff and guidelines, equipment, diagnostic facility and basic medicine was reported in 46%, 96%, 38% and 25% facilities respectively. In the logistic regression model, availability of diabetes mellitus services was better in primary level (aOR 2.62, 95% CI 1.78–4.77) and secondary level (aOR 3.26, 95% CI 1.82–9.05) facilities than community facilities. Similarly, readiness of diabetes mellitus care was also better in these facilities (aOR 2.55, 95% CI 1.05–4.71 for primary and aOR 2.75, 95% CI 1.80–4.32 for secondary facilities). Besides, private TB facilities had better availability (aOR 2.84, 95% CI 1.75–5.89) and readiness (aOR 2.52, 95% CI 1.32–4.29) for diabetes mellitus care. Conclusion Availability and readiness for providing diabetes mellitus services in TB care providing facilities in Bangladesh is inadequate. …

by Ekkehard Hiller, Verena Hörz, Reinhard Sting Corynebacterium pseudotuberculosis (CPS) is an important bacterial animal pathogen. CPS causes chronic, debilitating and currently incurable infectious diseases affecting a wide range of livestock and wild herbivores including camelids worldwide. Belonging to the Corynebacterium diphtheriae complex, this pathogen can also infect humans. The classical characterization of CPS is typically based on the testing of nitrate reductase activity, separating the two biovars Equi and Ovis. However, more refined resolutions are required to unravel routes of infection. This was realized in our study by generating and analyzing whole genome sequencing (WGS) data. Using newly created core genome multilocus sequence typing (cgMLST) profiles we were the first to discover isolates grouping in a cluster adjacent to clusters formed by CPS biovar Equi isolates. This novel cluster includes CPS isolates from alpacas, llamas, camels and dromedaries, which are characterized by a lack of nitrate reductase activity as encountered in biovar Ovis. This is of special interest for molecular epidemiology. Nevertheless, these isolates bear the genes of the nitrate locus, which are characteristic of biovar Equi isolates. However, sequence analysis of the genes narG and narH of the nitrate locus revealed indels leading to frameshifts and inactivity of the enzymes involved in nitrate reduction. Interestingly, one CPS isolate originating from another lama with an insertion in the MFS transporter (narT) is adjacent to a cluster formed by ovine CPS isolates biovar Equi. Based on this knowledge, the combination of biochemical and PCR based molecular biological nitrate reductase detection can be used for a fast and uncomplicated classification of isolates in routine diagnostics in order to check the origin of camelid CPS isolates. Further analysis revealed that partial sequencing of the ABC transporter substrate binding protein (CP258_RS07935) is a powerful tool to assign the biovars and the novel genomovar.

Volume 13, Issue 1, December 2024 .