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by Michael Sciaudone, Renzo Carpena, Maritza Calderón, Patricia Sheen, Mirko Zimic, Jorge Coronel, Robert H. Gilman, Natalie M. Bowman Tuberculosis remains one of the leading causes of death worldwide, especially in low- and middle-income countries. Tuberculosis treatment and control efforts are hindered by the difficulty in making the diagnosis, as currently available diagnostic tests are too slow, too expensive, or not sufficiently sensitive. Recombinase polymerase amplification (RPA) is a novel technique that allows for the amplification of DNA rapidly, at constant temperature, and with minimal expense. We calculated and compared the limit of detection, sensitivity, and specificity of two RPA-based assays for the diagnosis of pulmonary tuberculosis, using two sets of published primers. We also calculated and compared the assays’ limits of detection and compared their performance using two different DNA extraction methods prior to amplification (a commercially available DNA extraction kit vs. the chelex method). The RPA-lateral flow assay had a limit of detection of 5 fg/μL of DNA, a sensitivity of 53.2%, and a specificity of 93.3%, while the real time-RPA assay had a limit of detection of 25 fg/μL of DNA, a sensitivity of 85.1%, and a specificity of 93.3%. There was no difference in assay performance when DNA extraction was carried out using the commercial kit vs. the chelex method. The real-time RPA assay has adequate sensitivity and specificity for the diagnosis of pulmonary tuberculosis and could be a viable diagnostic tool in resource-limited settings, but the lateral flow assay did not perform as well, perhaps due to the fact we used stored sputum specimens from a biorepository. More work is needed to optimize the RPA-lateral flow assay, to get a more accurate estimate of its specificity and sensitivity using prospectively collected specimens, and to develop both assays into point-of-care tests that can be easily deployed in the field.

Global campaigns to control HIV, tuberculosis, malaria, and vaccine-preventable illnesses showed that large-scale impact can be achieved by using additional international financing to support selected, evidence-based, high-impact investment areas and to catalyse domestic resource mobilisation. Building on this paradigm, we make the case for targeting additional international funding for selected high-impact investments in primary health care. We have identified and costed a set of concrete, evidence-based investments that donors could support, which would be expected to have major impacts at an affordable cost.

ObjectiveTo assess healthcare providers’ intentions and the associated factors to use mobile phone-based short message service (SMS) to support adherence and care of tuberculosis (TB) patients in the Oromia region of southwest Ethiopia. Study designAn institutional-based cross-sectional study was conducted from October to November 2022. Study settingThe study was conducted in public hospitals which include Mettu Karl referral hospital, Dembi Hospital, Bedelle Hospital, Darimu Hospital and Chora Hospital in Ilu Aba Bor and Buno Bedelle zones. ParticipantsA total of 625 (54.9% male and 45.1% female) health professionals participated in the study. The study participants were selected using a simple random sampling technique. All health professionals permanently working in Ilu Aba Bor and Buno Bedelle zone hospitals were included in this study. However, health professionals with less than 6 months of experience and those who were not present during the data collection period were excluded from this study. Outcome measureThe intention to use mobile phone-based SMS to support TB patients. ResultsHealthcare professionals’ intention to use mobile SMS was 54.4%. Effort expectancy had a significant direct effect on attitude (β=0.162, p

Journal Name: The American Journal of Tropical Medicine and Hygiene Volume: 109 Issue: 6 Pages: 1266-1269 …

To describe demographics, clinical features, and treatment outcomes of patients with highly drug-resistant tuberculosis (TB) in Ukraine, and to evaluate risk factors for an unsuccessful outcome.

by Gabriel Morey-León, Paulina M. Mejía-Ponce, Juan Carlos Granda Pardo, Karen Muñoz-Mawyin, Juan Carlos Fernández-Cadena, Evelyn García-Moreira, Derly Andrade-Molina, Cuauhtémoc Licona-Cassani, Luisa Berná Introduction Tuberculosis (TB) is among the deadliest diseases worldwide, and its impact is mainly due to the continuous emergence of resistant isolates during treatment due to the laborious process of resistance diagnosis, nonadherence to treatment and circulation of previously resistant isolates of Mycobacterium tuberculosis. In this study, we evaluated the performance and functionalities of web-based tools, including Mykrobe, TB-profiler, PhyResSE, KvarQ, and SAM-TB, for detecting resistance in 88 Ecuadorian isolates of Mycobacterium tuberculosis drug susceptibility tested previously. Statistical analysis was used to determine the correlation between genomic and phenotypic analysis. Our results showed that with the exception of KvarQ, all tools had the highest correlation with the conventional drug susceptibility test (DST) for global resistance detection (98% agreement and 0.941 Cohen’s kappa), while SAM-TB, PhyResSE, TB-profiler and Mykrobe had better correlations with DST for first-line drug analysis individually. We also identified that in our study, only 50% of mutations characterized by the web-based tools in the rpoB, katG, embB, pncA, gyrA and rrs regions were canonical and included in the World Health Organization (WHO) catalogue. Our findings suggest that SAM-TB, PhyResSE, TB-profiler and Mykrobe were efficient in determining canonical resistance-related mutations, but more analysis is needed to improve second-line detection. Improving surveillance programs using whole-genome sequencing tools for first-line drugs, MDR-TB and XDR-TB is essential to understand the molecular epidemiology of TB in Ecuador. Importance Tuberculosis, an infectious disease caused by Mycobacterium tuberculosis, most commonly affects the lungs and is often spread through the air when infected people cough, sneeze, or spit. However, despite the existence of effective drug treatment, patient adherence, long duration of treatment, and late diagnosis have reduced the effectiveness of therapy and increased drug resistance. The increase in resistant cases, added to the impact of the COVID-19 pandemic, has highlighted the importance of implementing efficient and timely diagnostic methodologies worldwide. The significance of our research is in evaluating and identifying a more efficient and user-friendly web-based tool to characterize resistance in Mycobacterium tuberculosis by whole-genome sequencing, which will allow more routine application to improve TB strain surveillance programs locally. …

AbstractMultidrug-resistant(MDR) tuberculosis in Southern Africa is of great concern, exacerbated by the spread of a clone harboring a mutation missed by Xpert Ultra. In Southern Mozambique, the presence of such mutation and rising cases of non-MDR isoniazid resistance highlights the need to ensure accurate detection of antimicrobial-resistance in the country.

Abstract Background The purpose of this study was to evaluate the diagnostic value of the GeneXpert® MTB/RIF (Xpert®), Auramine O staining method, and Lowenstein-Jensen medium for bacteriologically confirmed pulmonary tuberculosis and explore the effects of the sputum bacillary load (SBL) and qRT‒PCR threshold cycle (Ct) value on the detection methods. Methods We retrospectively analysed the results in the Department of Infectious Disease for 49 months. The χ2 test was used to compare the performances of each method, receiver operating characteristic curve analysis was used to determine the optimal cut-off values, and the factors associated with a false-negative result from Xpert® were analysed by logistic regression. Results Simultaneous analysis of 980 sputum specimens showed that the positive detection rate of Xpert® did not increase with increasing SBL, and there were differences between the three when SBL ≤ 1 + (all P 

Abstract Introduction The urgent need for new treatments for multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is evident. However, the classic randomized controlled trial (RCT) approach faces ethical and practical constraints, making alternative research designs and treatment strategies necessary, such as single-arm trials and host-directed therapies (HDTs). Methods Our study adopts a randomized withdrawal trial design for MDR-TB to maximize resource allocation and better mimic real-world conditions. Patients’ treatment regimens are initially based on drug resistance profiles and patient’s preference, and later, treatment-responsive cases are randomized to different treatment durations. Alongside, a single-arm trial is being conducted to evaluate the potential of sulfasalazine (SASP) as an HDT for pre-XDR-TB, as well as another short-course regimen without HDT for pre-XDR-TB. Both approaches account for the limitations in second-line anti-TB drug resistance testing in various regions. Discussion Although our study designs may lack the internal validity commonly associated with RCTs, they offer advantages in external validity, feasibility, and ethical appropriateness. These designs align with real-world clinical settings and also open doors for exploring alternative treatments like SASP for tackling drug-resistant TB forms. Ultimately, our research aims to strike a balance between scientific rigor and practical utility, offering valuable insights into treating MDR-TB and pre-XDR-TB in a challenging global health landscape. In summary, our study employs innovative trial designs and treatment strategies to address the complexities of treating drug-resistant TB, fulfilling a critical gap between ideal clinical trials and the reality of constrained resources and ethical considerations. Trail registration Chictr.org.cn, ChiCTR2100045930. Registered on April 29, 2021. …

Abstract Background GeneXpert MTB/RIF (Xpert) assay was applied widely to detect Mycobacterium tuberculosis (MTB) and rifampicin resistance. Methods Retrospectively investigated the association among treatment histories, phenotypic drug susceptibility testing (pDST) results, and clinical outcomes of patients infected with probe A absent mutation isolate confirmed by Xpert. Results 63 patients with only probe A absent mutation and 40 with additional pDST results were analyzed. 24 (60.0%) patients had molecular-phenotypic discordant rifampicin (RIF) susceptibility testing results, including 12 (12/13, 92.3%) new tuberculosis (TB) patients and 12 (12/27, 44.4%) retreated ones. 28 (28/39, 71.8%) retreated patients received first-line treatment regime within two years with failed outcomes. New patients had better treatment outcomes than retreated ones (successful: 83.3% VS. 53.8%; P value = 0.02). The clinical results of RIF-susceptible TB confirmed by pDST were not better than RIF-resistant TB (successful: 62.5% VS. 50.0%; P value = 0.43). INH-resistant TB and INH-susceptible TB had similar treatment outcomes too (successful: 61.5% VS. 50.0%; P value = 0.48). 11 (11/12, 91.7%) new patients treated with the short treatment regimen (STR) had successful outcomes. Conclusions More than half of mono probe A absent isolates had RIF molecular-phenotypic discordance results, especially in new patients. Probe A mutations were significantly associated with unsuccessful clinical outcomes, whether the pDST results were RIF susceptible or not. STR was the best choice for new patients. Trial registration retrospectively registered in Wuhan Jinyintan Hospital (No. 2021-KY-16). …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

American Journal of Respiratory and Critical Care Medicine, Volume 208, Issue 11, Page 1246-1247, December 1, 2023.

SummaryMacrophage activation results in the accumulation of endogenous metabolites capable of adopting immunomodulatory roles; one such bioactive metabolite is itaconate. After macrophage stimulation, the TCA-cycle intermediate cis-aconitate is converted to itaconate (by aconitate decarboxylase-1, ACOD1) in the mitochondrial matrix. Recent studies have highlighted the potential of targeting itaconate as a therapeutic strategy for lung diseases such as asthma, idiopathic pulmonary fibrosis (IPF), and respiratory infections. This review aims to bring together evidence which highlights a role for itaconate in chronic lung diseases (such as asthma and pulmonary fibrosis) and respiratory infections (such as SARS-CoV-2, influenza and Mycobacterium tuberculosis infection). A better understanding of the role of itaconate in lung disease could pave the way for novel therapeutic interventions and improve patient outcomes in respiratory disorders.

Clinical Microbiology Reviews, Ahead of Print.

Bedaquiline-resistance gain, for which we identified risk factors, was common in these programmatically treated patients with sustained culture positivity. Our study highlights risks associated with implementing life-saving new drugs and shows evidence of bedaquiline-resistance transmission. Routine drug susceptibility testing should urgently accompany scale-up of new drugs; however, rapid drug susceptibility testing for bedaquiline remains challenging given the diversity of variants observed.

by Philomina Afful, Godwin Adjei Vechey, Peter Kipo Leta, Foster Bediako Gbafu, Fortress Yayra Aku Multidrug-resistant Tuberculosis (MDR-TB) remains a global health concern. The disease results in a prolonged treatment and hence, poses a financial burden to affected individuals and their families. The Ghana National TB Control Programme (NTP) has made extensive efforts to control the menace, however, it remains a concern. This study, therefore, aimed to determine the predictors of multidrug-resistant TB in the Cape Coast Teaching Hospital of Ghana. An unmatched case-control study involving 37 cases and 111 controls was conducted using data of TB cases registered for treatment between January 2018 and December 2020 at the Cape Coast Teaching Hospital. Socio-demographic, individual level and social characteristics information were collected from respondents through telephone surveys, face-to-face interviews and review of records using a structured questionnaire built in the Kobo Collect Toolbox. The data was exported to Stata version 16.0 for analysis. Chi-square test and multiple logistic regression were used to determine the predictors of MDR-TB. Associations were considered statistically significant at a 95% confidence interval with a p-value of less than 0.05. The results revealed that the majority (25 [67.6%]) of MDR-TB cases and controls (76 [68.5%]) were aged 30 years and above with a median age of 36.5 (IQR: 28–50) years for all respondents, while 20 (54.1%) of MDR-TB cases and 33 (29.7%) of controls lived in households with one room residences for their families. The following predictors for MDR-TB were identified: BCG vaccination status (AOR = 0.17,95% CI:0.07–0.45), long distance to health facility (AOR = 4.11, 95% CI: 1.55–10.87), number of rooms in residence (AOR = 0.37,95% CI: 0.14–0.99) and first place of visit upon noticing TB symptom (AOR = 4.22,95% CI:1.31–13.64). Predictors of MDR-TB in the current study were multi-faceted. Measures to control MDR-TB should target socio-demographic, health-seeking behaviour and social-related concerns.

Abstract Background The purpose of this study was to evaluate the diagnostic value of the GeneXpert® MTB/RIF (Xpert®), Auramine O staining method, and Lowenstein-Jensen medium for bacteriologically confirmed pulmonary tuberculosis and explore the effects of the sputum bacillary load (SBL) and qRT‒PCR threshold cycle (Ct) value on the detection methods. Methods We retrospectively analysed the results in the Department of Infectious Disease for 49 months. The χ2 test was used to compare the performances of each method, receiver operating characteristic curve analysis was used to determine the optimal cut-off values, and the factors associated with a false-negative result from Xpert® were analysed by logistic regression. Results Simultaneous analysis of 980 sputum specimens showed that the positive detection rate of Xpert® did not increase with increasing SBL, and there were differences between the three when SBL ≤ 1 + (all P 

Abstract Introduction The urgent need for new treatments for multidrug-resistant tuberculosis (MDR-TB) and pre-extensively drug-resistant tuberculosis (pre-XDR-TB) is evident. However, the classic randomized controlled trial (RCT) approach faces ethical and practical constraints, making alternative research designs and treatment strategies necessary, such as single-arm trials and host-directed therapies (HDTs). Methods Our study adopts a randomized withdrawal trial design for MDR-TB to maximize resource allocation and better mimic real-world conditions. Patients’ treatment regimens are initially based on drug resistance profiles and patient’s preference, and later, treatment-responsive cases are randomized to different treatment durations. Alongside, a single-arm trial is being conducted to evaluate the potential of sulfasalazine (SASP) as an HDT for pre-XDR-TB, as well as another short-course regimen without HDT for pre-XDR-TB. Both approaches account for the limitations in second-line anti-TB drug resistance testing in various regions. Discussion Although our study designs may lack the internal validity commonly associated with RCTs, they offer advantages in external validity, feasibility, and ethical appropriateness. These designs align with real-world clinical settings and also open doors for exploring alternative treatments like SASP for tackling drug-resistant TB forms. Ultimately, our research aims to strike a balance between scientific rigor and practical utility, offering valuable insights into treating MDR-TB and pre-XDR-TB in a challenging global health landscape. In summary, our study employs innovative trial designs and treatment strategies to address the complexities of treating drug-resistant TB, fulfilling a critical gap between ideal clinical trials and the reality of constrained resources and ethical considerations. Trail registration Chictr.org.cn, ChiCTR2100045930. Registered on April 29, 2021. …

Abstract Background GeneXpert MTB/RIF (Xpert) assay was applied widely to detect Mycobacterium tuberculosis (MTB) and rifampicin resistance. Methods Retrospectively investigated the association among treatment histories, phenotypic drug susceptibility testing (pDST) results, and clinical outcomes of patients infected with probe A absent mutation isolate confirmed by Xpert. Results 63 patients with only probe A absent mutation and 40 with additional pDST results were analyzed. 24 (60.0%) patients had molecular-phenotypic discordant rifampicin (RIF) susceptibility testing results, including 12 (12/13, 92.3%) new tuberculosis (TB) patients and 12 (12/27, 44.4%) retreated ones. 28 (28/39, 71.8%) retreated patients received first-line treatment regime within two years with failed outcomes. New patients had better treatment outcomes than retreated ones (successful: 83.3% VS. 53.8%; P value = 0.02). The clinical results of RIF-susceptible TB confirmed by pDST were not better than RIF-resistant TB (successful: 62.5% VS. 50.0%; P value = 0.43). INH-resistant TB and INH-susceptible TB had similar treatment outcomes too (successful: 61.5% VS. 50.0%; P value = 0.48). 11 (11/12, 91.7%) new patients treated with the short treatment regimen (STR) had successful outcomes. Conclusions More than half of mono probe A absent isolates had RIF molecular-phenotypic discordance results, especially in new patients. Probe A mutations were significantly associated with unsuccessful clinical outcomes, whether the pDST results were RIF susceptible or not. STR was the best choice for new patients. Trial registration retrospectively registered in Wuhan Jinyintan Hospital (No. 2021-KY-16). …

BackgroundTuberculosis (TB) is a main concern of health care workers in sub-Saharan Africa. Healthcare workers have the potential to have contact with TB patients and are the main stakeholders in healthcare settings to implement TB infection control, and the poor practice of TB infection control may increase the risk of transmission of TB in healthcare settings. However, there is no consistent conclusion on the TB infection control practice among healthcare workers in Ethiopia. Thus, this study aimed to determine the pooled magnitude of TB infection control practice and associated factors among healthcare workers in Ethiopia. MethodsThis systematic review and meta-analysis will be done by following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The following databases will be used to search for articles: PubMed, Cochrane Library, Google Scholar and grey literatures. The quality of studies will be assessed using the Joanna Briggs Institute (JBI) critical appraisal checklist. The data from included studies will be extracted using Microsoft Excel V.2016, and the extracted data will be analysed using STATA V.16. Forest plot and I2 statistics will be done for heterogeneity. A funnel plot and Egger’s regression test will be conducted to check for publication bias. Potential sources of bias will be identified by subgroup analysis and meta-regression. Any type of study design conducted in Ethiopia and in English language will be included. Ethics and disseminationEthics approval is not required, and the findings will be published in peer-reviewed journal. PROSPERO registration numberCRD42023393580. …

Infection and Immunity, Volume 91, Issue 11, November 2023.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Clinical Microbiology Reviews, Ahead of Print.

AbstractWe explored the utility of brief Mycobacterium tuberculosis whole-genome sequencing (WGS) “snapshots” at a sentinel site within Lima, Peru for evaluating local transmission dynamics over time. Within a 17 km2 area, 15/70 (21%) isolates with WGS collected during 2011-2012 and 22/81 (27%) collected during 2020-2021 were clustered (p = 0.414), and additional isolates clustered with those from outside the area. Isolates from the later period were disproportionately related to large historic clusters in Lima from the earlier period. WGS snapshots at a sentinel site may not be useful for monitoring transmission, but monitoring the persistence of large transmission clusters might be.

The ChAdOx1 85A–MVA85A regimen was safe and induced stronger Ag85A-specific responses than BCG revaccination. Our findings support further development of booster tuberculosis vaccines.

Proceedings of the National Academy of Sciences, Volume 120, Issue 47, November 2023.

Background: Exposure to HIV and antiretroviral therapy (ART) in utero may influence infant growth and development. Most available evidence predates adoption of universal ART (Option B+ ART regimens). In a recent cohort, we compared growth and development in HIV-exposed uninfected (HEU) to HIV-unexposed (HUU) infants. Design: Prospective cohort study: data from Impact of Maternal HIV on Mycobacterium Tuberculosis Infection among Peripartum Women and their Infants (MiTIPS) in Western Kenya. Methods: Women were enrolled during pregnancy. Mother-infant pairs were followed until 24 months postpartum. We used multivariable linear mixed-effects models to compare growth rates (weight-for-age z-score [WAZ] and height-for-age z-score [HAZ]) and multivariable linear regression to compare overall development between HEU and HUU children. Results: About 51.8% (184/355) of the infants were HEU, 3.9% low birthweight (…

by Ineke Spruijt, Yalda Alam, Huong Nguyen, Bakyt Myrzaliev, Muratbek Ahmatov, Bethrand Odume, Lillian Mtei, Agnes Gebhard, Mustapha Gidado, Degu Jerene Background The measures undertaken to control COVID-19 have disrupted many platforms including tuberculosis (TB) healthcare services. Consequently, declines in TB notifications have been observed in various countries. We visualized changes over time in TB and SARS-CoV-2 infection notifications and reported on country-specific strategies to retain TB care and prevention services in Kyrgyzstan, Nigeria, Tanzania, and Vietnam. Methods We collected and visualized quarterly, retrospective, and country-specific data (Quarter (Q) 1 2018- Q1 2021) on SARS-CoV-2 infection and TB notifications. Additionally, we conducted a country-specific landscape assessment on COVID-19 measures, including lockdowns, operational level strategy of TB care and prevention services, and strategies employed to recover and retain those services. We used negative binomial regression models to assess the association between the installation of COVID-19 measures and changes in TB notifications. Results TB notifications declined in Kyrgyzstan and Vietnam, and (slightly) increased in Nigeria and Tanzania. The changes in TB notifications were associated with the installation of various COVID-19 prevention measures for Kyrgyzstan and Vietnam (declines) and Nigeria (increases). All countries reported reduced TB screening and testing activities. Countries reported the following strategies to retain TB prevention and care services: digital solutions for treatment adherence support, capacity building, and monitor & evaluation activities; adjustment in medication supply/delivery & quantity, including home delivery, pick up points, and month supply; integrated TB/COVID-19 screening & diagnostic platform; and the use of community health care workers. Conclusion Following the COVID-19 pandemic, we did not observe consistent changes in TB notifications across countries. However, all countries reported lower operating levels of TB prevention and care services. Digital health solutions, community-based interventions, and the integration of COVID-19 and TB testing services were employed to recover and retain those services. …

Abstract Background Both tuberculosis (TB) and diabetes mellitus (DM) are major public health problems threatening global health. TB patients with DM have a higher bacterial burden and affect the absorption and metabolism for anti-TB drugs. Drug-resistant TB (DR-TB) with DM make control TB more difficult. Methods This study was completed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guideline. We searched PubMed, Excerpta Medica Database (EMBASE), Web of Science, ScienceDirect and Cochrance Library for literature published in English until July 2022. Papers were limited to those reporting the association between DM and treatment outcomes among DR-TB and multidrug-resistant TB (MDR-TB) patients. The strength of association was presented as odds ratios (ORs) and their 95% confidence intervals (CIs) using the fixed-effects or random-effects models. This study was registered with PROSPERO, number CRD: 42,022,350,214. Results A total of twenty-five studies involving 16,905 DR-TB participants were included in the meta-analysis, of which 10,124 (59.89%) participants were MDR-TB patients, and 1,952 (11.54%) had DM history. In DR-TB patients, the pooled OR was 1.56 (95% CI: 1.24–1.96) for unsuccessful outcomes, 0.64 (95% CI: 0.44–0.94) for cured treatment outcomes, 0.63 (95% CI: 0.46–0.86) for completed treatment outcomes, and 1.28 (95% CI: 1.03–1.58) for treatment failure. Among MDR-TB patients, the pooled OR was 1.57 (95% CI: 1.20–2.04) for unsuccessful treatment outcomes, 0.55 (95% CI: 0.35–0.87) for cured treatment outcomes, 0.66 (95% CI: 0.46–0.93) for treatment completed treatment outcomes and 1.37 (95% CI: 1.08–1.75) for treatment failure. Conclusion DM is a risk factor for adverse outcomes of DR-TB or MDR-TB patients. Controlling hyperglycemia may contribute to the favorite prognosis of TB. Our findings support the importance for diagnosing DM in DR-TB /MDR-TB, and it is needed to control glucose and therapeutic monitoring during the treatment of DR-TB /MDR-TB patients. …

ObjectivesTreatment for multidrug-resistant/rifampicin-resistant tuberculosis (MDR/RR-TB) is increasingly transitioning from hospital-centred to community-based care. A national policy for decentralised programmatic MDR/RR-TB care was adopted in South Africa in 2011. We explored variations in the implementation of care models in response to this change in policy, and the implications of these variations for people affected by MDR/RR-TB. DesignA mixed methods study was done of patient movements between healthcare facilities, reconstructed from laboratory records. Facility visits and staff interviews were used to determine reasons for movements. Participants and settingPeople identified with MDR/RR-TB from 13 high-burden districts within South Africa. Outcome measuresGeospatial movement patterns were used to identify organisational models. Reasons for patient movement and implications of different organisational models for people affected by MDR/RR-TB and the health system were determined. ResultsAmong 191 participants, six dominant geospatial movement patterns were identified, which varied in average hospital stay (0–281 days), average patient distance travelled (12–198 km) and number of health facilities involved in care (1–5 facilities). More centralised models were associated with longer delays to treatment initiation and lengthy hospitalisation. Decentralised models facilitated family-centred care and were associated with reduced time to treatment and hospitalisation duration. Responsiveness to the needs of people affected by MDR/RR-TB and health system constraints was achieved through implementation of flexible models, or the implementation of multiple models in a district. ConclusionsUnderstanding how models for organising care have evolved may assist policy implementers to tailor implementation to promote particular patterns of care organisation or encourage flexibility, based on patient needs and local health system resources. Our approach can contribute towards the development of a health systems typology for understanding how policy-driven models of service delivery are implemented in the context of variable resources. …

IntroductionTime from symptom onset to treatment initiation in tuberculosis (TB) remains stubbornly prolonged despite reductions in disease incidence. Delays may contribute to increased morbidity, mortality, onward spread of disease and poor patient experiences. Most delays occur prior to hospital referral. The average primary care healthcare provider in England is unlikely to see TB on a regular basis. Little is known about primary care diagnostic and referral challenges. Adults aged 65 years or older are more likely to experience delays. However, little is known about their journey from symptom onset to treatment initiation. Methods and analysisWe will carry out a narrative study including adults aged 65 years or older, living in the English Midlands and receiving treatment for active TB. Twelve English and 12 Urdu or Punjabi speakers will be recruited from TB clinics and interviewed. Their primary care records will be accessed, and the primary care story and secondary care letters will be extracted. Each of the data sources will be analysed using dialogical narrative analysis. Data will be triangulated within participants and across the data set. Ethics and disseminationThis study received approval from the Health Research Authority and the Research Ethics Committee in April 2022. Risk management and equity considerations have been made a priority. Findings will be disseminated through publication in open access peer-reviewed journals, presentations to policy makers, primary healthcare and secondary healthcare professionals, and through public facing materials developed in conjunction with patients, members of the pubic, TB services and charities. …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Publication date: Available online 15 November 2023 Source: Infectious Disease Modelling Author(s): Olusegun Michael Otunuga …

Antimicrobial Agents and Chemotherapy, Ahead of Print.

Clinical Microbiology Reviews, Ahead of Print.

by Shalu Verma-Kumar, David Abraham, Nandini Dendukuri, Jacob Varghese Cheeran, Raman Sukumar, Kithiganahalli Narayanaswamy Balaji …

Globally, millions of people are infected with Mycobacterium tuberculosis, with most cases concentrated in developing countries. The burden of tuberculosis (TB) is low in most industrialised countries, and clusters of cases mostly arise from index cases who acquired the disease overseas. In Australia, TB is mostly diagnosed among migrants from high TB burden countries, healthcare workers, and among communities of First Nations Peoples [1]. The high frequency among migrant populations is primarily due to reactivation of latent TB.

AbstractAdaptive platform trials can be more efficient than classic trials for developing new treatments. Moving from culture-based to simpler- or faster-to-measure biomarkers as efficacy surrogates may enhance this advantage. We performed a systematic review of treatment efficacy biomarkers in adults with tuberculosis.Platform trials can span different development phases. We grouped biomarkers as: α, bacterial load estimates used in phase 2a trials; β, early and end-of treatment endpoints, phase 2b-c trials; γ, post-treatment or trial-level estimates, phase 2c-3 trials. We considered as analysis unit (biomarker entry) each combination of biomarker, predicted outcome, and their respective measurement times or intervals. Performance metrics included: sensitivity, specificity, area under the receiver-operator curve (AUC), and correlation measures, ,and classified as poor, promising, or good.Eighty-six studies included 22864 participants. From 1356 biomarker entries, 318 were reported with the performance metrics of interest, with 103 promising and 41 good predictors. Group results: α, mycobacterial RNA and Lipoarabinomannan in sputum, and host metabolites in urine; β, mycobacterial RNA and host transcriptomic or cytokine signatures for early treatment response; γ, host transcriptomics for recurrence.A combination of biomarkers from different categories could help designing more efficient platform trials. Efforts to develop efficacy surrogates should be better coordinated.