179 research outputs found
Quality_of_nonrandomised_studies.xls
No full textA quality assessment of non-randomised studies for a systematic revie
Reductions in development assistance for health funding threaten decades of progress in Africa
No full textCountries across Africa face health crises driven by aid cuts, shifting demography, and infectious and environmental threats. Renewed public health strategies, smarter investment, and stronger surveillance can help, but reversing funding cuts is vital
Case-Finding Strategies for Drug-Resistant Tuberculosis: Protocol for a Scoping Review.
No full textBACKGROUND
Transmission of drug-resistant tuberculosis (DR-TB) is ongoing. Finding individuals with DR-TB and initiating treatment as early as possible is important to improve patient clinical outcomes and to break the chain of transmission to control the pandemic. To our knowledge systematic reviews assessing effectiveness, cost-effectiveness, acceptability, and feasibility of different case-finding strategies for DR-TB to inform research, policy, and practice have not been conducted, and it is unknown whether enough research exists to conduct such reviews. It is unknown whether case-finding strategies are similar for DR-TB and drug-susceptible TB and whether we can draw on findings from drug-susceptible reviews to inform decisions on case-finding strategies for DR-TB.
OBJECTIVE
This protocol aims to describe the available literature on case-finding for DR-TB and to describe case-finding strategies.
METHODS
We will screen systematic reviews, trials, qualitative studies, diagnostic test accuracy studies, and other primary research that specifically sought to improve DR-TB case detection. We will exclude studies that invited individuals seeking care for TB symptoms, those including individuals already diagnosed with TB, or laboratory-based studies. We will search the academic databases including MEDLINE, Embase, The Cochrane Library, Africa-Wide Information, CINAHL, Epistemonikos, and PROSPERO with no language or date restrictions. We will screen titles, abstracts, and full-text articles in duplicate. Data extraction and analyses will be performed using Excel (Microsoft Corp).
RESULTS
We will provide a narrative report with supporting figures or tables to summarize the data. A systems-based logic model, developed from a synthesis of case-finding strategies for drug-susceptible TB, will be used as a framework to describe different strategies, resulting pathways, and enhancements of pathways. The search will be conducted at the end of 2021. Title and abstract screening, full text screening, and data extraction will be undertaken from January to June 2022. Thereafter, analysis will be conducted, and results compiled.
CONCLUSIONS
This scoping review will chart existing literature on case-finding for DR-TB-this will help determine whether primary studies on effectiveness, cost-effectiveness, acceptability, and feasibility of different case-finding strategies for DR-TB exist and will help formulate potential questions for a systematic review. We will also describe case-finding strategies for DR-TB and how they fit into a model of case-finding pathways for drug-susceptible TB. This review has some limitations. One limitation is the diverse, inconsistent use of intervention terminology within the literature, which may result in missing relevant studies. Poor reporting of intervention strategies may also cause misunderstanding and misclassification of interventions. Lastly, case-finding strategies for DR-TB may not fit into a model developed from strategies for drug-susceptible TB. Nevertheless, such a situation will provide an opportunity to refine the model for future research. The review will guide further research to inform decisions on case-finding policies and practices for DR-TB.
INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID)
DERR1-10.2196/40009
Clinical evaluation of host transcriptional markers for tuberculosis diagnosis and treatment response monitoring
No full textThe World Health Organization (WHO) called for non-sputum-based tests for tuberculosis (TB). This thesis considered the role of host transcriptional markers (HTM) for diagnosis of latent TB infection (LTBI) and active pulmonary TB (ATB) and for ATB treatment monitoring.
To measure HTM expression, a multiplex reverse-transcriptase quantitative polymerase chain reaction (RT-qPCR) assay was developed for 17 genes. Participants were recruited in Blantyre, Malawi. Amongst predefined study populations were the following key groups: ATB patients, who expectorated Mycobacterial Growth Indicator Tube (MGIT) culture and Xpert MTB/RIF positive sputum; patients with other respiratory diseases (ORDs) who had negative sputum tests and were not diagnosed with ATB; LTBI patients, who were TB exposed (TBEx) household contacts of ATB patients with a positive Interferon Gamma Release Assay (IGRA); TBExIGRA- participants, who were contacts with a negative IGRA- result; and Healthy Controls (HCs), who were asymptomatic IGRA negative individuals without household TB exposure. Cross-sectional analyses evaluated whether HTM expression profiles could discriminate LTBI from HCs, LTBI from ATB, and ATB from ORDs. Patients receiving ATB treatment were followed for 8 months to compare sputum bacteriology tests (Time to Positivity in MGIT culture and the TB Molecular Bacterial Load Assay [TB-MBLA]) with HTM profiles for treatment monitoring.
LTBI was associated with suppression of gene expression compared to HCs. ZNF296 and KLF2 distinguished LTBI from HCs more accurately than other HTM. A proportion of TBExIGRA- negative participants exhibited similar HTM expression patterns to LTBI. ATB was associated with upregulated HTM expression compared to ORDs. CD64 most accurately distinguished ATB from ORDs. HIV co-infection did not affect HTM expression in either LTBI or ATB. HTM expression declined in response to treatment in a manner that mirrored bacteriological measures of treatment response.
Blood-based HTM have potential to improve LTBI and ATB diagnosis and monitor ATB treatment response."This studentship was supported by the Global St Andrews Doctoral Scholarship.The research work was supported by the Wellcome Trust Institutional Strategic Support fund of the University of St Andrews, grant code 204821/Z/16/Z. Additional funding was obtained from Helse Nord Tuberculosis Initiative (HNTI), and the Africa Centre for Public Health and Herbal Medicines (ACEPHEM), Kamuzu University of Health Sciences.""--Fundin
Drug-Resistant Tuberculosis Case-Finding Strategies: Scoping Review
No full textBackgroundFinding individuals with drug-resistant tuberculosis (DR-TB) is important to control the pandemic and improve patient clinical outcomes. To our knowledge, systematic reviews assessing the effectiveness, cost-effectiveness, acceptability, and feasibility of different DR-TB case-finding strategies to inform research, policy, and practice, have not been conducted and the scope of primary research is unknown.
ObjectiveWe therefore assessed the available literature on DR-TB case-finding strategies.
MethodsWe looked at systematic reviews, trials, qualitative studies, diagnostic test accuracy studies, and other primary research that sought to improve DR-TB case detection specifically. We excluded studies that included patients seeking care for tuberculosis (TB) symptoms, patients already diagnosed with TB, or were laboratory-based. We searched the academic databases of MEDLINE, Embase, The Cochrane Library, Africa-Wide Information, CINAHL (Cumulated Index to Nursing and Allied Health Literature), Epistemonikos, and PROSPERO (The International Prospective Register of Systematic Reviews) using no language or date restrictions. We screened titles, abstracts, and full-text articles in duplicate. Data extraction and analyses were carried out in Excel (Microsoft Corp).
ResultsWe screened 3646 titles and abstracts and 236 full-text articles. We identified 6 systematic reviews and 61 primary studies. Five reviews described the yield of contact investigation and focused on household contacts, airline contacts, comparison between drug-susceptible tuberculosis and DR-TB contacts, and concordance of DR-TB profiles between index cases and contacts. One review compared universal versus selective drug resistance testing. Primary studies described (1) 34 contact investigations, (2) 17 outbreak investigations, (3) 3 airline contact investigations, (4) 5 epidemiological analyses, (5) 1 public-private partnership program, and (6) an e-registry program. Primary studies were all descriptive and included cross-sectional and retrospective reviews of program data. No trials were identified. Data extraction from contact investigations was difficult due to incomplete reporting of relevant information.
ConclusionsExisting descriptive reviews can be updated, but there is a dearth of knowledge on the effectiveness, cost-effectiveness, acceptability, and feasibility of DR-TB case-finding strategies to inform policy and practice. There is also a need for standardization of terminology, design, and reporting of DR-TB case-finding studies
Non-Tuberculous Mycobacterial Pulmonary Disease identified during community-based screening for Mycobacterium Tuberculosis: a case report.
No full textThere is a rising prevalence of Non-Tuberculous Mycobacterial (NTM) disease in sub-Saharan Africa identified on culture specimens. However, distinguishing mycobacterial colonisations from infection from identified NTMs on culture in the sub-Saharan Africa setting remains to be established. A 49-year-old man presented with the cardinal symptoms of tuberculosis (TB) in a community TB prevalence survey in Blantyre, Malawi. Mycobacteriology was atypical, prompting a line probe assay which revealed Mycobacterium avium complex (MAC) species. The epidemiology of Mycobacterium tuberculosis complex (MTBC) is better known than that of NTM. Up-scaling culture and speciation may be a solution to this gap in knowledge of the burden of disease of NTM. Like most resource-poor settings, TB culture is not routinely done in the diagnosis and management of TB in Malawi. Furthermore, the treatment of NTM is not analogous to that of MTBC. The multi-drug regimens used for NTM disease treatment includes a newer macrolide (azithromycin, clarithromycin), ethambutol, and rifamycin, and require prolonged durations of therapy aimed at facilitating clearance of the mycobacteria and minimizing the emergence of drug resistance. Clinicians must thus be aware of this rising burden of NTM disease and consider other diagnostic options to better investigate this disease in patients
Specific human gene expression in response to infection is an effective marker for diagnosis of latent and active tuberculosis
No full textFunding: This work was supported by the Wellcome Trust Institutional Strategic Support Fund of the University of St Andrews, 204821/Z/16/Z and the Global St Andrews Doctoral Scholarship. Additional funding was obtained from Helse Nord Tuberculosis Initiative (HNTI), Pathology Department, Kamuzu University of Health Sciences.RNA sequencing and microarray analysis revealed transcriptional markers expressed in whole blood can differentiate active pulmonary TB (ATB) from other respiratory diseases (ORDs), and latent TB infection (LTBI) from healthy controls (HC). Here we describe a streamlined reverse transcriptase quantitative polymerase chain reaction (RT-qPCR) assay that could be applied at near point-of-care for diagnosing and distinguishing ATB from ORDs and LTBI from HC. A literature review was undertaken to identify the most plausible host-gene markers (HGM) of TB infection. Primers, and dual labelled hydrolysis probes were designed and analytically evaluated for accuracy in an in-vitro model of infection using a lung fibroblast cell-line. Best performing genes were multiplexed into panels of 2–4 targets and taken forward for clinical evaluation. Mycobacteria Growth Indicator Tube and QuantiFERON-TB Gold Plus were used as reference tests for ATB and LTBI respectively. A total of 16 HGM were selected and incorporated into five multiplex RT-qPCR panels. PCR assay efficiency of all evaluated targets was ≥ 90% with a median analytical sensitivity of 292 copies/µl [IQR: 215.0-358.3 copies/µl], and a median limit of quantification of 61.7 copies/µl [IQR: 29.4-176.3 copies/µl]. Clinically, ATB was characterised by higher gene expression than ORDs, while LTBI was associated with lower gene expression than HC, Kruskal-Wallis p < 0.0001. Crucially, BATF2, CD64, GBP5, C1QB, GBP6, DUSP3, and GAS6 exhibited high differentiative ability for ATB from ORDs, LTBI or HC while KLF2, PTPRC, NEMF, ASUN, and ZNF296 independently discriminated LTBI from HC. Our results show that different HGM maybe required for ATB and LTBI differentiation from ORDs or HC respectively and demonstrate the feasibility of host gene-based RT-qPCR to diagnose ATB and LTBI at near point-of-care.Peer reviewe
Effectiveness of spatially targeted interventions for control of HIV, tuberculosis, leprosy and malaria: a systematic review.
No full textBACKGROUND: As infectious diseases approach global elimination targets, spatial targeting is increasingly important to identify community hotspots of transmission and effectively target interventions. We aimed to synthesise relevant evidence to define best practice approaches and identify policy and research gaps. OBJECTIVE: To systematically appraise evidence for the effectiveness of spatially targeted community public health interventions for HIV, tuberculosis (TB), leprosy and malaria. DESIGN: Systematic review. DATA SOURCES: We searched Medline, Embase, Global Health, Web of Science and Cochrane Database of Systematic Reviews between 1 January 1993 and 22 March 2021. STUDY SELECTION: The studies had to include HIV or TB or leprosy or malaria and spatial hotspot definition, and community interventions. DATA EXTRACTION AND SYNTHESIS: A data extraction tool was used. For each study, we summarised approaches to identifying hotpots, intervention design and effectiveness of the intervention. RESULTS: Ten studies, including one cluster randomised trial and nine with alternative designs (before-after, comparator area), satisfied our inclusion criteria. Spatially targeted interventions for HIV (one USA study), TB (three USA) and leprosy (two Brazil, one Federated States of Micronesia) each used household location and disease density to define hotspots followed by community-based screening. Malaria studies (one each from India, Indonesia and Kenya) used household location and disease density for hotspot identification followed by complex interventions typically combining community screening, larviciding of stagnant water bodies, indoor residual spraying and mass drug administration. Evidence of effect was mixed. CONCLUSIONS: Studies investigating spatially targeted interventions were few in number, and mostly underpowered or otherwise limited methodologically, affecting interpretation of intervention impact. Applying advanced epidemiological methodologies supporting more robust hotspot identification and larger or more intensive interventions would strengthen the evidence-base for this increasingly important approach. PROSPERO REGISTRATION NUMBER: CRD42019130133
petermacp/tbcascade
No full textData and code to replicate analysis in Tuberculosis diagnosis cascade in Blantyre, Malawi: a prospective cohort study by Feasey H et al. 2020. Datasets are available as .csv files or as Stata .dta files, and code to reproduce analysis is available as Stata .do files. The file Entry-exit-data-codebook.xlsx provides the data dictionary
Emerg Infect Dis
No full textThe coronavirus disease (COVID-19) pandemic might affect tuberculosis (TB) diagnosis and patient care. We analyzed a citywide electronic TB register in Blantyre, Malawi and interviewed TB officers. Malawi did not have an official COVID-19 lockdown but closed schools and borders on March 23, 2020. In an interrupted time series analysis, we noted an immediate 35.9% reduction in TB notifications in April 2020; notifications recovered to near prepandemic numbers by December 2020. However, 333 fewer cumulative TB notifications were received than anticipated. Women and girls were affected more (30.7% fewer cases) than men and boys (20.9% fewer cases). Fear of COVID-19 infection, temporary facility closures, inadequate personal protective equipment, and COVID-19 stigma because of similar symptoms to TB were mentioned as reasons for fewer people being diagnosed with TB. Public health measures could benefit control of both TB and COVID-19, but only if TB diagnostic services remain accessible and are considered safe to attend.WT_/Wellcome TrustUnited Kingdom
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