68 research outputs found
Cost of point-of-care lateral flow urine lipoarabinomannan antigen testing in HIV-positive adults in South Africa
Aaron S. Karat - ORCID 0000-0001-9643-664X
https://orcid.org/0000-0001-9643-664XINTRODUCTION: The World Health Organization recommends point-of-care (POC) lateral flow urine lipoarabinomannan (LF-LAM) for tuberculosis (TB) diagnosis in selected human immunodeficiency virus (HIV) positive people. South Africa had 438 000 new TB episodes in 2016, 58.9% of which were contributed by HIV-positive people. LF-LAM is being considered for scale-up in South Africa.METHODS: We estimated the costs of using LF-LAM in
HIV-positive adults with CD4 counts 6 150 cells/ll
enrolled in the TB Fast Track Trial in South Africa. We
also estimated costs of POC haemoglobin (Hb), as this
was used in the study algorithm. Data on clinic-level (10
intervention clinics) and above-clinic-level costs were
collected.RESULTS: A total of 1307 LF-LAM tests were performed at 10 clinics over 24 months. The mean cliniclevel costs were US11.49 per patient.
The mean above-clinic-level unit costs for LF-LAM were
US23.55 per patient.CONCLUSION: At clinic level, the cost of LF-LAM was
comparable to other TB diagnostics in South Africa. It is
important to consider above-clinic-level costs for POC
tests, as these may be required to support roll-out and
ensure successful implementation.The trial sponsor was the London School of Hygiene & Tropical
Medicine, London, UK. The study was funded by Joint Global
Health Trials (UK Medical Research Council, UK Department for
International Development, Wellcome Trust). This UK-funded
award is part of the EDCTP2 programme supported by the
European Union. Alere donated materials for quality control of
their LAM assay. The funder and study sponsor had no role in the
study design or in the execution of the study, analysis and
interpretation of data, or decision to submit results for publication.https://doi.org/10.5588/ijtld.18.004622pubpub
Sensitivity of the lateral flow urine lipoarabinomannan assay in ambulant adults with advanced HIV disease: data from the TB Fast Track study.
BACKGROUND: WHO guidelines recommend the lateral flow urine lipoarabinomannan assay (LF-LAM) for TB diagnosis in hospitalised HIV-positive individuals. The role of LF-LAM among ambulant patients remains less well defined. We investigated the sensitivity of LF-LAM among ambulant HIV-positive adults in primary health clinics in South Africa. METHODS: We enrolled adults (aged ≥18 y) with CD4 counts of ≤150 cells/mm3 who had not received TB treatment or antiretroviral therapy in the preceding 3 or 6 mo, respectively. Research nurses performed the LF-LAM test on freshly voided urine. Results were compared with a reference standard of positive mycobacterial culture (sputum or urine). RESULTS: Of 1505 (54.5% female; median age 37 y; median CD4 count 73 cells/mm3) participants, 973 (64.7%) had a mycobacterial culture result; 105/973 (10.8%) were positive for Mycobacterium tuberculosis. LF-LAM sensitivity was 41.9% (95% CI 32.3 to 51.9%) and 19.0% (95% CI 12.0 to 27.9%) using grade 1+ and grade 2+ cut-off points, respectively. Sensitivity increased with severe immunosuppression and in the presence of poor prognostic indicators (low haemoglobin, body mass index). CONCLUSIONS: When used as the only TB diagnostic test, LF-LAM sensitivity is suboptimal, particularly using the grade 2+ cut-off. More sensitive tests for TB are needed that can be used in primary care settings
Verbal autopsy-assigned causes of death among adults being investigated for TB in South Africa
Aaron S. Karat - ORCID 0000-0001-9643-664X
https://orcid.org/0000-0001-9643-664XBackground: Adults being investigated for TB in South Africa experience high mortality, yet causes of death
(CoD) are not well defined. We determined CoD in this population using verbal autopsy (VA), and compared
HIV- and TB-associated CoD using physician-certified verbal autopsy (PCVA) and InterVA-4 software.Methods: All contactable consenting caregivers of participants who died during a trial comparing Xpert MTB/
RIF to smear microscopy were interviewed using the WHO VA tool. CoD were assigned using PCVA and
InterVA-4. Kappa statistic (K) and concordance correlation coefficient (CCC) were calculated for comparison.Results: Among 231 deaths, relatives of 137 deceased were interviewed. Of the 137 deceased 76 (55.4%)
were males, median age 41 years (IQR 33–50). PCVA assigned 70 (51.1%) TB immediate CoD (44 [62.8%] pulmonary TB; 26 [37.1%] extra-pulmonary TB); 21 (15.3%) HIV/AIDS-related; and 46 (33.5%) other CoD.
InterVA-4 assigned 48 (35.0%) TB deaths; 49 (35.7%) HIV/AIDS-related deaths; and 40 (29.1%) other CoD.
Agreement between PCVA and InterVA-4 CoD was slight at individual level (K=0.20; 95% CI 0.10–0.30) and
poor at population level (CCC 0.67; 95% CI 0.38–0.99).Conclusions: TB and HIV are leading CoD among adults being investigated for TB. PCVA and InterVA agreement at individual level was slight and poor at population level. VA methodology needs further development
where TB and HIV are common.This work was supported by Bill & Melinda Gates Foundation [Grant Number: OPP1034523] for funding the study.https://doi.org/10.1093/trstmh/trw058110pubpub
Estimating the contribution of transmission in primary healthcare clinics to community-wide TB disease incidence, and the impact of infection prevention and control interventions, in KwaZulu-Natal, South Africa.
BACKGROUND: There is a high risk of Mycobacterium tuberculosis (Mtb) transmission in healthcare facilities in high burden settings. WHO guidelines on tuberculosis (TB) infection prevention and control (IPC) recommend a range of measures to reduce transmission in healthcare settings. These were evaluated primarily based on evidence for their effects on transmission to healthcare workers in hospitals. To estimate the overall impact of IPC interventions, it is necessary to also consider their impact on community-wide TB incidence and mortality. METHODS: We developed an individual-based model of Mtb transmission in households, primary healthcare (PHC) clinics, and all other congregate settings. The model was parameterised using data from a high HIV prevalence community in South Africa, including data on social contact by setting, by sex, age, and HIV/antiretroviral therapy status; and data on TB prevalence in clinic attendees and the general population. We estimated the proportion of disease in adults that resulted from transmission in PHC clinics, and the impact of a range of IPC interventions in clinics on community-wide TB. RESULTS: We estimate that 7.6% (plausible range 3.9%-13.9%) of non-multidrug resistant and multidrug resistant TB in adults resulted directly from transmission in PHC clinics in the community in 2019. The proportion is higher in HIV-positive people, at 9.3% (4.8%-16.8%), compared with 5.3% (2.7%-10.1%) in HIV-negative people. We estimate that IPC interventions could reduce incident TB cases in the community in 2021-2030 by 3.4%-8.0%, and deaths by 3.0%-7.2%. CONCLUSIONS: A non-trivial proportion of TB results from transmission in clinics in the study community, particularly in HIV-positive people. Implementing IPC interventions could lead to moderate reductions in disease burden. We recommend that IPC measures in clinics should be implemented for their benefits to staff and patients, but also for their likely effects on TB incidence and mortality in the surrounding community
Time to change the way we think about tuberculosis infection prevention and control in health facilities: insights from recent research
In clinical settings where airborne pathogens, such as Mycobacterium tuberculosis, are prevalent, they constitute an important threat to health workers and people accessing healthcare. We report key insights from a 3-year project conducted in primary healthcare clinics in South Africa, alongside other recent tuberculosis infection prevention and control (TB-IPC) research. We discuss the fragmentation of TB-IPC policies and budgets; the characteristics of individuals attending clinics with prevalent pulmonary tuberculosis; clinic congestion and patient flow; clinic design and natural ventilation; and the facility-level determinants of the implementation (or not) of TB-IPC interventions. We present modeling studies that describe the contribution of M. tuberculosis transmission in clinics to the community tuberculosis burden and economic evaluations showing that TB-IPC interventions are highly cost-effective. We argue for a set of changes to TB-IPC, including better coordination of policymaking, clinic decongestion, changes to clinic design and building regulations, and budgeting for enablers to sustain implementation of TB-IPC interventions. Additional research is needed to find the most effective means of improving the implementation of TB-IPC interventions; to develop approaches to screening for prevalent pulmonary tuberculosis that do not rely on symptoms; and to identify groups of patients that can be seen in clinic less frequently
Evidence for the Use of Triage, Respiratory Isolation, and Effective Treatment to Reduce the Transmission of Mycobacterium Tuberculosis in Healthcare Settings: A Systematic Review.
Evidence is limited for infection prevention and control (IPC) measures reducing Mycobacterium tuberculosis (MTB) transmission in health facilities. This systematic review, 1 of 7 commissioned by the World Health Organization to inform the 2019 update of global tuberculosis (TB) IPC guidelines, asked: do triage and/or isolation and/or effective treatment of TB disease reduce MTB transmission in healthcare settings? Of 25 included articles, 19 reported latent TB infection (LTBI) incidence in healthcare workers (HCWs; absolute risk reductions 1%-21%); 5 reported TB disease incidence in HCWs (no/slight [high TB burden] or moderate [low burden] reduction) and 2 in human immunodeficiency virus-positive in-patients (6%-29% reduction). In total, 23/25 studies implemented multiple IPC measures; effects of individual measures could not be disaggregated. Packages of IPC measures appeared to reduce MTB transmission, but evidence for effectiveness of triage, isolation, or effective treatment, alone or in combination, was indirect and low quality. Harmonizing study designs and reporting frameworks will permit formal data syntheses and facilitate policy making
Tuberculosis infection prevention and control: why we need a whole systems approach.
Infection prevention and control (IPC) measures to reduce transmission of drug-resistant and drug-sensitive tuberculosis (TB) in health facilities are well described but poorly implemented. The implementation of TB IPC has been assessed primarily through quantitative and structured approaches that treat administrative, environmental, and personal protective measures as discrete entities. We present an on-going project entitled Umoya omuhle ("good air"), conducted in two provinces of South Africa, that adopts an interdisciplinary, 'whole systems' approach to problem analysis and intervention development for reducing nosocomial transmission of Mycobacterium tuberculosis (Mtb) through improved IPC. We suggest that TB IPC represents a complex intervention that is delivered within a dynamic context shaped by policy guidelines, health facility space, infrastructure, organisation of care, and management culture. Methods drawn from epidemiology, anthropology, and health policy and systems research enable rich contextual analysis of how nosocomial Mtb transmission occurs, as well as opportunities to address the problem holistically. A 'whole systems' approach can identify leverage points within the health facility infrastructure and organisation of care that can inform the design of interventions to reduce the risk of nosocomial Mtb transmission
Performance of verbal autopsy methods in estimating HIV-associated mortality among adults in South Africa
Aaron S. Karat - ORCID 0000-0001-9643-664X
https://orcid.org/0000-0001-9643-664XIntroduction Verbal autopsy (VA) can be integrated into civil registration and vital statistics systems, but its accuracy in determining HIV-associated causes of death (CoD) is uncertain. We assessed the sensitivity and specificity of VA questions in determining HIV status and antiretroviral therapy (ART) initiation and compared HIV-associated mortality fractions assigned by different VA interpretation methods.Methods Using the WHO 2012 instrument with added ART
questions, VA was conducted for deaths among adults with
known HIV status (356 HIV positive and 103 HIV negative)
in South Africa. CoD were assigned using physiciancertified VA (PCVA) and computer-coded VA (CCVA)
methods and compared with documented HIV statusResults The sensitivity of VA questions in detecting HIV
status and ART initiation was 84.3% (95% CI 80 to 88) and
91.0% (95% CI 86 to 95); 283/356 (79.5%) HIV-positive
individuals were assigned HIV-associated CoD by PCVA,
166 (46.6%) by InterVA-4.03, 201 (56.5%) by InterVA-5,
and 80 (22.5%) and 289 (81.2%) by SmartVA-Analyze
V.1.1.1 and V.1.2.1. Agreement between PCVA and older
CCVA methods was poor (chance-corrected concordance
[CCC] <0; cause-specific mortality fraction [CSMF]
accuracy ≤56%) but better between PCVA and updated
methods (CCC 0.21–0.75; CSMF accuracy 65%–98%).
All methods were specific (specificity 87% to 96%) in
assigning HIV-associated CoD.Conclusion All CCVA interpretation methods
underestimated the HIV-associated mortality fraction
compared with PCVA; InterVA-5 and SmartVA-Analyze
V.1.2.1 performed better than earlier versions. Changes
to VA methods and classification systems are needed to
track progress towards targets for reducing HIV-associated
mortality,This study was funded by a grant from the Bill & Melinda Gates Foundation (OPP1083118).http://dx.doi.org/10.1136/bmjgh-2018-0008333pubpub
Relational Dynamics of Treatment Behavior Among Individuals with Tuberculosis in High-Income Countries: A Scoping Review
Although tuberculosis (TB) incidence has significantly declined in high-income, low-incidence (HILI) countries, challenges remain in managing TB in vulnerable populations who may struggle to stay on anti-TB treatment (ATT). Factors associated with non-adherence to ATT are well documented; however, adherence is often narrowly conceived as a fixed binary variable that places emphasis on individual agency and the act of taking medicines, rather than on the demands of being on treatment more broadly. Further, the mechanisms through which documented factors act upon the experience of being on treatment are poorly understood. Adopting a relational approach that emphasizes the embeddedness of individuals within dynamic social, structural, and health systems contexts, this scoping review aims to synthesize qualitative evidence on experiences of being on ATT and mechanisms through which socio-ecological factors influence adherence in HILI countries. Six electronic databases were searched for peer-reviewed literature published in English between January 1990 and May 2020. Additional studies were obtained by searching references of included studies. Narrative synthesis was used to analyze qualitative data extracted from included studies. Of 28 included studies, the majority (86%) reported on health systems factors, followed by personal characteristics (82%), structural influences (61%), social factors (57%), and treatment related factors (50%). Included studies highlighted three points that underpin a relational approach to ATT behavior: 1) individual motivation and capacity to take ATT is dynamic and intertwined with, rather than separate from, social, health systems, and structural factors; 2) individuals' pre-existing experiences of health-seeking influence their views on treatment and their ability to commit to long-term regular medicine-taking; and 3) social, cultural, and political contexts play an important role in mediating how specific factors work to support or hinder ATT adherence behavior in different settings. Based on our analysis, we suggest that person-centered clinical management of tuberculosis should 1) acknowledge the ways in which ATT both disrupts and is managed within the everyday lives of individuals with TB; 2) appreciate that individuals' circumstances and the support and resources they can access may change over the course of treatment; and 3) display sensitivity towards context-specific social and cultural norms affecting individual and collective experiences of being on ATT
Direct estimates of absolute ventilation and estimated Mycobacterium tuberculosis transmission risk in clinics in South Africa
From PLOS via Jisc Publications RouterHistory: collection 2022, received 2022-01-26, accepted 2022-10-03, epub 2022-11-02Acknowledgements: We are grateful to the clinical and management staff at 10 clinics where we obtained ventilation measurements. We thank Thomas Murray, Harriet Gliddon, and Sinethemba Mabuyakhulu who assisted us with ventilation measurements in KZN. We are grateful to Rod Escombe, Ed Nardell, Jon Taylor, Don Milton, and Toby van Reenen for useful discussions about various aspects of ventilation science–they take no responsibility for the content of this manuscript.Publication status: PublishedFunder: Economic and Social Research Council; funder-id: http://dx.doi.org/10.13039/501100000269; Grant(s): ES/P008011/1Funder: Wellcome Trust; funder-id: http://dx.doi.org/10.13039/100004440; Grant(s): 218261/Z/19/ZFunder: National Institute for Health Research; funder-id: http://dx.doi.org/10.13039/501100000272Healthcare facilities are important sites for the transmission of pathogens spread via bioaerosols, such as Mycobacterium tuberculosis. Natural ventilation can play an important role in reducing this transmission. We aimed to measure rates of natural ventilation in clinics in KwaZulu-Natal and Western Cape provinces, South Africa, then use these measurements to estimate Mycobacterium tuberculosis transmission risk. We measured ventilation in clinic spaces using a tracer-gas release method. In spaces where this was not possible, we estimated ventilation using data on indoor and outdoor carbon dioxide levels. Ventilation was measured i) under usual conditions and ii) with all windows and doors fully open. Under various assumptions about infectiousness and duration of exposure, measured absolute ventilation rates were related to risk of Mycobacterium tuberculosis transmission using the Wells-Riley Equation. In 2019, we obtained ventilation measurements in 33 clinical spaces in 10 clinics: 13 consultation rooms, 16 waiting areas and 4 other clinical spaces. Under usual conditions, the absolute ventilation rate was much higher in waiting rooms (median 1769 m3/hr, range 338–4815 m3/hr) than in consultation rooms (median 197 m3/hr, range 0–1451 m3/hr). When compared with usual conditions, fully opening existing doors and windows resulted in a median two-fold increase in ventilation. Using standard assumptions about infectiousness, we estimated that a health worker would have a 24.8% annual risk of becoming infected with Mycobacterium tuberculosis, and that a patient would have an 0.1% risk of becoming infected per visit. Opening existing doors and windows and rearranging patient pathways to preferentially use better ventilated clinic spaces result in important reductions in Mycobacterium tuberculosis transmission risk. However, unless combined with other tuberculosis infection prevention and control interventions, these changes are insufficient to reduce risk to health workers, and other highly exposed individuals, to acceptable levels
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