scholarly journals Isoniazid or rifampicin preventive therapy with and without screening for subclinical TB: a modeling analysis

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Emily A. Kendall ◽  
Hamidah Hussain ◽  
Amber Kunkel ◽  
Rachel W. Kubiak ◽  
Anete Trajman ◽  
...  
Keyword(s):  
Scale Up ◽  
Preventive Therapy ◽  
Rifampicin Resistance ◽  
Isoniazid Resistance ◽  
Uncertainty Range ◽  
Symptomatic Disease ◽  
Resistant Disease ◽  
Modeling Analysis ◽  
Short Course ◽  
Radiographic Screening

Abstract Background Short-course, rifamycin-based regimens could facilitate scale-up of tuberculosis preventive therapy (TPT), but it is unclear how stringently tuberculosis (TB) disease should be ruled out before TPT use. Methods We developed a state-transition model of a TPT intervention among two TPT-eligible cohorts: adults newly diagnosed with HIV in South Africa (PWH) and TB household contacts in Pakistan (HHCs). We modeled two TPT regimens—4 months of rifampicin [4R] or 6 months of isoniazid [6H]—comparing each to a reference of no intervention. Before initiating TPT, TB disease was excluded either through symptom-only screening or with additional radiographic screening that could detect subclinical TB but might limit access to the TPT intervention. TPT’s potential curative effects on both latent and subclinical TB were modeled, as were both acquisitions of resistance and prevention of drug-resistant disease. Although all eligible individuals received the screening and/or TPT interventions, the modeled TB outcomes comprised only those with latent or subclinical TB that would have progressed to symptomatic disease if untreated. Results When prescribed after only symptom-based TB screening (such that individuals with subclinical TB were included among TPT recipients), 4R averted 45 active (i.e., symptomatic) TB cases (95% uncertainty range 24–79 cases or 40–89% of progressions to active TB) per 1000 PWH [17 (9–29, 43–94%) per 1000 HHCs]; 6H averted 37 (19–66, 52–73%) active TB cases among PWH [13 (7–23, 53–75%) among HHCs]. With this symptom-only screening, for each net rifampicin resistance case added by 4R, 12 (3–102) active TB cases were averted among PWH (37 [9–580] among HHCs); isoniazid-resistant TB was also reduced. Similarly, 6H after symptom-only screening increased isoniazid resistance while reducing overall and rifampicin-resistant active TB. Screening for subclinical TB before TPT eliminated this net increase in resistance to the TPT drug; however, if the screening requirement reduced TPT access by more than 10% (the estimated threshold for 4R among HHCs) to 30% (for 6H among PWH), it was likely to reduce the intervention’s overall TB prevention impact. Conclusions All modeled TPT strategies prevent TB relative to no intervention, and differences between TPT regimens or between screening approaches are small relative to uncertainty in the outcomes of any given strategy. If most TPT-eligible individuals can be screened for subclinical TB, then pairing such screening with rifamycin-based TPT maximizes active TB prevention and does not increase rifampicin resistance. Where subclinical TB cannot be routinely excluded without substantially reducing TPT access, the choice of TPT regimen requires weighing 4R’s efficacy advantages (as well as its greater safety and shorter duration that we did not directly model) against the consequences of rifampicin resistance in a small fraction of recipients.

scholarly journals Cost‐effectiveness of a 12 country‐intervention to scale up short course TB preventive therapy among people living with HIV

2020 ◽  
Vol 23 (10) ◽  
Author(s):  
Hyejeong Shin ◽  
Youngji Jo ◽  
Richard E Chaisson ◽  
Karin Turner ◽  
Gavin Churchyard ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Scale Up ◽  
Preventive Therapy ◽  
People Living With Hiv ◽  
Short Course ◽  
Living With Hiv

scholarly journals Integrated TB and HIV care for Mozambican children: temporal trends, site-level determinants of performance, and recommendations for improved TB preventive treatment

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
W. Chris Buck ◽  
Hanh Nguyen ◽  
Mariana Siapka ◽  
Lopa Basu ◽  
Jessica Greenberg Cowan ◽  
...  
Keyword(s):  
Temporal Trends ◽  
Scale Up ◽  
Preventive Treatment ◽  
Preventive Therapy ◽  
Pediatric Hiv ◽  
Hiv Care ◽  
Pediatric Care ◽  
P Value ◽  
Missed Opportunities ◽  
Art Initiation

Abstract Background Pediatric tuberculosis (TB), human immunodeficiency virus (HIV), and TB-HIV co-infection are health problems with evidence-based diagnostic and treatment algorithms that can reduce morbidity and mortality. Implementation and operational barriers affect adherence to guidelines in many resource-constrained settings, negatively affecting patient outcomes. This study aimed to assess performance in the pediatric HIV and TB care cascades in Mozambique. Methods A retrospective analysis of routine PEPFAR site-level HIV and TB data from 2012 to 2016 was performed. Patients 0–14 years of age were included. Descriptive statistics were used to report trends in TB and HIV indicators. Linear regression was done to assess associations of site-level variables with performance in the pediatric TB and HIV care cascades using 2016 data. Results Routine HIV testing and cotrimoxazole initiation for co-infected children in the TB program were nearly optimal at 99% and 96% in 2016, respectively. Antiretroviral therapy (ART) initiation was lower at 87%, but steadily improved from 2012 to 2016. From the HIV program, TB screening at the last consultation rose steadily over the study period, reaching 82% in 2016. The percentage of newly enrolled children who received either TB treatment or isoniazid preventive treatment (IPT) also steadily improved in all provinces, but in 2016 was only at 42% nationally. Larger volume sites were significantly more likely to complete the pediatric HIV and TB care cascades in 2016 (p value range 0.05 to < 0.001). Conclusions Mozambique has made significant strides in improving the pediatric care cascades for children with TB and HIV, but there were missed opportunities for TB diagnosis and prevention, with IPT utilization being particularly problematic. Strengthened TB/HIV programming that continues to focus on pediatric ART scale-up while improving delivery of TB preventive therapy, either with IPT or newer rifapentine-based regimens for age-eligible children, is needed.

Diagnostic accuracy of centralised assays for TB detection and detection of resistance to rifampicin and isoniazid: a systematic review and meta-analysis

2020 ◽  
Vol 57 (2) ◽  
pp. 2000747
Author(s):  
Mikashmi Kohli ◽  
Emily MacLean ◽  
Madhukar Pai ◽  
Samuel G. Schumacher ◽  
Claudia M. Denkinger
Keyword(s):  
Systematic Review ◽  
Diagnostic Accuracy ◽  
Meta Analysis ◽  
Tracheal Aspirate ◽  
Rifampicin Resistance ◽  
Isoniazid Resistance ◽  
Cross Sectional ◽  
Molecular Assays ◽  
Index Tests ◽  
Resistance Detection

Various diagnostic companies have developed high throughput molecular assays for tuberculosis (TB) and resistance detection for rifampicin and isoniazid. We performed a systematic review and meta-analyses to assess the diagnostic accuracy of five of these tests for pulmonary specimens. The tests included were Abbott RealTime MTB, Abbott RealTime RIF/INH, FluoroType MTB, FluoroType MTDBR and BD Max MDR-TB assay.A comprehensive search of six databases for relevant citations was performed. Cross-sectional, case-control, cohort studies, and randomised controlled trials of any of the index tests were included. Respiratory specimens (such as sputum, bronchoalveolar lavage, tracheal aspirate, etc.) or their culture isolates.A total of 21 included studies contributed 26 datasets. We could only meta-analyse data for three of the five assays identified, as data were limited for the remaining two. For TB detection, the included assays had a sensitivity of 91% or more and the specificity ranged from 97% to 100%. For rifampicin resistance detection, all the included assays had a sensitivity of more than 92%, with a specificity of 99–100%. Sensitivity for isoniazid resistance detection varied from 70 to 91%, with higher specificity of 99–100% across all index tests. Studies that included head-to-head comparisons of these assays with Xpert MTB/RIF for detection of TB and rifampicin resistance suggested comparable diagnostic accuracy.In people with symptoms of pulmonary TB, the centralised molecular assays demonstrate comparable diagnostic accuracy for detection of TB, rifampicin and isoniazid resistance to Xpert MTB/RIF assay, a WHO recommended molecular test.

Sarcoidosis

2013 ◽  
pp. 1434-1441
Author(s):  
Joachim Müller-Quernheim ◽  
Gernot Zissel ◽  
Antje Prasse
Keyword(s):  
Tumour Necrosis ◽  
Systemic Disease ◽  
Organ Damage ◽  
Immunosuppressive Agent ◽  
Clinical Findings ◽  
Immunosuppressive Regimen ◽  
Cytokine Network ◽  
Symptomatic Disease ◽  
Resistant Disease ◽  
Necrosis Factor

Sarcoidosis is a systemic disease characterized by non-necrotizing granulomata and manifestations in almost any organ. Diagnosis relies on the exclusion of other granulomatous disorders and a compatible pattern of symptoms and clinical findings. Inflammatory lesions and granulomata may undergo spontaneous resolution or persist in chronic disease with eventual fibrosis and permanent organ damage. Immunological disease mechanisms are linked to severe derangements of the cytokine network. In systemic resolution or under prednisolone therapy of symptomatic disease pro-inflammatory cytokines are downregulated and histological lesions may completely vanish. Corticosteroid-resistant disease, however, requires treatment with an immunosuppressive regimen consisting of prednisolone and an immunosuppressive agent or anti-tumour necrosis factor (TNF) monoclonal antibodies.

scholarly journals The Health and Economic Burdens of Lymphatic Filariasis Prior to Mass Drug Administration Programs

2019 ◽  
Vol 70 (12) ◽  
pp. 2561-2567 ◽  
Author(s):  
Christopher G Mathew ◽  
Alison A Bettis ◽  
Brian K Chu ◽  
Mike English ◽  
Eric A Ottesen ◽  
...  
Keyword(s):  
Lymphatic Filariasis ◽  
Drug Administration ◽  
Mass Drug Administration ◽  
Economic Burden ◽  
Scale Up ◽  
Public Health Problem ◽  
Clinical Disease ◽  
Productivity Costs ◽  
Symptomatic Disease ◽  
Life Years

Abstract Background The Global Programme to Eliminate Lymphatic Filariasis (GPELF) was launched in 2000 with the goal of eliminating lymphatic filariasis (LF) as a public health problem by 2020. Despite considerable progress, the current prevalence is around 60% of the 2000 figure, with the deadline looming a year away. Consequently, there is a continued need for investment in both the mass drug administration (MDA) and morbidity management programs, and this paper aims to demonstrate that need by estimating the health and economic burdens of LF prior to MDA programs starting in GPELF areas. Methods A previously developed model was used to estimate the numbers of individuals infected and individuals with symptomatic disease, along with the attributable number of disability-adjusted life years (DALYs). The economic burden was calculated by quantifying the costs incurred by the health-care system in managing clinical cases, the patients’ out-of-pocket costs, and their productivity costs. Results Prior to the MDA program, approximately 129 million people were infected with LF, of which 43 million had clinical disease, corresponding to a DALY burden of 5.25 million. The average annual economic burden per chronic case was US $115, the majority of which resulted from productivity costs. The total economic burden of LF was estimated at US $5.8 billion annually. Conclusions These results demonstrate the magnitude of the LF burden and highlight the continued need to support the GPELF. Patients with clinical disease bore the majority of the economic burden, but will not benefit much from the current MDA program, which is aimed at reducing transmission. This assessment further highlights the need to scale up morbidity management programs.

scholarly journals Declining Trends in Childhood TB Notifications and Profile of Notified Patients in the City of Harare, Zimbabwe, from 2009 to 2018

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Phoebe Nzombe ◽  
Srinath Satyanarayana ◽  
Hannock Tweya ◽  
Collins Timire ◽  
Kelvin Charambira ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Scale Up ◽  
Preventive Therapy ◽  
Hiv Positive ◽  
Drug Resistant ◽  
Pulmonary Tb ◽  
Childhood Tb ◽  
Clinical Profiles ◽  
The City

Globally, childhood tuberculosis (TB among those aged <15 years) is a neglected component of national TB programmes in high TB burden countries. Zimbabwe, a country in southern Africa, is a high burden country for TB, TB-HIV, and drug-resistant TB. In this study, we assessed trends in annual childhood TB notifications in Harare (the capital of Zimbabwe) from 2009 to 2018 and the demographic, clinical profiles, and treatment outcomes of childhood TB patients notified from 2015–2017 by reviewing the national TB programme records and reports. Overall, there was a decline in the total number of TB patients (all ages) from 5,943 in 2009 to 2,831 in 2018. However, the number of childhood TB patients had declined exponentially 6-fold from 583 patients (117 per 100,000 children) in 2009 to 107 patients (18 per 100,000 children) in 2018. Of the 615 childhood TB patients notified between 2015 and 2017, 556 (89%) patient records were available. There were 53% males, 61% were aged <5 years, 92% were new TB patients, 85% had pulmonary TB, and 89% were treated for-drug sensitive TB, 3% for drug-resistant TB, and 40% were HIV positive (of whom 59% were on ART). Although 58% had successful treatment outcomes, the treatment outcomes of 40% were unknown (not recorded or not evaluated), indicating severe gaps in TB care. The disproportionate decline in childhood TB notifications could be due to the reduction in the TB burden among HIV positive individuals from the scale up of antiretroviral therapy and isoniazid preventive therapy. However, the country is experiencing economic challenges which could also contribute to the disproportionate decline in childhood TB notification and gaps in quality of care. There is an urgent need to understand the reasons for the declining trends and the gaps in care.

Electric Field and Spinning Performance in Needleless Electrospinning

2014 ◽  
Vol 1048 ◽  
pp. 26-30 ◽  
Author(s):  
Xin Wang ◽  
Yuan Zhao ◽  
Hao Wang ◽  
Guang Ming Cai
Keyword(s):  
Experimental Investigation ◽  
Electric Field ◽  
Scale Up ◽  
Key Factors ◽  
Needleless Electrospinning ◽  
Modeling Analysis ◽  
Experimental Parameters ◽  
Spun Fiber ◽  
The Relationship

Different spinnerets can be used to generate needleless electrospinning with the potential to scale up the production of nanofibers. However, the electrospinning performance, normally refers to the quality of the as-spun fiber and the production rate, is dramatically different from different spinnerets. This study focuses on the electric field of different spinnerets under the same experimental parameters so as to understand the key factors that affect the electrospinning performance of upward needleless electrospinning. Modeling analysis suggested that the electric field could be further concentrated by optimizing the geometry of spinneret. Experimental investigation on needleless electrospinning from different spinnerets proved that the electrospinning performance was improved greatly with the optimization of the electric field of spinneret. Understanding of the relationship between electric field and spinning performance would benefit the design and development of needleless electrospinning.

scholarly journals Evaluation of routine Isoniazid Preventive Therapy among People Living with HIV for reducing Tuberculosis; a retrospective cohort study in Tanzania (2012-2016)

2020 ◽  
Author(s):  
Werner Maokola ◽  
Bernard Ngowi ◽  
Lovett Lawson ◽  
Michael Mahande ◽  
Jim Todd ◽  
...  
Keyword(s):  
Cohort Study ◽  
Functional Status ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Scale Up ◽  
Preventive Therapy ◽  
Isoniazid Preventive Therapy ◽  
Hiv Care ◽  
People Living With Hiv ◽  
Living With Hiv

Abstract Background: Isoniazid Preventive Therapy (IPT) reduced Tuberculosis (TB) among People Living with HIV (PLHIV). Despite this, uptake has been reported to be sub-optimal . We describe characteristics of visits in which PLHIV were screened TB negative (as the main source for IPT initiation), determine characteristics of visits in which PLHIV were initiated on IPT as well as determined factors associated with IPT initiation to inform program scale up and improve quality of service.Methods : Retrospective cohort study design which involved PLHIV enrolled into care and treatment clinics in Dar es Salaam, Iringa and Njombe regions from January 2012 to December 2016. The study aimed at evaluating implementation of IPT among PLHIV. Data analysis was conducted using STATA.Results: A total 173,746 were enrolled in CTC in the 3 regions during the period of follow up and made a total of 2,638,876 visits. Of the eligible visits, only 24,429 (1.26%) were initiated on IPT. In multivariate analysis, 50 years and more (aOR=3.42, 95% CI: 3.07-3.82, P<0.01), bedridden functional status individuals with bedridden functional status (aOR=4.56, 95% CI:2.45-8.49, P<0.01) and WHO clinical stage II had higher odds of IPT initiation (aOR=1.18, 95% CI:1.13-1.23, P<0.01). Furthermore, enrolment in 2016 (aOR=2.92, 95% CI:2.79-3.06, P<0.01), enrolment in hospitals (aOR=1.84, 95% CI:1.77-1.90, P<0.01), enrolment in public health facilities (aOR=1.82, 95% CI: 1.75-1.90, P<0.01) and been on care for more than one year (aOR=6.77, 95% CI: 5.25-8.73, P<0.000) were also more likely to be initiated on IPT. Enrollment in Iringa (aOR=0.44, 95% CI: 0.41-0.47, P<0.01) and good adherence (aOR=0.56, 95% CI 0.47-0.67, P<0.01) was less likely to be initiated on IPT.Conclusions: Our study documented low IPT initiation proportion among those who were enrolled in HIV care and eligible in the 3 regions during the study period. Variations in IPT initiation among regions signals different dynamics affecting IPT uptake in different regions and hence customized approaches in quality improvement. Implementation research is needed to understand health system as well as cultural barriers in the uptake of IPT intervention.

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