Innovative approaches to end TB in Pakistan: a review of TB REACH projects from 2010 to 2020

BACKGROUND: TB REACH is a grant-making initiative launched by the Stop TB Partnership in January 2010 to support innovative approaches and technologies to find and treat people with active TB disease, drug-resistant TB, or TB infection. Since then, TB REACH has launched eight Waves of funding to pilot untested, but promising technologies, tools, and approaches. The objective of this paper was to review the grants implemented in Pakistan in the decade since TB REACH’s inception and to summarize the approaches used, document the results, and assess the impact of these projects on local and international policy. METHODS: We searched the TB REACH’s Grant Management System (GMS), which is a database for information on all grants awarded through the initiative, for recipient organisations in Pakistan from 2010 until June 2020. Data was abstracted for the following topic areas: type of grant, focus of work, case finding strategies, risk groups screened and impact on case finding. RESULTS: Through eight waves of funding, TB REACH has supported 28 grants for 21 different interventions in Pakistan worth a total of USD 13.4 million. Overall, 19 of these projects aimed to improve detection, linkage to treatment and reporting of TB and two were product innovation grants for developing resources and materials to aide TB service delivery. CONCLUSION: TB REACH support has facilitated the introduction of new technologies, establishment of innovative processes in both public and private sector and approaches for addressing TB in key populations. The TB response in Pakistan and globally will continue to require innovation and disruption of ‘business as usual' approaches if we are to End TB

Assessment of Specific Methanogenic Activity from Cow Dung

The specific methanogenic activity (SMA) is a test to measure the producing potential of an anaerobic bacteria until it’s allowing a relevant organic loading rates to be applied for a selected substrate. Commonly, acetate is used as substrate for the SMA test. Anaerobic bacteria were mostly taken from an anaerobic digester and cow dung was also implemented as a source of an anaerobic bacteria. However, the results of SMA of cow dung was less reported. Therefore, this study is initiated to determine the potential of methane production from the cow dung by using the SMA test. Prior the SMA test, the cow dung was characterized for solids where the results showed that the cow dung is having 12.00 g L-1 for total solid and 10.50 g L-1 for volatile solid. The SMA test was conducted at mesophilic condition by using an automatic methane potential system test (AMPTS II) and the SMA of the cow dung was found as 0.04 in unit g COD-CH4 g-1VS-1d-1. The significance of this research is to determine the anaerobic bacteria potential of cow dung for use in the anaerobic digestion process, which offers numerous advantages for manufacturing, particularly in industrial applications such as methane production (fuel)

Assessment of Specific Methanogenic Activity from Cow Dung

The specific methanogenic activity (SMA) is a test to measure the producing potential of an anaerobic bacteria until it’s allowing a relevant organic loading rates to be applied for a selected substrate. Commonly, acetate is used as substrate for the SMA test. Anaerobic bacteria were mostly taken from an anaerobic digester and cow dung was also implemented as a source of an anaerobic bacteria. However, the results of SMA of cow dung was less reported. Therefore, this study is initiated to determine the potential of methane production from the cow dung by using the SMA test. Prior the SMA test, the cow dung was characterized for solids where the results showed that the cow dung is having 12.00 g L-1 for total solid and 10.50 g L-1 for volatile solid. The SMA test was conducted at mesophilic condition by using an automatic methane potential system test (AMPTS II) and the SMA of the cow dung was found as 0.04 in unit g COD-CH4 g-1VS-1d-1. The significance of this research is to determine the anaerobic bacteria potential of cow dung for use in the anaerobic digestion process, which offers numerous advantages for manufacturing, particularly in industrial applications such as methane production (fuel)

Video-based abnormal behaviour detection in smart surveillance systems

Due to increasing demand for security, the instant detection of abnormal behavior in video surveillance systems becomes a critical issue in a smart surveillance system. The currently applied semiautomatic systems mainly depend on human intervention to detect the abnormal activities and suspicious human behaviours from video context. Due to these limitations, it has become an urgent need for intelligence systems to avoid the very slow response and reduce the human observer and interventions. In this paper, a method that can trace abnormalities of human behaviour from video is presented. Techniques related to bounding box measurements and descriptions for behaviour representation were used. Moreover, the performance evaluation of the proposed method is presented

Computer vision based driver assistance drowsiness detection

Nowadays, drowsiness is a serious cause of traffic accidents, a problem of major concern to society. Driver fatigue or sleepiness decreases the driver’s reaction time, reduces attention, and affects the quality of decision making which impairs the driving experience. Therefore, in this paper, a drowsiness detection system is designed based on computer vision, using a cascade of classifiers based on Haar-like features. The system is able to detect the face and eyes of the driver and determine the eyes closure or opening, which concludes the drowsiness of the driver. The paper presents the five primary steps involves which are: video acquirement, frame separation, face detection, eyes detection and drowsiness detection

Association of diabetes, smoking, and alcohol use with subclinical-to-symptomatic spectrum of tuberculosis in 16 countries: an individual participant data meta-analysis of national tuberculosis prevalence surveys

Summary Background Non-communicable diseases (NCDs) and NCD risk factors, such as smoking, increase the risk for tuberculosis (TB). Data are scarce on the risk of prevalent TB associated with these factors in the context of population-wide systematic screening and on the association between NCDs and NCD risk factors with different manifestations of TB, where ∼50% being asymptomatic but bacteriologically positive (subclinical). We did an individual participant data (IPD) meta-analysis of national and sub-national TB prevalence surveys to synthesise the evidence on the risk of symptomatic and subclinical TB in people with NCDs or risk factors, which could help countries to plan screening activities. Methods In this systematic review and IPD meta-analysis, we identified eligible prevalence surveys in low-income and middle-income countries that reported at least one NCD (e.g., diabetes) or NCD risk factor (e.g., smoking, alcohol use) through the archive maintained by the World Health Organization and by searching in Medline and Embase from January 1, 2000 to August 10, 2021. The search was updated on March 23, 2023. We performed a one-stage meta-analysis using multivariable multinomial models. We estimated the proportion of and the odds ratio for subclinical and symptomatic TB compared to people without TB for current smoking, alcohol use, and self-reported diabetes, adjusted for age and gender. Subclinical TB was defined as microbiologically confirmed TB without symptoms of current cough, fever, night sweats, or weight loss and symptomatic TB with at least one of these symptoms. We assessed heterogeneity using forest plots and I2 statistic. Missing variables were imputed through multi-level multiple imputation. This study is registered with PROSPERO (CRD42021272679). Findings We obtained IPD from 16 national surveys out of 21 national and five sub-national surveys identified (five in Asia and 11 in Africa, N = 740,815). Across surveys, 15.1%–56.7% of TB were subclinical (median: 38.1%). In the multivariable model, current smoking was associated with both subclinical (OR 1.67, 95% CI 1.27–2.40) and symptomatic TB (OR 1.49, 95% CI 1.34–1.66). Self-reported diabetes was associated with symptomatic TB (OR 1.67, 95% CI 1.17–2.40) but not with subclinical TB (OR 0.92, 95% CI 0.55–1.55). For alcohol drinking ≥ twice per week vs no alcohol drinking, the estimates were imprecise (OR 1.59, 95% CI 0.70–3.62) for subclinical TB and OR 1.43, 95% CI 0.59–3.46 for symptomatic TB). For the association between current smoking and symptomatic TB, I2 was high (76.5% (95% CI 62.0–85.4), while the direction of the point estimates was consistent except for three surveys with wide CIs. Interpretation Our findings suggest that current smokers are more likely to have both symptomatic and subclinical TB. These individuals can, therefore, be prioritised for intensified screening, such as the use of chest X-ray in the context of community-based screening. People with self-reported diabetes are also more likely to have symptomatic TB, but the association is unclear for subclinical TB

Association of diabetes, smoking, and alcohol use with subclinical-to-symptomatic spectrum of tuberculosis in 16 countries: an individual participant data meta-analysis of national tuberculosis prevalence surveys

Background Non-communicable diseases (NCDs) and NCD risk factors, such as smoking, increase the risk for tuberculosis (TB). Data are scarce on the risk of prevalent TB associated with these factors in the context of population-wide systematic screening and on the association between NCDs and NCD risk factors with different manifestations of TB, where ∼50% being asymptomatic but bacteriologically positive (subclinical). We did an individual participant data (IPD) meta-analysis of national and sub-national TB prevalence surveys to synthesise the evidence on the risk of symptomatic and subclinical TB in people with NCDs or risk factors, which could help countries to plan screening activities. Methods In this systematic review and IPD meta-analysis, we identified eligible prevalence surveys in low-income and middle-income countries that reported at least one NCD (e.g., diabetes) or NCD risk factor (e.g., smoking, alcohol use) through the archive maintained by the World Health Organization and by searching in Medline and Embase from January 1, 2000 to August 10, 2021. The search was updated on March 23, 2023. We performed a one-stage meta-analysis using multivariable multinomial models. We estimated the proportion of and the odds ratio for subclinical and symptomatic TB compared to people without TB for current smoking, alcohol use, and self-reported diabetes, adjusted for age and gender. Subclinical TB was defined as microbiologically confirmed TB without symptoms of current cough, fever, night sweats, or weight loss and symptomatic TB with at least one of these symptoms. We assessed heterogeneity using forest plots and I2 statistic. Missing variables were imputed through multi-level multiple imputation. This study is registered with PROSPERO (CRD42021272679). Findings We obtained IPD from 16 national surveys out of 21 national and five sub-national surveys identified (five in Asia and 11 in Africa, N = 740,815). Across surveys, 15.1%–56.7% of TB were subclinical (median: 38.1%). In the multivariable model, current smoking was associated with both subclinical (OR 1.67, 95% CI 1.27–2.40) and symptomatic TB (OR 1.49, 95% CI 1.34–1.66). Self-reported diabetes was associated with symptomatic TB (OR 1.67, 95% CI 1.17–2.40) but not with subclinical TB (OR 0.92, 95% CI 0.55–1.55). For alcohol drinking ≥ twice per week vs no alcohol drinking, the estimates were imprecise (OR 1.59, 95% CI 0.70–3.62) for subclinical TB and OR 1.43, 95% CI 0.59–3.46 for symptomatic TB). For the association between current smoking and symptomatic TB, I2 was high (76.5% (95% CI 62.0–85.4), while the direction of the point estimates was consistent except for three surveys with wide CIs. Interpretation Our findings suggest that current smokers are more likely to have both symptomatic and subclinical TB. These individuals can, therefore, be prioritised for intensified screening, such as the use of chest X-ray in the context of community-based screening. People with self-reported diabetes are also more likely to have symptomatic TB, but the association is unclear for subclinical TB

Tobacco smoking clusters in households affected by tuberculosis in an individual participant data meta-analysis of national tuberculosis prevalence surveys: Time for household-wide interventions?

Tuberculosis (TB) and non-communicable diseases (NCD) share predisposing risk factors. TB-associated NCD might cluster within households affected with TB requiring shared prevention and care strategies. We conducted an individual participant data meta-analysis of national TB prevalence surveys to determine whether NCD cluster in members of households with TB. We identified eligible surveys that reported at least one NCD or NCD risk factor through the archive maintained by the World Health Organization and searching in Medline and Embase from 1 January 2000 to 10 August 2021, which was updated on 23 March 2023. We compared the prevalence of NCD and their risk factors between people who do not have TB living in households with at least one person with TB (members of households with TB), and members of households without TB. We included 16 surveys (n = 740,815) from Asia and Africa. In a multivariable model adjusted for age and gender, the odds of smoking was higher among members of households with TB (adjusted odds ratio (aOR) 1.23; 95% CI: 1.11–1.38), compared with members of households without TB. The analysis did not find a significant difference in the prevalence of alcohol drinking, diabetes, hypertension, or BMI between members of households with and without TB. Studies evaluating household-wide interventions for smoking to reduce its dual impact on TB and NCD may be warranted. Systematically screening for NCD using objective diagnostic methods is needed to understand the actual burden of NCD and inform comprehensive interventions

Treating children and adolescents with hepatitis C: policies and practices

The development of Direct Acting Antivirals (DAAs) has dramatically transformed the treatment of hepatitis C (HCV) infection and spurred the global movement to eliminate viral hepatitis by 2030. However, current levels of treatment coverage are insufficient to meet elimination goals. This thesis aims to investigate the treatment of children infected with hepatitis C, and to examine the policies and practices for their diagnosis, treatment, and care to inform the roll out of DAAs for paediatric treatment. This PhD comprises five studies: (i) a systematic review of DAA safety and effectiveness; (ii) a global review of national hepatitis policies; (iii) a global survey of DAA utilisation and availability, healthcare workers’ (HCWs) preferences and programmatic barriers to delivering paediatric HCV treatments; (iv) a national survey on policy-practice gaps and DAA uptake in Russia; and (v) analysis of DAA treatment outcomes and DAA uptake for HCV/human immunodeficiency virus (HIV) co-infected children and adolescents using real-world data from European HIV cohorts. Results from these studies show that although DAAs are safe and effective for treatment of HCV mono-infected and HCV/HIV co-infected children and adolescents, national HCV policies in most countries do not include recommendations on paediatric testing or treatment. Although HCWs are strongly in favour of treating children, they face barriers in delivering treatment which include absence of national guidelines supporting treatment, limited availability of DAAs, high cost, and lack of paediatric formulations. To achieve the ambitious elimination targets, it is essential to improve access to treatment for all, including the 3.26 million children and adolescents living with HCV. The barriers to service delivery identified here will help policy makers and implementers design interventions to scale up DAAs for children. Results will also contribute to development of treatment guidelines, especially filling the gap in evidence on DAA use for HCV/HIV co-infected children