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Background: Despite a high asthma burden in Kenya, insights into asthma management practices, including prescription of short-acting β2-agonists (SABAs), are lacking. Therefore, this study describes patient demographics, disease characteristics, and asthma treatment patterns in the Kenyan cohort of the SABA use IN Asthma (SABINA) III study. Methods: Patients with asthma (aged ≥ 12 years) with medical records containing data for ≥ 12 months prior to the study visit from 19 sites across Kenya were included in this cross-sectional study and classified by investigator-defined asthma severity (guided by the 2017 Global Initiative for Asthma [GINA] recommendations) and practice type (primary/specialist care). Data on severe exacerbation history, prescribed asthma treatments, and over-the-counter (OTC) SABA purchases in the 12 months before the study visit and asthma symptom control at the time of the study visit were collated using electronic case report forms. All analyses were descriptive in nature. Results: Overall, 405 patients were analyzed (mean age, 44.4 years; female, 68.9%), of whom 54.8% and 45.2% were enrolled by primary care clinicians and specialists, respectively. Most patients were classified with mild asthma (76.0%, GINA treatment steps 1−2) and were overweight or obese (57.0%). Only 19.5% of patients reported full healthcare reimbursement, with 59% receiving no healthcare reimbursement. The mean asthma duration of patients was 13.5 years. Asthma was partly controlled/uncontrolled in 78.0% of patients, with 61.5% experiencing ≥ 1 severe exacerbation in the preceding 12 months. Crucially, 71.9% of patients were prescribed ≥ 3 SABA canisters, defined as over-prescription; 34.8% were prescribed ≥ 10 SABA canisters. Additionally, 38.8% of patients purchased SABA OTC, of whom 66.2% purchased ≥ 3 SABA canisters. Among patients with both SABA purchases and prescriptions, 95.5% and 57.1% had prescriptions for ≥ 3 and ≥ 10 SABA canisters, respectively. Inhaled corticosteroids (ICS), ICS with a long-acting β2-agonist fixed-dose combination, and oral corticosteroid bursts were prescribed to 58.8%, 24.7%, and 22.7% of patients, respectively. Conclusions: SABA over-prescription occurred in almost three-quarters of patients, with over one-third of patients purchasing SABA OTC. Therefore, SABA over-prescription is a major public health concern in Kenya, underscoring an urgent need to align clinical practices with latest evidence-based recommendations. [ABSTRACT FROM AUTHOR]

• Tuberculosis remains a major global public health threat. • The End TB Strategy and United Nations targets for TB are all off track. • The COVID-19 pandemic aggravated an already sub-optimal global TB response. • Achieving TB targets will require optimized use of existing tools and new tools. • Social determinants and financing of TB need to be addressed. To review the data presented in the 2021 WHO global TB report and discuss the current constraints in the global response. The WHO global TB reports, consolidate TB data from countries and provide up to date assessment of the global TB epidemic. We reviewed the data presented in the 2021 report. We noted that the 2021 WHO global TB report presents a rather grim picture on the trajectory of the global epidemic of TB including a stagnation in the annual decline in TB incidence, a decline in TB notifications and an increase in estimated TB deaths. All the targets set at the 2018 United Nations High Level Meeting on TB were off track. The sub-optimal global performance on achieving TB control targets in 2020 is attributed to the on-going COVID-19 pandemic, however, TB programs were already off track well before the onset of the pandemic, suggesting that the pandemic amplified an already fragile global TB response. We emphasize that ending the global TB epidemic will require bold leadership, optimization of existing interventions, widespread coverage, addressing social determinants of TB and importantly mobilization of adequate funding required for TB care and prevention. [ABSTRACT FROM AUTHOR]

• In 2020, COVID-19 dislodged TB as the top infectious disease cause of mortality globally. • Globally, an estimated 10.0 million people developed active TB disease in 2019, with 1.4 million TB deaths. • The WHO regions of South-East Asia, Africa, and the Western Pacific had the most cases of TB. • Progress in achieving the United Nations (UN) General Assembly End TB targets remains slow. • TB services need to be ramped up, and underlying drivers of TB need be addressed. The October 2020 Global TB report reviews TB control strategies and United Nations (UN) targets set in the political declaration at the September 2018 UN General Assembly high-level meeting on TB held in New York. Progress in TB care and prevention has been very slow. In 2019, TB remained the most common cause of death from a single infectious pathogen. Globally, an estimated 10.0 million people developed TB disease in 2019, and there were an estimated 1.2 million TB deaths among HIV-negative people and an additional 208, 000 deaths among people living with HIV. Adults accounted for 88% and children for 12% of people with TB. The WHO regions of South-East Asia (44%), Africa (25%), and the Western Pacific (18%) had the most people with TB. Eight countries accounted for two thirds of the global total: India (26%), Indonesia (8.5%), China (8.4%), the Philippines (6.0%), Pakistan (5.7%), Nigeria (4.4%), Bangladesh (3.6%) and South Africa (3.6%). Only 30% of the 3.5 million five-year target for children treated for TB was met. Major advances have been development of new all oral regimens for MDRTB and new regimens for preventive therapy. In 2020, the COVID-19 pandemic dislodged TB from the top infectious disease cause of mortality globally. Notably, global TB control efforts were not on track even before the advent of the COVID-19 pandemic. Many challenges remain to improve sub-optimal TB treatment and prevention services. Tuberculosis screening and diagnostic test services need to be ramped up. The major drivers of TB remain undernutrition, poverty, diabetes, tobacco smoking, and household air pollution and these need be addressed to achieve the WHO 2035 TB care and prevention targets. National programs need to include interventions for post-tuberculosis holistic wellbeing. From first detection of COVID-19 global coordination and political will with huge financial investments have led to the development of effective vaccines against SARS-CoV2 infection. The world now needs to similarly focus on development of new vaccines for TB utilizing new technological methods. [ABSTRACT FROM AUTHOR]

• The key measures needed to end TB by 2030 are: • Investment in implementation research leading to scale-up of active case finding. • More engagement with multi-sectoral approaches to tackle social determinants of TB. • Better design and alignment of health services with patient needs and preferences. Tuberculosis (TB) remains a major public health threat. In 2018, an estimated 10 million people fell ill with TB and 1.5 million died of the disease. The End TB Strategy envisages an end to TB as a public health threat and has set ambitious targets to reduce TB incidence and mortality by 90% and 95%, respectively, by 2035 compared with 2015. In this paper we describe the progress that is being made towards the achievement of these targets and highlight the challenges that are hampering this progress. The development and deployment of new tools will certainly accelerate progress towards ending TB. We believe that the end of TB is realizable if there are sustained efforts to actively find TB cases, a more robust multi-sectoral approach to tackle social determinants of TB, and improved person-centred health services. [ABSTRACT FROM AUTHOR]

An estimated 1.8 billion people worldwide have a latent tuberculosis infection (LTBI), with wide variations in LTBI rates across countries. LTBI can be due to infection with either drug-sensitive or drug-resistant Mycobacterium tuberculosis (Mtb) strains. Accurate data on the prevalence of LTBI due to multidrug-resistant (MDR) Mtb strains are unavailable, since the strains cannot be isolated for resistance testing. There are no 'gold standard' tests for accurately diagnosing LTBI. Only three tests are currently available and approved by the World Health Organization (WHO) for the diagnosis of LTBI: the now outdated tuberculin skin test (TST), developed a century year ago, and the two interferon-gamma release assays (IGRAs) developed and rolled out over the past decade, the QuantiFERON (Qiagen, Germany) and T-SPOT.TB (Oxford Immunotec, United Kingdom) tests. These latter tests are not ideal due to issues of sensitivity, specificity, inability to distinguish infection with MDR-Mtb strains, and high costs. Achieving the WHO End TB Strategy target of an 80% reduction in global TB incidence by 2030 will require a major reduction in the number of persons with LTBI progressing to active TB disease. Critical to this will be the development of new diagnostic tests that are better than currently available LTBI tests at predicting who is at risk of progression to active TB disease. The diagnostic product development portfolio for LTBI appears to have reached the end of the road. Every attempt to make optimal use of currently available IGRAs using WHO LTBI guidelines for LTBI testing and treatment must be made to achieve WHO End TB strategy targets. [ABSTRACT FROM AUTHOR]

Lung health in Africa is of great public health concern. To exchange knowledge, communicate the latest scientific advances in lung health, build the capacity of young researchers, and provide a platform for networking of lung health stakeholders in Africa, the Pan African Thoracic Society (PATS), in partnership with the Respiratory Society of Kenya organized and held the 3rd Biennial PATS congress, from June 7–10, 2023 in Mombasa, Kenya. There were a total of 30 conference sessions, which included six skills building workshops, two research dissemination workshops, six plenary sessions, and five each of pediatric, adult, and thoracic surgery symposia. A total of 60 abstracts were presented, including 27 oral abstracts and 33 posters. A wide range of issues for lung health in Africa emerged. These include the emerging role of the environment, especially climate change and global warming, on lung health, the threat posed by the use of tobacco and other nicotine products in Africa, the high burden of lung infections, insecurity of medical oxygen supply systems, and high burden of chronic respiratory disease. In this paper, we summarize the proceedings of this conference and draw lessons that can be used to advance lung health in the African continent. [ABSTRACT FROM AUTHOR]

The treatment of tuberculosis is based on combinations of drugs that directly target Mycobacterium tuberculosis. A new global initiative is now focusing on a complementary approach of developing adjunct host-directed therapies. [ABSTRACT FROM AUTHOR]

Chronic pulmonary aspergillosis (CPA) is a recognized complication of pulmonary tuberculosis (TB). In 2015, the World Health Organization reported 2.2 million new cases of nonbacteriologically confirmed pulmonary TB; some of these patients probably had undiagnosed CPA. In October 2016, the Global Action Fund for Fungal Infections convened an international expert panel to develop a case definition of CPA for resource-constrained settings. This panel defined CPA as illness for >3 months and all of the following: 1) weight loss, persistent cough, and/or hemoptysis; 2) chest images showing progressive cavitary infiltrates and/or a fungal ball and/or pericavitary fibrosis or infiltrates or pleural thickening; and 3) a positive Aspergillus IgG assay result or other evidence of Aspergillus infection. The proposed definition will facilitate advancements in research, practice, and policy in lower- and middle-income countries as well as in resource-constrained settings. [ABSTRACT FROM AUTHOR]

• The COVID-19 pandemic has impacted negatively on Africa's health systems • COVID-19 disruptions on TB and other health services need to be urgently addressed • Strengthening health systems will require visionary political leadership • Innovations in service delivery and technological adaptations remain critical • Beyond modeling, actual country-level data is required to guide decision making The unprecedented and ongoing COVID-19 pandemic has exposed weaknesses in African countries' health systems. The impact of shifted focus on COVID-19 for the past 2 years on routine health services, especially those for the epidemics of Tuberculosis, HIV/AIDS and Malaria, have been dramatic in both quantity and quality. In this article, we reflect on the COVID-19 related disruptions on the Tuberculosis, HIV/AIDS and Malaria routine health services across Africa. The COVID-19 pandemic resulted in disruptions of routine health services and diversion of already limited available resources in sub-Saharan Africa. As a result, disease programs like TB, malaria and HIV have recorded gaps in prevention and treatment with the prospects of reversing gains made towards meeting global targets. The extent of the disruption is yet to be fully quantified at country level as most data available is from modelling estimates before and during the pandemic. Accurate country-level data is required to convince donors and governments to invest more into revamping these health services and help prepare for managing future pandemics without disruption of routine services. Increasing government expenditure on health is a critical part of Africa's economic policy. Strengthening health systems at various levels to overcome the negative impacts of COVID-19, and preparing for future epidemics will require strong visionary political leadership. Innovations in service delivery and technological adaptations are required as countries aim to limit disruptions to routine services. [ABSTRACT FROM AUTHOR]

• MDR-TB is difficult to manage; updated clinical guidance of new drug use is needed • No recent systematic review/meta-analysis on delamanid (DLM) is available • In observational studies including DLM (591 patients) the success rate was 80.9% • In experimental studies including DLM (391 patients) the success rate was 72.5% • Few adverse events attributable to DLM were reported Multidrug-resistant tuberculosis (MDR-TB) is a life-threatening condition needing long poly-chemotherapy regimens. As no systematic reviews/meta-analysis is available to comprehensively evaluate the role of delamanid (DLM), we evaluated its effectiveness and safety. We reviewed the relevant scientific literature published up to January 20, 2022. The pooled success treatment rate with 95% confidence intervals (CI) was assessed using a random-effect model. We assessed studies for quality and bias, and considered P<0.05 to be statistically significant. After reviewing 626 records, we identified 25 studies that met the inclusion criteria, 22 observational and 3 experimental, with 1276 and 411 patients, respectively. In observational studies the overall pooled treatment success rate of DLM-containing regimens was 80.9% (95% CI 72.6-87.2) with no evidence of publication bias (Begg's test; P >0.05). The overall pooled treatment success rate in DLM and bedaquiline-containing regimens was 75.2% (95% CI 68.1-81.1) with no evidence of publication bias (Begg's test; P >0.05). In experimental studies the pooled treatment success rate of DLM-containing regimens was 72.5 (95% CI 44.2-89.8, P <0.001, I2: 95.1%) with no evidence of publication bias (Begg's test; P >0.05). In MDR-TB patients receiving DLM, culture conversion and treatment success rates were high despite extensive resistance with limited adverse events. [ABSTRACT FROM AUTHOR]

Clinical presentation of asthma is variable, and its diagnosis can be a major challenge in routine health-care practice, especially in low-and-middle-income countries. The aim of asthma management is to achieve optimal asthma control and to reduce the risk of asthma exacerbations and mortality. In the Middle East and in Africa (MEA), several patient- and physician-related factors lead to misdiagnosis and suboptimal management of asthma. A panel of experts comprising of specialists as well as general health-care professionals met to identify challenges and provide recommendations for the management of asthma in MEA. The major challenges identified for diagnosis of asthma were lack of adequate knowledge about the disease, lack of specialized diagnostic facilities, limited access to spirometry, and social stigma associated with asthma. The prime challenges for management of asthma in MEA were identified as overreliance on short-acting β-agonists (SABAs), underprescription of inhaled corticosteroids (ICS), nonadherence to prescribed medications, and inadequate insurance coverage for its treatment. The experts endorsed adapting the Global Initiative for Asthma guidelines at country and regional levels for effective management of asthma and to alleviate the overuse of SABAs as reliever medications. Stringent control over SABA use, discouraging over-the-counter availability of SABA, and using as-needed low-dose ICS and formoterol as rescue medications in mild cases were suggested to reduce the overreliance on SABAs. Encouraging SABA alone-free clinical practice in both outpatient and emergency department settings is also imperative. We present the recommendations for the management of asthma along with proposed regional adaptations of international guidelines for MEA. [ABSTRACT FROM AUTHOR]

Vaccines are considered as a therapeutic area for children; the scientific community focuses mainly on managing chronic disease when it comes to adults. There currently is an increase in the burden of vaccine preventable illnesses in adults. Adult vaccination has been shown to dramatically increase the health and quality of life of older populations. Therefore, adult vaccinations need to be approached as a public health issue, similar to smoking cessation programs, for example. According to the Kenya Non-Communicable Diseases and injuries poverty commission report, 2018. Kenya has a high percentage of disability adjusted life years (DALYs) from communicable diseases at 63%, while non-communicable diseases (NCDs) contribute 30% of the DALYs. Specific to pneumococcal pneumonia (PP) in adults, the Global burden of disease (GBD) study in 2016 found that 2,377,697 people of all ages died from lower respiratory tract infections (LRTI) in 2016. Of these, more people died from Streptococcus pneumonia(SP) than from all other studied respiratory pathogens combined. While the incidence of LRTIs in children under five years old was reducing, partly as a result of well-established vaccination programs in children, the incidence, morbidity and mortality of PP was increasing in older populations. The expert recommendations included the following; i) all individuals 65 years of age and above, and individuals with a predisposing comorbidity regardless of age, should receive the pneumococcal vaccine; ii) several systemic modules can be emulated from the successful childhood vaccines programs onto an adult vaccine program; iii) formulation of an effective vaccine program will require collaboration from the public, the government, healthcare providers, and the media, to create awareness; iv) stakeholders who need to be involved in vaccine policy development and implementation include medical professional associations, nurses, pharmacists, clinical officers, payers (private and public insurances), government, medical learning institutions and faith-based medical organizations. [ABSTRACT FROM AUTHOR]

• BCG-derived peptide develops high reactivity to SARS-CoV-2. • BCG vaccine increases nonspecific immune responses through adjuvant effect. • BCG effect could be harnessed as cross protection against severe forms of COVID-19. • Clinical trials for the effectiveness of BCG vaccination against COVID-19 are needed. After a century of controversies on its usefulness in protection against TB, underlying mechanisms of action, and benefits in various groups and geographical areas, the BCG vaccine is yet again a focus of global attention- this time due to the global COVID-19 pandemic caused by the novel severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). Recent studies have shown that human CD4+ and CD8+ T-cells primed with a BCG-derived peptide developed high reactivity to its corresponding SARS-CoV-2-derived peptide. Furthermore, BCG vaccine has been shown to substantially increase interferon-gamma (IFN-g) production and its effects on CD4+ T-cells and these non-specific immune responses through adjuvant effect could be harnessed as cross protection against severe forms of COVID-19.The completion of ongoing BGG trials is important as they may shed light on the mechanisms underlying BCG-mediated immunity and could lead to improved efficacy, increased tolerance of treatment, and identification of other ways of combining BCG with other immunotherapies. [ABSTRACT FROM AUTHOR]

• Globally, Zoonotic TB remains a poorly monitored and an important unaddressed burden. • Zoonotic TB primarily from consumption M. bovis contaminated unpasteurized dairy products. • Novel zoonotic TB strains (e.g. M. orygis), warrants more attention and intervention. • Early detection and control of M. bovis in cattle remains the mainstay of reducing zoonotic TB risk. • Reverse zoonosis to animals of treatment resistant TB strains is a threat to eliminating TB. Despite slow reductions in the annual burden of active human tuberculosis (TB) cases, zoonotic TB (zTB) remains a poorly monitored and an important unaddressed global problem. There is a higher incidence in some regions and countries, especially where close association exists between growing numbers of cattle (the major source of Mycobacterium bovis) and people, many suffering from poverty, and where dairy products are consumed unpasteurised. More attention needs to be focused on possible increased zTB incidence resulting from growth in dairy production globally and increased demand in low income countries in particular. Evidence of new zoonotic mycobacterial strains in South Asia and Africa (e.g. M. orygis), warrants urgent assessment of prevalence, potential drivers and risk in order to develop appropriate interventions. Control of M. bovis infection in cattle through detect and cull policies remain the mainstay of reducing zTB risk, whilst in certain circumstances animal vaccination is proving beneficial. New point of care diagnostics will help to detect animal infections and human cases. Given the high burden of human tuberculosis (caused by M. tuberculosis) in endemic areas, animals are affected by reverse zoonosis, including multi-drug resistant strains. This, may create drug resistant reservoirs of infection in animals. Like COVID-19, zTB is evolving in an ever-changing global landscape. [ABSTRACT FROM AUTHOR]

The article discusses issues related to the planned control and elimination of tuberculosis from 2010 to 2050. The global control of tuberculosis faces several challenges, including the emergence of roughly 9.4 million new cases in 2008, as well as multidrug-resistant tuberculosis. An overview of the Stop TB Strategy is presented. The article also enumerates possible strategies to reduce costs for patients with tuberculosis and their families and emphasizes the need to intensify research on new medical technologies for prevention, diagnosis, and treatment.

Coronavirus disease has disrupted tuberculosis services globally. Data from 33 centers in 16 countries on 5 continents showed that attendance at tuberculosis centers was lower during the first 4 months of the pandemic in 2020 than for the same period in 2019. Resources are needed to ensure tuberculosis care continuity during the pandemic. [ABSTRACT FROM AUTHOR]

• Updated clinical guidance on MDR-TB is needed. • Several new MDR-TB diagnostics have been recently approved by WHO to complement existing tools. • To design a regimen, 4–5 active drugs are needed with a treatment duration up to 24 months. • Post-treatment sequelae might require pulmonary rehabilitation. • LTBI management and infection control are core elements of the MDR-TB public health approach. The continuous flow of new research articles on MDR-TB diagnosis, treatment, prevention and rehabilitation requires frequent update of existing guidelines. This review is aimed at providing clinicians and public health staff with an updated and easy-to-consult document arising from consensus of Global Tuberculosis Network (GTN) experts. The core published documents and guidelines have been reviewed, including the recently published MDR-TB WHO rapid advice and ATS/CDC/ERS/IDSA guidelines. After a rapid review of epidemiology and risk factors, the clinical priorities on MDR-TB diagnosis (including whole genome sequencing and drug-susceptibility testing interpretations) and treatment (treatment design and management, TB in children) are discussed. Furthermore, the review comprehensively describes the latest information on contact tracing and LTBI management in MDR-TB contacts, while providing guidance on post-treatment functional evaluation and rehabilitation of TB sequelae, infection control and other public health priorities. [ABSTRACT FROM AUTHOR]

Chronic pulmonary aspergillosis (CPA) is a recognized complication of pulmonary tuberculosis (TB). In 2015, the World Health Organization reported 2.2 million new cases of nonbacteriologically confirmed pulmonary TB; some of these patients probably had undiagnosed CPA. In October 2016, the Global Action Fund for Fungal Infections convened an international expert panel to develop a case definition of CPA for resource-constrained settings. This panel defined CPA as illness for >3 months and all of the following: 1) weight loss, persistent cough, and/or hemoptysis; 2) chest images showing progressive cavitary infiltrates and/or a fungal ball and/or pericavitary fibrosis or infiltrates or pleural thickening; and 3) a positive Aspergillus IgG assay result or other evidence of Aspergillus infection. The proposed definition will facilitate advancements in research, practice, and policy in lower- and middle-income countries as well as in resource-constrained settings. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of non-communicable diseases (NCDs) is rising in low- and middle-income countries, including Kenya, disproportionately to the rest of the world. Our objective was to quantify patient payments to obtain NCD screening, diagnosis, and treatment services in the public and private sector in Kenya and evaluate patients’ ability to pay for the services. Methods and findings: We collected payment data on cardiovascular diseases, diabetes, breast and cervical cancer, and respiratory diseases from Kenyatta National Hospital, the main tertiary public hospital, and the Kibera South Health Center—a public outpatient facility, and private sector practitioners and hospitals. We developed detailed treatment frameworks for each NCD and used an itemization cost approach to estimate payments. Patient affordability metrics were derived from Kenyan government surveys and national datasets. Results compare public and private costs in U.S. dollars. NCD screening costs ranged from $4 to $36, while diagnostic procedures, particularly for breast and cervical cancer, were substantially more expensive. Annual hypertension medication costs ranged from $26 to $234 and $418 to $987 in public and private facilities, respectively. Stroke admissions ($1,874 versus $16,711) and dialysis for chronic kidney disease ($5,338 versus $11,024) were among the most expensive treatments. Cervical and breast cancer treatment cost for stage III (curative approach) was about $1,500 in public facilities and more than $7,500 in the private facilities. A large proportion of Kenyans aged 15 to 49 years do not have health insurance, which makes NCD services unaffordable for most people given the overall high cost of services relative to income (average household expenditure per adult is $413 per annum). Conclusions: There is substantial variation in patient costs between the public and private sectors. Most NCD diagnosis and treatment costs, even in the public sector, represent a substantial economic burden that can result in catastrophic expenditures. [ABSTRACT FROM AUTHOR]

Highlights • Tuberculin skin test (TST) is over a century old but it continues to be used widely. • When IGRAs were introduced it was anticipated that they would rapidly replace TST. • Neither TST nor IGRAs have a high accuracy for predicting active TB. • Latest WHO recommendations are that either TST or IGRA can be used to test for LTBI. • TST will be clinically useful until more accurate tests become available. Abstract Objective To make an informed viewpoint on the usefulness of Tuberculin Skin test (TST) compared to Interferon Gamma Release Assays (IGRAs) for diagnosis of Latent TB Infection (LTBI) in different geographical settings. Methods We reviewed the current literature on TST compared to IGRA, including national implementation of WHO LTBI recommendations and retrospective data over the past 7 years at the National Institute for Infectious Diseases "L. Spallanzani" as indirect indicator of usage of both tests under actual programmatic conditions. Results Current national guidelines vary considerably, reflecting the uncertainty and rapidly evolving evidence about the potential use of these tests. Data from Institute "L. Spallanzani" showed IGRA concordance in TST positive subjects only in 54.74% of subjects, while there was strong concordance between two tests in TST negative subjects (93.78%). Conclusion Neither IGRAs nor TST can distinguish active TB from LTBI. TST will continue to be clinically useful in low and high TB endemic areas until more accurate and predictive tests will become available. Clinical judgment remains fundamental in choosing between IGRA/TST tests and interpreting their results. [ABSTRACT FROM AUTHOR]

Summary Tuberculosis (TB) remains a global emergency, with an estimated 9.6 million new TB cases worldwide reported in 2014. Twenty-eight percent of these cases were in the World Health Organization (WHO) Africa Region, where the annual case detection rate was 281 per 100 000 population—more than double the global average of 133 per 100 000. Of the 9.6 million people who developed TB, an estimated 1.2 million (12%) were HIV-positive, and the Africa Region accounted for 74% of these cases. Three million people with TB remain undiagnosed and untreated. Globally, an estimated 480 000 had multidrug-resistant TB (MDR-TB). Whilst of the African countries, only South Africa has reported a high prevalence of MDR-TB, it is likely that all of Sub-Saharan Africa has an unreported high load of drug-resistant TB. Tragically, in 2014, only 48% of individuals diagnosed with MDR-TB had successful treatment and an estimated 190 000 people died of MDR-TB. Of the global TB funding gap of US$ 0.8 billion, the largest funding gap was in the Africa Region, amounting to US$ 0.4 billion in 2015. The MDR-TB pandemic in particular now threatens to devastate entire regions and may fundamentally alter the life-expectancy and demographic profile of many countries in Sub-Saharan Africa. The theme designated for this year's World TB Day, March 24, 2016, is ‘Unite to End TB’. From the Africa Region, there is an urgent need to seriously address the political, economic, and social factors that influence host– Mycobacterium tuberculosis interactions and result in disease. Recent political and funder initiatives that provide renewed hope for the alleviation of Africa's TB and TB/HIV problems are discussed. [ABSTRACT FROM AUTHOR]

Christian Lienhardt and colleagues describe the research efforts needed to end the global tuberculosis epidemic by 2035. [ABSTRACT FROM AUTHOR]

Tuberculosis (TB) today remains a global emergency affecting 9.0 million people globally. The African Region bears the highest global TB/HIV burden and over 50% of TB cases in SSA are co-infected with HIV. An estimated 1.5 million died from the TB globally in 2013. A large majority of the 360,000 HIV-positive TB cases who died were from sub-Saharan Africa. Research and development is an important pillar of the WHO post-2015 global TB strategy. Advances in development of diagnostics, drugs, host-directed therapies, and vaccines will require evaluation under field conditions through multi-centre clinical trials at different geographical locations. Thus it is critically important that these evaluations are fully supported by all African governments and the capacity, trained staff and infrastructure required to perform the research and evaluations is built and made available. This viewpoint article reviews the opportunities provided by recently launched second programme (2015-2024) of the European & Developing Countries Clinical Trials Partnership (EDCTP2) for tackling the TB epidemic in Africa through its magnanimous portfolio. The unique opportunities provided by EDCTP2 for leadership of scientific research in TB and other diseases fully devolving to Africa are also covered. [ABSTRACT FROM AUTHOR]

COVID-19 stalled the world in 2020 and continues to be the greatest health crisis of this generation. While the apparent case fatality rates across fluctuates around ~2% globally, associated mortality/death rate (deaths per million population) varies distinctly across regions from the global average of ~600 per million population. Heterogeneous factors have been linked with COVID-19 associated mortalities and these include age, share of geriatric population, comorbidities, trained immunity and climatic conditions. Apart from direct or indirect role of endemic diseases, dietary factors and host immunity in regulating COVID-19 severity, human behaviour will inevitably control outcome of this pandemic. Comprehensive understanding of these factors will have a bearing on management of future health crises. • COVID-19 serves an exceptional reminder plethora of factors can predispose the population to the pathogenic diseases. • Analysis of biological and non-biological factors can broaden our understanding on COVID-19 severity and mortality globally. • Besides direct interventional strategies, host-directed responses can also be utilized against microbial infections. • Understanding global population differences will aid in the management of future health crises. [ABSTRACT FROM AUTHOR]

Background: The 2007 WHO algorithm for diagnosis of smear-negative pulmonary tuberculosis (PTB) including Mycobacterium tuberculosis (MTB) culture was evaluated in a HIV prevalent area of Kenya. Methods: PTB smear-negative adult suspects were included in a prospective diagnostic study (2009-2011). In addition, program data (2008-2009) were retrospectively analysed. At the first consultation, clinical examination, chest X-ray, and sputum culture (Thin-Layer-Agar and Lowenstein-Jensen) were performed. Patients not started on TB treatment were clinically re-assessed after antibiotic course. The algorithm performance was calculated using culture as reference standard. Results: 380 patients were included prospectively and 406 analyzed retrospectively. Culture was positive for MTB in 17.5% (61/348) and 21.8% (72/330) of cases. Sensitivity of the clinical-radiological algorithm was 55.0% and 31.9% in the prospective study and the program data analysis, respectively. Specificity, positive and negative predictive values were 72.9%, 29.7% and 88.6% in the prospective study and 79.8%, 30.7% and 80.8% in the program data analysis. Performing culture increased the number of confirmed TB patients started on treatment by 43.3% in the prospective study and by 44.4% in the program data analysis. Median time to treatment of confirmed TB patients was 6 days in the prospective study and 27 days in the retrospective study. Inter-reader agreement for X-ray interpretation between the study clinician and a radiologist was low (Kappa coefficient = 0.11, 95%CI: 0.09-0.12). In a multivariate logistic analysis, past TB history, number of symptoms and signs at the clinical exam were independently associated with risk of overtreatment. Conclusion: The clinical-radiological algorithm is suboptimal to diagnose smear-negative PTB. Culture increases significantly the proportion of confirmed TB cases started on treatment. Better access to rapid MTB culture and development of new diagnostic tests is necessary. [ABSTRACT FROM AUTHOR]

The article focuses on the developments in the global control efforts and challenges of tuberculosis, which is one of the common causes of death worldwide. It states that the world and some regions are on track to attain the Millennium Development Goal of reducing the incidence of tuberculosis and the Stop TB partnership target to reduce the 1990 mortality rates by half by 2015, except for Africa. It says that drug-resistant tuberculosis and scaling-up of tuberculosis remains challenging.

Summary: Operational research in low-income countries has a key role in filling the gap between what we know from research and what we do with that knowledge—the so-called know–do gap, or implementation gap. Planned research that does not tangibly affect policies and practices is ineffective and wasteful, especially in settings where resources are scarce and disease burden is high. Clear parameters are urgently needed to measure and judge the success of operational research. We define operational research and its relation with policy and practice, identify why operational research might fail to affect policy and practice, and offer possible solutions to address these shortcomings. We also propose measures of success for operational research. Adoption and use of these measures could help to ensure that operational research better changes policy and practice and improves health-care delivery and disease programmes. [Copyright &y& Elsevier]

Background: Good adherence to treatment is crucial to control tuberculosis (TB). Efficiency and feasibility of directly observed therapy (DOT) under routine program conditions have been questioned. As an alternative, Médecins sans Frontières introduced self-administered therapy (SAT) in several TB programs. We aimed to measure adherence to TB treatment among patients receiving TB chemotherapy with fixed dose combination (FDC) under SAT at the Homa Bay district hospital (Kenya). A second objective was to compare the adherence agreement between different assessment tools. Methods: We conducted a cross-sectional survey amongst a series of new TB patients receiving 6 months of standard TB chemotherapy with FDC under SAT. Adherence was assessed at home with urine testing for Isoniazid (INH), pill count, interviewer-administered questionnaire and visual analogue scale (VAS). Results: In November 2008 and in June 2009, 212 of 279 eligible patients were assessed for adherence. Overall, 95.2% [95%CI: 91.3-97.7] of the patients reported not having missed a tablet in the last 4 days. On the VAS, complete adherence was estimated at 92.5% [95%CI: 88.0-95.6]. INH urine test was positive for 97.6% [95%CI: 94.6-99.2] of the patients. Pill count could be assessed among only 70% of the interviewed patients. Among them, it was complete for 82.3% [95%CI: 75.1-88.1]. Among the 212 surveyed patients, 193 (91.0%) were successfully treated (cured or treatment completed). The data suggest a fair agreement between the questionnaire and the INH urine test (k = 0.43) and between the questionnaire and the VAS (k = 0.40). Agreement was poor between the other adherence tools. Conclusion: These results suggest that SAT, together with the FDC, allows achieving appropriate adherence to antituberculosis treatment in a high TB and HIV burden area. The use of a combination of a VAS and a questionnaire can be an adequate approach to monitor adherence to TB treatment in routine program conditions. [ABSTRACT FROM AUTHOR]

The author reflects on the importance of strengthening the health services in Africa. He states that performing research is the most important part of the strengthening process. The major challenge to provide health services in Africa is shortage of the health care workers. The author emphasizes on the importance of integration between the local health services and the research team in optimizing the health care services. However, the funding problem, according to the author, is a problem in research work.

Despite extensive global efforts in the fight against killer infectious diseases, they still cause one in four deaths worldwide and are important causes of long-term functional disability arising from tissue damage. The continuing epidemics of tuberculosis, HIV, malaria, and influenza, and the emergence of novel zoonotic pathogens represent major clinical management challenges worldwide. Newer approaches to improving treatment outcomes are needed to reduce the high morbidity and mortality caused by infectious diseases. Recent insights into pathogen-host interactions, pathogenesis, inflammatory pathways, and the host's innate and acquired immune responses are leading to identification and development of a wide range of host-directed therapies with different mechanisms of action. Host-directed therapeutic strategies are now becoming viable adjuncts to standard antimicrobial treatment. Host-directed therapies include commonly used drugs for non-communicable diseases with good safety profiles, immunomodulatory agents, biologics (eg monoclonal antibodies), nutritional products, and cellular therapy using the patient's own immune or bone marrow mesenchymal stromal cells. We discuss clinically relevant examples of progress in identifying host-directed therapies as adjunct treatment options for bacterial, viral, and parasitic infectious diseases. [ABSTRACT FROM AUTHOR]

Tuberculosis is the leading infectious cause of death worldwide, with 9·6 million cases and 1·5 million deaths reported in 2014. WHO estimates 480,000 cases of these were multidrug resistant (MDR). Less than half of patients who entered into treatment for MDR tuberculosis successfully completed that treatment, mainly due to high mortality and loss to follow-up. These in turn illustrate weaknesses in current treatment regimens and national tuberculosis programmes, coupled with operational treatment challenges. In this Review we provide an update on recent developments in the tuberculosis drug-development pipeline (including new and repurposed antimicrobials and host-directed drugs) as they are applied to new regimens to shorten and improve outcomes of tuberculosis treatment. Several new or repurposed antimicrobial drugs are in advanced trial stages for MDR tuberculosis, and two new antimicrobial drug candidates are in early-stage trials. Several trials to reduce the duration of therapy in MDR and drug-susceptible tuberculosis are ongoing. A wide range of candidate host-directed therapies are being developed to accelerate eradication of infection, prevent new drug resistance, and prevent permanent lung injury. As these drugs have been approved for other clinical indications, they are now ready for repurposing for tuberculosis in phase 2 clinical trials. We assess risks associated with evaluation of new treatment regimens, and highlight opportunities to advance tuberculosis research generally through regulatory innovation in MDR tuberculosis. Progress in tuberculosis-specific biomarkers (including culture conversion, PET and CT imaging, and gene expression profiles) can support this innovation. Several global initiatives now provide unique opportunities to tackle the tuberculosis epidemic through collaborative partnerships between high-income countries and middle-income and low-income countries for clinical trials training and research, allowing funders to coordinate several national and regional programmes for greatest overall effect. [ABSTRACT FROM AUTHOR]

Tuberculosis is unique among the major infectious diseases in that it lacks accurate rapid point-of-care diagnostic tests. Failure to control the spread of tuberculosis is largely due to our inability to detect and treat all infectious cases of pulmonary tuberculosis in a timely fashion, allowing continued Mycobacterium tuberculosis transmission within communities. Currently recommended gold-standard diagnostic tests for tuberculosis are laboratory based, and multiple investigations may be necessary over a period of weeks or months before a diagnosis is made. Several new diagnostic tests have recently become available for detecting active tuberculosis disease, screening for latent M. tuberculosis infection, and identifying drug-resistant strains of M. tuberculosis. However, progress toward a robust point-of-care test has been limited, and novel biomarker discovery remains challenging. In the absence of effective prevention strategies, high rates of early case detection and subsequent cure are required for global tuberculosis control. Early case detection is dependent on test accuracy, accessibility, cost, and complexity, but also depends on the political will and funder investment to deliver optimal, sustainable care to those worst affected by the tuberculosis and human immunodeficiency virus epidemics. This review highlights unanswered questions, challenges, recent advances, unresolved operational and technical issues, needs, and opportunities related to tuberculosis diagnostics. [ABSTRACT FROM PUBLISHER]

Tuberculosis was declared a global emergency by the World Health Organization (WHO) in 1993. Following the declaration and the promotion in 1995 of directly observed treatment short course (DOTS), a cost-effective strategy to contain the tuberculosis epidemic, nearly 7 million lives have been saved compared with the pre-DOTS era, high cure rates have been achieved in most countries worldwide, and the global incidence of tuberculosis has been in a slow decline since the early 2000s. However, the emergence and spread of multidrug-resistant (MDR) tuberculosis, extensively drug-resistant (XDR) tuberculosis, and more recently, totally drug-resistant tuberculosis pose a threat to global tuberculosis control. Multidrug-resistant tuberculosis is a man-made problem. Laboratory facilities for drug susceptibility testing are inadequate in most tuberculosis-endemic countries, especially in Africa; thus diagnosis is missed, routine surveillance is not implemented, and the actual numbers of global drug-resistant tuberculosis cases have yet to be estimated. This exposes an ominous situation and reveals an urgent need for commitment by national programs to health system improvement because the response to MDR tuberculosis requires strong health services in general. Multidrug-resistant tuberculosis and XDR tuberculosis greatly complicate patient management within resource-poor national tuberculosis programs, reducing treatment efficacy and increasing the cost of treatment to the extent that it could bankrupt healthcare financing in tuberculosis-endemic areas. Why, despite nearly 20 years of WHO-promoted activity and >12 years of MDR tuberculosis–specific activity, has the country response to the drug-resistant tuberculosis epidemic been so ineffectual? The current dilemmas, unanswered questions, operational issues, challenges, and priority needs for global drug resistance screening and surveillance, improved treatment regimens, and management of outcomes and prevention of DR tuberculosis are discussed. [ABSTRACT FROM PUBLISHER]