Global Burden Of Tuberculosis Research Articles

Spatial patterns and multilevel analysis of factors associated with paediatric tuberculosis in India

BackgroundTuberculosis (TB) is a serious global health problem that remains as leading cause of high mortality and morbidity in children. Despite India with a high global tuberculosis burden, very few studies have specifically addressed the problem of TB among children, a vulnerable group where delayed diagnosis aggravates the morbidity. MethodsIdentifying the hotspots with high risk of Paediatric TB by employing a localized clustering method can help in developing regional policies for eliminating TB. Factors specified at various levels must be taken into account in studies of health aetiology and their practical applications for disease control. Multilevel analysis is a viable analytic technique for including components identified at many levels in an epidemiologic study and the interindividual variances can be inferred using multilevel analysis. ResultsIn this study, the incidence of tuberculosis pertaining to individual-level attributes are elucidated at district and state level through a multilevel model using the information from National Family Health Survey-5, carried out in 2019–20 comprising 636,699 households over 28 states and 8 union territories of India and the spatial method has detected 62 hotspots. ConclusionThe model expresses a nested structure with districts and states having significant contribution in the variation of paediatric TB and the autocorrelation pattern exhibited by the hotspots emphasises the need for targeted TB elimination programs.

Global Burden of Tuberculosis in Adolescents and Young Adults: 1990-2019.

Tuberculosis (TB) is a major health threat in adolescents and young adults. However, its burden in this population remains unclear. This study aimed to assess TB burden and changing trends in individuals aged 10 to 24 years from 1990 to 2019. All data were obtained from the Global Burden of Disease Study 2019. We calculated the percentage of relative changes in incident cases, deaths, and disability-adjusted life years (DALYs). The temporal trends of the incidence, mortality, and DALYs were assessed using estimated annual percentage changes (EAPCs). At global level, TB incidence (per 100 000 population) decreased from 144.12 in 1990 to 97.56 in 2019, with average 1.28% (95% confidence interval [CI]: 1.36%-1.19%) of decline per year. Similar decreasing trends occurred across sex, age, sociodemographic index regions, and in most Global Burden of Disease study regions and countries. TB incidence in female adolescents decreased faster than that in male. However, there was an increasing trend in the incidence of extensively drug-resistant TB (EAPC = 11.23, 95% CI: 8.22-14.33) and multidrug-resistant TB without extensive drug resistance (EAPC = 3.28, 95% CI: 1.73-4.86). South Africa had the highest increase in TB incidence (EAPC = 3.51, 95% CI: 3.11-3.92). Global TB incidence, mortality, and DALYs in adolescents and young adults decreased from 1990 to 2019. However, the incidence of drug-resistant TB increased. TB remains a threat in adolescents and young adults worldwide, especially in low- and middle-income countries.

Global and regional estimates of tuberculosis burden attributed to high fasting plasma glucose from 1990 to 2019: emphasis on earlier glycemic control

BackgroundPrevious studies have shown subjects suffering from diabetes or persistent hyperglycemia were more likely to develop tuberculosis (TB). However, the global burden of TB attributed to high fasting plasma glucose (HFPG) remains unclear. This study aimed to characterize the global, regional, and national TB burden attributed to HFPG from 1990 to 2019.MethodsWith Global Burden of Disease study 2019, the numbers and age-standardized mortality rates (ASMR) and age-standardized disability-adjusted life years (DALY) rates (ASDR) of TB attributed to HFPG at global, regional, and national levels from 1990 to 2019 were extracted. The locally weighted regression model was applied to estimate the TB burden for different socio-demographic index (SDI) regions.ResultsGlobally, the ASMR and ASDR attributed to HFPG were 2.70 (95% UI, 1.64–3.94) and 79.70 (95% UI, 50.26–112.51) per 100,000 population in 1990, respectively. These rates decreased to 1.46 (95% UI, 0.91–2.08) and 45.53 (95% UI, 29.06–62.29) in 2019. The TB burden attributed to HFPG remained high in low SDI and Central Sub-Saharan Africa regions, while it declined with most significantly in high SDI and East Asia regions. Additionally, the ASMR and ASDR of TB attributed to HFPG were significantly higher in the male and the elderly population.ConclusionsThe global TB burden attributable to HFPG decreased from 1990 to 2019, but remained high in low SDI regions among high-risk populations. Thus, urgent efforts are required to enhance the awareness of early glycemic control and TB treatment to alleviate the severe situation.

Global, regional, and national age-specific progress towards the 2020 milestones of the WHO End TB Strategy: a systematic analysis for the Global Burden of Disease Study 2021.

Global evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020. We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990-2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality surveillance data, and 9 site-years of minimally invasive tissue sample (MITS) diagnoses data as inputs into the Cause of Death Ensemble modelling platform. Age-specific HIV and tuberculosis deaths were established with a population attributable fraction approach. We analysed all available population-based data sources, including prevalence surveys, annual case notifications, tuberculin surveys, and tuberculosis mortality, in DisMod-MR 2.1 to produce internally consistent age-specific estimates of tuberculosis incidence, prevalence, and mortality. We also estimated age-specific tuberculosis mortality without HIV co-infection that is attributable to the independent and combined effects of three risk factors (smoking, alcohol use, and diabetes). As a secondary analysis, we examined the potential impact of the COVID-19 pandemic on tuberculosis mortality without HIV co-infection by comparing expected tuberculosis deaths, modelled with trends in tuberculosis deaths from 2015 to 2019 in vital registration data, with observed tuberculosis deaths in 2020 and 2021 for countries with available cause-specific mortality data. We estimated 9·40 million (95% uncertainty interval [UI] 8·36 to 10·5) tuberculosis incident cases and 1·35 million (1·23 to 1·52) deaths due to tuberculosis in 2021. At the global level, the all-age tuberculosis incidence rate declined by 6·26% (5·27 to 7·25) between 2015 and 2020 (the WHO End TB strategy evaluation period). 15 of 204 countries achieved a 20% decrease in all-age tuberculosis incidence between 2015 and 2020, eight of which were in western sub-Saharan Africa. When stratified by age, global tuberculosis incidence rates decreased by 16·5% (14·8 to 18·4) in children younger than 5 years, 16·2% (14·2 to 17·9) in those aged 5-14 years, 6·29% (5·05 to 7·70) in those aged 15-49 years, 5·72% (4·02 to 7·39) in those aged 50-69 years, and 8·48% (6·74 to 10·4) in those aged 70 years and older, from 2015 to 2020. Global tuberculosis deaths decreased by 11·9% (5·77 to 17·0) from 2015 to 2020. 17 countries attained a 35% reduction in deaths due to tuberculosis between 2015 and 2020, most of which were in eastern Europe (six countries) and central Europe (four countries). There was variable progress by age: a 35·3% (26·7 to 41·7) decrease in tuberculosis deaths in children younger than 5 years, a 29·5% (25·5 to 34·1) decrease in those aged 5-14 years, a 15·2% (10·0 to 20·2) decrease in those aged 15-49 years, a 7·97% (0·472 to 14·1) decrease in those aged 50-69 years, and a 3·29% (-5·56 to 9·07) decrease in those aged 70 years and older. Removing the combined effects of the three attributable risk factors would have reduced the number of all-age tuberculosis deaths from 1·39 million (1·28 to 1·54) to 1·00 million (0·703 to 1·23) in 2020, representing a 36·5% (21·5 to 54·8) reduction in tuberculosis deaths compared to those observed in 2015. 41 countries were included in our analysis of the impact of the COVID-19 pandemic on tuberculosis deaths without HIV co-infection in 2020, and 20 countries were included in the analysis for 2021. In 2020, 50 900 (95% CI 49 700 to 52 400) deaths were expected across all ages, compared to an observed 45 500 deaths, corresponding to 5340 (4070 to 6920) fewer deaths; in 2021, 39 600 (38 300 to 41 100) deaths were expected across all ages compared to an observed 39 000 deaths, corresponding to 657 (-713 to 2180) fewer deaths. Despite accelerated progress in reducing the global burden of tuberculosis in the past decade, the world did not attain the first interim milestones of the WHO End TB Strategy in 2020. The pace of decline has been unequal with respect to age, with older adults (ie, those aged >50 years) having the slowest progress. As countries refine their national tuberculosis programmes and recalibrate for achieving the 2035 targets, they could consider learning from the strategies of countries that achieved the 2020 milestones, as well as consider targeted interventions to improve outcomes in older age groups. Bill & Melinda Gates Foundation.

CHILDHOOD TUBERCULOSIS: STUDY OF CLINICAL PROFILE OF TUBERCULOSIS IN PEDIATRIC PATIENTS AND CORRELATION OF CB-NAAT RESULT IN CLINICALLY SUSPECTED TUBERCULOSIS

Introduction: Tuberculosis is a chronic infectious disease caused by predominantly Mycobacterium tubercle bacilli. Pediatric tuberculosis is among the top 10 causes of death in children. India accounts for one fourth of the global tuberculosis burden, standing one among the thirty high TB burden countries. Hence, children in India are at increased risk of acquiring TB infection and developing TB disease and death following infection. Latent TB infection in children may be reactivated in later life and become active adulthood tuberculosis and thereby a potent TB reservoir in the community. Aim: To study clinical profile of tuberculosis in pediatric patients and correlation of CB-NAAT result in clinically suspected tuberculosisat tertiary care center. Method: Prospective Observational study from1 August 2020 to 31 August 2022. Result: Out of 52 patients cough was presenting symptom of 19(36.53%), fever was present in 25(48.07%), loss of weight >5% in last 3 month was present in 12(23.07%),fever(83.8 %) was most dominant symptom. Out of 52 patients, tachypnoea was presenting sign in 5(9.6%), ascites was present in 5(9.6%) and lymphadenopathy for more than 2 weeks were present in 25(48.07%). Out of 52 patients Anaemia was present in 42(80.76%), High ESR was present in 22(42.30%) and Mantoux test was positive in 16(30.76%). Conclusion: Reliable diagnosis of tuberculosiscan be done by clinical parameters like presence of tachypnea, fever and lymphadenopathy. CB NAAT in correlation to clinical parameters is very useful for diagnosis of tubercular cases.

Clinical research progress of novel antituberculosis drugs on multidrug-resistant tuberculosis.

Multidrug-resistant tuberculosis (MDR-TB) has become a critical challenge to public health, and the prevention and treatment of MDR-TB are of great significance in reducing the global burden of tuberculosis. How to improve the effectiveness and safety of chemotherapy for MDR-TB is a pressing issue that needs to be addressed in tuberculosis control efforts. This article provides a comprehensive review of the clinical application of new antituberculosis drugs in MDR-TB, aiming to provide a scientific basis for the prevention and treatment strategy of MDR-TB.

Global tuberculosis burden in Russia and the world as a public health problem (historical and analytical review)

Based on an analysis of archive materials, scientific publications and official statistics obtained from 56 sources, the global tuberculosis burden was assessed. In 1918 in Russia, tuberculosis mortality made 360 cases per 100,000 population, exceeding that in other industrial countries: in England this rate was 113.0; in the USA – 148.0; in Switzerland – 201.0; in Italy – 209.0; in France – 226.0; in Germany – 230.0; and in Japan (1920) – 234 cases respectively. Having undergone colossal socio-economic catastrophes like no other country, Russia achieved significant success in the fight against tuberculosis: in 1913, tuberculosis incidence was 733.0 per 100,000 population, tuberculosis mortality was 276.8; while in 2021 these made 31.1 and 4.3 respectively. In 2021, WHO excluded Russia from the list of countries with a high burden of tuberculosis. However, in Russia as well as in the other BRICS countries, the burden of MDR TB and TB/HIV co-infection still remains high, which requires allocation of resources to reduce their spread.

Pulmonary function outcomes after tuberculosis treatment in children: a systematic review and meta-analysis

BackgroundDespite tuberculosis (TB) being a curable disease, current guidelines fail to account for the long-term outcomes of post-tuberculosis lung disease—a cause of global morbidity despite successful completion of effective treatment....

Data-driven epidemiologic approach to conducting site feasibility for a global phase III tuberculosis vaccine clinical trial.

An efficacious tuberculosis (TB) vaccine is critical to reducing the global burden of TB. TB vaccine trials require the identification of multiple sites globally that have both a high incidence of TB and the capacity to conduct a clinical trial. To expand the diversity of potential phase III TB vaccine trial sites to be considered for inclusion, we describe a novel epidemiologic method that incorporates approaches from a variety of public health practices. Our approach incorporates analytic methodology to enable quantification and validation of qualitative information from disparate data sources, and epidemiologic analysis to systematically assess site-specific TB epidemiology. The integration of robust data-driven practices, and more quantitatively focused analysis, allowed for the objective evaluation of sites, which resulted in the identification of sites and catchment areas with high TB burden that may not have been previously considered. This suggests that an integrated epidemiologic methodology, not traditionally utilized for clinical trial site evaluations, could be integrated into site feasibility assessments as it results in more rapid site identification and reduces unintended bias.

Conference report: WHO meeting summary on mRNA-based tuberculosis vaccine development

Tuberculosis (TB) is a global health emergency. Across the globe, approximately 2 billion people are currently infected with Mycobacterium tuberculosis (Mtb), and of those, 5–10% may progress to become ill and potentially transmit the bacterium. In 2021, nearly 10.6 million people developed TB disease and 1.6 million died. There is an urgent need for accelerated development of new TB-focused interventions, in particular, improved TB vaccines. However, progress in developing highly effective TB vaccines has been slow and is chronically under-resourced. The mRNA vaccine platform may offer an opportunity to accelerate development of new TB vaccines.In April 2023, the World Health Organization convened global experts to discuss the feasibility and potential value of mRNA-based vaccines for TB. Here we report on meeting deliberations related to the current TB vaccine pipeline and potential novel antigens, the status of efforts to identify correlates of protection, potential clinical development strategies and considerations for community acceptance of new TB vaccines based on this relatively new platform. The role of industry collaborations, ethics, social science, and responsibility to the global community regarding transparency and manufacturing capacity building were discussed through expert presentations and panel sessions. The overall conclusion of the meeting is that mRNA-based vaccines constitute a potentially powerful new tool for reducing the global burden of TB.

Pulmonary Tuberculosis and Rifampicin Resistant Mycobacterium Tuberculosis in Children and Adolescents using Gene Xpert MTB/RIF Assay in Tigray, Northern Ethiopia.

Tuberculosis (TB) continues to be a global health problem. While childhood TB contributes 10% to the global TB burden, the paucibacillary nature of TB disease in children and the absence of reliable diagnostic methods have made MTB diagnosis in children to be a great challenge. This study aimed to determine the prevalence of MTB and rifampicin-resistant MTB (RR-MTB) among children using Gene Xpert MTB/RIF Assay in Tigray, Ethiopia. A retrospective database study was conducted among children in ten governmental hospitals in the Tigray region. Gene Xpert MTB/RIF results of sputum/gastric lavage samples from children with presumptive TB from January 2016 to December 2019 were extracted using a data extraction sheet. Data were collected and analyzed using Statistical Package for the Social Sciences version 21. The prevalence of bacteriologically confirmed MTB by Gene-Xpert in children with presumptive TB was 7.3% (95% CI: 6.7%-7.9%) and the proportion of those that were Gene-Xpert MTB positive who also have rifampicin resistance was 10.9% (95% CI: 8.2-13.6%). Older children aged 11-15 years [AOR = 1.76; 95% CI = 1.33-2.33, p < 0.001] and adolescents 16-17 years [AOR = 2.18; 95% CI = 1.63-2.92, p < 0.001] were more likely to be MTB positive. Relapse cases [AOR = 1.66; 95% CI = 1.09-2.51, p = 0.017] and lost/failure cases [AOR = 8.82; 95% CI = 3.94-19.76, p < 0.001] were more likely to have MTB compared to the new cases. The proportion of MTB-positive among the TB presumptive patients was 7.3%. The proportion of rifampicin-resistant TB to all positive patients was 10.9%. Female participants had more MTB than males (or younger children). The result highlights the need for due attention in children because it is very helpful in determining the future control of the disease.

Divergent proinflammatory immune responses associated with the differential susceptibility of cattle breeds to tuberculosis.

Tuberculosis (TB) in the bovine is one of the most predominant chronic debilitating infectious diseases primarily caused by Mycobacterium bovis. Besides, the incidence of TB in humans due to M. bovis, and that in bovines (bovine TB, bTB) due to M. tuberculosis- indicates cattle as a major reservoir of zoonotic TB. While India accounts for the highest global burden of both TB and multidrug-resistant TB in humans, systematic evaluation of bTB prevalence in India is largely lacking. Recent reports emphasized markedly greater bTB prevalence in exotic and crossbred cattle compared to indigenous cattle breeds that represent more than one-third of the total cattle population in India, which is the largest globally. This study aimed at elucidating the immune responses underlying the differential bTB incidence in prominent indigenous (Sahiwal), and crossbred (Sahiwal x Holstein Friesian) cattle reared in India. Employing the standard Single Intradermal Tuberculin Test (SITT), and mycobacterial gene-targeting single as well as multiplex-PCR-based screening revealed higher incidences of bovine tuberculin reactors as well as Mycobacterium tuberculosis Complex specific PCR positivity amongst the crossbred cattle. Further, ex vivo mycobacterial infection in cultures of bovine peripheral blood mononuclear cells (PBMC) from SITT, and myco-PCR negative healthy cattle exhibited significantly higher intracellular growth of M. bovis BCG, and M. tuberculosis H37Ra in the crossbred cattle PBMCs compared to native cattle. In addition, native cattle PBMCs induced higher pro-inflammatory cytokines and signaling pathways, such as interferon-gamma (IFN-γ), interleukin-17 (IL-17), tank binding kinase-1 (TBK-1), and nitric oxide (NO) upon exposure to live mycobacterial infection in comparison to PBMCs from crossbred cattle that exhibited higher expression of IL-1β transcripts. Together, these findings highlight that differences in the innate immune responses of these cattle breeds might be contributing to the differential susceptibility to bTB infection, and the resultant disparity in bTB incidence amongst indigenous, and crossbred cattle.

Drug-Induced Hypersensitivity Reaction and Re-Introduction of Anti-Tubercular Drugs (ATT): A Case Report and Review of Literature

Tuberculosis (TB) is a communicable disease caused by the bacillus Mycobacterium tuberculosis and is the leading cause of death by a single infectious agent overall. According to the WHO Global TB Report, India contributes to 26% of the global burden of TB. Currently, a four-drug regimen comprising Rifampicin, Isoniazid, Pyrazinamide, and Ethambutol is approved for the treatment of drug-sensitive TB. The management of cutaneous adverse drug reactions to anti-tubercular drugs is akin to a double-edged sword, with discontinuation of ATT increasing the risk of developing disseminated and drug-resistant tuberculosis, and continuation leading to persistence or exacerbation of the adverse drug reaction (ADR). The risk of developing an ADR to anti-tubercular therapy (ATT) varies from 8 to 85% in various studies [10]. The prevalence of rashes associated with ATT shows that the maculopapular rash (42.5%) is the most frequently observed type, followed by urticarial, lichenoid, DRESS, AGEP, and exfoliative dermatitis (17). The drugs associated with Cutaneous ADRs from the lowest to the highest risk are Isoniazid, Rifampicin, Pyrazinamide, Ethionamide, Cycloserine, Ethambutol, Para-aminosalicylic acid (PAS), and Streptomycin (25). We present a case and approach to the re-introduction of first-line anti-tubercular drugs after hypersensitivity with fixed-dose combinations.&#x0D; Keywords: Tuberculosis, Mycobacterium tuberculosis, adverse drug reaction, anti-tubercular therapy

Wollamide Cyclic Hexapeptides Synergize with Established and New Tuberculosis Antibiotics in Targeting Mycobacterium tuberculosis.

Shorter and more effective treatment regimens as well as new drugs are urgent priorities for reducing the immense global burden of tuberculosis (TB). As treatment of TB currently requires multiple antibiotics with diverse mechanisms of action, any new drug lead requires assessment of potential interactions with existing TB antibiotics. We previously described the discovery of wollamides, a new class of Streptomyces-derived cyclic hexapeptides with antimycobacterial activity. To further assess the value of the wollamide pharmacophore as an antimycobacterial lead, we determined wollamide interactions with first- and second-line TB antibiotics by determining fractional inhibitory combination index and zero interaction potency scores. In vitro two-way and multiway interaction analyses revealed that wollamide B1 synergizes with ethambutol, pretomanid, delamanid, and para-aminosalicylic acid in inhibiting the replication and promoting the killing of phylogenetically diverse clinical and reference strains of the Mycobacterium tuberculosis complex (MTBC). Wollamide B1 antimycobacterial activity was not compromised in multi- and extensively drug-resistant MTBC strains. Moreover, growth-inhibitory antimycobacterial activity of the combination of bedaquiline/pretomanid/linezolid was further enhanced by wollamide B1, and wollamide B1 did not compromise the antimycobacterial activity of the isoniazid/rifampicin/ethambutol combination. Collectively, these findings add new dimensions to the desirable characteristics of the wollamide pharmacophore as an antimycobacterial lead compound. IMPORTANCE Tuberculosis (TB) is an infectious disease that affects millions of people globally, with 1.6 million deaths annually. TB treatment requires combinations of multiple different antibiotics for many months, and toxic side effects can occur. Therefore, shorter, safer, more effective TB therapies are required, and these should ideally also be effective against drug-resistant strains of the bacteria that cause TB. This study shows that wollamide B1, a chemically optimized member of a new class of antibacterial compounds, inhibits the growth of drug-sensitive as well as multidrug-resistant Mycobacterium tuberculosis isolated from TB patients. In combination with TB antibiotics, wollamide B1 synergistically enhances the activity of several antibiotics, including complex drug combinations that are currently used for TB treatment. These new insights expand the catalogue of the desirable characteristics of wollamide B1 as an antimycobacterial lead compound that might inspire the development of improved TB treatments.

When should we be able to divert the cost of tuberculosis to other diseases?

Dear Editor, A country’s development and progress are based on its economy and gross domestic product (GDP). A recently published article in your journal introduces the past, present, and future of the Indian economy specifically related to healthcare. The author has nicely described the high burden of communicable and noncommunicable diseases. The authors have covered tuberculosis (TB) under communicable disease. We want to add some perspective to point out the status of TB burden on the Indian health economy.[1] Southeast Asian countries share more than 40% of the global TB burden and India is one of them. India belongs to the bracket of lower-middle-income countries.[2] Each and every single expenditure thing will have an effect on our country’s economy, either the share market or the healthcare system. As per recently published data, the Indian economy cost around $32 billion every year in TB-related fatalities.[1] TB is an old and infectious disease that makes a patient immunocompromised. TB patients have more chance to get other infectious diseases which makes patient’s life more troublesome in health and wealth both ways. The World Health Organization (WHO) and Government provide free testing and treatment for TB patients but this is not enough to control and eliminate the disease.[3] Majority of the patients belong to the lower and lower-middle-class family, which does not have the facility to get proper nutritious food; due to malnourishment, the patient does not get the treatment benefits that they need. Various studies revealed that several risk factors are responsible for the development of TB specifically drug-resistant TB and malnutrition, low body mass index, and low economy are few of them.[4] The Indian government is giving some amount to the patient to comply with treatment but that is not enough. To get benefits from the government, patients need to pass various documentary processes. Many patients stop the treatment in between due to these hectic procedures.[5] WHO and the government had the goal of END TB program to eradicate TB from India by the year 2025. Government and supportive people are on the right way but coronavirus disease 2019 (COVID-19) pandemic took us back foot.[6] TB not only is a fatal disease but also puts a lot of stress on the treasury. So, if TB is eliminated, a lot of funds can then be diverted to take care of other infectious diseases. So realistically, we can eliminate TB maybe by 2030. Out of all the programs mentioned, maybe TB is one entity, we can believe can be taken care of monetarily. Financial support and sponsorship Nil. Conflicts of interest There are no conflicts of interest.

An Epidemic of Drug Resistance: Tuberculosis in the Twenty-First Century.

With an estimated two billion people being carriers of latent tuberculosis infection (LTBI), the gains achieved by increasing access to diagnostics and treatment, although substantial, have had a modest impact on the global burden of tuberculosis (TB). At the same time, increased access to treatment has had the unintended consequence that drug-resistant TB (DR-TB) has increased dramatically. Earlier TB control strategies strongly emphasizing medical treatment have failed to address these issues effectively. The current strategy to eliminate TB by 2050 is accompanied by a call for a paradigm shift, emphasizing patient rights and equity more. Based on ethnographic fieldwork in Odisha, India, and global-level TB conferences, this paper contrasts the dynamics of global health policy and strategy-making with the lived realities of patients with DR-TB. A more thorough rethinking of the biosocial dynamics that impact the pathogenic disease is required to develop a comprehensive paradigm shift for TB control in the twenty-first century.

Antimicrobial Peptides: A Promising Strategy for Anti-tuberculosis Therapeutics.

The high global burden of tuberculosis (TB) and the increasing emergence of the drugresistant (DR) strain of Mycobacterium tuberculosis (Mtb) emphasize the urgent need for novel antimycobacterial agents. Antimicrobial peptides (AMPs) are small peptides widely existing in a variety of organisms and usually have amphiphilic cationic structures, which have a selective affinity to the negatively charged bacterial cell wall. Besides direct bactericidal mechanisms, including interacting with the bacterial cell membrane and interfering with the biosynthesis of the cell wall, DNA, or protein, some AMPs are involved in the host's innate immunity. AMPs are promising alternative or complementary agents for the treatment of DR-TB, given their various antibacterial mechanisms and low cytotoxicity. A large number of AMPs, synthetic or natural, from human to bacteriophage sources, have displayed potent anti-mycobacterial activity in vitro and in vivo. In this review, we summarized the features, antimycobacterial activity, and mechanisms of action of the AMPs according to their sources. Although AMPs have not yet met the expectations for clinical application due to their low bioavailabilities, high cost, and difficulties in large-scale production, their potent antimycobacterial activity and action mechanisms, which are different from conventional antibiotics, make them promising antibacterial agents against DR-Mtb in the future.

Prevalence and factors associated with tuberculosis among the mining communities in Mererani, Tanzania.

Tuberculosis (TB) is among diseases of global health importance with Sub Saharan Africa (SSA) accounting for 25% of the global TB burden. TB prevalence among miners in SSA is estimated at 3,000-7,000/100,000, which is about 3 to 10-times higher than in the general population. The study's objective was to determine the prevalence of TB and associated risk factors among mining communities in Mererani, northern Tanzania. This was a cross-sectional study conducted from April 2019 to November 2021 involving current Small Scale Miners (SSM) and the General Community (GC). A total of 660 participants, 330 SSM and 330 GC were evaluated for the presence of TB. Data were analysed using Statistical Package for the Social Sciences (SPSS) database (IBM SPSS Statistics Version 27.0.0.0). Binary logistic regression (Generalized Linear Mixed Model) was used to determine the association between TB and independent predictors. Prevalence of TB was 7%, about 24-times higher than the national prevalence of 0.295%. Participants from the general community had higher prevalence of TB 7.9% than SSM (6.1%). Both for SSM and the GC, TB was found to be associated with: lower education level (aOR = 3.62, 95%CI = 1.16-11.28), previous lung disease (aOR = 4.30, 95%CI = 1.48-12.53) and having symptoms of TB (aOR = 3.24, 95%CI = 1.38-7.64). Specifically for the SSM, TB was found to be associated with Human Immunodeficiency Virus (HIV) infection (aOR = 8.28, 95%CI = 1.21-56.66). Though significant progress has been attained in the control of the TB epidemic in Tanzania, still hot spots with significantly high burden of TB exists, including miners. More importantly, populations surrounding the mining areas, are equally affected, and needs more engagement in the control of TB so as to realize the Global End TB targets of 2035.

Withaferin A Protects against Primary and Recurrent Tuberculosis by Modulating Mycobacterium-Specific Host Immune Responses.

The fate of Mycobacterium tuberculosis infection is governed by immune signaling pathways that can either eliminate the pathogen or result in tuberculosis (TB). Anti-TB therapy (ATT) is extensive and is efficacious only against active, drug-sensitive strains of M. tuberculosis. Due to severe side effects, ATT often causes impairment of host immunity, making it imperative to use novel immunotherapeutics for better clinical outcomes. In this study, we have explored the immunomodulatory potential of withaferin A (WA) as an immunotherapeutic against TB. Here, we demonstrate that WA can constrain intracellular drug-sensitive and -resistant strains of M. tuberculosis by augmenting host immune responses. We also established the potential of WA treatment in conjunction with isoniazid. We show that WA directs the host macrophages toward defensive M1 polarization and enhances TH1 and TH17 immune responses against M. tuberculosis infection. The reduced bacterial burden upon T cell adoptive transfer further corroborated the augmented T cell responses. Interestingly, WA stimulated the generation of T cell memory populations by instigating STAT signaling, thereby reducing the rate of TB recurrence due to reactivation and reinfection. We substantiate the prospects of WA as a potent adjunct immunomodulator that enriches protective memory cells by prompting STAT signaling and improves host defense against M. tuberculosis. IMPORTANCE Despite being extensive, conventional antituberculosis therapy (ATT) is barely proficient in providing sterile immunity to tuberculosis (TB). Failure to constrain the escalating global TB burden due to the emergence of drug-resistant bacterial strains and immune dampening effects of ATT necessitates adjunct immunotherapeutics for better clinical outcomes. We evaluated the prospects of withaferin A (WA), an active constituent of Withania somnifera, as an adjunct immunomodulator against diverse M. tuberculosis strains. WA efficiently restricts the progression of TB by stimulating antimycobacterial host responses, protective immune signaling, and activation of diverse immune cell populations. Protective effects of WA can be attributed to the enrichment of memory T cells by induction of STAT signaling, thereby enhancing resistance to reinfections and reactivation of disease. We ascertained the immunotherapeutic potential of WA in boosting host immune responses against M. tuberculosis.

Trends in Rifampicin Resistance Among Children With Presumptive TB in the Pre-COVID and COVID-Era

Publications on COVID-19's impact on the global tuberculosis burden are from adult cohorts, pediatric data are lacking for inform decision. We compared the TB trends in southern Nigerian children in the pre-COVID-19 and COVID-19 era. This was a retrospective, cross-sectional study of early morning sputum/gastric washing or stool samples from children with presumptive TB evaluated using GeneXpert in a tertiary hospital from January 2016 to May 2022. Of the 20 589 persons screened for presumed TB in the pre-COVID-19 and the COVID-19 era, only 1104 (88.7%) of 1245 children had complete data for analysis. In the COVID era, a significantly higher number of children were presumed to have TB 755 (68.4%), P < .001. The overall incidence of MTB detected by Xpert MTB/RIF during the study period was 6.4% (71/1104). The incidence of MTB in the pre-COVID-19 era was 24/349 (6.9%), which was slightly higher than the COVID-19 era (47/755; 6.2%), P > .05). The annual trends of MTB detected peaked in 2019 [18/115; 15.7%] in the pre-COVID-19 era, then plummeted to 12/228 (5.3%) in 2020 in the COVID-19 era, and reached its all-time low of 6/160 (3.8%) in the first half of 2022, (P < .001). The overall incidence of Rifampicin-resistant TB (RR-TB) was 2.8% among the MTB detected cases and all occurred in the COVID-19 era. This study found a significant decline in MTB diagnosis and in the emergence of RR-TB in the COVID-19 era. This necessitates re-prioritizing worldwide efforts to manage childhood tuberculosis, including increased testing, if the aim of eliminating tuberculosis by 2035 is to be met.