A systematic review and meta-analysis of the catastrophic costs incurred by tuberculosis patients

One of the strategies of the World Health Organization End Tuberculosis (TB) was to reduce the catastrophic costs incurred by TB-affected families to 0% by 2020.Catastrophic cost is defined by the total cost related to TB management exceeding 20% of the annual pre-TB household income. This study aimed to estimate the pooled proportion of TB affected households who incurred catastrophic costs. We searched PubMed, SciELO, Scopus, Embase, Google Scholar, ProQuest, SAGE, and Web of Science databases according to Preferred Reporting Items of the Systematic Reviews and Meta-Analysis (PRISMA) guidelines till November 20, 2020. Eligible studies were identified and data on catastrophic costs due to TB were extracted. We performed a meta-analysis to generate the pooled proportion of patients with TB facing catastrophic costs. From 5114 studies identified, 29 articles were included in the final analysis. The pooled proportion of patients faced catastrophic costs was (43%, 95% CI [34–51]). Meta-regression revealed that country, drug sensitivity, and Human immune-deficiency Virus (HIV) co-infection were the main predictors of such costs. Catastrophic costs incurred by drug sensitive, drug resistant, and HIV co-infection were 32%, 81%, and 81%, respectively. The catastrophic costs incurred were lower among active than passive case findings (12% vs. 30%). Half (50%) of TB-affected households faced catastrophic health expenditure at 10% cut-off point. The financial burden of patients seeking TB diagnosis and treatment continues to be a worldwide impediment. Therefore, the End TB approach should rely on socioeconomic support and cost-cutting initiatives.PROSPERO registration: CRD42020221283.

Optimized loading dose strategies for bedaquiline when restarting interrupted drug-resistant tuberculosis treatment

Interruption of treatment is common in drug-resistant tuberculosis patients. Bedaquiline has a long terminal half-life therefore, restarting after an interruption without a loading dose could increase the risk of suboptimal treatment outcome and resistance development. We aimed to identify the most suitable loading dose strategies for bedaquiline restart after an interruption. A model-based simulation study was performed. Pharmacokinetic profiles of bedaquiline and its metabolite M2 (associated with QT-prolongation) were simulated for 5000 virtual patients for different durations and starting points of treatment interruption. Weekly bedaquiline area under the concentration-time curve (AUC) and M2 maximum concentration (Cmax) deviation before interruption and after reloading were assessed to evaluate the efficacy and safety respectively of the reloading strategies. Bedaquiline weekly AUC and M2 Cmax deviation were mainly driven by the duration of interruption and only marginally by the starting point of interruption. For interruptions with a duration shorter than two weeks, no new loading dose is needed. For interruptions with durations between two weeks and one month, one month and one year, and longer than one year, reloading periods of three days, one week, and two weeks, respectively, are recommended. This reloading strategy results in an average bedaquiline AUC deviation of 1.88% to 5.98% compared with -16.4% to -59.8% without reloading for interruptions of two weeks and one year respectively, without increasing M2 Cmax. This study presents easy-to-implement reloading strategies for restarting a patient on bedaquiline treatment after an interruption.

Profile of Tuberculosis in Children and Adolescent at Dr. Soetomo General Hospital Surabaya

Introduction: Tuberculosis is one of ten leading causes of death worldwide, including Indonesia. Indonesia is one of seven countries that causes 64% deaths due to tuberculosis. Tuberculosis is caused by Mycobacterium tuberculosis through droplet nuclei in the air. It can occur to any group age, including children and adolescent, if there is a contact history of people with tuberculosis infection. In 2016, one million children had tuberculosis and around 250,000 children died because of tuberculosis. This study aimed to know the profile of tuberculosis in children and adolescent at Dr. Soetomo General Hospital Surabaya.Methods: This was a descriptive study using retrospective approach. Sample of this study was collected from electronic medical record provided by Dr. Soetomo General Hospital Surabaya using statistic formula of single sample for estimated population proportions of children and adolescent with tuberculosis from 2013-2017, with total samples of 149 people.Results: There were 149 samples of children and adolescent patients with tuberculosis. Most of the children were mostly 0-4 years old and 57% were female. 84% of the children had been immunized with BCG and classified as moderate, and 35% were under nutritional status. This study showed that 67% of the children in household contacts of adult tuberculosis patients also had tuberculosis. The most frequent symptoms of tuberculosis in children and adolescent were fever (72%) and cough (80%).Conclusion: Tuberculosis in children and adolescent is more likely to occur in children than adolescent, especially children within group age of 0-4 years old. The number of pulmonary tuberculosis in children and adolescent are higher than extrapulmonary tuberculosis.

Treatment Motivation in Lung Tuberculosis Patients at Public Health Centres in Denpasar City during COVID-19 Pandemic

Treatment motivation among patients were heavily influenced by duration of therapy and existing side effects. TB supervisors motivated patients in their therapy. Limited communication from TB supervisors due to COVID-19 pandemic risked lowering treatment motivation in TB patients. Objective: get a general description of treatment motivation in TB patients from PHC in Denpasar. Method: descriptive observational with cross-sectional design in March – August 2021 at five PHC in Denpasar area. This study was done online using questionnaire with Google Forms application. Motivation is grouped into low, moderate, and high based on scores from internal factors, external factors, confidence in treatment, and interpersonal help seeking. Results: 86% of patients (43 people) had high treatment motivation, 12% of patients (6 people) have moderate treatment motivation, and two percent of patients (1 people) had low treatment motivation. Summary: Most of TB patients had high treatment motivation (86%). Communication between TB supervisors and patients are highly advised to motivate patients and increase success rate of therapy. Keywords: [Anti tuberculosis drugs, Lung tuberculosis, Treatment motivation].

Pancreatic Tuberculosis: Current Update on Clinical Manifestation and Diagnostic Modalities

Pancreatic tuberculosis is a very rare disease in either immunocompetent or immunocompromised hosts.The incidence of pancreatic tuberculosis was reported to be less than 4.7% in an autopsy series on tuberculosis patients in 1944 and 2% in another autopsy series in 1966.Despite that, in recent times, an increase in the number of reports of pancreatic TB has been noted.This condition is possibly caused by an improvement in diagnostic imaging tools, the development of different techniques that make obtaining specimens from the pancreas possible, and an increase in HIV prevalence worldwide. Therefore, this review article discusses the current update in the clinical manifestations and diagnostic modalities of pancreatic tuberculosis.Pancreatic tuberculosis is a very rare condition with a various range of non-specific clinical presentation and image features overlapping with those seen in pancreatic neoplasia. A combination of diagnostic modalities should be done to establish a diagnosis of pancreatic tuberculosis. Currently, direct histopathological examination is the best way of diagnosing tuberculosis. US/CT/EUS-guided biopsy is the recommended diagnostic technique. Most patients with pancreatic tuberculosis respond well to anti-tuberculosis drugs.

Shedding Light on Autophagy During Human Tuberculosis. A Long Way to Go

Immunity against Mycobacterium tuberculosis (Mtb) is highly complex, and the outcome of the infection depends on the role of several immune mediators with particular temporal dynamics on the host microenvironment. Autophagy is a central homeostatic mechanism that plays a role on immunity against intracellular pathogens, including Mtb. Enhanced autophagy in macrophages mediates elimination of intracellular Mtb through lytic and antimicrobial properties only found in autolysosomes. Additionally, it has been demonstrated that standard anti-tuberculosis chemotherapy depends on host autophagy to coordinate successful antimicrobial responses to mycobacteria. Notably, autophagy constitutes an anti-inflammatory mechanism that protects against endomembrane damage triggered by several endogenous components or infectious agents and precludes excessive inflammation. It has also been reported that autophagy can be modulated by cytokines and other immunological signals. Most of the studies on autophagy as a defense mechanism against Mycobacterium have been performed using murine models or human cell lines. However, very limited information exists about the autophagic response in cells from tuberculosis patients. Herein, we review studies that face the autophagy process in tuberculosis patients as a component of the immune response of the human host against an intracellular microorganism such as Mtb. Interestingly, these findings might contribute to recognize new targets for the development of novel therapeutic tools to combat Mtb. Actually, either as a potential successful vaccine or a complementary immunotherapy, efforts are needed to further elucidate the role of autophagy during the immune response of the human host, which will allow to achieve protective and therapeutic benefits in human tuberculosis.