Treatment Of To Tuberculosis Research Articles

Household costs incurred when seeking and receiving paediatric tuberculosis services: a survey in Cameroon and Kenya

Background Elimination of catastrophic costs due to tuberculosis (TB) is one of the three targets of the World Health Organization (WHO) End TB Strategy. Limited data have yet been reported on the costs experienced by households of children receiving TB services. We quantified the economic impact on households with children seeking and receiving TB services during the Catalyzing Pediatric TB Innovations (CaP-TB) project in Cameroon and Kenya. Methods Within the INPUT stepped-wedge cluster-randomised study evaluating the effect of CaP-TB integration of TB services in paediatric entry points, we designed a cross-sectional facility-based survey with retrospective data collection using a standardised questionnaire adapted from the WHO Global taskforce on TB patient cost generic survey instrument. Caregivers of children receiving TB services (screening, diagnosis and treatment of drug-sensitive TB) during the CaP-TB project were interviewed between November 2020 and June 2021. Direct medical, direct non-medical, and indirect costs for TB services were analysed following WHO Global taskforce recommendations. We used the human capital and output-based approaches to estimating income loss. All costs are presented in 2021 US dollars. Results A total of 56 caregivers representing their households (Cameroon, 26, and Kenya, 30) were interviewed. The median household costs for TB services, estimated using the human capital approach, were $255 (IQR; $130-631) in Cameroon and $120 ($65-236) in Kenya. The main cost drivers across both countries were direct non-medical costs (transportation and food), 52%; and medical costs, 34%. Approximately 50% of households reported experiencing dissavings (taking a loan, or selling an asset) to deal with costs related to TB disease. Using a threshold of 20% of annual household income, 50% (95%CI; 37-63%) of households experienced catastrophic costs when using the human capital approach; (46% (95%CI; 29-65%) in Cameroon and 53% (95%CI; 36-70%) in Kenya). Estimated costs and incidence of catastrophic costs increased when using the output-based approach in a sensitivity analysis. Conclusions Accessing and receiving TB services for children results in high levels of cost to households, despite the provision of free TB services. Strategies to reduce costs for TB services for children need to address social protection measures or explore decentralisation. Registration: https://clinicaltrials.gov/ct2/show/NCT03862261.

Artemisia annua and Artemisia afra extracts exhibit strong bactericidal activity against Mycobacterium tuberculosis

Ethnopharmacological relevanceEmergence of drug-resistant and multidrug-resistant Mycobacterium tuberculosis (Mtb) strains is a major barrier to tuberculosis (TB) eradication, as it leads to longer treatment regimens and in many cases treatment failure. Thus, there is an urgent need to explore new TB drugs and combinations, in order to shorten TB treatment and improve outcomes. Here, we evaluated the potential of two Asian and African traditional medicinal plants, Artemisia annua, a natural source of artemisinin (AN), and Artemisia afra, as sources of novel antitubercular agents. Aim of the studyOur goal was to measure the activity of A. annua and A. afra extracts against Mtb as potential natural and inexpensive therapies for TB treatment, or as sources of compounds that could be further developed into effective treatments. Materials and methodsThe minimum inhibitory concentrations (MICs) of A. annua and A. afra dichloromethane extracts were determined, and concentrations above the MICs were used to evaluate their ability to kill Mtb and Mycobacterium abscessus in vitro. ResultsPrevious studies showed that A. annua and A. afra inhibit Mtb growth. Here, we show for the first time that Artemisia extracts have a strong bactericidal activity against Mtb. The killing effect of A. annua was much stronger than equivalent concentrations of pure AN, suggesting that A. annua extracts kill Mtb through a combination of AN and additional compounds. A. afra, which produces very little AN, displayed bactericidal activity against Mtb that was substantial but weaker than that of A. annua. In addition, we measured the activity of Artemisia extracts against Mycobacterium abscessus. Interestingly, we observed that while A. annua is not bactericidal, it inhibits growth of M. abscessus, highlighting the potential of this plant in combinatory therapies to treat M. abscessus infections. ConclusionOur results indicate that Artemisia extracts have an enormous potential for treatment of TB and M. abscessus infections, and that these plants contain bactericidal compounds in addition to AN. Combination of extracts with existing antibiotics may not only improve treatment outcomes but also reduce the emergence of resistance to other drugs.

Status of vitamin D and the associated host factors in pulmonary tuberculosis patients and their household contacts: A cross sectional study

Innate immunity plays an important role in pathophysiology of tuberculosis which is influenced by various host factors. One such factor is vitamin D which, along with its associated molecule, can alter the host defense against Mycobacterium Tuberculosis (M.Tb.) via altered production of cathelicidin and nitric oxide, both having bactericidal effect. Therefore, assessment of vitamin D and its associated molecules in tuberculosis patients and household contacts as compared to healthy controls were done and the implication of these findings in susceptibility to tuberculosis (TB) was studied. 80 active TB patients, 75 household contacts and 70 healthy controls were included. Vitamin D receptor (VDR), vitamin D binding protein (VDBP) and inducible nitric oxide synthase (iNOS) mRNA levels were studied using quantitative PCR. Serum VDR, cathelicidin, and iNOS levels were measured using ELISA. Vitamin D and NO levels were measured in serum using chemiluminescence based immunoassay and greiss reaction based colorimetry kit respectively. Decreased serum levels of vitamin D were observed in active TB patients as compared to healthy controls (p < 0.001). VDR and iNOS mRNA levels were found to be significantly lower in active TB patients compared to household contacts and healthy controls (p < 0.0001 and 0.005 respectively). VDBP mRNA expression was found to be lower in active TB group as compared to household contacts and healthy controls however the difference was not found to be significant (p > 0.21). Although, mRNA expression of VDR, VDR protein and iNOS along with vitamin D levels were significantly (p < 0.05) higher in household contacts compared to active TB group. However, levels of iNOS, NO and cathelicidin were found to be higher in TB patients as compared to household contacts and healthy controls (p < 0.01, 0.05 and 0.01 respectively). Higher levels of Vitamin D along with VDR and iNOS expression in household contacts as compared to active TB patients suggest vitamin D might have a protective role against TB plausibly decreasing disease susceptibility. Low vitamin D levels in active TB patients warrants further studies to determine the role of vitamin D supplementation in prevention and treatment of TB.

Adherence interventions and outcomes of tuberculosis treatment: A systematic review and meta-analysis of trials and observational studies.

BackgroundIncomplete adherence to tuberculosis (TB) treatment increases the risk of delayed culture conversion with continued transmission in the community, as well as treatment failure, relapse, and development or amplification of drug resistance. We conducted a systematic review and meta-analysis of adherence interventions, including directly observed therapy (DOT), to determine which approaches lead to improved TB treatment outcomes.Methods and findingsWe systematically reviewed Medline as well as the references of published review articles for relevant studies of adherence to multidrug treatment of both drug-susceptible and drug-resistant TB through February 3, 2018. We included randomized controlled trials (RCTs) as well as prospective and retrospective cohort studies (CSs) with an internal or external control group that evaluated any adherence intervention and conducted a meta-analysis of their impact on TB treatment outcomes. Our search identified 7,729 articles, of which 129 met the inclusion criteria for quantitative analysis. Seven adherence categories were identified, including DOT offered by different providers and at various locations, reminders and tracers, incentives and enablers, patient education, digital technologies (short message services [SMSs] via mobile phones and video-observed therapy [VOT]), staff education, and combinations of these interventions. When compared with DOT alone, self-administered therapy (SAT) was associated with lower rates of treatment success (CS: risk ratio [RR] 0.81, 95% CI 0.73–0.89; RCT: RR 0.94, 95% CI 0.89–0.98), adherence (CS: RR 0.83, 95% CI 0.75–0.93), and sputum smear conversion (RCT: RR 0.92, 95% CI 0.87–0.98) as well as higher rates of development of drug resistance (CS: RR 4.19, 95% CI 2.34–7.49). When compared to DOT provided by healthcare providers, DOT provided by family members was associated with a lower rate of adherence (CS: RR 0.86, 95% CI 0.79–0.94). DOT delivery in the community versus at the clinic was associated with a higher rate of treatment success (CS: RR 1.08, 95% CI 1.01–1.15) and sputum conversion at the end of two months (CS: RR 1.05, 95% CI 1.02–1.08) as well as lower rates of treatment failure (CS: RR 0.56, 95% CI 0.33–0.95) and loss to follow-up (CS: RR 0.63, 95% CI 0.40–0.98). Medication monitors improved adherence and treatment success and VOT was comparable with DOT. SMS reminders led to a higher treatment completion rate in one RCT and were associated with higher rates of cure and sputum conversion when used in combination with medication monitors. TB treatment outcomes improved when patient education, healthcare provider education, incentives and enablers, psychological interventions, reminders and tracers, or mobile digital technologies were employed. Our findings are limited by the heterogeneity of the included studies and lack of standardized research methodology on adherence interventions.ConclusionTB treatment outcomes are improved with the use of adherence interventions, such as patient education and counseling, incentives and enablers, psychological interventions, reminders and tracers, and digital health technologies. Trained healthcare providers as well as community delivery provides patient-centered DOT options that both enhance adherence and improve treatment outcomes as compared to unsupervised, SAT alone.

Factors influencing adherence to tuberculosis treatment in Asmara, Eritrea: a qualitative study

BackgroundNon-adherence to tuberculosis (TB) treatment is an important barrier for TB prevention and control. Poor adherence may result in prolonged disease infectiousness, drug resistance, relapse and death. The aim of this study was to assess factors influencing adherence to tuberculosis treatment in selected health facilities in Asmara, Eritrea.MethodsA qualitative study which included in-depth interviews with 12 TB patients, three focus group discussions in selected health facilities in which one group comprised eight patients and key informant interviews with three health workers. Data analysis was done by translating and transcribing the verbatim of the interviews and focus group discussions. Transcribed data was then analysed using thematic framework procedure.ResultsThis study found that patients lacked knowledge about the cause, transmission and duration of treatment of TB. The most common reason mentioned for discontinuing treatment was the patient “felt cured”. Almost half of the respondents did not know the standard treatment duration and the consequences they face if they halt treatment. Patients reported losing their job when their diagnosis was known, were too ill to continue working or unable to find daily work due to time-consuming treatment arrangements. With few exceptions, the majority of patients reported that the short distance to the clinic encouraged them to attend regular treatment follow-up. Most of the respondents were unable to get enough food, leading to stress and feelings of hopelessness. Lack of social support for most of the patients was a critical factor for adherence as were stigma, medication side effects and long treatment duration. Recognized as an enabler to treatment adherence, health workers had good communication and positive attitude towards their patients.ConclusionLack of knowledge, loss of income, stigma and lack of social support, drug side effects and long treatment duration emerged as important barriers for treatment adherence. Short distances to health facilities, good communication and accepting attitude of health care providers emerged as enablers for treatment adherence. For better treatment adherence, comprehensive health education at treatment sites, patient’s family members and the community at large and strengthening of social support structures need to be addressed.

Factors influencing knowledge on completion of treatment among TB patients under directly observed treatment strategy, in selected health facilities in Embu County, Kenya.

IntroductionThe World Health Organization (WHO) promotes the Directly Observed Treatment (DOT) strategy as the standard to increase adherence to Tuberculosis (TB) medication. However, cases of retreatment and Multi Drug Resistant continue to be reported in many parts of Kenya. This study sought to determine the factors influencing the completion of tuberculosis medication among TB patients in Embu County, Kenya.MethodsA descriptive cross-sectional study was conducted on a population of tuberculosis patients under DOT attending selected TB treatment clinics in Embu County, in Kenya. One hundred and forty TB patients interviewed within a period of 3 months. Data were analyzed using SPSS version 17.0 and included Bivariate and Multivariate Analysis. The level of significance was p≤ 0.05.ResultsThe male and female participants were 61.4% and 38.6% respectively. The mean age of the respondents was 35±31.34-39.3 years. For the majority (52%) of the participants, the highest level of education was primary education. The unemployed participants formed the highest number of the respondent in the study (73%). The majorities (91.4%0) of the respondents were under the home-based DOT strategy (91.4%, 95% C.I: 85.5-95.5). Bivariate analysis using Chi-square showed that the level of education (p=0.003), patients feeling uncomfortable during supervision (p=0.01), and knowledge regarding the frequency of taking medication (p=0.004) were all significantly associated with knowledge regarding the importance of completion of medication. However, none of these factors was significant after multivariate analysis.ConclusionMost participants did not know the importance of completion of medication. TB programs should come up with better ways to educate TB patients on the importance of supervision and treatment completion during the treatment of TB. The education programs should focus on influencing the attitudes of patients and creating awareness about the importance of treatment completion. The TB programs should be designed towards eliminating the factors influencing the completion of TB medication.

Genetic susceptibility in tuberculosis

The importance of host genetic factors in determining susceptibility to tuberculosis (TB) has been studied extensively using various methods, such as case-control, candidate gene and genome-wide linkage studies. Several important candidate genes like human leucocyte antigen/alleles and non-human leucocyte antigen genes, such as cytokines and their receptors, chemokines and their receptors, pattern recognition receptors (including toll-like receptors, mannose binding lectin and the dendritic cell-specific intercellular adhesion molecule-3 grabbing nonintegrin), solute carrier family 11A member 1 (formerly known as natural resistance-associated macrophage protein 1) and purinergic P2X7 receptor gene polymorphisms, have been associated with differential susceptibility to TB in various ethnic populations. This heterogeneity has been explained by host-pathogen and gene-environment interactions and evolutionary selection pressures. Although the achievements of genetics studies might not yet have advanced the prevention and treatment of TB, researchers have begun to widen their scope of investigation to encompass these practical considerations.

Review: Managing TB in the 21st century: existing and novel drug therapies

With an estimated one-third of the world's population infected with Mycobacterium tuberculosis (MTB) and approximately 1.6 million deaths in 2006 attributed to tuberculosis (TB) world-wide, TB remains a major public health concern today. Considerable advances have been made in the effective treatment of TB, in particular with the adoption of directly observed therapy short course (DOTS), in national TB control programs, but in spite of this the currently available regimens are suboptimal. The long courses of therapy required, together with significant medication side-effects and resulting difficulties with adherence to therapy all contribute to increasing problems with emerging drug resistance. There is thus an urgent need for new antituberculous drug development, especially to enable effective shorter course therapy for drug-susceptible and resistant TB, to find effective drugs for treatment of drug-resistant TB, to shorten therapy for latent TB infection and to reduce drug interactions in combination with antiretroviral therapy, a major issue in the treatment of HIV co-infected patients. This review will attempt to summarize the current recommendations for treatment of TB and then describe the most promising new antimicrobials with activity against MTB, focusing on the ones currently undergoing clinical trials.

Neutrophil-mediated innate immune resistance to mycobacteria.

Neutrophils contain antimicrobial peptides with antituberculous activity, but their contribution to immune resistance to tuberculosis (TB) infection has not been previously investigated to our knowledge. We determined differential white cell counts in peripheral blood of 189 adults who had come into contact with patients diagnosed with active TB in London, United Kingdom, and evaluated them for evidence of TB infection and capacity to restrict mycobacterial growth in whole-blood assays. Risk of TB infection was inversely and independently associated with peripheral blood neutrophil count in contacts of patients diagnosed with pulmonary TB. The ability of whole blood to restrict growth of Mycobacterium bovis bacille Calmette Guérin and Mycobacterium tuberculosis was impaired 7.3- and 3.1-fold, respectively, by neutrophil depletion. In microbiological media, human neutrophil peptides (HNPs) 1-3 killed M. tuberculosis. The neutrophil peptides cathelicidin LL-37 and lipocalin 2 restricted growth of the organism, the latter in an iron-dependent manner. Black African participants had lower neutrophil counts and lower circulating concentrations of HNP1-3 and lipocalin 2 than south Asian and white participants. Neutrophils contribute substantially to innate resistance to TB infection, an activity associated with their antimicrobial peptides. Elucidation of the regulation of neutrophil antimicrobial peptides could facilitate prevention and treatment of TB.

Sharing the burden of TB/HIV? Costs and financing of public–private partnerships for tuberculosis treatment in South Africa

To explore the economic costs and sources of financing for different public-private partnership (PPP) arrangements to tuberculosis (TB) provision involving both workplace and non-profit private providers in South Africa. The financing required for the different models from the perspective of the provincial TB programme, provider, and the patient are considered. Two models of TB provider partnerships were evaluated, relative to sole public provision: public-private workplace (PWP) and public-private non-government (PNP). The cost analysis was undertaken from a societal perspective. Costs were collected retrospectively to consider both the financial and economic costs. Patient costs were estimated using a retrospective structured patient interview. Expansion of PPPs could potentially lead to reduced government sector financing requirements for new patients: government financing would require $609-690 per new patient treated in the purely public model, in contrast to PNP sites which would only need to $130-139 per patient and $36-46 with the PWP model. Moreover, there are no patient costs associated with the treatment in the employer-based facilities and the cost to the patient supervised in the community is, on average, three times lower than in public sector facilities. The results suggest that there is a strong economic case for expanding PPP involvement in TB treatment in the process of scaling up. The cost to the government per new patient treated could be reduced by enhanced partnership between the private and public sectors.

Tuberculosis Infection, a Challenge to Diagnose and Treatment in Hemodialysis Patients

PURPOSE OF STUDY: The immunologic rearrangements in chronic renal failure have increased the susceptibility to tuberculosis (TB) infection. We present our experience in the diagnosis and treatment of TB among hemodialysis patients in our centre. METHODS: Since 1997–2001 tuberculosis was diagnosed in 26 patients (17 male, 9 female, mean age: 44.5 ± 14.3 years, HD duration 52.6 ± 34.1 months) that make an incidence of %2 per year. RESULTS: TB infection was characterized with an insidious while the main symptoms were fever in 80.7%, weight loss in 46.1% and night sweats in 30.7% of the patients. PPD skin test was ≥ 10 mm in 46.1%, 5–10 mm in 30.8%, and anergic in 23.1% of the patients. The major site of presentation was extrapulmonary TB in 76.9% of the patients predominating as lymphadenitis in 11 patients where as there were bone involvements in 2, peritoneum 4, and liver granuloma formation in liver in 1 patient. In addition to 4 patients with pulmonary involvement, 2 patients were diagnosed to have miliary TB. Our therapy protocol included administration of morfazinamid and ethambutol for 2 months and isoniazid, rifampicin for 9 months. In patients with miliary TB streptomycin was added to therapy. Mortality rate was 15.3%, while the rest of the patients were completely cured of TB. Old age, presences of malnutrition and infection with other bacterial agents have been found to be the major factors influencing the morbidity and mortality in these patients. CONCLUSION: There is a high incidence of TB infection in HD patients in Turkey. Insidious onset and extrapulmonary involvement are challenging problems in the diagnosis. Mortality rate is still high despite appropriate treatment.