Exploring health care providers' engagement in prevention and management of multidrug resistant Tuberculosis and its factors in Hadiya Zone health care facilities: qualitative study.

BACKGROUND: Engagement of healthcare providers is one of the World Health Organization strategies devised for prevention and provision of patient centered care for multidrug resistant tuberculosis. The need for current research question rose because of the gaps in evidence on health professional's engagement and its factors in multidrug resistant tuberculosis service delivery as per the protocol in the prevention and management of multidrug resistant tuberculosis. PURPOSE: The purpose of this study was to explore the level of health care providers' engagement in multidrug resistant tuberculosis prevention and management and influencing factors in Hadiya Zone health facilities, Southern Ethiopia. METHODS: Descriptive phenomenological qualitative study design was employed between 02 May and 09 May, 2019. We conducted a key informant interview and focus group discussions using purposely selected healthcare experts working as directly observed treatment short course providers in multidrug resistant tuberculosis treatment initiation centers, program managers, and focal persons. Verbatim transcripts were translated to English and exported to open code 4.02 for line-by-line coding and categorization of meanings into same emergent themes. Thematic analysis was conducted based on predefined themes for multidrug resistant tuberculosis prevention and management and core findings under each theme were supported by domain summaries in our final interpretation of the results. To maintain the rigors, Lincoln and Guba's parallel quality criteria of trustworthiness was used particularly, credibility, dependability, transferability, confirmability and reflexivity. RESULTS: Total of 26 service providers, program managers, and focal persons were participated through four focus group discussion and five key informant interviews. The study explored factors for engagement of health care providers in the prevention and management of multidrug resistant tuberculosis in five emergent themes such as patients' causes, perceived susceptibility, seeking support, professional incompetence and poor linkage of the health care facilities. Our findings also suggest that service providers require additional training, particularly in programmatic management of drug-resistant tuberculosis. CONCLUSION: The study explored five emergent themes: patient's underlying causes, seeking support, perceived susceptibility, professionals' incompetence and health facilities poor linkage. Community awareness creation to avoid fear of discrimination through provision of support for those with multidrug resistant tuberculosis is expected from health care providers using social behavioral change communication strategies. Furthermore, program managers need to follow the recommendations of World Health Organization for engaging healthcare professionals in the prevention and management of multidrug resistant tuberculosis and cascade trainings in clinical programmatic management of the disease for healthcare professionals.

Pharmacokinetics and Optimal Dosing of Levofloxacin in Children for Drug-Resistant Tuberculosis: An Individual Patient Data Meta-Analysis.

BACKGROUND: Each year 25 000-32 000 children develop rifampicin- or multidrug-resistant tuberculosis (RR/MDR-TB), and many more require preventive treatment. Levofloxacin is a key component of RR/MDR-TB treatment and prevention, but the existing pharmacokinetic data in children have not yet been comprehensively summarized. We aimed to characterize levofloxacin pharmacokinetics through an individual patient data meta-analysis of available studies and to determine optimal dosing in children. METHODS: Levofloxacin concentration and demographic data were pooled from 5 studies and analyzed using nonlinear mixed effects modeling. Simulations were performed using current World Health Organization (WHO)-recommended and model-informed optimized doses. Optimal levofloxacin doses were identified to target median adult area under the time-concentration curve (AUC)24 of 101 mg·h/L given current standard adult doses. RESULTS: Data from 242 children (2.8 years [0.2-16.8] was used). Apparent clearance was 3.16 L/h for a 13-kg child. Age affected clearance, reaching 50% maturation at birth and 90% maturation at 8 months. Nondispersible tablets had 29% lower apparent oral bioavailability compared to dispersible tablets. Median exposures at current WHO-recommended doses were below the AUC target for children weighing <24 kg and under <10 years, resulting in approximately half of the exposure in adults. Model-informed doses of 16-33 mg/kg for dispersible tablets or 16-50 mg/kg for nondispersible tablets were required to meet the AUC target without significantly exceeding the median adult Cmax. CONCLUSIONS: Revised weight-band dosing guidelines with doses of >20 mg/kg are required to ensure adequate exposure. Further studies are needed to determine safety and tolerability of these higher doses.

The Impact of Preventive Treatment for Multidrug- and Rifampin-Resistant Tuberculosis Exceeds Trial-Based Estimates.

BACKGROUND: Several clinical trials of tuberculosis preventive treatment (TPT) for household contacts of patients with multidrug- or rifampin-resistant tuberculosis (MDR/RR-TB) are nearing completion. The potential benefits of delivering TPT to MDR/RR-TB contacts extend beyond the outcomes that clinical trials can measure. METHODS: We developed an agent-based, household-structured TB and MDR/RR-TB transmission model, calibrated to an illustrative setting in India. We simulated contact investigation in households of patients with MDR/RR-TB, comparing an MDR/RR-TPT regimen (assuming 6-month duration, 70% efficacy) and associated active case finding against alternatives of contact investigation without TPT or no household intervention. We simulated the TB and MDR/RR-TB incidence averted relative to placebo over 2 years, as measurable by a typical trial, as well as the incidence averted over a longer time horizon, in the broader population, and relative to no contact investigation. RESULTS: Observing TPT and placebo recipients for 2 years as in a typical trial, MDR/RR-TPT was measured to prevent 72% (interquartile range, 45%-100%) of incident MDR/RR-TB among recipients; the median number needed to treat (NNT) to prevent 1 MDR/RR-TB case was 73, compared to placebo. This NNT decreased to 54 with 13-18 years of observation, to 27 when downstream transmission effects were also considered, and to 12 when the effects of active TB screening were included by comparing to a no-household-contact-intervention scenario. CONCLUSIONS: If forthcoming trial results demonstrate efficacy, the long-term population impact of TPT for MDR/RR-TB-including the large effect of increased active TB detection among MDR/RR-TB contacts-could be much greater than suggested by trial outcomes alone.

Effectiveness and safety of tuberculosis preventive treatment for contacts of patients with multidrug-resistant tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Contacts of patients with multidrug-resistant tuberculosis (MDR-TB) are at risk of developing TB disease. Tuberculosis preventive treatment (TPT) is an intervention that can potentially reduce this risk. OBJECTIVES: To evaluate the effectiveness and safety of TPT for contacts of patients with MDR-TB. DATA SOURCES: EMBASE, PubMed, Web of Science, and the Cochrane Library were searched for eligible studies on 24 July 2023, without start date restrictions. STUDY ELIGIBILITY CRITERIA: We included studies that compared TPT with no treatment in contacts of patients with MDR-TB and reported outcomes of progression to TB disease. PARTICIPANTS: Contacts of patients with MDR-TB. INTERVENTIONS: TPT. ASSESSMENT OF RISK OF BIAS: A modified version of the Newcastle-Ottawa Scale was used. METHODS OF DATA SYNTHESIS: Random-effects meta-analysis was utilized to calculate the relative risk for disease progression to TB in contacts of patients with MDR-TB who received TPT compared to those who did not. Additionally, completion, adverse effect, and discontinued rates were assessed. RESULTS: Involving 1105 individuals from 11 studies, the pooled relative risk for disease progression in contacts receiving TPT versus those without treatment was 0.34 (95% CI: 0.16-0.72). Subgroup analysis indicated a lower pooled relative risk for regimens based on the drug-resistance profile of the index patients with TB compared to uniform treatment regimens (0.22 [95% CI: 0.06-0.84] vs. 0.49 [95% CI: 0.17-1.35]), although not statistically significant. The pooled completed rate was 83.8%, adverse effect rate was 22.9%, and discontinued rate was 6.5%. After excluding the levofloxacin and pyrazinamide regimen study, the completed rate increased to 88.0%, and adverse effects and discontinued rates decreased to 8.0% and 4.0%, respectively. DISCUSSION: TPT reduces TB disease progression risk in contacts of patients with MDR-TB. Tailored TPT regimens based on drug-resistance profiles may offer additional benefits. Furthermore, efforts to improve completed rates and manage adverse effects are essential for optimizing effectiveness and safety.

More Tailored Approaches to Tuberculosis Treatment and Prevention.

Recent advances in the treatment of tuberculosis (TB) have led to improvements unprecedented in our lifetime. Decades of research in developing new drugs, especially for multidrug-resistant TB, have created not only multiple new antituberculous agents but also a new approach to development and treatment, with a focus on maximizing the benefit to the individual patient. Prevention of TB disease has also been improved and recognized as a critical component of global TB control. While the momentum is positive, it will take continued investment at all levels, especially training of new dedicated TB researchers and advocates around the world, to maintain this progress.

[Diagnosis and Treatment Outcomes and Influencing Factors of Multidrug-Resistant Tuberculosis Based on Patient Pathway].

Multidrug-resistant tuberculosis (MDR-TB) has become one of the major challenges in the global tuberculosis (TB) control.Despite years of efforts on MDR-TB control,the treatment success rates in China have increased slowly,which indicates possible deficiencies in the management of prevention and control work.Therefore,it is necessary to analyze the current status of MDR-TB prevention and treatment based on the patient pathway.This review summarizes the current drop-out situation of MDR-TB patients in the diagnosis and treatment pathway and the factors affecting patients' outcomes in the whole pathway,so as to provide a scientific reference for the prevention and control of MDR-TB.

Epidemiology of tuberculosis in Mongolia: analysis of surveillance data, 2015-2019.

Mongolia has a high tuberculosis (TB) burden. Data from routine paper-based surveillance were used to describe the epidemiology of TB in Mongolia; the data included testing presumptive TB cases, TB notifications, drug-resistant cases, treatment outcomes and notifications in prisoners. The proportion of the population tested for TB increased between 2015 and 2019. The number and rate per 100 000 population of TB notifications decreased between 2015 and 2018 and then increased in 2019. Most TB notifications in 2019 were in the capital, Ulaanbaatar (59.3%), followed by the central (16.8%), Khangai (10.4%), east (8.5%) and west (5.0%) regions. About half of TB notifications nationally were bacteriologically confirmed (45.4% in 2015, 48.1% in 2019), with the proportion of bacteriologically confirmed TB per province or district varying from 0% to 66%. High TB notification rates were observed in 2019 for males aged 15-54 years (202 per 100 000population) and females aged 15-34 years (190 per 100 000 population). Treatment success for all forms of TB was 90% in 2019 but was below the 90% target for bacteriologically confirmed cases. Between 2015 and 2019, the number of RR/MDR-TB notifications ranged from 265 to 211. The Mongolian National Tuberculosis Programme needs to continue its efforts in TB control, to further increase the programmatic impact and reduce the TB burden. It is recommended that Mongolia continue to increase TB screening, the use of Xpert testing, contact investigations and preventive treatments, and targeting interventions to the high-burden areas identified in this subnational analysis.

[Progress in research of prophylactic therapy in contacts of rifampicin-resistant tuberculosis patients].

Tuberculosis (TB) prophylactic therapy for latent infection, which can reduce the risk for the development of active TB, is an important measure in TB control. China recommends prophylactic therapy for latent tuberculosis infection (LTBI) in some key populations to reduce the risk for TB. Contacts of patients with multi-drug and rifampicin-resistant TB (MDR/RR-TB) are at high risk for the infection with drug-resistant pathogen, however, no unified prophylactic therapy regimen has been recommended for LTBI due to exposure to MDR/RR-TB patients. This paper summarizes the current MDR/RR-TB prophylactic therapy regimen and its protection effect based on the results of the retrieval of literature, guidelines, expert consensus and technical specifications to provide reference for the prevention and control of LTBI.

Clinician perspectives of drug-resistant tuberculosis care services in the Philippines.

BACKGROUND/OBJECTIVES: In the Philippines, treatment success rates for drug-resistant tuberculosis (DR-TB) remains low and little is known about the quality of DR-TB services. This study aimed to explore clinician's perspectives of DR-TB care services. METHODS: We conducted semi-structured in-depth interviews from January-March 2018 with 11 providers selected purposively to explore the barriers associated with DR-TB care service delivery, best practices, and recommendations for enhancing patient care. Emerging themes were organized according to the socio-ecological framework. RESULTS: Five major themes were identified: (1) nurses do not feel empowered; (2) particular patients are left behind and more vulnerable than others; (3) infection control practices, fear, and limited capacity in rural health centers; (4) financial insecurity due to program reimbursement mechanisms; and (5) local government support is limited and requires more involvement in support of DR-TB elimination activities. Best practices focused on tailored approaches that eliminated structural, economic, and motivational barriers for patients. Participants recommended financial support from local government units, nutritional assistance for patients, and refresher training for healthcare workers. CONCLUSION: The findings provide additional understanding regarding the barriers that limit successful DR-TB care delivery and provide critical information to improve clinical practice and develop public health interventions for frontline staff including nurses in the Philippines. These strategies could ultimately reduce disparities associated with access to care and treatment adherence, if implemented.

Progress in research of prophylactic therapy in contacts of rifampicin-resistant tuberculosis patients / 中华流行病学杂志

Tuberculosis (TB) prophylactic therapy for latent infection, which can reduce the risk for the development of active TB, is an important measure in TB control. China recommends prophylactic therapy for latent tuberculosis infection (LTBI) in some key populations to reduce the risk for TB. Contacts of patients with multi-drug and rifampicin-resistant TB (MDR/RR-TB) are at high risk for the infection with drug-resistant pathogen, however, no unified prophylactic therapy regimen has been recommended for LTBI due to exposure to MDR/RR-TB patients. This paper summarizes the current MDR/RR-TB prophylactic therapy regimen and its protection effect based on the results of the retrieval of literature, guidelines, expert consensus and technical specifications to provide reference for the prevention and control of LTBI.

Diagnosis and Treatment Outcomes and Influencing Factors of Multidrug-Resistant Tuberculosis Based on Patient Pathway / 中国医学科学院学报

Multidrug-resistant tuberculosis (MDR-TB) has become one of the major challenges in the global tuberculosis (TB) control.Despite years of efforts on MDR-TB control,the treatment success rates in China have increased slowly,which indicates possible deficiencies in the management of prevention and control work.Therefore,it is necessary to analyze the current status of MDR-TB prevention and treatment based on the patient pathway.This review summarizes the current drop-out situation of MDR-TB patients in the diagnosis and treatment pathway and the factors affecting patients' outcomes in the whole pathway,so as to provide a scientific reference for the prevention and control of MDR-TB.

Knowledge of multidrug-resistant tuberculosis amongst Durban University of Technology students in KwaZulu-Natal, South Africa: the need for integrating public health education.

Background: Kwazulu-Natal is the epicenter of South Africa's Multidrug-resistant Tuberculosis (MDR-TB) burden which represents a growing threat to public health. Knowledge and awareness of MDR-TB are crucial for effective management and University students are an important vehicle for knowledge transfer of public health education. Objective: This study aimed to evaluate the knowledge of MDR TB and risk factors for transmission, prevention, treatment and control of MDR-TB among Durban University of Technology (DUT) students. Methods: This quantitative cross-sectional study was conducted among 150 randomly sampled undergraduate students from 3 faculties and data was collected using a validated questionnaire. Results: While a majority of participants (70.67%) had previous knowledge on TB, only 30.67% knew of MDR-TB. Only 23.49% of students reported knowledge of preventative measures associated with MDR TB. Women had a lower probability of having knowledge of MDR-TB compared to men (OR=0.45; CI:0.22,0.95; p<0.05) and students from the Accounting and Informatics faculty were less likely to believe that MDR-TB was a life-threatening illness (OR=0.24; CI:0.05,1.44; p<0.05) and showed limited knowledge of MDR-TB transmission. Conclusion: This study showed that students lacked knowledge of MDR-TB with respect to risk factors, treatment and prevention, which necessitates intervention strategies at a tertiary level to educate and inform students about MDR-TB.

Caregiver willingness to give TPT to children living with drug-resistant TB patients.

BACKGROUND Pediatric household contacts (HHCs) of patients with multidrug-resistant TB (MDR-TB) are at high risk of infection and active disease. Evidence of caregiver willingness to give MDR-TB preventive therapy (TPT) to children is limited.METHODS This was a cross-sectional study of HHCs of patients with MDR-TB to assess caregiver willingness to give TPT to children aged <13 years.RESULTS Of 743 adult and adolescent HHCs, 299 reported caring for children aged <13 years of age. The median caregiver age was 35 years (IQR 27-48); 75% were women. Among caregivers, 89% were willing to give children MDR TPT. In unadjusted analyses, increased willingness was associated with TB-related knowledge (OR 5.1, 95% CI 2.3-11.3), belief that one can die of MDR-TB (OR 5.2, 95% CI 1.2-23.4), concern for MDR-TB transmission to child (OR 4.5, 95% CI 1.6-12.4), confidence in properly taking TPT (OR 4.5, 95% CI 1.6-12.6), comfort telling family about TPT (OR 5.5, 95% CI 2.1-14.3), and willingness to take TPT oneself (OR 35.1, 95% CI 11.0-112.8).CONCLUSIONS A high percentage of caregivers living with MDR- or rifampicin-resistant TB patients were willing to give children a hypothetical MDR TPT. These results provide important evidence for the potential uptake of effective MDR TPT when implemented.

Practical and psychosocial challenges faced by caregivers influence the acceptability of multidrug-resistant tuberculosis preventive therapy for young children.

Drug-resistant (DR) strains of Mycobacterium tuberculosis (M. tb) are increasingly recognised as a threat to global tuberculosis (TB) control efforts. Identifying people with DR-TB exposure/ infection and providing TB preventive therapy (TPT) is a public health priority. TB guidelines advise the evaluation of household contacts of newly diagnosed TB cases, with the provision of TPT to vulnerable populations, including young children (<5 years). Many children become infected with TB through exposure in their household. Levofloxacin is under evaluation as TPT in children exposed to M. tb strains with resistance to rifampicin and isoniazid (multidrug-resistant TB; MDR-TB). Prior to opening a phase 3 prevention trial in children <5 years exposed to MDR-TB, the pharmacokinetics and safety of a novel formulation of levofloxacin given daily was evaluated as part of a lead-in study. We conducted an exploratory qualitative study of 10 caregivers' experiences of administering this formulation. We explored how the acceptability of levofloxacin as TPT is shaped by the broader impacts of MDR-TB on the overall psychological, social, and financial wellbeing of caregivers, many of whom also had experienced MDR-TB. Caregivers reported that the novel levofloxacin formulation was acceptable. However, caregivers described significant psychosocial challenges in the process of incorporating TPT administration to their children into their daily lives, including financial instability, withdrawal of social support and stigma. When caregivers themselves were sick, these challenges became even more acute. Although new child-friendly formulations can ameliorate some of the pragmatic challenges related to TPT preparation and administration, the overall psychosocial burden on caregivers responsible for administering TPT remains a major determinant of effective MDR-TB prevention in children.

The global impact of household contact management for children on multidrug-resistant and rifampicin-resistant tuberculosis cases, deaths, and health-system costs in 2019: a modelling study.

BACKGROUND: Estimates suggest that at least 30 000 children develop multidrug-resistant or rifampicin-resistant tuberculosis each year. Despite household contact management (HCM) being widely recommended, it is rarely done. METHODS: We used mathematical modelling to evaluate the potential country-level and global effects and cost-effectiveness of multidrug-resistant or rifampicin-resistant tuberculosis HCM for children younger than 15 years who are living with a person with newly diagnosed multidrug-resistant or rifampicin-resistant tuberculosis. We compared a baseline of no HCM with several HCM strategies and tuberculosis preventive therapy regimens, calculating the effect on multidrug-resistant or rifampicin-resistant tuberculosis cases, deaths, and health-system costs. All HCM strategies involved the screening of children for prevalent tuberculosis disease but with tuberculosis preventive therapy either not given or targeted dependent on age, HIV status, and result of tuberculin skin test. We evaluated the use of fluoroquinolones (ie, levofloxacin and moxifloxacin), delamanid, and bedaquiline as tuberculosis preventive therapy. FINDINGS: Compared with a baseline without HCM, HCM for all adults diagnosed with multidrug-resistant or rifampicin-resistant tuberculosis in 2019 would have entailed screening 227 000 children (95% uncertainty interval [UI]: 205 000-252 000) younger than 15 years globally, and averted 2350 tuberculosis deaths (1940-2790), costing an additional US$63 million (74-95 million). If all the children within the household who had been in contact with the person with multidrug-resistant or rifampicin-resistant tuberculosis received tuberculosis preventive therapy with levofloxacin, 5620 incident tuberculosis cases (95% UI 4540-6890) and an additional 1240 deaths (970-1540) would have been prevented. Incremental cost-effectiveness ratios were lower than half of per-capita gross domestic product for most interventions in most countries. Targeting only children younger than 5 years and those living with HIV reduced the number of incident cases and deaths averted, but improved cost-effectiveness. Tuberculosis preventive therapy with delamanid increased the effect, in terms of reduced incidence and mortality, compared with levofloxacin. INTERPRETATION: HCM for patients with multidrug-resistant or rifampicin-resistant tuberculosis is cost-effective in most settings and could avert a substantial proportion of multidrug-resistant or rifampicin-resistant tuberculosis cases and deaths in children globally. FUNDING: UK Medical Research Council.