scholarly journals Challenges in recruiting children to a multidrug-resistant TB prevention trial

2021 ◽  
Vol 25 (10) ◽  
pp. 814-822
Author(s):  
S. Purchase ◽  
E. Batist ◽  
N. Mmile ◽  
S. Nkosi ◽  
J. Workman ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Preventive Therapy ◽  
Prevention Trial ◽  
Flow Diagram ◽  
Data Systems ◽  
Successful Recruitment ◽  
Mdr Tb ◽  
Prevention Studies ◽  
Prevention Trials ◽  
Index Cases

BACKGROUND: Recruitment to randomised clinical trials can be challenging and slow recruitment has serious consequences. This study aimed to summarise and reflect on the challenges in enrolling young children to a multidrug-resistant TB (MDR-TB) prevention trial in South Africa.METHODS: Recruitment to the Tuberculosis Child Multidrug-resistant Preventive Therapy Trial (TB-CHAMP) was tracked using an electronic recruiting platform, which was used to generate a recruiting flow diagram. Structured personnel questionnaires, meeting minutes and workshop notes were thematically analysed to elucidate barriers and solutions.RESULT: Of 3,682 (85.3%) adult rifampicin (RIF) resistant index cases with pre-screening outcomes, 1597 (43.4%) reported having no children under 5 years in the household and 562 (15.3%) were RIF-monoresistant. More than nine index cases were pre-screened for each child enrolled. Numerous barriers to recruitment were identified. Thorough recruitment planning, customised tracking data systems, a dedicated recruiting team with strong leadership, adequate resources to recruit across large geographic areas, and excellent relationships with routine TB services emerged as key factors to ensure successful recruitment.CONCLUSION: Recruitment of children into MDR-TB prevention trials can be difficult. Several MDR-TB prevention trials are underway, and lessons learnt from TB-CHAMP will be relevant to these and other TB prevention studies.

scholarly journals Willingness to Take Multidrug-resistant Tuberculosis (MDR-TB) Preventive Therapy Among Adult and Adolescent Household Contacts of MDR-TB Index Cases: An International Multisite Cross-sectional Study

2019 ◽  
Vol 70 (3) ◽  
pp. 436-445
Author(s):  
Nishi Suryavanshi ◽  
Matthew Murrill ◽  
Amita Gupta ◽  
Michael Hughes ◽  
Anneke Hesseling ◽  
...  
Keyword(s):  
Multidrug Resistant ◽  
Cross Sectional Study ◽  
Preventive Therapy ◽  
Sectional Study ◽  
Cross Sectional ◽  
Household Contacts ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb ◽  
Index Cases

Abstract Background Household contacts (HHCs) of individuals with multidrug-resistant tuberculosis (MDR-TB) are at high risk of infection and subsequent disease. There is limited evidence on the willingness of MDR-TB HHCs to take MDR-TB preventive therapy (MDR TPT) to decrease their risk of TB disease. Methods In this cross-sectional study of HHCs of MDR-TB and rifampicin-resistant tuberculosis (RR-TB) index cases from 16 clinical research sites in 8 countries, enrollees were interviewed to assess willingness to take a hypothetical, newly developed MDR TPT if offered. To identify factors associated with willingness to take MDR TPT, a marginal logistic model was fitted using generalized estimating equations to account for household-level clustering. Results From 278 MDR-TB/RR-TB index case households, 743 HHCs were enrolled; the median age of HHCs was 33 (interquartile range, 22–49) years, and 62% were women. HHC willingness to take hypothetical MDR TPT was high (79%) and remained high even with the potential for mild side effects (70%). Increased willingness was significantly associated with current employment or schooling (adjusted odds ratio [aOR], 1.83 [95% confidence interval {CI}, 1.07–3.13]), appropriate TB-related knowledge (aOR, 2.22 [95% CI, 1.23–3.99]), confidence in taking MDR TPT (aOR, 7.16 [95% CI, 3.33–15.42]), and being comfortable telling others about taking MDR TPT (aOR, 2.29 [95% CI, 1.29–4.06]). Conclusions The high percentage of HHCs of MDR-TB/RR-TB index cases willing to take hypothetical MDR TPT provides important evidence for the potential uptake of effective MDR TPT when implemented. Identified HHC-level variables associated with willingness may inform education and counseling efforts to increase HHC confidence in and uptake of MDR TPT.

scholarly journals Feasibility of Identifying Household Contacts of Rifampin-and Multidrug-resistant Tuberculosis Cases at High Risk of Progression to Tuberculosis Disease

2019 ◽  
Vol 70 (3) ◽  
pp. 425-435 ◽  
Author(s):  
Amita Gupta ◽  
Susan Swindells ◽  
Soyeon Kim ◽  
Michael D Hughes ◽  
Linda Naini ◽  
...  
Keyword(s):  
High Risk ◽  
Multidrug Resistant ◽  
Cross Sectional Study ◽  
Preventive Therapy ◽  
Interferon Gamma Release Assay ◽  
Cross Sectional ◽  
Household Contacts ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Abstract Background We assessed multidrug-resistant tuberculosis (MDR-TB) cases and their household contacts (HHCs) to inform the development of an interventional clinical trial. Methods We conducted a cross-sectional study of adult MDR-TB cases and their HHCs in 8 countries with high TB burdens. HHCs underwent symptom screenings, chest radiographies, sputum TB bacteriologies, TB infection (TBI) testing (tuberculin skin test [TST] and interferon gamma release assay [IGRA]), and human immunodeficiency virus (HIV) testing. Results From October 2015 to April 2016, 1016 HHCs from 284 MDR-TB cases were enrolled. At diagnosis, 69% of MDR-TB cases were positive for acid-fast bacilli sputum smears and 43% had cavitary disease; at study entry, 35% remained smear positive after a median MDR-TB treatment duration of 8.8 weeks. There were 9 HHCs that were diagnosed with TB prior to entry and excluded. Of the remaining 1007 HHCs, 41% were male and the median age was 25 years. There were 121 (12%) HHCs that had new cases of TB identified: 17 (2%) were confirmed, 33 (3%) probable, and 71 (7%) possible TB cases. The TBI prevalence (defined as either TST or IGRA positivity) was 72% and varied by age, test used, and country. Of 1007 HHCs, 775 (77%) were considered high-risk per these mutually exclusive groups: 102 (10%) were aged <5 years; 63 (6%) were aged ≥5 and were infected with HIV; and 610 (61%) were aged ≥5 years, were negative for HIV or had an unknown HIV status, and were TBI positive. Only 21 (2%) HHCs were on preventive therapy. Conclusions The majority of HHCs in these high-burden countries were at high risk of TB disease and infection, yet few were receiving routine preventive therapy. Trials of novel, preventive therapies are urgently needed to inform treatment policy and practice.

scholarly journals Pharmacokinetics and Safety of Ofloxacin in Children with Drug-Resistant Tuberculosis

2015 ◽  
Vol 59 (10) ◽  
pp. 6073-6079 ◽  
Author(s):  
Anthony J. Garcia-Prats ◽  
Heather R. Draper ◽  
Stephanie Thee ◽  
Kelly E. Dooley ◽  
Helen M. McIlleron ◽  
...  
Keyword(s):  
Body Weight ◽  
Multivariable Analysis ◽  
Multidrug Resistant ◽  
Preventive Therapy ◽  
Pharmacokinetic Parameters ◽  
Time Curve ◽  
Treatment Regimens ◽  
Tb Treatment ◽  
Resistant Tuberculosis ◽  
Mdr Tb

ABSTRACTOfloxacin is widely used for the treatment of multidrug-resistant tuberculosis (MDR-TB). Data on its pharmacokinetics and safety in children are limited. It is not known whether the current internationally recommended pediatric dosage of 15 to 20 mg/kg of body weight achieves exposures reached in adults with tuberculosis after a standard 800-mg dose (adult median area under the concentration-time curve from 0 to 24 h [AUC0–24], 103 μg · h/ml). We assessed the pharmacokinetics and safety of ofloxacin in children <15 years old routinely receiving ofloxacin for MDR-TB treatment or preventive therapy. Plasma samples were collected predose and at 1, 2, 4, 8, and either 6 or 11 h after a 20-mg/kg dose. Pharmacokinetic parameters were calculated using noncompartmental analysis. Children with MDR-TB disease underwent long-term safety monitoring. Of 85 children (median age, 3.4 years), 11 (13%) were HIV infected, and of 79 children with evaluable data, 14 (18%) were underweight. The ofloxacin mean (range) maximum concentration (Cmax), AUC0–8, and half-life were 8.97 μg/ml (2.47 to 14.4), 44.2 μg · h/ml (12.1 to 75.8), and 3.49 h (1.89 to 6.95), respectively. The mean AUC0–24, estimated in 72 participants, was 66.7 μg · h/ml (range, 18.8 to 120.7). In multivariable analysis, AUC0–24was increased by 1.46 μg · h/ml for each 1-kg increase in body weight (95% confidence interval [CI], 0.44 to 2.47;P= 0.006); no other assessed variable contributed to the model. No grade 3 or 4 events at least possibly attributed to ofloxacin were observed. Ofloxacin was safe and well tolerated in children with MDR-TB, but exposures were well below reported adult values, suggesting that dosage modification may be required to optimize MDR-TB treatment regimens in children.

scholarly journals Drug susceptibility patterns of Mycobacterium tuberculosis from adults with multidrug-resistant tuberculosis and implications for a household contact preventive therapy trial

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Anne-Marie Demers ◽  
◽  
Soyeon Kim ◽  
Sara McCallum ◽  
Kathleen Eisenach ◽  
...  
Keyword(s):  
Mycobacterium Tuberculosis ◽  
Sputum Sample ◽  
Drug Susceptibility ◽  
Multidrug Resistant ◽  
Preventive Therapy ◽  
Drug Susceptibility Testing ◽  
Study Entry ◽  
Resistant Tuberculosis ◽  
Mdr Tb ◽  
Therapy Trial

Abstract Background Drug susceptibility testing (DST) patterns of Mycobacterium tuberculosis (MTB) from patients with rifampicin-resistant tuberculosis (RR-TB) or multidrug-resistant TB (MDR-TB; or resistant to rifampicin and isoniazid (INH)), are important to guide preventive therapy for their household contacts (HHCs). Methods As part of a feasibility study done in preparation for an MDR-TB preventive therapy trial in HHCs, smear, Xpert MTB/RIF, Hain MTBDRplus, culture and DST results of index MDR-TB patients were obtained from routine TB programs. A sputum sample was collected at study entry and evaluated by the same tests. Not all tests were performed on all specimens due to variations in test availability. Results Three hundred eight adults with reported RR/MDR-TB were enrolled from 16 participating sites in 8 countries. Their median age was 36 years, and 36% were HIV-infected. Routine testing on all 308 were confirmed as having RR-TB, but only 75% were documented as having MDR-TB. The majority of those not classified as having MDR-TB were because only rifampicin resistance was tested. At study entry (median 59 days after MDR-TB treatment initiation), 280 participants (91%) were able to produce sputum for the study, of whom 147 (53%) still had detectable MTB. All but 2 of these 147 had rifampicin DST done, with resistance detected in 89%. Almost half (47%) of the 147 specimens had INH DST done, with 83% resistance. Therefore, 20% of the 280 study specimens had MDR-TB confirmed. Overall, DST for second-line drugs were available in only 35% of the 308 routine specimens and 15% of 280 study specimens. Conclusions RR-TB was detected in all routine specimens but only 75% had documented MDR-TB, illustrating the need for expanded DST beyond Xpert MTB/RIF to target preventive therapy for HHC.

scholarly journals Is Chemoprophylaxis for Child Contacts of Drug-Resistant TB Patients Beneficial? A Systematic Review

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
C. Padmapriyadarsini ◽  
Mrinalini Das ◽  
Sharath Burugina Nagaraja ◽  
Mahalakshmi Rajendran ◽  
Richard Kirubakaran ◽  
...  
Keyword(s):  
Systematic Review ◽  
Case Reports ◽  
Meta Analysis ◽  
Multidrug Resistant ◽  
Preventive Therapy ◽  
Eligibility Criteria ◽  
Clinical Registries ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

Background. Preventive therapy for child contacts of multidrug-resistant tuberculosis (MDR-TB) patients is poorly studied, and no consensus about the role and the rationale of chemoprophylaxis has been reached. Objective. To conduct systematic review with an aim to determine the effectiveness of TB preventive therapy in reducing the incidence of TB disease in pediatric contacts of MDR-TB patients. Methods. We conducted a literature search for randomized control trials, cohort studies, and case reports of chemoprophylaxis for pediatric contacts of MDR-TB patients in PubMed, EMBASE, Cochrane Databases of Systematic Reviews, metaRegister of Controlled Trials, and other clinical registries through March 2017, using appropriate search strategy. In addition we searched abstracts from international conferences and references of published articles and reviews. Results. Of the 153 references assessed from various databases, seven studies were identified as relevant after adaption of eligibility criteria and assessed for systematic review. Of these, only two studies contributed data for the pooled meta-analysis. Conclusions. Though the available evidences suggest that the chemoprophylaxis for child contacts of MDR-TB patients is beneficial, data to support or reject preventive therapy is very limited. Further clinical research, in Tb endemic settings like India, needs to be performed to prove the beneficial effect of chemoprophylaxis for pediatric contacts of MDR-TB.

scholarly journals Preventive Therapy for Multidrug Resistant Latent Tuberculosis Infection: An Ethical Imperative with Ethical Barriers to Implementation?

2020 ◽  
pp. 19-35
Author(s):  
Binh Nguyen ◽  
Greg J. Fox ◽  
Paul H. Mason ◽  
Justin T. Denholm
Keyword(s):  
Social Impact ◽  
Latent Tuberculosis Infection ◽  
Latent Tuberculosis ◽  
Multidrug Resistant ◽  
Preventive Therapy ◽  
Tuberculosis Infection ◽  
Drug Resistant ◽  
Case Examples ◽  
Resistant Infection ◽  
Mdr Tb

Abstract Multidrug resistant tuberculosis (MDR-TB) has a substantial impact on individuals and communities globally, including lengthy, expensive and burdensome therapy with high rates of treatment failure and death. Strategies to prevent disease are well established for those who acquire latent tuberculosis infection (LTBI) after exposure to drug susceptible TB (DS-TB). However, there has been limited research or programmatic experience regarding the prevention of MDR-TB. Accordingly, while global recommendations strongly emphasize the need to deliver LTBI therapy after TB exposure, most programs do not do so where MDR LTBI is identified. The paucity of prospective randomized trial evidence for the effectiveness of MDR LTBI therapy, and concerns regarding its adverse effects, have been used to justify a reluctance to scale up programmatic interventions to prevent MDR-TB, or to participate in research evaluating such strategies. However, such a response fails to adequately balance potential risks of therapy with the substantial harms associated with inaction. Furthermore, the cost of inaction falls disproportionately on the most vulnerable members of society, including children. Delays in implementing proven preventive strategies may also mask hidden programmatic concerns, particularly regarding the financial cost and other burdens of treating drug resistant infection. Reticence to engage with preventative therapy for MDR-TB, even in the absence of high-level evidence, may run counter to the best interests of individuals who have been exposed to MDR-TB. This chapter will explore ethical tensions raised by expanding access to preventative therapies for MDR-TB, and consider how ethically optimal responses to this adverse condition may be evaluated. An ethical perspective on evidentiary burden will be addressed, emphasizing how MDR LTBI research may both offer, and be shaped by, paradigmatic insights into human research ethics more generally. Emerging research and illustrations from the authors programmatic engagement in Vietnam are offered as case examples, because social and community expectations and norms may challenge, or support, implementation of therapy for drug-resistant infection. Such circumstances prompt consideration of the broader questions of social impact, such as the potential for widespread preventive therapy to accelerate the development of antimicrobial resistance.

scholarly journals Implications of a school outbreak of multidrug-resistant tuberculosis in Northern China

2018 ◽  
Vol 146 (5) ◽  
pp. 584-588 ◽  
Author(s):  
Xiaoguang Wu ◽  
Yu Pang ◽  
Yanhua Song ◽  
Wenzhu Dong ◽  
Tingting Zhang ◽  
...  
Keyword(s):  
Treatment Outcomes ◽  
Diagnostic Delay ◽  
Northern China ◽  
Multidrug Resistant ◽  
Preventive Therapy ◽  
Primary Role ◽  
Pulmonary Tb ◽  
Resistant Tuberculosis ◽  
Multidrug Resistant Tuberculosis ◽  
Mdr Tb

AbstractIn this study, we identified a multidrug-resistant tuberculosis (MDR-TB) outbreak in a high school in northern China. The aim of this work was to describe TB transmission, drug resistance and treatment outcomes for this patient cluster. In January 2017, pulmonary TB was identified in a 17-year-old boy in northern China. Subsequently, a total of 11 TB cases were identified during 6-month follow-up of attendees of the same school. Of five students with latent TB infection (LTBI) receiving isoniazid preventive therapy (IPT), two pulmonary TB cases (40.0%) emerged in March and April, for an active case rate not significantly different from that of the non-IPT group (4/16, 25.0%, P = 0.598). All TB patients were first treated with a standardised first-line treatment regimen administered by the local TB hospital, with 11 of 12 active TB patients exhibiting poor treatment outcomes. Further data demonstrated that all nine patient isolates collected during this outbreak were MDR-TB and shared a common genotypic profile. In conclusion, our data demonstrate that diagnostic delay for the index MDR-TB case of this outbreak played a primary role in transmission of MDR-TB infection within a school setting. Importantly, IPT failed to prevent progression of MDR-TB from LTBI to active TB.

scholarly journals Levofloxacin versus placebo for the treatment of latent tuberculosis among contacts of patients with multidrug-resistant tuberculosis (the VQUIN MDR trial): a protocol for a randomised controlled trial

BMJ Open ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. e033945 ◽  
Author(s):  
Greg J Fox ◽  
Cam Binh Nguyen ◽  
Thu Anh Nguyen ◽  
Phuong Thuy Tran ◽  
Ben J Marais ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Controlled Trial ◽  
Latent Tuberculosis ◽  
Multidrug Resistant ◽  
Preventive Therapy ◽  
Positive Tuberculin Skin Test ◽  
Primary Study ◽  
Double Blind ◽  
Mdr Tb ◽  
Randomised Controlled

IntroductionTreatment of latent tuberculosis infection (LTBI) plays a substantial role in the prevention of drug-susceptible tuberculosis (TB). However, clinical trials to evaluate the efficacy of preventive therapy for presumed multidrug-resistant (MDR) LTBI are lacking. This trial aims to evaluate the efficacy of the antibiotic levofloxacin in preventing the development of active TB among latently infected contacts of index patients with MDR-TB.Methods and analysisA double-blind placebo-controlled parallel group randomised controlled trial will be conducted in 10 provinces of Vietnam. Household contacts living with patients with bacteriologically confirmed rifampicin-resistant or MDR-TB will be eligible for recruitment if they have a positive tuberculin skin test or are known to be immunosuppressed, and do not have active TB. Participants will be randomised to receive either levofloxacin or placebo tablets once per day for 6 months. Screening for incident TB will be performed at 6 months intervals. The primary study outcome is the incidence of bacteriologically confirmed TB within 30 months after randomisation. Analysis will be by intention to treat, using Poisson regression.EthicsEthical approval from the University of Sydney Human Research Ethics Committee was obtained on 29 April 2015 (2014/929), and from the Vietnam Ministry of Health Institutional Review Board on 30 September 2015 (4040/QD-BYT).DisseminationFindings of the study will be published in peer-reviewed publications and conference presentations.Trial registration numberACTRN12616000215426.

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