High Multidrug-resistant Tuberculosis Research Articles

Patients' perceived quality of care and their satisfaction with care given for MDR-TB at referral hospitals in Ethiopia.

There is presently dearth of evidence in Ethiopia on patients' perception on quality of care given for multi-drug resistant tuberculosis (MDR-TB) and their satisfaction with the care and services they receive for the disease. Moreover, there is no evidence on the experiences and practices of caregivers for MDR-TB regarding the functionality of the programmatic management of MDR-TB at referral hospitals in Ethiopia. Thus, this study was conducted to address these gaps. Evidence in these areas would help to institute interventions that could enhance patient satisfaction and their adherence to the treatment given for MDR-TB. This study employed an inductive phenomenological approach to investigate patients' perception of the quality of care given for MDR-TB, level of their satisfaction with the care they received for MDR-TB and the experiences and practices of caregivers for MDR-TB on the functionality of the programmatic management of MDR-TB at referral hospitals in Ethiopia. The data were analysed manually, and that helped to get more control over the data. The majority of the patients were satisfied with the compassionate communication and clinical care they received at hospitals. However, as no doctor was dedicated exclusively for the MDR-TB centre of the hospitals, patients could not get timely medical attention during emergent medical conditions. Patients were dissatisfied with the poor communication and uncaring practice of caregivers found at treatment follow-up centres (TFCs). Patients perceived that socio-economic difficulties are both the cause of MDR-TB and it has also challenged their ability to cope-up with the disease and its treatment. Patients were dissatisfied with the poor quality and inadequate quantity of the socio-economic support they got from the programme. Despite the high MDR-TB and HIV/AIDS co-infection, services for both diseases were not available under one roof. Socio-economic challenges, inadequate socio-economic support, absence of integrated care for MDR-TB and HIV/AIDS, and the uncaring practice of caregivers at treatment follow-up centres are found to negatively affect patients' perceived quality of care and their satisfaction with the care given for MDR-TB. Addressing these challenges is recommended to assist patients' coping ability with MDR-TB and its treatment.

Contact screening and management in a high-transmission MDR-TB setting in Papua New Guinea: Progress, challenges and future directions

Daru, South Fly District, Papua New Guinea is a high transmission setting for multidrug-resistant tuberculosis (MDR-TB). An emergency response by the Government in 2014 established a high-quality model for treatment and care. Household contact screening and management commenced in 2016 with TB preventive treatment (TPT) for well young child (<5 years) contacts of people with drug-susceptible TB and later expanded to young child contacts of MDR-TB. The model of care is community-based and led by non-specialist health workers, under supervision. An electronic medical record system supports care, reporting and operational research. Community engagement and education has been central, with a concerted focus on peer-led counselling and patient-centred services to improve TPT uptake and completion. Challenges include the application of households as the unit of intervention for detection of active TB and TPT provision. Our implementation experience in Daru has highlighted significant population mixing dynamics with most transmission likely occurring outside the household. We propose a community-wide screening approach with the provision of TPT based on testing to include older children, adolescents, and young adults. As there is the possibility of MDR-TB infection irrespective of the drug susceptibility of the household index case, a novel option is a combination TPT regimen of 6 months of daily isoniazid and levofloxacin (6HLfx). A sensitive aged-related algorithm to detect and exclude active TB is being developed. Ongoing community engagement, quality data systems with operational research to evaluate approaches are critical in high transmission MDR-TB settings.

Prediction of drug resistance by Sanger sequencing of Mycobacterium tuberculosis complex strains isolated from multidrug resistant tuberculosis suspect patients in Ethiopia.

BackgroundEthiopia is one of the high multidrug-resistant tuberculosis (MDR-TB) burden countries. However, phenotypic drug susceptibility testing can take several weeks due to the slow growth of Mycobacterium tuberculosis complex (MTBC) strains. In this study, we assessed the performance of a Sanger sequencing approach to predict resistance against five anti-tuberculosis drugs and the pattern of resistance mediating mutations.MethodsWe enrolled 226 MTBC culture-positive MDR-TB suspects and collected sputum specimens and socio-demographic and TB related data from each suspect between June 2015 and December 2016 in Addis Ababa, Ethiopia. Phenotypic drug susceptibility testing (pDST) for rifampicin, isoniazid, pyrazinamide, ethambutol, and streptomycin using BACTEC MGIT 960 was compared with the results of a Sanger sequencing analysis of seven resistance determining regions in the genes rpoB, katG, fabG-inhA, pncA, embB, rpsL, and rrs.ResultDNA isolation for Sanger sequencing was successfully extracted from 92.5% (209/226) of the MTBC positive cultures, and the remaining 7.5% (17/226) strains were excluded from the final analysis. Based on pDST results, drug resistance proportions were as follows: isoniazid: 109/209 (52.2%), streptomycin: 93/209 (44.5%), rifampicin: 88/209 (42.1%), ethambutol: 74/209 (35.4%), and pyrazinamide: 69/209 (33.0%). Resistance against isoniazid was mainly mediated by the mutation katG S315T (97/209, 46.4%) and resistance against rifampicin by rpoB S531L (58/209, 27.8%). The dominating resistance-conferring mutations for ethambutol, streptomycin, and pyrazinamide affected codon 306 in embB (48/209, 21.1%), codon 88 in rpsL (43/209, 20.6%), and codon 65 in pncA (19/209, 9.1%), respectively. We observed a high agreement between phenotypic and genotypic DST, such as 89.9% (at 95% confidence interval [CI], 84.2%–95.8%) for isoniazid, 95.5% (95% CI, 91.2%–99.8%) for rifampicin, 98.6% (95% CI, 95.9–100%) for ethambutol, 91.3% (95% CI, 84.6–98.1%) for pyrazinamide and 57.0% (95% CI, 46.9%–67.1%) for streptomycin.ConclusionWe detected canonical mutations implicated in resistance to rifampicin, isoniazid, pyrazinamide, ethambutol, and streptomycin. High agreement with phenotypic DST results for all drugs renders Sanger sequencing promising to be performed as a complementary measure to routine phenotypic DST in Ethiopia. Sanger sequencing directly from sputum may accelerate accurate clinical decision-making in the future.

Time trend prediction and spatial–temporal analysis of multidrug-resistant tuberculosis in Guizhou Province, China, during 2014–2020

BackgroundGuizhou is located in the southwest of China with high multidrug-resistant tuberculosis (MDR-TB) epidemic. To fight this disease, Guizhou provincial authorities have made efforts to establish MDR-TB service system and perform the strategies for active case finding since 2014. The expanded case finding starting from 2019 and COVID-19 pandemic may affect the cases distribution. Thus, this study aims to analyze MDR-TB epidemic status from 2014 to 2020 for the first time in Guizhou in order to guide control strategies.MethodsData of notified MDR-TB cases were extracted from the National TB Surveillance System correspond to population information for each county of Guizhou from 2014 to 2020. The percentage change was calculated to quantify the change of cases from 2014 to 2020. Time trend and seasonality of case series were analyzed by a seasonal autoregressive integrated moving average (SARIMA) model. Spatial–temporal distribution at county-level was explored by spatial autocorrelation analysis and spatial–temporal scan statistic.ResultsGuizhou has 9 prefectures and 88 counties. In this study, 1,666 notified MDR-TB cases were included from 2014–2020. The number of cases increased yearly. Between 2014 and 2019, the percentage increase ranged from 6.7 to 21.0%. From 2019 to 2020, the percentage increase was 62.1%. The seasonal trend illustrated that most cases were observed during the autumn with the trough in February. Only in 2020, a peak admission was observed in June. This may be caused by COVID-19 pandemic restrictions being lifted until May 2020. The spatial–temporal heterogeneity revealed that over the years, most MDR-TB cases stably aggregated over four prefectures in the northwest, covering Bijie, Guiyang, Liupanshui and Zunyi. Three prefectures (Anshun, Tongren and Qiandongnan) only exhibited case clusters in 2020.ConclusionThis study identified the upward trend with seasonality and spatial−temporal clusters of MDR-TB cases in Guizhou from 2014 to 2020. The fast rising of cases and different distribution from the past in 2020 were affected by the expanded case finding from 2019 and COVID-19. The results suggest that control efforts should target at high-risk periods and areas by prioritizing resources allocation to increase cases detection capacity and better access to treatment.

Developing strategies to address barriers for tuberculosis case finding and retention in care among refugees in slums in Kampala, Uganda: a qualitative study using the COM-B model

BackgroundGlobally, displaced populations face an increased burden of tuberculosis (TB). Uganda is currently hosting unprecedented big numbers of refugees from the East African region. Recent evidence shows increased spread of multi-drug resistant TB (MDR-TB) across East Africa as a result of migrants from Somalia- a high MDR-TB prevalent country, calling for urgent identification and management of cases for the countries in the region. One of the strategies recommended is optimization of diagnosis, treatment and prevention of TB in refugees. This study aimed at exploring the barriers to and facilitators for TB case finding and retention in care among urban slum refugees and suggestions on how to improve. This was to guide the development of interventions to improve TB case finding and retention in care among the said population.MethodsA cross-sectional study utilizing qualitative methods was conducted among refugees in an urban slum in Kampala City, Uganda. Key informant interviews with health care workers and community leaders and in-depths interviews with refugee TB patients and care takers of TB patients were conducted (30 interviews in total). Interview questions were based on constructs from the COMB-B model (Capability, Opportunity and Motivation Model of Behaviour change). Manual content analysis was performed and identified targeted intervention strategies guided by the related Behavior Change Wheel implementation framework.ResultsKey barriers included; physical capability (availability of and easily accessible private facilities in the community with no capacity to diagnose and treat TB), psychological capability (lack of knowledge about TB among refugees), social opportunity (wide spread TB stigma and language barrier), physical opportunity (poor living conditions, mobility of refugees), reflective motivation (lack of facilitation for health workers), automatic motivation (discrimination and rejection of TB patients). Facilitators were; physical capability (availability of free TB services in the public health facilities), social opportunity (availability of translators). We identified education, incentivization, training, enablement, and restructuring of the service environment as relevant intervention functions with potential to address barriers to and enhance facilitators of TB case finding and retention among refugees in urban slums.ConclusionThe key barriers to TB control among refugees living urban slums in Kampala- Uganda, included; poor access to health services, limited knowledge about TB, TB stigma, language barrier and lack of facilitation of community health workers. Identified intervention strategies included; education, training, enablement, environmental restructuring and persuasion. The findings could serve as a guide for the design and implementation of interventions for improving the same.

A retrospective analytical study of treatment outcomes among multi drug resistant tuberculosis patients

Background: India is amongst one of the high multidrug resistant tuberculosis (MDR-TB) burden countries globally with a huge contribution given by the state of Uttar Pradesh. Programmatic Management of Drug Resistant Tuberculosis, initiated in 2007 has taken over the disorganized and unsupervised treatment practice in India. However, regular scrutiny is required which points out both its success and failure. Aim & Objective: This study was conducted to evaluate final treatment outcomes among MDR-TB patients on standard Category IV regimen Settings and Design: Retrospective analysis was done using secondary data from medical records of all patients. Methods and Material: Data of all MDR-TB patients registered under RNTCP at King George’s Medical University, Lucknow from 2013 to 2016 was collected. Demographic details along with pre-defined treatment outcomes were recorded (cured, treatment completed, death, treatment failure, treatment default and transfer to higher centre). Statistical analysis used: Descriptive statistics using numbers and percentage. Results: The records of 3580 MDR tuberculosis patients registered at drug resistant tuberculosis centre in King George’s Medical University from January 2013 to December 2016 were included which consisted of 67%males and 33%female. Mean age of presentation was 31.17 years (95% CI 30.75-31.59). Mean weight of patients was 40.16 kg (95% CI 39.89-40.43). Year wise distribution of registered cases from 2013 to 2016 was 611, 799, 984 and 1186 patients respectively. Amongst 3580 patients, 30.39% were declared cured, 25.50% completed treatment, 21.39% died, 0.84% showed treatment failure, 12.54% were defaulters, 2.35% were transferred out to higher centre, 6.5% were shifted to regimen for Extensive drug resistant (EDR) TB, 0.16% patients needed to stop treatment due to ADR and 0.33% patient were still on treatment. Conclusion: The treatment success rate of MDR?TB patients is still low. Measures to improve treatment adherence as in National tuberculosis elimination programme (NTEP) attempts to further improve the success rate.

Explorative Analysis of Treatment Outcomes of Levofloxacin- and Moxifloxacin-Based Regimens and Outcome Predictors in Ethiopian MDR-TB Patients: A Prospective Observational Cohort Study

Purpose/BackgroundAlthough Ethiopia is among the thirty high multi-drug resistant tuberculosis (MDR-TB) burden countries in the world, comparative therapeutic efficacy of moxifloxacin and levofloxacin has not been explored, particularly in MDR-TB patients. We therefore aimed to prospectively compare clinical outcomes and determine potential predictors of the outcomes among patients on moxifloxacin or levofloxacin-based MDR-TB drug regimens.MethodsWe analyzed clinical parameters and laboratory data of eighty MDR-TB patients on moxifloxacin- or levofloxacin-based regimens. The clinical outcomes were compared using the Kaplan–Meier survival functions and the outcome definitions of the 2013 World Health Organization. Monthly sputum culture conversions and a molecular line probe assay results were also assessed. Observed outcomes and patient-related variables between the two groups were compared using chi-square, Wilcoxon Rank and Fisher exact tests. We also determined the potential predictors influencing treatment outcomes of moxifloxacin and levofloxacin using Cox proportional hazard model.ResultsThe levofloxacin-based treatment group had a lower failure rate and adverse drug events as well as better treatment success than the moxifloxacin-based group. Overall treatment success was 65%. Disaggregating the data revealed that 53.8% were cured, 11.2% completed treatment, 10.0% died, 11.2% failed, and 13.8% were lost-to-follow-up. The line probe assay result showed that 11.3% of the clinical isolates were resistant to fluoroquinolones and 3.8% were resistant to both fluoroquinolones and injectable anti-TB agents. Treatment regimen type, culture conversion rate, alcohol use, cavity lesion, serum levels of creatinine and alanine aminotransferase were independent predictors of treatment outcome.ConclusionThe levofloxacin-based regimen group has a better overall treatment success than the moxifloxacin-based group among MDR-TB patients. Clinical parameters and substance use history of the patients influenced treatment outcomes. We recommend further broader clinical studies to substantiate our findings as an input to review MDR-TB treatment guidelines.

Local Transmission Plays No Important Role in the Occurrence of Multidrug-Resistant Tuberculosis in Immigrants to Canada: An In-depth Epidemiologic Analysis.

Multidrug-resistant (MDR) tuberculosis has increased among migrants in Canada. The cause(s) of this increase is unknown. We performed a retrospective cohort study in a Canadian province with substantially increased immigration between 1982-2001 and 2002-2019. The proportion of MDR tuberculosis among migrants arriving from high MDR (HMDR) tuberculosis burden countries during these 2 periods was used to estimate the proportion of cases due to immigration versus change in proportion in the country of birth. Epidemiologic, spatiotemporal, and drug resistance pattern data were used to confirm local transmission. Fifty-two of 3514 (1.48%) foreign-born culture-positive tuberculosis patients had MDR tuberculosis: 8 (0.6%) in 1982-2001 and 44 (2.0%) in 2002-2019. Between time periods, the proportion of MDR tuberculosis among migrants with tuberculosis from HMDR tuberculosis countries increased from 1.11% to 3.62%, P = .003; 31.6% attributable to recent immigration and 68.4% to a higher proportion of MDR tuberculosis in cases arrived from HMDR tuberculosis countries. No cases of MDR tuberculosis were attributable to local transmission. In stark contrast to HMDR tuberculosis countries, local transmission plays no important role in the occurrence of MDR tuberculosis in Canada. Improved tuberculosis programming in HMDR tuberculosis countries is urgently needed.

Factors Associated with Multi-Drug Resistant Tuberculosis among TB Patients in Selected Treatment Centers of Amhara Region: A Case-Control Study

Multi-drug Resistant Tuberculosis (MDR-TB) is found to be a major public health problem both in developed and developing countries. Ethiopia is one of the 30 high MDR-TB burden countries in the world. Although several studies were done to identify the determinants of MDR-TB, the reported findings are heterogeneous across the world. Unmatched case-control study was conducted at Debre Markose Referral Hospital, Debre Birhan Referral Hospital, and Boru Media District Hospital in Amhara Region, Northern Ethiopia, from March 01/2019- April 30/2019. Cases were all tuberculosis patients with culture or line probe assay confirmed mycobacterium tuberculosis resistant to at least both Isoniazid and Rifampicin and registered on second-line TB treatment. Controls were all patients with Bacteriological (molecular) proven drug-susceptible TB strains and whose recent smears result were turned to negative and registered as cured from January 01/2014 - December 31/2018. A pre-tested checklist was used to collect the data. Of the total reviewed documents (393), 98 cases and 295 controls were involved in this study. And, 54(55.1%) among cases and 162(54.9%) among controls were males. sixty nine(70.4%) among cases and 163(55.3) among controls were within the age group of 26-45 years. In the multivariable logistic regression analysis, age between 26-45 years old (AOR=3.35; 95% CI: 1.15, 9.77), previous history of TB treatment (AOR= 14.2; 95%CI: 7.8, 25.3) and being HIV positive (AOR=4.4; 95% CI: 1.8, 10.4) were significantly associated with MDR-TB. Age between 26-45 years old, previously treated cases and TB/HIV co-infection were identified as the determinants of MDR-TB. Special attention should be given to age between 26-45 years old, previous history of TB treatment and TB/HIV co-infection to prevent and control MDR-TB in the local context.

Characteristics of pulmonary multidrug-resistant tuberculosis patients in Tigray Region, Ethiopia: A cross-sectional study

Tuberculosis (TB) is among the top 10 causes of mortality and the first killer among infectious diseases worldwide. One of the factors fuelling the TB epidemic is the global rise of multidrug resistant TB (MDR-TB). The aim of this study was to determine the magnitude and factors associated with MDR-TB in the Tigray Region, Ethiopia. This study employed a facility-based cross-sectional study design, which was conducted between July 2018 and August 2019. The inclusion criteria for the study participants were GeneXpert-positive who were not under treatment for TB, PTB patients' ≥15 years of age and who provided written informed consent. A total of 300 participants were enrolled in the study, with a structured questionnaire used to collect data on clinical, sociodemographic and behavioral factors. Sputum samples were collected and processed for acid-fast bacilli staining, culture and drug susceptibility testing. Drug susceptibility testing was performed using a line probe assay. Logistic regression was used to analyze associations between outcome and predictor variables. The overall proportion of MDR-TB was 16.7% (11.6% and 32.7% for new and previously treated patients, respectively). Of the total MDR-TB isolates, 5.3% were pre-XDR-TB. The proportion of MDR-TB/HIV co-infection was 21.1%. A previous history of TB treatment AOR 3.75; 95% CI (0.7-2.24), cigarette smoking AOR 6.09; CI (1.65-2.50) and patients who had an intermittent fever (AOR = 2.54, 95% CI = 1.21-5.4) were strongly associated with MDR-TB development. The magnitude of MDR-TB observed among new and previously treated patients is very alarming, which calls for an urgent need for intervention. The high proportion of MDR-TB among newly diagnosed cases indicates ongoing transmission, which suggests the need for enhanced TB control program performance to interrupt transmission. The increased proportion of MDR-TB among previously treated cases indicates a need for better patient management to prevent the evolution of drug resistance. Assessing the TB control program performance gaps and an optimal implementation of the WHO recommended priority actions for the management of drug-resistant TB, is imperative to help reduce the current high MDR-TB burden in the study region.

Multidrug-resistant tuberculosis surveillance and cascade of care in Madagascar: a five-year (2012\u20132017) retrospective study

BackgroundIn Madagascar, the multidrug-resistant tuberculosis (MDR-TB) surveillance programme was launched in late 2012 wherein previously treated TB cases and symptomatic MDR-TB contacts (hereafter called presumptive MDR-TB cases) undergo drug susceptibility testing. This retrospective review had per aim to provide an update on the national MDR-TB epidemiology, assess and enhance programmatic performance and assess Madagascar’s MDR-TB cascade of care.MethodsFor 2012–2017, national TB control programme notification, clinical management data and reference laboratory data were gathered. The development and coverage of the surveillance programme, the MDR-TB epidemiology and programmatic performance indicators were assessed using descriptive, logistic and spatial statistical analyses. Data for 2017 was further used to map Madagascar’s TB and MDR-TB cascade of care.ResultsThe geographical coverage and diagnostic and referral capacities of the MDR-TB surveillance programme were gradually expanded whereas regional variations persist with regard to coverage, referral rates and sample referral delays. Overall, the rate of MDR-TB among presumptive MDR-TB cases remained relatively stable, ranging between 3.9% in 2013 and 4.4% in 2017. Most MDR-TB patients were lost in the second gap of the cascade pertaining to MDR-TB cases reaching diagnostic centres but failing to be accurately diagnosed (59.0%). This poor success in diagnosis of MDR-TB is due to both the current use of low-sensitivity smear microscopy as a first-line diagnostic assay for TB and the limited access to any form of drug susceptibility testing. Presumptive MDR-TB patients’ sample referral took a mean delay of 28 days before testing. Seventy-five percent of diagnosed MDR-TB patients were appropriately initiated on treatment, and 33% reached long-term recurrence-free survival.ConclusionsAn expansion of the coverage and strengthening of MDR-TB diagnostic and management capacities are indicated across all regions of Madagascar. With current limitations, the surveillance programme data is likely to underestimate the true MDR-TB burden in the country and an updated national MDR-TB prevalence survey is warranted. In absence of multiple drivers of an MDR-TB epidemic, including high MDR-TB rates, high HIV infection rates and inter-country migration, Madagascar is in a favourable starting position for MDR-TB control and elimination.

Tuberculosis knowledge and attitude among non-health science university students needs attention: a cross-sectional study in three Ethiopian universities

BackgroundEthiopia is among the 14 high TB, TB/HIV and MDR-TB burden countries globally. Prior studies indicate students attending universities in Ethiopia may be at increased risk for active tuberculosis (TB) relative to the general population, mainly due to the dramatic increase in expansion of the enrollment scale of universities.This study sought to gain insight about non-health science university students’ TB knowledge and attitudes to help develop a strategy for TB education in this population.MethodsA cross-sectional study was conducted from October to December 2018 among non-health science university students at three eastern Ethiopia public universities. Participants were considered having ‘good’ knowledge on TB when they correctly mentioned the communicability, means of transmission and prevention methods of TB and recognized modern medicine as the best treatment for TB. Participants were considered as having ‘acceptable’ attitude towards TB when they indicated they would seek immediate care for TB diagnosis, not hide a TB diagnosis and feel compassion to help people with TB.ResultsA total of 1720 non-health science university students participated. Only 614 (35.7%) of the students had ‘good’ knowledge on TB. This differed significantly between universities, with students from Haramaya and Dire Dawa universities more likely to have ‘good’ TB knowledge than their counterparts from Jigjiga University [COR (Crude Odds Ratio):1.62 and 1.94, respectively; and 95% Confidence Interval (CI): (1.236, 2.079) and (1.511, 2.483), respectively]. Only a third of students, 555 (32.3%) mentioned ‘bacteria’ as causing TB, and 836 students (48.6%) had ever heard of Multi Drug Resistant-TB (MDR-TB). An ‘acceptable’ attitude towards people with TB was observed in 666 students (38.7%). Even though 739 students (43%) felt compassion and desire to help TB patients, 213 (12%) and 382 (22%) mentioned they fear and tend to stay away from TB patients, respectively.ConclusionsThe present study revealed that non-health science university students lack important TB knowledge and have misconceptions about TB in eastern Ethiopia. University administrators and other stakeholders striving against TB should provide due attention to university settings and consider development of student education programs to improve awareness and knowledge of TB disease.

Multidrug Resistant Mycobacterium tuberculosis Among Military and Civilian Personnel seen at a Tertiary Military Hospital, Manila, Philippines (2015-2018).

About one third of the world population is estimated to be infected with Mycobacterium tuberculosis (MTB), and this proportion is expected to be higher in countries with a high tuberculosis (TB) burden. The Philippines is both a high tuberculosis burden and a high multidrug resistant tuberculosis (MDR-TB) burden country. Though TB has been extensively described in the civilian population, there is limited data on TB in the military population. The objectives are: (1) To determine MTB/MDR-TB prevalence among military and civilian patients in the Philippines presenting with clinically suspected TB in a tertiary military hospital and (2) To determine performance of direct sputum smear microscopy (DSSM) using Ziehl-Neelsen (ZN) staining compared to Xpert MTB/RIF real-time reverse transcriptase polymerase chain reaction. Sputum samples were obtained from patients, clinically suspected with TB, and/or with TB associated signs/symptoms. Sputum specimens were tested using DSSM with ZN staining and Xpert MTB/RIF assay (Cepheid, Sunnyvale, California) and patient demographic and clinical data were collected. From March 2015 to December 2018, a total of 795 (173 military personnel [164 active duty and 9 retired]; 618 civilians; and 4 with no data on military/civilian status) patients with TB associated symptoms or clinically suspected with TB were tested. Overall, MTB prevalence was 81/795 (10%). MTB prevalence among active duty and retired military personnel were 27/164 (16%) and 4/9 (44%), respectively while MTB prevalence for civilian patients was 50/618 (8%) (p value=0.0003; OR=2.48 [95% C.I. 1.5-4]). Among active and retired military personnel who tested positive for MTB, rifampin resistance was 4/27 (15%) and 1/4 (25%), respectively, while rifampin resistance for civilian patients was 9/50 (18%) (p value=1; OR=0.88 [95% C.I. 0.26-2.90]). For active duty military personnel, average MTB prevalence (based on Xpert MTB/RIF) covering years 2015-2018 was 21% and ranged from 13% to 35%, while average rifampin resistance among MTB positive active duty military personnel was 15% and ranged from 0% to 25%. Overall sensitivity and specificity of DSSM compared to Xpert MTB/RIF were 70% and 96%, respectively. Positive and negative predictive values of DSSM to accurately categorize MTB in symptomatic cases (with Xpert MTB/RIF as "true positive" reference) were 74% and 95%, respectively. Performance of DSSM varied according to MTB load detected by Xpert MTB/RIF with increasing DSSM sensitivity observed as the MTB load detected by Xpert MTB/RIF increased (p=0.02). This report describes high MTB and MDR-TB prevalence rates among symptomatic military patients with military personnel having higher odds of MTB infection compared to the civilian patients in the study. Since DSSM (ZN) sensitivity greatly varied depending on MTB load, the Xpert MTB/RIF should be used as a first-line diagnostic tool to identify MTB and detect rifampin resistance among presumptive TB cases instead of DSSM (ZN) microscopy.

Outcomes of Community-Based Systematic Screening of Household Contacts of Patients with Multidrug-Resistant Tuberculosis in Myanmar.

Screening of household contacts of patients with multidrug-resistant tuberculosis (MDR-TB) is a crucial active TB case-finding intervention. Before 2016, this intervention had not been implemented in Myanmar, a country with a high MDR-TB burden. In 2016, a community-based screening of household contacts of MDR-TB patients using a systematic TB-screening algorithm (symptom screening and chest radiography followed by sputum smear microscopy and Xpert-MTB/RIF assays) was implemented in 33 townships in Myanmar. We assessed the implementation of this intervention, how well the screening algorithm was followed, and the yield of active TB. Data collected between April 2016 and March 2017 were analyzed using logistic and log-binomial regression. Of 620 household contacts of 210 MDR-TB patients enrolled for screening, 620 (100%) underwent TB symptom screening and 505 (81%) underwent chest radiography. Of 240 (39%) symptomatic household contacts, 71 (30%) were not further screened according to the algorithm. Children aged <15 years were less likely to follow the algorithm. Twenty-four contacts were diagnosed with active TB, including two rifampicin- resistant cases (yield of active TB = 3.9%, 95% CI: 2.3%–6.5%). The highest yield was found among children aged <5 years (10.0%, 95% CI: 3.6%–24.7%). Household contact screening should be strengthened, continued, and scaled up for all MDR-TB patients in Myanmar.

Epidemiology of drug-resistant tuberculosis in Chongqing, China: A retrospective observational study from 2010 to 2017.

China is one of the top 30 countries with high multidrug-resistant tuberculosis (MDR-TB) and rifampin-resistant tuberculosis (RR-TB) burden. Chongqing is a southwest city of China with a large rural population. A retrospective observational study has been performed based on routine tuberculosis (TB) surveillance data in Chongqing from 2010 to 2017. The MDR/RR-TB notification rate increased from 0.03 cases per 100,000 population in 2010 to 2.1 cases per 100,000 population in 2017. The extensively drug-resistant TB (XDR-TB) notification rate has increased to 0.09 cases per 100,000 population in 2017. There was a decreasing detection gap between the number of notified MDR/RR-TB cases and the estimate number of MDR/RR-TB cases in new TB cases. The treatment success rate of MDR/RR-TB was 59% (95% confidence interval [CI], 53%-65%) in this period. Despite the progress achieved, the prevalence of MDR/RR-TB was still high facing challenges including detection gaps in new TB cases, the regional disparity, and the high risk for MDR/RR-TB in elderly people and farmers. Sustained government financing and policy support should be guaranteed in the future.

Drug resistance and epidemiology characteristics of multidrug-resistant tuberculosis patients in 17 provinces of China.

As China is one of high MDR-TB burden countries, it is important to determine the drug resistant pattern and clinical characteristics of multidrug resistant tuberculosis (MDR-TB). We conducted a comprehensive and nationwide study on MDR-TB in 17 provinces for the period from June 2009 to June 2015, and a total of 1154 cases of MDR-TB were finally investigated. The study sought to assess the clinical features and contrast drug susceptibility profiles of MDR-TB patients in China. Cavitary disease, young age, and long duration of TB disease among MDR-TB patients were important predictors. A high resistance proportion of first-line drugs was observed in Beijing, Shanghai and Tianjin. Resistant proportions of second-line anti-TB drugs in western region for amikacin, aminosalicylic acid, and levofloxacin were higher than eastern and central regions. High levels of drug resistance were seen in earlier cases (before 2011) and outpatients. We found high levels of resistance to 1st- and 2nd-line drugs in all settings, with considerable variabilities in terms of different Directly Observed Treatment Short Course (DOTS) programme, level of economic development(eastern, central and western regions) and patient source (inpatients and outpatients). Timely drug susceptibility testing (DST) and effective management are necessary to ensure an early detection of MDR-TB and its proper treatment.

Evolving rifampicin and isoniazid mono-resistance in a high multidrug-resistant and extensively drug-resistant tuberculosis region: a retrospective data analysis

ObjectivesSouth Africa ranks among the highest drug-resistant tuberculosis (DR-TB) burdened countries in the world. This study assessed the changes in resistance levels in culture confirmed Mycobacterium tuberculosis (MTB) in the...

Non-commercial phenotypic assays for the detection of Mycobacterium tuberculosis drug resistance: a systematic review.

Several rapid non-commercial culture-based methods and assays for drug susceptibility testing (DST) of Mycobacterium tuberculosis have emerged over the last decades. The aim of the current review was to summarise evidence on the performance of microscopic observation of drug susceptibility (MODS), thin-layer agar (TLA) and colorimetric redox-indicator (CRI) assays for detection of resistance to first- and second-line anti-tuberculosis (TB) drugs. Forty-three publications satisfying selection criteria were selected for data extraction. MODS and CRI assays demonstrated pooled sensitivity and specificity of > 93% for the detection of resistance to rifampicin and isoniazid and confirmed their utility for an accurate detection of multidrug-resistant TB (MDR-TB) in various settings. Sensitivity and specificity values for indirect DST for ethambutol (EMB) using CRI assays were 94.0% and 82.0%, respectively, suggesting that CRIs could be used to rule out resistance to EMB. Performance for other drugs varied more substantially across the reports. There was no sufficient evidence on the performance of the TLA assay for making any conclusion on its utility for DST. Our data suggests that non-commercial assays could be used for a rapid and accurate DST in settings where the use of commercial World Health Organization-endorsed assays could be limited due to a variety of reasons including limited resources, laboratory facilities or trained personnel. While inexpensive and easy-to-perform MODS and TLA assays can be used in low-income settings, using CRI assays for determination of minimal inhibitory concentrations may be implemented in middle- and high-income countries with high MDR-TB burden to guide clinical management of TB patients.

THE TREATMENT CASCADE: THE USE OF PREVENTATIVE PHARMACOTHERAPY FOR LATENT TB INFECTION FOLLOWING HIGH RISK NOSOCOMIAL EXPOSURE TO MULTIDRUG-RESISTANT TB

SESSION TITLE: Tuesday Abstract Posters SESSION TYPE: Original Investigation Posters PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM PURPOSE: This observational cohort study assessed the uptake and tolerability of preventative therapy for high-risk contacts of an index case with smear positive pulmonary MDR-TB across two tertiary hospitals in Sydney, Australia. With almost half a million new cases of multidrug resistant tuberculosis (MDR-TB) in 2018, active case finding and consideration of preventative therapy among specific high-risk contacts is a top priority. Patient acceptance and tolerability of preventative for latent MDR-TB was examined through a telephone delivered questionnaire. METHODS: Contacts were investigated if they had a high risk of exposure, defined as greater than 8 hours of close contact with the index case during the period of infectiousness. After the exclusion of active tuberculosis, contacts with evidence of latent tuberculosis were offered a 9-month course of a fluoroquinolone (moxifloxacin) and all were followed with chest X-ray and clinical review for two years from exposure. Following informed consent, contacts were further invited to complete a questionnaire relating to their experience. RESULTS: In total, 122 people were identified as having high risk exposure to the index case (household contacts, patients and health care workers). Of these, 94 (77%) attended an initial assessment in the chest clinic and 32 (34%) had evidence of latent tuberculosis (positive IGRA or TST). Of the 32 high-risk MDR-TB contacts with latent tuberculosis, 22 choose ongoing CXR surveillance, 9 commenced preventative treatment and 1 did not attend follow up. Reasons cited for not choosing preventative therapy were risks of adverse side effects and concerns about negative job consequences. Of those that took preventative pharmacotherapy, 7 of 9 (78%) attended final 2-year follow up. 6 of 7 (86%) patients treated for latent tuberculosis completed the prescribed course. No cases of incident tuberculosis were detected after 2 years of follow up. CONCLUSIONS: Preventative therapy with moxifloxacin was tolerated well by high risk MDR-TB contacts with evidence of latent tuberculosis infection; however uptake of preventive therapy was limited. CLINICAL IMPLICATIONS: Each case of MDR-TB disease may expose multiple people to their disease and it is known that these people are at an increased risk of developing tuberculosis disease in the future, there is a lack of high quality evidence on the effectiveness of preventative therapy. Research that explores patient acceptance and tolerability of preventative for latent MDR-TB is lacking. Our study adds to the body of knowledge in ascertaining how to treat and manage high risk contacts of MDR-TB disease. DISCLOSURES: no disclosure on file for Byrne Anthony; No relevant relationships by Liam Beiglari, source=Web Response Recipient of study drug (rifapentine) relationship with Sanofi Please note: $20001 - $100000 Added 06/20/2019 by Greg Fox, source=Web Response, value=in kind supply of study drug No relevant relationships by PAUL LILBURN, source=Web Response

Development and validation of a multiplex UHPLC-MS/MS method for the determination of the investigational antibiotic against multi-resistant tuberculosis macozinone (PBTZ169) and five active metabolites in human plasma

The emergence of Mycobacterium tuberculosis strains resistant to current first-line antibiotic regimens constitutes a major global health threat. New treatments against multidrug-resistant tuberculosis (MDR-TB) are thus eagerly needed in particular in countries with a high MDR-TB prevalence. In this context, macozinone (PBTZ169), a promising drug candidate with an unique mode of action and highly potent in vitro tuberculocidal properties against MDR Mycobacterium strains, has now reached the clinical phase and has been notably tested in healthy male volunteers in Switzerland. To that endeavor, a multiplex UHPLC-MS/MS method has been developed for the sensitive and accurate human plasma levels determination of PBTZ169 along with five metabolites retaining in vitro anti-TB activity. Plasma protein precipitation with methanol was carried out as a simplified sample clean-up procedure followed by direct injection of the undiluted supernatant for the bioanalysis of the six analytes within 5 min, using 1.8 μm reversed-phase chromatography coupled to triple quadrupole mass spectrometry employing electrospray ionization in the positive mode. Stable isotopically-labelled PBTZ169 was used as internal standard (ISTD), while metabolites could be reliably quantified using two unlabeled chemical analogues selected as ISTD from a large in-house analogous compounds library. The overall methodology was fully validated according to current recommendations (FDA, EMEA) for bioanalytical methods, which include selectivity, carryover, qualitative and quantitative matrix effect, extraction recovery, process efficiency, trueness, precision, accuracy profiles, method and instrument detection limits, integrity to dilution, anticoagulant comparison and short- and long-term stabilities. Stability studies on the reduced metabolite H2-PBTZ169 have shown no significant impact on the actual PBTZ169 concentrations determined with the proposed assay. This simplified, rapid, sensitive and robust methodology has been applied to the bioanalysis of human plasma samples collected within the frame of a phase I clinical study in healthy volunteers receiving PBTZ169.