Addressing the drug-resistant tuberculosis challenge through implementing a mixed model of care in Uganda

Worldwide, Drug-resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale-up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 RR-TB/MDR-TB cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale-up plan. To scale up care, the National TB and leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Routine NTLP DR-TB program data on treatment initiation site, number of patients enrolled, their demographic characteristics, patient category, disease classification (based on disease site and human immunodeficiency virus (HIV) status), on co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) statuses, culture results, smear results and treatment outcomes (6, 12, and 24 months) from 2012 to 2017 RR-TB/MDR-TB cohorts were collected from all the 15 DR-TB treatment initiation sites and descriptive analysis was done using STATA version 14.2. We presented outcomes as the number of patient backlog cleared, DR-TB initiation sites, RR-TB/DR-TB cumulative patients enrolled, percentage of co-infected patients on the six, twelve interim and 24 months treatment outcomes as per the Uganda NTLP 2016 Programmatic Management of drug-resistant Tuberculosis (PMDT) guidelines (NTLP, 2016). Over the period 2013–2015, the RR-TB/MDR-TB Treatment success rate (TSR) was sustained between 70.1% and 74.1%, a performance that is well above the global TSR average rate of 50%. Additionally, the cure rate increased from 48.8% to 66.8% (P = 0.03). The Uganda DR-TB mixed model of care coupled with early application of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges.

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Addressing the drug resistant tuberculosis challenge through implementing a mixed model of care in Uganda, 2012- 2017

10.21203/rs.2.10568/v1 ◽

2019 ◽

Author(s):

Samuel Kasozi ◽

Nicholas Sebuliba Kirirabwa ◽

Derrick Kimuli ◽

Henry Luwaga ◽

Enock Kizito ◽

...

Keyword(s):

Mixed Model ◽

Treatment Initiation ◽

Treatment Success ◽

Scale Up ◽

Sub Saharan Africa ◽

Drug Resistant ◽

Model Of Care ◽

Drug Resistant Tuberculosis ◽

Tb Treatment ◽

Resistant Tuberculosis

Abstract Background Worldwide, Drug resistant Tuberculosis (DR-TB) remains a big problem; the diagnostic capacity has superseded the DR-TB clinical management capacity thereby causing ethical challenges. In Sub-Saharan Africa, treatment is either inadequate or lacking and some diagnosed patients are on treatment waiting lists. In Uganda, various health system challenges impeded scale up of DR-TB care in 2012; only three treatment initiation facilities existed, with only 41 of the estimated 1010 cases enrolled on treatment yet 300 were on the waiting list and there was no DR-TB treatment scale up plan. To scale up care, National TB/Leprosy Program (NTLP) with partners rolled out a DR-TB mixed model of care. In this paper, we share achievements and outcomes resulting from the implementation of this mixed Model of DR-TB care. Methods Routine NTLP DR-TB program data from 2013 to 2017 cohorts was collected from all the 15 DR-TB treatment initiation sites and analyzed using STATA version 14.2. We presented outcomes as the number of patient backlog cleared, DR-TB initiation sites, cumulative patients enrolled, percentage of co-infected patients on co-trimoxazole preventive therapy (CPT) and antiretroviral therapy (ART) as well as the six, twelve interim and 24 months treatment outcomes as per the Uganda NTLP 2016 Programmatic Management of drug Resistant Tuberculosis (PMDT) guidelines. Results Over the period 2013-2017, DR-TB treatment initiation sites increased from three to 15, cumulative patient enrollment rose from 41 to 1,311 and the 300-patient backlog was cleared. Treatment success rate (TSR) of 73% was achieved above the global TSR average rate of 50%. Conclusions The Uganda DR-TB mixed model of care coupled with early application of continuous improvement approaches, enhanced cohort reviews and use of multi-disciplinary teams allowed for rapid DR-TB program expansion, rapid clearance of patient backlog, attainment of high cumulative enrollment and high treatment success rates. Sustainability of these achievements is needed to further reduce the DR-TB burden in the country. We highly recommend this mixed model of care in settings with similar challenges.

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Predicting the Outcomes of New Short-Course Regimens for Multi-Drug Resistant Tuberculosis Using Intrahost and Pharmacokinetic-Pharmacodynamic Modelling

10.1101/369991 ◽

2018 ◽

Author(s):

Tan N Doan ◽

Pengxing Cao ◽

Theophilus I Emeto ◽

James M McCaw ◽

Emma S McBryde

Keyword(s):

Treatment Duration ◽

Treatment Success ◽

Empirical Evaluation ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multi Drug Resistant Tuberculosis ◽

Short Course ◽

Mdr Tb

ABSTRACTShort-course regimens for multi-drug resistant tuberculosis (MDR-TB) are urgently needed. Limited data suggest that the new drug, bedaquiline (BDQ), may have the potential to shorten MDR-TB treatment to less than six months when used in conjunction with standard anti-TB drugs. However, the feasibility of BDQ in shortening MDR-TB treatment duration remains to be established. Mathematical modelling provides a platform to investigate different treatment regimens and predict their efficacy. We developed a mathematical model to capture the immune response to TB inside a human host environment. This model was then combined with a pharmacokinetic-pharmacodynamic model to simulate various short-course BDQ-containing regimens. Our modelling suggests that BDQ could reduce MDR-TB treatment duration to just 18 weeks (four months) while still maintaining a very high treatment success rate (100% for daily BDQ for two weeks, or 95% for daily BDQ for one week during the intensive phase). The estimated time to bacterial clearance of these regimens ranges from 27 to 33 days. Our findings provide the justification for empirical evaluation of short-course BDQ-containing regimens. If short-course BDQ-containing regimens are found to improve outcomes then we anticipate clear cost-savings and a subsequent improvement in the efficiency of national TB programs.

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Abstract #1036 Hypothyroidism Induced by Multi Drug Resistant Tuberculosis (MDR-TB) Treatment

Endocrine Practice ◽

10.1016/s1530-891x(20)47401-4 ◽

2018 ◽

Vol 24 ◽

pp. 236

Author(s):

Rulli Rosandi

Keyword(s):

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multi Drug Resistant Tuberculosis ◽

Mdr Tb

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Trends, Characteristics and Treatment Outcomes of Patients with Drug-Resistant Tuberculosis in Uzbekistan: 2013–2018

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18094663 ◽

2021 ◽

Vol 18 (9) ◽

pp. 4663

Author(s):

Khasan Safaev ◽

Nargiza Parpieva ◽

Irina Liverko ◽

Sharofiddin Yuldashev ◽

Kostyantyn Dumchev ◽

...

Keyword(s):

Risk Factors ◽

Treatment Outcomes ◽

Treatment Success ◽

National Level ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Loss To Follow Up ◽

Resistant Tuberculosis ◽

Mdr Tb

Uzbekistan has a high burden of drug-resistant tuberculosis (TB). Although conventional treatment for multidrug-resistant TB (MDR-TB) and extensively drug-resistant TB (XDR-TB) has been available since 2013, there has been no systematic documentation about its use and effectiveness. We therefore documented at national level the trends, characteristics, and outcomes of patients with drug-resistant TB enrolled for treatment from 2013–2018 and assessed risk factors for unfavorable treatment outcomes (death, failure, loss to follow-up, treatment continuation, change to XDR-TB regimen) in patients treated in Tashkent city from 2016–2017. This was a cohort study using secondary aggregate and individual patient data. Between 2013 and 2018, MDR-TB numbers were stable between 2347 and 2653 per annum, while XDR-TB numbers increased from 33 to 433 per annum. At national level, treatment success (cured and treatment completed) for MDR-TB decreased annually from 63% to 57%, while treatment success for XDR-TB increased annually from 24% to 57%. On multivariable analysis, risk factors for unfavorable outcomes, death, and loss to follow-up in drug-resistant TB patients treated in Tashkent city included XDR-TB, male sex, increasing age, previous TB treatment, alcohol abuse, and associated comorbidities (cardiovascular and liver disease, diabetes, and HIV/AIDS). Reasons for these findings and programmatic implications are discussed.

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Prevalence and factors associated with non-adherence to multi-drug resistant tuberculosis (MDR-TB) treatment at Mulago National Referral Hospital, Kampala, Uganda

African Health Sciences ◽

10.4314/ahs.v21i1.12 ◽

2021 ◽

Vol 21 (1) ◽

pp. 238-47

Author(s):

Charles Batte ◽

Martha S Namusobya ◽

Racheal Kirabo ◽

John Mukisa ◽

Susan Adakun ◽

...

Keyword(s):

Mulago Hospital ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Factors Associated ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multi Drug Resistant Tuberculosis ◽

Mdr Tb ◽

History Of ◽

Previously Treated

Background: In Uganda, 12% of previously treated TB cases and 1.6% of new cases have MDR-TB and require specialized treatment and care. Adherence is crucial for improving MDR-TB treatment outcomes. There is paucity of information on the extent to which these patients adhere to treatment and what the drivers of non-adherence are. Methods: We conducted a cohort study using retrospectively collected routine program data for patients treated for MDR- TB between January 2012 – May 2016 at Mulago Hospital. We extracted anonymized data on non-adherence (missing 10% or more of DOT), socio-economic, demographic, and treatment characteristics of the patients. All participants were sen- sitive to MDR-TB drugs after second line Drug Susceptible Testing (DST) at entry into the study. Factors associated with non-adherence to MDR-TB treatment were determined using generalized linear models for the binomial family with log link and robust standard errors. We considered a p- value less than 0.05 as statistically significant. Results: The records of 227 MDR- TB patients met the inclusion criteria, 39.4% of whom were female, 32.6% aged be- tween 25 – 34 years, and 54.6% living with HIV/AIDS. About 11.9% of the patients were non-adherent. The main driver for non-adherence was history of previous DR-TB treatment; previously treated DR-TB patients were 3.46 (Adjusted prev- alence ratio: 3.46, 95 % CI: 1.68 - 7.14) times more likely to be non-adherent. Conclusion: One in 10 MDR-TB patients treated at Mulago hospital is non-adherent to treatment. History of previous DR- TB treatment was significantly associated with non-adherence in this study. MDR-TB program should strengthen adherence counselling, strengthen DST surveillance, and close monitoring for previously treated DR-TB patients. Keywords: Non-adherence; multi-drug resistant tuberculosis; treatment.

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Cost comparison of nine-month treatment regimens with 20-month standardized care for the treatment of rifampicin-resistant/multi-drug resistant tuberculosis in Nigeria

PLoS ONE ◽

10.1371/journal.pone.0241065 ◽

2020 ◽

Vol 15 (12) ◽

pp. e0241065

Author(s):

Florence O. Bada ◽

Nick Blok ◽

Evaezi Okpokoro ◽

Saswata Dutt ◽

Christopher Akolo ◽

...

Keyword(s):

Treatment Regimen ◽

Treatment Success ◽

Cost Savings ◽

Drug Resistant ◽

Second Line ◽

Success Rates ◽

Drug Resistant Tuberculosis ◽

Treatment Regimens ◽

Resistant Tuberculosis ◽

Mdr Tb

Background Globally, drug resistant tuberculosis (DR-TB) continues to be a public health threat. Nigeria, which accounts for a significant proportion of the global burden of rifampicin/multi-drug resistant-TB (RR/MDR-TB) had a funding gap of $168 million dollars for TB treatment in 2018. Since 2010, Nigeria has utilized five different models of care for RR/MDR-TB (Models A-E); Models A, B and C based on a standardized WHO-approved treatment regimen of 20–24 months, were phased out between 2015 and 2019 and replaced by Models D and E. Model D is a fully ambulatory model of 9–12 months during which a shorter treatment regimen including a second-line injectable agent is utilized. Model E is identical to Model D but has patients hospitalized for the first four months of care while Model F which is to be introduced in 2020, is a fully ambulatory, oral bedaquiline-containing shorter treatment regimen of 9–12 months. Treatment models for RR/MDR-TB of 20–24 months duration have had treatment success rates of 52–66% while shorter treatment regimens have reported success rates of 85% and above. In addition, replacing the second-line injectable agent in a shorter treatment regimen with bedaquiline has been found to further improve treatment success in patients with fluoroquinolone-susceptible RR/MDR-TB. Reliable cost data for RR/MDR-TB care are limited, specifically costs of models that utilize shorter treatment regimens and which are vital to guide Nigeria through the provision of RR/MDR-TB care at scale. We therefore conducted a cost analysis of shorter treatment regimens in use and to be used in Nigeria (Models D, E and F) and compared them to three models of longer duration utilized previously in Nigeria (Models A, B and C) to identify any changes in cost from transitioning from Models A-C to Models D-F and opportunities for cost savings. Methods We obtained costs for TB diagnostic and monitoring tests, in-patient and out-patient care from a previous study, inflated these costs to 2019 NGN and then converted to 2020 USD. We obtained other costs from the average of six health facilities and drug costs from the global drug facility. We modeled treatment on strict adherence to two Nigerian National guidelines for programmatic and clinical management of drug-resistant tuberculosis. Results We estimated that the total costs of care from the health sector perspective for Models D, E and F were $4,334, $7,705 and $3,420 respectively. This is significantly lower than the costs of Models A, B and C which were $14,781, $12, 113, $7,572 respectively. Conclusion Replacing Models A–C with Models D and E reduced the costs of RR/MDR-TB care in Nigeria by approximately $5,470 (48%) per patient treated and transitioning from Models D and E to Model F would result in further cost savings of $914 to $4,285 (21 to 56%) for every patient placed on Model F. If the improved outcomes of patients managed using bedaquiline-containing shorter treatment regimens in other countries can be attained in Nigeria, Model F would be the recommended model for the scale up of RR/MDR-TB care in Nigeria.

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Adverse Drug Reactions in Patients put on Multi Drug Resistant Tuberculosis (MDR-TB) Treatment in Seven Districts of Central Gujarat

Journal of Young Pharmacists ◽

10.5530/jyp.2015.4s.3 ◽

2015 ◽

Vol 7 (4s) ◽

pp. 425-431 ◽

Cited By ~ 2

Author(s):

Sangita Vashrambhai Patel ◽

Nimavat Kapil Bhikhubhai ◽

Alpesh Bhimabhai patel ◽

Kalpita Samrat Shringarpure ◽

Kedar Gautambhai Mehta ◽

...

Keyword(s):

Adverse Drug Reactions ◽

Drug Resistant ◽

Drug Reactions ◽

Drug Resistant Tuberculosis ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multi Drug Resistant Tuberculosis ◽

Mdr Tb

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A suggested algorithm for detection of multi drug-resistant tuberculosis in Zimbabwe

The Journal of Infection in Developing Countries ◽

10.3855/jidc.8009 ◽

2017 ◽

Vol 11 (08) ◽

pp. 611-618 ◽

Cited By ~ 1

Author(s):

Beauty Makamure ◽

Salome Makumbirofa ◽

Tsitsi Bandason ◽

Paul Leccese ◽

Reggie Mutetwa ◽

...

Keyword(s):

Diagnostic Accuracy ◽

Scale Up ◽

Drug Susceptibility ◽

Lower Sensitivity ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Early Results ◽

Multi Drug Resistant Tuberculosis ◽

Mdr Tb

Introduction: Rapid genotypic and phenotypic methods for multi-drug-resistant-tuberculosis (MDR-TB) detection are now widely available. Zimbabwe adopted the use of GeneXpert-MTB/RIF, microscopic-observation-drug-susceptibility-assay (MODS) and Mycobacteria-Growth-Indicator-Tube (MGIT) drug-susceptibility-testing (DST). Data is limited on the ideal combination of use of these methods in resource limited settings. Methodology: Between August 2014 to July 2015, 211 sputa from MDR-TB suspects were tested with GeneXpert-MTB/RIF, MODS, manual-MGIT and Lowenstein-Jensen (LJ)-DST to determine diagnostic accuracy and turnaround-time (TAT), with LJ-DST as the gold standard. A performance score ranking table for diagnostic accuracy, TAT, costs, facilities and expertise requirements, was used to determine the most favourable tool. Results: GeneXpert-MTB/RIF sensitivity was 96% (95%CI:80-100) and specificity was 95% (95%CI:90-97). MODS sensitivity was 88% (95%CI:68-97) and specificity was 97% (95%CI:87-100). Manual MGIT-DST had slightly lower sensitivity of 80% (95%CI:59-93). Median time to detection of MDR-TB was <1 day (IQR:0-0) for Xpert, 14 days (IQR:11-31) for MODS, 21 days (IQR:7-22) for MGIT-DST and 28 days (IQR:25-28) for LJ-DST. Operational costs for MODS, MGIT-DST, and GeneXpert-MTB/RIF were $21.20, $27.52 and $39.76 respectively. From a summation of scores including facility and expertise requirements per diagnostic technique, GeneXpert-MTB/RIF was the most favourable tool, followed by MODS and MGIT-DST. Conclusions: For best scale-up of MDR-TB diagnosis in Zimbabwe, GeneXpert-MTB/RIF can be used for rapid detection of TB in smear negative cases, RIF-susceptibility for early treatment initiation and probable MDR-TB. MODS can rapidly confirm probable MDR-TB detected by GeneXpert-MTB/RIF, manual-MGIT can provide early results for susceptibility to other antibiotics, with affordable costs, with LJ-DST confirming discordant DSTs.

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Prevalence and risk factors of multi-drug resistant tuberculosis in Dalian, China

Journal of International Medical Research ◽

10.1177/0300060516687429 ◽

2017 ◽

Vol 45 (6) ◽

pp. 1779-1786 ◽

Cited By ~ 9

Author(s):

Xin-Tong Lv ◽

Xi-Wei Lu ◽

Xiao-Yan Shi ◽

Ling Zhou

Keyword(s):

Risk Factors ◽

Population History ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Tb Treatment ◽

Resistant Tuberculosis ◽

Multi Drug Resistant Tuberculosis ◽

Mdr Tb ◽

Previously Treated Patients ◽

Previously Treated

Objectives To investigate the prevalence and risk factors associated with multi-drug resistant tuberculosis (MDR–TB) in Dalian, China. Methods This was a retrospective review of data from patients attending a TB clinic in Dalian, China between 2012 and 2015. Demographic and drug susceptibility data were retrieved from TB treatment cards. Univariate logistic analysis was used to assess the association between risk factors and MDR–TB. Results Among the 3552 patients who were smear positive for Mycobacterium tuberculosis (MTB), 2918 (82.2%) had positive MTB cultures and 1106 (31.1%) had isolates that showed resistance to at least one drug. The overall prevalence of MDR–TB was 10.1% (359/3552; 131/2261 [5.8%] newly diagnosed and 228/1291 [17.7%] previously treated patients). Importantly, 75 extensively drug-resistant TB isolates were detected from 25 newly treated and 50 previously treated patients. In total, 215 (6.1%) patients were infected with a poly-resistant strain of MTB. Previously treated patients and older patients were more likely to develop MDR–TB. Conclusions The study showed a high prevalence of MDR–TB among the study population. History of previous TB treatment and older age were associated with MDR–TB.

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