Diagnosis and Interim Treatment Outcomes from the First Cohort of Multidrug-Resistant Tuberculosis Patients in Tanzania.

Kibong'oto National Tuberculosis Hospital (KNTH), Kilimanjaro, Tanzania. Characterize the diagnostic process and interim treatment outcomes from patients treated for multidrug-resistant tuberculosis (MDR-TB) in Tanzania. A retrospective cohort study was performed among all patients treated at KNTH for pulmonary MDR-TB between November 2009 and September 2011. Sixty-one culture-positive MDR-TB patients initiated therapy, 60 (98%) with a prior history of TB treatment. Forty-one (67%) were male and 9 (14%) were HIV infected with a mean CD4 count of 424 (±106) cells/µl. The median time from specimen collection to MDR-TB diagnosis and from diagnosis to initiation of MDR-TB treatment was 138 days (IQR 101-159) and 131 days (IQR 32-233), respectively. Following treatment initiation four (7%) patients died (all HIV negative), 3 (5%) defaulted, and the remaining 54 (89%) completed the intensive phase. Most adverse drug reactions were mild to moderate and did not require discontinuation of treatment. Median time to culture conversion was 2 months (IQR 1-3) and did not vary by HIV status. In 28 isolates available for additional second-line drug susceptibility testing, fluoroquinolone, aminoglycoside and para-aminosalicylic acid resistance was rare yet ethionamide resistance was present in 9 (32%). The majority of MDR-TB patients from this cohort had survived a prolonged referral process, had multiple episodes of prior TB treatment, but did not have advanced AIDS and converted to culture negative early while completing an intensive inpatient regimen without serious adverse event. Further study is required to determine the clinical impact of second-line drug susceptibility testing and the feasibility of alternatives to prolonged hospitalization

Determination of plasma concentrations of levofloxacin by high performance liquid chromatography for use at a multidrug-resistant tuberculosis hospital in Tanzania.

Therapeutic drug monitoring may improve multidrug-resistant tuberculosis (MDR-TB) treatment outcomes. Levofloxacin demonstrates significant individual pharmacokinetic variability. Thus, we sought to develop and validate a high-performance liquid chromatography (HPLC) method with ultraviolet (UV) detection for levofloxacin in patients on MDR-TB treatment. The HPLC-UV method is based on a solid phase extraction (SPE) and a direct injection into the HPLC system. The limit of quantification was 0.25 μg/mL, and the assay was linear over the concentration range of 0.25-15 μg/mL (y = 0.5668x-0.0603, R2 = 0.9992) for the determination of levofloxacin in plasma. The HPLC-UV methodology achieved excellent accuracy and reproducibility along a clinically meaningful range. The intra-assay RSD% of low, medium, and high quality control samples (QC) were 1.93, 2.44, and 1.90, respectively, while the inter-assay RSD% were 3.74, 5.65, and 3.30, respectively. The mean recovery was 96.84%. This method was then utilized to measure levofloxacin concentrations from patients' plasma samples from a retrospective cohort of consecutive enrolled subjects treated for MDR-TB at the national TB hospital in Tanzania during 5/3/2013-8/31/2015. Plasma was collected at 2 hours after levofloxacin administration, the time of estimated peak concentration (eCmax) treatment. Forty-one MDR-TB patients had plasma available and 39 had traceable programmatic outcomes. Only 13 (32%) patients had any plasma concentration that reached the lower range of the expected literature derived Cmax with the median eCmax being 5.86 (3.33-9.08 μg/ml). Using Classification and Regression Tree analysis, an eCmax ≥7.55 μg/mL was identified as the threshold which best predicted cure. Analyzing this CART derived threshold on treatment outcome, the time to sputum culture conversion was 38.3 ± 22.7 days vs. 47.8 ± 26.5 days (p = 0.27) and a greater proportion were cured, in 10 out of 15 (66.7%) vs. 6 out of 18 (33.3%) (p = 0.06) respectively. Furthermore, one patient with an eCmax/minimum inhibitory concentration (MIC) of only 1.13 acquired extensively drug resistant (XDR)-TB while undergoing treatment. The individual variability of levofloxacin concentrations in MDR-TB patients from Tanzania supports further study of the application of onsite therapeutic drug monitoring and MIC testing

Epidemiology and treatment outcomes of recurrent tuberculosis in Tanzania from 2018 to 2021 using the National TB dataset.

BackgroundPatients with recurrent TB have an increased risk of higher mortality, lower success rate, and a relatively feeble likelihood of treatment completion than those with new-onset TB. This study aimed to assess the epidemiology of recurrent TB in Tanzania; specifically, we aim to determine the prevalence of TB recurrence and factors associated with unfavourable treatment outcomes among patients with recurrent TB in Tanzania from 2018 to 2021.MethodsIn this cross-sectional study, we utilized Tanzania's routinely collected national TB program data. The study involved a cohort of TB patients over a fixed treatment period registered in the TB and Leprosy case-based District Health Information System (DHIS2-ETL) database from 2018 to 2021 in Tanzania. We included patients' sociodemographic and clinical factors, facility characteristics, and TB treatment outcomes. We conducted bivariate analysis and multivariable multi-level mixed effects logistic regression of factors associated with TB recurrence and TB treatment outcomes to account for the correlations at the facility level. A purposeful selection method was used; the multivariable model included apriori selected variables (Age, Sex, and HIV status) and variables with a p-value FindingsA total of 319,717 participants were included in the study; the majority were adults aged 25-49 (44.2%, n = 141,193) and above 50 years (31.6%, n = 101,039). About two-thirds were male (60.4%, n = 192,986), and more than one-fifth of participants (22.8%, n = 72,396) were HIV positive. Nearly two in every hundred TB patients had a recurrent TB episode (2.0%, n = 6,723). About 10% of patients with recurrent TB had unfavourable treatment outcomes (9.6%, n = 519). The odds of poor treatment outcomes were two-fold higher for participants receiving treatment at the central (aOR = 2.24; 95% CI 1.33-3.78) and coastal zones (aOR = 2.20; 95% CI 1.40-3.47) than the northern zone. HIV-positive participants had 62% extra odds of unfavourable treatment outcomes compared to their HIV-negative counterparts (aOR = 1.62; 95% CI 1.25-2.11). Bacteriological TB diagnosis (aOR = 1.39; 95% CI 1.02-1.90) was associated with a 39% additional risk of unfavourable treatment outcomes as compared to clinical TB diagnosis. Compared to community-based DOT, patients who received DOT at the facility had 1.39 times the odds of poor treatment outcomes (aOR = 1.39; 95%CI 1.04-1.85).ConclusionTB recurrence in Tanzania accounts for 2% of all TB cases, and it is associated with poor treatment outcomes. Unfavourable treatment outcomes were recorded in 10% of patients with recurrent TB. Poor TB treatment outcome was associated with HIV-positive status, facility-based DOT, bacteriologically confirmed TB and receiving treatment at the hospital level, differing among regions. We recommend post-treatment follow-up for patients with recurrent TB, especially those coinfected with HIV. We also propose close follow-up for patients treated at the hospital facility level and strengthening primary health facilities in TB detection and management to facilitate early treatment initiation

Inter-assay variability of calibration curve, Intra-day precision and Inter-day precision.

<p>Inter-assay variability of calibration curve, Intra-day precision and Inter-day precision.</p

Patient characteristics.

<p>Patient characteristics.</p

Distributions of plasma concentrations of levofloxacin by pretreatment characteristics.

<p>A) eCmax lack of correlation with Age [R2 0.0404] B) eCmax lack of correlation with mg/kg levofloxacin dose [R2 0.0038] C) eCmax by Gender; mean eCmax for Males was 6.64 and Females 7.18, p = 0.74 D) eCmax by HIV Status; mean eCmax for those who were Positive was 5.94 and Negative 7.35, p = 0.34</p

Enhancing Tuberculosis Case-Finding: A Case of Quality Improvement Initiative in Tanzania

Background: Tanzania is 1 of the 30 high TB burden countries and 1 of the 13 countries in which 75% of people with TB are unaccounted for and that is prioritized for the Global Fund Catalytic investment and Strategic Initiative support. Tanzania decided to strengthen its National TB Programme to find these people with TB who are unaccounted for by identifying evidence-driven innovations to deliver high-quality services and to improve the efficiency of TB case-finding. A quality improvement (QI) initiative was implemented by the National Tuberculosis and Leprosy Programme to enhance TB case-finding. The initiative involved identifying gaps in the quality of services, introducing new tools, improving the work capacity of health care workers through training and mentorship sessions, strengthening laboratory and referral services, and implementing mandatory TB screening of all patients attending health facilities. We aimed to assess the effectiveness of QI initiative to enhance TB case-findings at the health facility level. Method: A cross-sectional design, and intervention and control facilities randomly selected for an evaluation of the QI initiative were used. Twenty facilities from the Dodoma region across all health care system levels (dispensaries, health centres, and hospitals) were involved in this evaluation. The facilities were randomly divided into either the intervention or control groups at a 1:1 ratio (10 intervention and 10 control facilities). Data routinely collected from program registers from January 2016 to June 2017 were used. Result: The evaluation registered a 52% increase in TB case notification in Q1 of 2017 compared with in Q1 of 2016 and, similarly, a 52% increase in Q2 of 2017 compared with in Q2 of 2016, with 9 out of 10 intervention sites reporting increases in their quarterly TB case notifications. There were no positive changes in the &lsquo;control facilities&rsquo; where routine services were provided, with half of the facilities showing a decrease in TB case notification from baseline. Conclusion: This QI initiative has the potential to support a long-term comprehensive approach to ending TB and to improve the quality of the foundations of the health care system. This initiative sets a reliable pace for health facilities to efficiently respond to and manage TB case-finding interventions put into action. Tanzania&rsquo;s experience with implementing QI interventions could serve as a model for improving TB case notifications in other settings

CART derived eC_max and outcomes.

<p>CART derived eC_max and outcomes.</p

Representative HPLC-UV chromatogram for levofloxacin with phenacetin (Internal standard).

<p>Representative Chromatogram for Levofloxacin.</p