First report of multi-drug resistant tuberculosis in a systemic lupus erythematosus patient.

BackgroundTreatment of a multi-drug resistant tuberculosis (MDR-TB) patient is clinically challenging, requiring a minimum of 18 months of therapy. Its occurrence in a systemic lupus erythromatosus (SLE) patient may complicate management of both MDR-TB and SLE. This is the first descriptive report of MDR-TB in an SLE patient.Case presentationA 19-year old female receiving long-term prednisolone for SLE was diagnosed with MDR-TB. She was started on MDR-TB treatment regimen and prednisolone was replaced with azathioprine. After an initial response to therapy, patient experienced a flare of lupus symptoms. Imaging studies revealed avascular necrosis of right femoral head. She was then treated with intravenous methyl-prednisolone, followed by maintenance corticosteroid. Azathioprine was discontinued due to hematological toxicity and failure to control SLE. Her symptoms of lupus regressed and did not re-occur for the duration of her MDR-TB treatment. Patient was declared cured of MDR-TB after 18 months of ATT. She is currently scheduled for a total hip replacement surgery.ConclusionsThis case highlights the challenges of simultaneously managing MDR-TB and SLE in a patient due to their over-lapping signs and symptoms, drug-drug interactions, and the need for use of immunomodulatory agents in the absence of standard guidelines and documented previous experiences. Our experience underscores the importance of appropriate selection of treatment regimens for both MDR-TB and SLE

Characteristics of drug-resistant tuberculosis in Abkhazia (Georgia), a high-prevalence area in Eastern Europe

Although multidrug-resistant (MDR) tuberculosis (TB) is a major public health problem in Eastern Europe, the factors contributing to emergence, spread and containment of MDR-TB are not well defined. Here, we analysed the characteristics of drug-resistant TB in a cross-sectional study in Abkhazia (Georgia) between 2003 and 2005, where standard short-course chemotherapy is supplemented with individualized drug-resistance therapy. Drug susceptibility testing (DST) and molecular typing were carried out for Mycobacterium tuberculosis complex strains from consecutive smear-positive TB patients. Out of 366 patients, 60.4% were resistant to any first-line drugs and 21% had MDR-TB. Overall, 25% of all strains belong to the Beijing genotype, which was found to be strongly associated with the risk of MDR-TB (OR 25.9, 95% CI 10.2-66.0) and transmission (OR 2.8, 95% CI 1.6-5.0). One dominant MDR Beijing clone represents 23% of all MDR-TB cases. The level of MDR-TB did not decline during the study period, coinciding with increasing levels of MDR Beijing strains among previously treated cases. Standard chemotherapy plus individualized drug-resistance therapy, guided by conventional DST, might be not sufficient to control MDR-TB in Eastern Europe in light of the spread of "highly transmissible" MDR Beijing strains circulating in the community

Multidrug resistant pulmonary tuberculosis treatment regimens and patient outcomes: an individual patient data meta-analysis of 9,153 patients.

Treatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB

Treatment of tuberculosis in a region with high drug resistance: Outcomes, drug resistance amplification and re-infection

Introduction: Emerging antituberculosis drug resistance is a serious threat for tuberculosis (TB) control, especially in Eastern European countries. Methods: We combined drug susceptibility results and molecular strain typing data with treatment outcome reports to assess the influence of drug resistance on TB treatment outcomes in a prospective cohort of patients from Abkhazia (Georgia). Patients received individualized treatment regimens based on drug susceptibility testing (DST) results. Definitions for antituberculosis drug resistance and treatment outcomes were in line with current WHO recommendations. First and second line DST, and molecular typing were performed in a supranational laboratory for Mycobacterium tuberculosis (MTB) strains from consecutive sputum smear-positive TB patients at baseline and during treatment. Results: At baseline, MTB strains were fully drug-susceptible in 189/326 (58.0%) of patients. Resistance to at least H or R (PDR-TB) and multidrug-resistance (MDR-TB) were found in 69/326 (21.2%) and 68/326 (20.9%) of strains, respectively. Three MDR-TB strains were also extensively resistant (XDR-TB). During treatment, 3/189 (1.6%) fully susceptible patients at baseline were re-infected with a MDR-TB strain and 2/58 (3.4%) PDR-TB patients became MDR-TB due to resistance amplification. 5/ 47 (10.6%) MDR- patients became XDR-TB during treatment. Treatment success was observed in 161/189 (85.2%), 54/69 (78.3%) and 22/68 (32.3%) of patients with fully drug susceptible, PDR- and MDR-TB, respectively. Development of ofloxacin resistance was significantly associated with a negative treatment outcome. Conclusion: In Abkhazia, a region with high prevalence of drug resistant TB, the use of individualized MDR-TB treatment regimens resulted in poor treatment outcomes and XDR-TB amplification. Nosocomial transmission of MDR-TB emphasizes the importance of infection control in hospitals

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

Multidrug-resistant tuberculosis surveillance and cascade of care in Madagascar: a five-year (2012-2017) retrospective study

In 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.; For 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.; The 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.; An 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

Determinan Kejadian Multi-drug Resistant Tuberculosis di Rumah Sakit Dr. Sardjito YOGYAKARTA

Determinant of multi-drug resistant tuberculosis events at Dr. Sardjito Hospital Yogyakarta PurposeThe purpose of this study was to identify the determinants of multidrug resistant events in patients with tuberculosis in Dr. Sardjito Hospital in Yogyakarta.MethodsA cross-sectional study was conducted involving 122 patients with suspected MDR TB consisting of 61 cases of MDR TB and 61 non MDR TB cases. The data collected were secondary data from MDR TB.06 registers, medical records, MDR TB.03 registers, and MDR TB patients' baseline data forms at Dr. Sardjito Hospital Yogyakarta from January 2012 until September 2016. Data were analyzed to determine the correlation between independent variables and dependent variable using Chi-Square tests, and to know the most dominant risk factors using multiple logistic regression tests.Results MDR TB patients' characteristics showed there were more males (63.93%), age >45 years (52.46%), previously TB treatment (96.72%), never smoking (75.41%), no contacts with MDR TB patients (86.89%), and never examined for HIV-AIDS (59.02%). The analysis showed there was no significant association between age, sex, previous TB treatment, smoking, contact with MDR TB patients, and HIV-AIDS status with MDR TB incidence in Dr. Sardjito Hospital Yogyakarta (p value >0.05).Conclusion The variables of age, sex, previous TB treatment, smoking, contacts with MDR TB patients, and HIV-AIDS status were not risk factors for MDR TB incidence in Dr. Sardjito Hospital in Yogyakarta

Intra-urban variation in tuberculosis and community socioeconomic deprivation in Lisbon metropolitan area: a Bayesian approach

Background: Multidrug resistant tuberculosis (MDR-TB) is a recognized threat to global efforts to TB control and remains a priority of the National Tuberculosis Programs. Additionally, social determinants and socioeconomic deprivation have since long been associated with worse health and perceived as important risk factors for TB. This study aimed to analyze the spatial distribution of non-MDR-TB and MDR-TB across parishes of the Lisbon metropolitan area of Portugal and to estimate the association between non-MDR-TB and MDR-TB and socioeconomic deprivation. Methods: In this study, we used hierarchical Bayesian spatial models to analyze the spatial distribution of notification of non-MDR-TB and MDR-TB cases for the period from 2000 to 2016 across 127 parishes of the seven municipalities of the Lisbon metropolitan area (Almada, Amadora, Lisboa, Loures, Odivelas, Oeiras, Sintra), using the Portuguese TB Surveillance System (SVIG-TB). In order to characterise the populations, we used the European Deprivation Index for Portugal (EDI-PT) as an indicator of poverty and estimated the association between non-MDR-TB and MDR-TB and socioeconomic deprivation. Results: The notification rates per 10,000 population of non-MDR TB ranged from 18.95 to 217.49 notifications and that of MDR TB ranged from 0.83 to 3.70. We identified 54 high-risk areas for non-MDR-TB and 13 high-risk areas for MDR-TB. Parishes in the third [relative risk (RR) = 1.281, 95% credible interval (CrI): 1.021–1.606], fourth (RR = 1.786, 95% CrI: 1.420–2.241) and fifth (RR = 1.935, 95% CrI: 1.536–2.438) quintile of socioeconomic deprivation presented higher non-MDR-TB notifications rates. Parishes in the fourth (RR = 2.246, 95% CrI: 1.374–3.684) and fifth (RR = 1.828, 95% CrI: 1.049–3.155) quintile of socioeconomic deprivation also presented higher MDR-TB notifications rates. Conclusions: We demonstrated significant heterogeneity in the spatial distribution of both non-MDR-TB and MDR-TB at the parish level and we found that socioeconomically disadvantaged parishes are disproportionally affected by both non-MDR-TB and MDR-TB. Our findings suggest that the emergence of MDR-TB and transmission are specific from each location and often different from the non-MDR-TB settings. We identified priority areas for intervention for a more efficient plan of control and prevention of non-MDR-TB and MDR-TB. Graphical Abstract: [Figure not available: see fulltext.] © 2022, The Author(s).This work has been funded by National funds, through the Foundation for Science and Technology (FCT)—project UIDB/50026/2020, UIDP/50026/2020 and PTDC/SAU-PUB/29521/2017. This study was also supported by FEDER through the Operational Programme Competitiveness and Internationalization and national funding through the Foundation for Science and Technology—FCT (Portuguese Ministry of Science, Technology and Higher Education) under the Unidade de Investigação em Epidemiologia—Instituto de Saúde Pública da Universidade do Porto (EPIUnit) (UIDB/04750/2020). Ana Isabel Ribeiro was supported by National Funds through FCT, under the programme of ‘Stimulus of Scientific Employment—Individual Support’ within the contract CEECIND/02386/2018

A Path Analysis on the Biopsychosocial Determinants of Multi Drug Resistant Tuberculosis in Surakarta

Background: Multidrug-resistant tuberculosis (MDR-TB) causes significant problem and cost for national TB control program. MDR-TB constitutes an increasing public health concern globally. The prevalence of MDR-TB is as high as 50%. One third of all newly detected TB patients are infected with MDR strains. This study aimed to analyze the bio-psychosocial determinants of MDR-TB in Surakarta, Central Java. Subjects and Method: This was a case control study conducted in Dr. Moewardi Hospital and BBKPM, Surakarta, from September to November 2017. A sample consisting of 76 MDR-TB patients and 228 non MDR-TB patients were selected for this study by fixed disease sampling. The dependent variable was MDR-TB. The independent variables were age, drug-taking adherence, depression, comorbidity, drug side-effect, drug-taking supervisor, and family income. The data were collected using a set of questionnaire and analyzed by path analysis. Results: MDR-TB directly increased with the lack of drug-taking adherence (b= -1.7; 95% CI= -2.23 to -1.07; p= 0.001) and comorbidity (b= 1.5; 95% CI= 0.76 to 2.30; p= 0.001). MDR-TB indirectly increased with depression, drug side effect, weak drug-taking supervision, and older age. Conclusion: MDR-TB directly increases with the lack of drug-taking adherence and comorbidity. MDR-TB indirectly increases with depression, drug side effect, weak drug-taking supervision, and older age. Keywords: bio-psychosocial determinants, MDR-T

Multidrug resistant tuberculosis in HIV positive patients and its effect on Interleukin-2 and Interferon-γ

Background:  This is a case control study aimed to detect plasma level of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) cytokines in multidrug resistant tuberculosis (MDR-TB) co-infected with human immunodeficiency virus (HIV) patients and multidrug resistant tuberculosis (MDR-TB) monoinfected patients. Methods: This study determined the differences in plasma concentrations of pro-inflammatory (IL-2 and IFN-γ) cytokines in MDR-TB co-infected with HIV patients and MDR-TB monoinfected patients. Plasma levels of IL-2 and IFN-γ were measured in 130 participants (comprising 15 MDR-TB/HIV co-infected treatment naïve patients, 15 MDR-TB/HIV co-infected treatment experienced patients, 20 MDR-TB monoinfected treatment naïve patients, 20 MDR-TB monoinfected treatment experienced patients, 20 drug susceptible tuberculosis (DS-TB) co-infected with HIV treatment experienced patients and 40 apparently healthy control groups) using enzyme-linked immunosorbant assay (ELISA). Results: Shows that the mean plasma level of IL-2 (210.02 ± 59.27 pg/ml) measured in MDR-TB co-infected with HIV treatment-naïve patients (group 1a) was significantly (p < /em><0.026) lower compared to MDR-TB monoinfected treatment-naïve patients (244.20±108.07 pg/ml). Conversely the mean plasma levels of IFN-γ was significantly (p < /em><0.041) higher in MDR-TB/HIV co-infected treatment-naïve patients (group 1a) (8.31±3.56 pg/ml) compared to MDR-TB monoinfected treatment-naïve patients (group 2a) (6.89±2.14 pg/ml). Conclusion: Our study revealed significantly reduced plasma level of IL-2 in MDR-TB and HIV co-infected patients compared with MDR-TB monoinfected subjects, suggesting a more advanced immunodeficiency in co-infected patients