Diagnosis Of Multidrug-resistant Tuberculosis Research Articles

Risk factors for diagnosis and treatment delay among patients with multidrug-resistant tuberculosis in Hunan Province, China.

Multidrug-resistant tuberculosis (MDR-TB) is a global health threat associated with high morbidity and mortality rates. Diagnosis and treatment delays are associated with poor treatment outcomes in patients with MDR-TB. However, the risk factors associated with these delays are not robustly investigated, particularly in high TB burden countries such as China. Therefore, this study aimed to measure the length of diagnosis and treatment delays and identify their risk factors among patients with MDR-TB in Hunan province. A retrospective cohort study was conducted using MDR-TB data from Hunan province between 2013 and 2018. The main outcomes of the study were diagnosis and treatment delay, defined as more than 14days from the date of symptom to diagnosis confirmation (i.e., diagnosis delay) and from diagnosis to treatment commencement (i.e., treatment delay). A multivariable logistic regression model was fitted, and an adjusted odds ratio (AOR) with a 95% confidence interval (CI) was used to identify factors associated with diagnosis and treatment delay. In total, 1,248 MDR-TB patients were included in this study. The median length of diagnosis delays was 27days, and treatment delays were one day. The proportion of MDR-TB patients who experienced diagnosis and treatment delay was 62.82% (95% CI: 60.09-65.46) and 30.77% (95% CI: 28.27-33.39), respectively. The odds of experiencing MDR-TB diagnosis delay among patients coming through referral and tracing was reduced by 41% (AOR = 0.59, 95% CI: 0.45-0.76) relative to patients identified through consultations due to symptoms. The odds of experiencing diagnosis delay among ≥ 65years were 65% (AOR = 0.35, 0.14-0.91) lower than under-15 children. The odds of developing treatment delay among foreign nationalities and people from other provinces were double(AOR = 2.00, 95% CI: 1.31-3.06)compared to the local populations. Similarly, the odds of experiencing treatment delay among severely ill patients were nearly 2.5 timeshigher (AOR = 2.49, 95% CI: 1.41-4.42)compared to patients who were not severely ill.On the other hand, previously treated TB cases had nearly 40% (AOR = 0.59, 95% CI: 0.42-0.85) lower odds of developing treatment delay compared with new MDR-TB cases. Similarly, other ethnic minority groups had nearly 40% (AOR = 0.57, 95% CI: 0.34-0.96) lower odds of experiencing treatment delay than the Han majority. Many MDR-TB patients experience long diagnosis and treatment delays in Hunan province. Strengthening active case detection can significantly reduce diagnosis delays among MDR-TB patients. Moreover, giving attention to patients who are new to MDR-TB treatment, are severely ill, or are from areas outside Hunan province will potentially reduce the burden of treatment delay among MDR-TB patients.

Evaluation of the multiple doses thiozonide’s pharmacokinetics in patients diagnosed with pulmonary tuberculosis with multidrug-resistant or extensively drug-resistant <i>Mycobacterium tuberculosis</i>

Relevance. The increase in the number of cases of multidrug-resistant tuberculosis (MDR-TB) determines the relevance of the development of new anti-TB drugs (ATDs). Determining the pharmacokinetics of a drug in the context of MDR-TB therapy is an integral part of the study of the original drug. Objective. Evaluation of the pharmacokinetic properties of a new original drug, thiozonide, in patients with MDR-TB with multiple doses of the drug. Methods. Thiozonide was used in patients with a verified diagnosis of MDR-TB as part of a clinical trial according to protocol No. THIO22 "Multicenter 12-week doubleblind, randomized, placebo-controlled clinical trial on the selection of optimal dosages of the drug thiozonide, capsules (CJSC Pharm-Sintez") for against the background of standard anti-tuberculosis chemotherapy in patients diagnosed with pulmonary tuberculosis with multidrug-resistant or extensively drugresistant Mycobacterium tuberculosis” (permission of the Ministry of Health of the Russian Federation No. 661 dated 11/24/2014). Results. The pharmacokinetic characteristics of thiozonide were determined during its repeated use in patients diagnosed with pulmonary tuberculosis with multidrug-resistant or extensively drug-resistant mycobacterium tuberculosis, receiving standard anti-tuberculosis chemotherapy, by HPLC with mass spectrometric detection. The time to reach the maximum concentration T max of thiozonide with repeated administration at a dose of 200 mg, 400 mg and 600 mg was 4.21 ± 1.23 hours, 4.9 ± 1.08 and 5.29 ± 0.91, respectively; the half-life T1/2 for the same dosages of the drug was 7.84 ± 1.86, 7.56 ± 1.92 and 6.3 ± 2.12 hours, respectively. The maximum concentration of thiozonide after taking the drug thiozoinide by volunteers was Cmax was observed at the level of 1386.89 ± 533.68 ng / ml in the group taking 200 mg of thiozonide per day, 2684.48 ± 712.40 when taking the drug at a dosage of 400 mg and 5558, 99 ± 2143.81 – at a dosage of 600 mg. Conclusion. A linear dependence of the maximum concentration and the area under the pharmacokinetic curve on the dose taken and also the average concentration of thiozonide in the blood plasma of patients with pulmonary tuberculosis with multidrug resistance of the causative agent of the disease was revealed.

Addressing patients' unmet needs related to multidrug-resistant tuberculosis (MDR-TB) care: A qualitative research study from Pune city, India.

We aimed to identify and describe the unmet needs of patients with multidrug-resistant tuberculosis (MDR-TB). As a part of larger cross-sectional mixed-methods (qualitative and quantitative data) study on pathways to MDR-TB care, here we present the qualitative component. We interviewed 128 (56 men and 72 women) individuals who had MDR-TB, aged > = 15 years, registered and treated under the National TB Elimination Program (NTEP) in Pune city of India. We carried out thematic analysis of participants' narratives. We found that delays in diagnosis, lack of counseling, late referral to the NTEP and unwarranted expenditure were the main barriers to care that study participants experienced in the private sector. Provider dismissal of symptoms, non-courteous behavior, lack of hygiene in the referral centers, forced stay with other patients and lack of support for psychological/psychiatric problems were identified as a few additional challenges that participants faced at the NTEP care centers. Using qualitative data from experiences of participants with MDR-TB, we identify patients' several unmet needs, attention to which can improve MDR-TB care. Educating private providers about MDR-TB risk and available rapid molecular assays can help the timely diagnosis of MDR-TB and reduce patients' out of pocket costs. At the RNTCP/NTEP, measures such as training health workers to build rapport with patients, maintaining hygienic environments in the health centers with adequate isolation of participants with MDR from other serious cases, referral of patients with psychiatric symptoms to mental health specialists and monitoring drug shortages can help in improving care delivery.

Economic burden of multidrug-resistant tuberculosis on patients and households: a global systematic review and meta-analysis

Multidrug-resistant tuberculosis (MDR-TB) is a major health threat worldwide, causing a significant economic burden to patients and their families. Due to the longer duration of treatment and expensive second-line medicine, the economic burden of MDR-TB is assumed to be higher than drug-susceptible TB. However, the costs associated with MDR-TB are yet to be comprehensively quantified. We conducted this systematic review and meta-analysis to determine the global burden of catastrophic costs associated with MDR-TB on patients and their households. We systematically searched five databases (CINHAL, MEDLINE, Embase, Scopus, and Web of Science) from inception to 2 September 2022 for studies reporting catastrophic costs on patients and affected families of MDR-TB. The primary outcome of our study was the proportion of patients and households with catastrophic costs. Costs were considered catastrophic when a patient spends 20% or more of their annual household income on their MDR-TB diagnosis and care. The pooled proportion of catastrophic cost was determined using a random-effects meta-analysis. Publication bias was assessed using visualization of the funnel plots and the Egger regression test. Heterogeneity was assessed using I2, and sub-group analysis was conducted using study covariates as stratification variables. Finally, we used the Preferred Reporting Items for Reporting Systematic Review and Meta-Analysis-20 (PRISMA-20). The research protocol was registered in PROSPERO (CRD42021250909). Our search identified 6635 studies, of which 11 were included after the screening. MDR-TB patients incurred total costs ranging from $USD 650 to $USD 8266 during treatment. The mean direct cost and indirect cost incurred by MDR-TB patients were $USD 1936.25 (SD ± $USD 1897.03) and $USD 1200.35 (SD ± $USD 489.76), respectively. The overall burden of catastrophic cost among MDR-TB patients and households was 81.58% (95% Confidence Interval (CI) 74.13–89.04%). The catastrophic costs incurred by MDR-TB patients were significantly higher than previously reported for DS-TB patients. MDR-TB patients incurred more expenditure for direct costs than indirect costs. Social protection and financial support for patients and affected families are needed to mitigate the catastrophic economic consequences of MDR-TB.

Isoniazid Resistance Level and Associated Resistance Conferring-mutations in Rifampicin Resistant Mycobacterium tuberculosis

Background: Multidrug resistant tuberculosis (MDR-TB) is a global public health problem causing treatment failure. Rifampicin (RIF) resistance has been used as a surrogate marker for MDR-TB diagnosis, but level of isoniazid (INH) resistance and associated resistance conferring mutations for INH in rifampicin-resistant TB cases are little known. Objective: The objective of this study was to determine level of isoniazid resistance and associated resistance conferring mutations in rifampicin resistant Mycobacterium tuberculosis (MTB) in sputum samples. Methods: A total 53 RIF resistant MTB isolates in sputum, detected by Xpert-MTB RIF assay were enrolled in the study. Culture positive samples were tested by BACTEC MGIT 960 system and level of isoniazid resistance was determined, defined as minimum inhibitory concentration of INH of >0.4 µg/mL and 0.1-0.4 µg/mL as high level and low level INH resistance respectively. Distribution of mutation in katG (codon 315) and inhA promoter (-5, -8, -15 and -16) genes by Real-time PCR among the different degrees of INH resistance was investigated. Results: Among the growth positive isolates, 68.8% of the resistant isolates had high level INH resistance, where katG was found to be the prominent mutation, with or without combined with inhA mutation. Positive predictive value (PPV) of katG mutation was 84.6% in detecting a high level of INH resistance. Low level resistance was present in 31.3% isolates, conferring mutation in inhA and katG in equal percentage (40%), but no detectable mutations were found in 20% low level INH resistant MTB isolates. The PPV of inhA mutation was 33.3% in detection low level resistance. Conclusion: Most of the INH resistant isolates conferred high level resistance and were associated with katG mutation. Evaluation of level INH resistance before using high dose INH will help to avoid dose dependent toxicity and to determine an appropriate treatment regimen. Bangladesh Medical Res Counc Bull 2023; 49(2): 120-125

Predictor Factors of Multi-Drug Resistance Tuberculose on the Characteristics of Chest Radiographic Lesions

This research aimed to demonstrate some predictors of screening diagnosis of multi-drug-resistant tuberculosis (MDR-TB). Researchers determined several predictors as a screening diagnosis of MDR-TB, based on clinical symptoms, WHO criteria, chest radiographic lesions, and sputum smear microscopy. The method demonstrated a correlation between several factors as predictors of the MDR-TB diagnosis consisting of clinical symptoms, WHO criteria, BTA sputum, and cross-sectional chest radiograph lesions, based on examination of Gene X-pert for suspected MDR-TB. The results demonstrated a significant and positive odds ratio value of the relationship between variables: 1). Clinical symptoms (p:0.000) with the largest percentage of coughing with shortness of breath exhibiting 51.32% and coughing exhibiting 27.9%; 2). WHO criteria are among others, new patients (p:0.000; OR:3); 3). Chest radiographic lesion: consolidation (p: 0.000; OR: 3); pleural thickening (p:0.003; OR:2); Fibrosis (p:0.000; OR:6) with location on the medial right (p:0.000; OR:2) and left inferior (p:0.000; OR:3). The BTA sputum is (p:0.000; OR:8). The predictors for screening the diagnosis of MDR-TB are coughing, and shortness of breath. Other WHO criteria include radiographic lesions, fibrosis, consolidation, pleural thickening with the location of lesions either left inferior or medial right and positive smear sputum results.

The course of multidrug-resistant pulmonary tuberculosis in HIV-infected people with COVID-19

Aim. To analyze the course of multidrug-resistant tuberculosis (MDR-TB) in HIV-infected people, depending on the time to COVID-19 diagnosis, using the example of clinical cases from our own observation. Materials and methods. The article presents 3 clinical cases of our own observation of MDR-TB in HIV-infected persons depending on the time to COVID-19 diagnosis in patients, who were treated in the Pulmonary Tuberculosis Department No. 2, clinical base of the Department of Tuberculosis and Pulmonology ZSMU – Municipal non-profit enterprise “Zaporizhzhia Regional Phthisiopulmonology Clinical Medical and Diagnostic Center” of Zaporizhzhia Regional Council. Results. In clinical case 1, in an HIV-infected patient, MDR TB was detected after COVID-19. This clinical case has shown that after mild and treated COVID-19, even on the background of severe immunosuppression, but with AMBT and ART timely prescribed, MDR-TB in the patient had a favorable course with positive dynamics. In clinical case 2, in an HIV-infected patient, MDR-TB was detected concomitantly with COVID-19. The clinical case indicated that the patient received all 3 therapies for MDR-TB, HIV and COVID-19 in full and on time. In contrast to clinical case 1, the patient was diagnosed with a more severe process that required a longer period of treatment, although it was effective. In clinical case 3, an HIV-infected patient with COVID-19 was diagnosed after 5 months of MDR-TB treatment. Against this background, there was culture positivity. But after prescription of appropriate COVID-19 treatment against the background of AMBT and ART, positive dynamics and culture negativity were determined. All 3 patients completed antimycobacterial therapy of MDR-TB with results – recovery. Conclusions. Regardless of the HIV infection duration with underlying severe immunosuppression (<200 CD4 lymphocyte cells) and the time to COVID-19 diagnosis (before, during or after the diagnosis of MDR-TB) on the background of timely therapy of MDR-TB, HIV and COVID-19, positive results can be achieved while saving the lives of patients.

Multidrug Resistant Tuberculosis: Trends and Control

Multidrug resistant tuberculosis (MDR-TB) has been an area of growing concern and is posing a threat to the control of tuberculosis (TB). The exact magnitude of problem of resistance to anti-tuberculosis drugs worldwide was not known till the 1994-97 global project on anti-tuberculosis drug resistance surveillance initiated by the World Health Organization (WHO) and International Union Against Tuberculosis and Lung Diseases (IUATLD). The Global Tuberculosis Report 2014 estimated that an 3.5% of newly diagnosed and 20.5% of previously treated.TB cases had MDR-TB. It has been estimated that 480,000 cases emerged and 210,000 deaths occurred due to MDR-TB globally in 2013. In India, estimates showed that the prevalence of MDR-TB among new and previously treated patients was 2.2% and 15%, respectively. It is estimated that 99,000 cases of MDR-TB emerge every year of which 62,000 were among notified cases of TB in 2013. The MDR-TB is a human-made problem and results largely from poorly managed cases of TB. Adequate, timely diagnosis and optimal treatment of MDR-TB will help curb the epidemic. Efforts must be focused on the effective use of anti-tuberculosis drugs in every new patient, so as to prevent the emergence of MDR-TB.

Barriers faced by patients in the diagnosis of multidrug-resistant tuberculosis in Brazil.

ABSTRACTOBJECTIVE To understand patients’ narratives about the barriers they faced in the diagnosis and treatment of multidrug-resistant tuberculosis, and their consequences in Rio de Janeiro State, Brazil.METHODS This is a qualitative cross-sectional study with non-probabilistic sampling. A theoretical saturation criterion was considered for composing the number of interviewees. Semi-structured interviews were conducted from August to December 2019 with 31 patients undergoing treatment for multidrug-resistant tuberculosis at an outpatient referral center in Rio de Janeiro. Data were transcribed and processed with the aid of the NVIVO software. Interviews were evaluated by content analysis, and their themes, cross-referenced with participants’ characterization data.RESULTS Our main findings were: a) participants show a high proportion of primary drug resistance, b) patients experience delays in the diagnosis and effective treatment of multidrug-resistant tuberculosis ; c) healthcare providers fail to value or seek the diagnosis of drug-resistant tuberculosis, thus beginning the inadequate treatment for drug-susceptible tuberculosis, d) primary health units show low report rates of active case-finding and contact monitoring, and e) patients show poor knowledge about the disease.CONCLUSIONS We need to improve referral systems, and access to the diagnosis and effective treatment of multidrug-resistant tuberculosis; conduct an active investigation of contacts; intensify the training of healthcare providers, in collaboration with medical and nursing schools, in both public and private systems; and promote campaigns to educate the population on tuberculosis signs and symptoms.

Fluorescence Biosensor for One-Step Simultaneous Detection of Mycobacterium tuberculosis Multidrug-Resistant Genes Using nanoCoTPyP and Double Quantum Dots.

The diagnosis of multidrug-resistant tuberculosis (MDR-TB) is crucial for the subsequent drug guidance to improve therapy and control the spread of this infectious disease. Herein, we developed a novel florescence biosensor for simultaneous detection of Mycobacterium tuberculosis (Mtb) multidrug-resistant genes (rpoB531 for rifampicin and katG315 for isoniazid) by using our synthesized nanocobalt 5,10,15,20-tetra(4-pyridyl)-21H,23H-porphine (nanoCoTPyP) and double quantum dots (QDs). Several nanoCoTPyPs with different charges and morphology were successfully prepared via the surfactant-assisted method and their quenching ability and restoring efficiency for DNA detection were systematically analyzed. It was found that spherical nanoCoTPyP with positive charge exhibited excellent quenching effect and sensing performance for the two DNAs' detection due to its affinity differences towards single-stranded DNA (ssDNA) and double-stranded DNA (dsDNA). ssDNA attached on QDs (QDs-ssDNA) was specifically hybridized with targets to form QDs-dsDNA, resulting in fluorescence recovery due to the disruption of the interactions between nanoCoTPyP and ssDNA. Two drug-resistant genes could be simultaneously quantified in a single run and relatively low limits of detection (LODs) were obtained (24 pM for T1 and 20 pM for T2). Furthermore, the accuracy and reliability of our method were verified by testing clinical samples. This simple and low-cost approach had great potential to be applied in clinical diagnosis of MDR-TB.

Radiological evidence in clinical prevalence of hematological changes in multidrug resistant pulmonary tuberculosis

Background: Globally, tuberculosis is the leading cause of death. India accounts for the highest proportion of drug resistant tuberculosis among all other countries. Objectives: This study investigated the changes in hematological parameters with respect to radiological evidences in multidrug resistant tuberculosis patients. Materials and Methods: The study enrolled a total of 273 patients with the confirmative diagnosis of multidrug resistant tuberculosis. The radiological evidences were classified into mild, moderate and severe lung involvement. Results: The chest radiographs illustrated tracheal deviation (74), loss of lung volume (35), pleural effusion (25), lobar collapse and fibrotic manifestations. The defensive leucocytes, phagocytic neutrophils, anucleated platelet cells and platelet volume observed an increase with severe lung grading (p<0.0001). Reduced lymphocyte count, mean platelet size observed with the intense lung involvement. Prevalence of normocytic, normochromic anemia, anisocytosis was prominent in these patients. The erythrocyte sedimentation rate observed no significant changes in the categorized radiological grades of lung. Radiological grading reported a weak positive correlation with the hematological parameters. Conclusion: The study noticed the changes in the complete blood count parameters with radiological signs and recommend monitoring of these investigations in determining the progression of the lung involvement in the multidrug resistant pulmonary tuberculosis patients.

The lived experiences and psychosocial impact of hearing loss on the quality of life of adults with Multidrug-Resistant Tuberculosis.

BackgroundAminoglycosides used in the treatment of Multidrug-Resistant Tuberculosis (MDR-TB) are known to result in hearing loss. The effects of an acquired hearing loss with an MDR-TB diagnosis may have an increased adverse impact on the overall quality of life of an individual; however, there is minimal research in the area.ObjectivesThis study explores the psychological and emotional impact of hearing loss in adults with MDR-TB; and describes the experiences of the social, economic, and vocational impact of hearing loss in adults with MDR-TB.MethodA qualitative research study was conducted on 10 participants, with a confirmed diagnosis of MDR-TB and hearing loss. The researcher used a semi-structured questionnaire to collect data during face-to-face, audio-recorded interviews.ResultsHearing loss in patients diagnosed with MDR-TB has a significant adverse impact on the lived experiences of patients. Stigma, discrimination, psychological distress, adverse changes in family status and family relationships, financial constraints, and social challenges were some of the common issues reported by participants. Unemployment posed a significant challenge, resulting in participants having no economic stability because of MDR-TB, which was then worsened by the hearing loss; consequently, generating a great deal of stress. Participants reported feelings of worthlessness, a loss of identity, lack of motivation, feelings of embarrassment, and loss of independence.ConclusionThere is a significant irreversible social, psychological, and economic impact of hearing loss that has a direct impact on the lived experiences of MDR-TB patients and their families even after cure of MDR-TB. There is a need for improved treatment methods with psychosocial intervention strategies that equip patients to alleviate the adverse effects they experience.

Effect of Mixed Infections with Mycobacterium tuberculosis and Nontuberculous Mycobacteria on Diagnosis of Multidrug-Resistant Tuberculosis: A Retrospective Multicentre Study in China.

BackgroundCorrect species identification is essential before initiation of TB treatment, due to substantial drug susceptibility profile differences among mycobacterial species. Given that nontuberculous mycobacteria (NTM) are frequently resistant to first-line anti-tuberculosis drugs, cases with mixed infections with Mycobacterium tuberculosis (MTB) and NTM tend to be diagnosed as multidrug-resistant tuberculosis (MDR-TB) cases. Here we report results of a retrospective multicentre study that was conducted to determine the prevalence of TB-NTM infections in previously diagnosed laboratory-confirmed multidrug-resistant tuberculosis (MDR-TB) patients using phenotypic drug susceptibility testing. The results were then used to identify risk factors associated with susceptibility to mixed infections.MethodsFrom January 2019 through December 2019, we retrospectively collected MDR-TB isolates from three TB specialised hospitals. Species identifications of isolates were performed using the MeltPro Myco assay.ResultsA total of 837 MDR-TB isolates were analysed, of which 22 isolates (2.6%) were found to contain a mixture of NTM and MTB organisms. Significant differences in prevalence rates of mixed infections across regions were observed, with prevalence rates ranging from 0.0% (0/213) in Beijing to 3.4% (12/353) in Fuzhou to 3.7% (10/271) in Guangzhou. Among the 22 patients with NTM-TB mixed infections, a total of five different mycobacterial species were identified, of which the most prevalent species was Mycobacterium intracellulare. Notably, a history of previous TB episodes correlated with higher mixed infection risk.ConclusionThe results reported here demonstrated that mixed infections with MTB and NTM occurred in approximately 3% of suspected MDR-TB patients in China. These findings raise concerns about the accuracy of molecular diagnostics-based species identification tests and draw attention to the possibility that NTM-MTB mixed infections will be misdiagnosed as MDR-TB in high TB burden settings.

Effect modification of greenness on PM2.5 associated all-cause mortality in a multidrug-resistant tuberculosis cohort

RationaleEvidence for the association between fine particulate matter (PM2.5) and mortality among patients with tuberculosis (TB) is limited. Whether greenness protects air pollution-related mortality among patients with multidrug-resistant tuberculosis (MDR-TB)...

GeneXpert contribution in the diagnosis of multi-resistant tuberculosis in new cases at the National University Hospital Centre of Pneumo-Phtisiology of Cotonou (Benin)

The diagnosis of bacteriologically confirmed pulmonary tuberculosis in Benin and in other developing countries relies on the search for acid-fast bacilli through microscopy despite its limited sensitivity. The objective of this study is to evaluate the contribution of the Xpert test in the diagnosis of multidrug-resistant tuberculosis in all new suspects received at the Centre National Hospitalier Universitaire de Pneumo-Phtisiologie de Cotonou (CNHU-PPC) of Benin. The biological material consisted of sputum from new suspected TB patients received at CNHU-PPC during the third quarter of 2018. A total of two thousand three hundred and seventy-five (2375) suspected patients were included in the study, of which 52% were men and 48% were women. The most representative age range was 15-24 years, 28%. GeneXpert was able to diagnose pulmonary tuberculosis in 10.02% of patients, including 9.7% rifampicin-susceptible and 0.3% rifampicin-resistant patients who could not be detected by microscopy. This molecular diagnostic tool is of great value for the diagnosis of multidrug-resistant tuberculosis in new suspects.

Tuberculosis Pathways to Care and Transmission of Multidrug Resistance in India.

RationaleIndia is experiencing a regional increase in cases of multidrug-resistant tuberculosis (MDR-TB).ObjectivesGiven the complexity of MDR-TB diagnosis and care, we sought to address key knowledge gaps in MDR risk factors, care delays, and drivers of delay to help guide disease control.MethodsFrom January 2018 to September 2019, we conducted interviews with adults registered with the National TB Elimination Program for MDR (n = 128) and non–MDR-TB (n = 269) treatment to quantitatively and qualitatively study care pathways. We collected treatment records and GeneXpert-TB/RIF diagnostic reports.Measurements and Main ResultsMDR-TB was associated with young age and crowded residence. GeneXpert rifampicin resistance diversity was measured at 72.5% Probe E. Median time from symptom onset to diagnosis of MDR was 90 days versus 60 days for non-MDR, Wilcoxon P < 0.01. Delay decreased by a median of 30 days among non-MDR patients with wider access to GeneXpert, Wilcoxon P = 0.02. Pathways to care were complex, with a median (interquartile range) of 4 (3–5) and 3 (2–4) encounters for MDR and non-MDR, respectively. Of patients with MDR-TB, 68% had their first encounter in the private sector, and this was associated with a larger number of subsequent healthcare encounters and catastrophic expenditure.ConclusionsThe association of MDR with young age, crowding, and low genotypic diversity raises concerns of ongoing MDR transmission fueled by long delays in care. Delays are decreasing with GeneXpert use, suggesting the need for routine use in presumptive TB. Qualitatively, we identify the need to improve patient retention in the National TB Elimination Program and highlight patients’ trust relationship with private providers.

Dynamics of the incidence of the relapses in patients with pulmonary tuberculosis

BACKGROUND. Among countries of Europe in Ukraine the incidence and mortality rate from tuberculosis (TB), including the incidence of the relapses in patients with pulmonary tuberculosis (RPT), remain high. Absence of the national program of fight from TB, lack of financing of anti-TB measures, unsatisfactory statistical information confirm the necessity of study of situation from relapses in patients with RPT and development of measures on their warning.&#x0D; OBJECTIVE. To estimate the features of dynamics of the incidence of RPT in the last few years and consisting of epidemic situation of TB in a country.&#x0D; MATERIALS AND METHODS. An analysis of official statistical reports of anti-TB establishments of administrative territories of Ukraine, information of SI “Center of Public Health of the Ministry of Health of Ukraine” and SI “Center of Medical Statistics of the Ministry of Health of Ukraine” in the last few years.&#x0D; RESULTS AND DISCUSSION. By the features of dynamics of the incidence of RPT in the last few years in a country are high the incidence in patients with RPT with sputum positive smears with comparison in the incidence in patients with RPT with sputum negative smears; decline of index on 46,0 %; high part of RPT with sputum positive smears among patients with TB sputum positive smears (the TB new cases + relapses); diminishing of amount of cases of TB which the diagnosis of multidrug-resistant TB is confirmed, from them growth of percent of patients with extended resistant of Mycobacterium tuberculosis. The signs of epidemic situation are: decline of the TB incidence of lights (the new cases + relapses); high percent of patients sputum positive smears; high TB incidence among children by age 15-17; diminishing of the TB mortality rate and his prevalence; absence of changes of index prevalence of TB among children by age 0-17 and 0-14.&#x0D; CONCLUSIONS. The analysis of statistical data testifies to the presence of failings in an exposure and treatment of patients with the relapses of TB, on the necessity of introduction of complex anti-TB measures for warning of relapses within the framework of the national program of fight from TB.

Validation of the Real Time Polymerase Chain Reaction (qPCR) coupled to melting curves as an alternative tool for the diagnosis of Multi-Drug Resistant Tuberculosis

La tuberculosis es una enfermedad infecto-contagiosa, causada por diversas especies del Complejo Mycobacterium tuberculosis, actualmente se estima que un tercio de la población mundial se encuentra afectada por lo que representa una amenaza para la salud pública, principalmente por el surgimiento de cepas Multidrogorresistentes (TB-MDR). En Bolivia se reportaron 7.538 personas enfermas con Tuberculosis, los últimos datos sobre TB-MDR indican un aumento de 0,2% por año, el año 2019 se registró un 3,1% de TB-MDR. Actualmente en nuestro país se emplean métodos moleculares para la identificación de este agente infeccioso; no obstante, existen muy pocos o ningún trabajo acerca de la aplicación de métodos moleculares para la detección precisa y efectiva de cepas TB-MDR que otorguen validez a los resultados emitidos. Este trabajo resuelve el cuestionamiento de, si la PCR en tiempo real (RT-qPCR) acoplada a curvas melting es una herramienta de diagnóstico alternativo aplicable, para la identificación de Tuberculosis Multidrogorresistente. Materiales y Métodos: Se trabajó con 74 cepas de Mycobaterium tuberculosis fenotípicamente identificadas por cultivo (método de las proporciones, Canetti Rist) como gold standar. El material genético para las pruebas moleculares se obtuvo por el método de columnas, se utilizaron dos controles primarios para la determinación de resistencia a los fármacos Isoniacida y Rifampicina, tanto los controles como las muestras se procesaron por RT-qPCR acoplada a curvas melting, mediante cambios de temperatura de disociación. Resultados: Loa parámetros de test diagnóstico de la prueba demostraron sensibilidad: 67.4%, especificidad: 83.3%, Exactitud: 73.97%, VPP: 85.3%, VPN: 64.1% para Isoniacida. Mientras que para Rifampicina: Sensibilidad: 97%, especificidad: 20%, exactitud: 58.9%, VPP: 55.4% y VPN: 87.5%. Conclusión: El método evaluado para la determinación de resistencia a Isoniacida presenta un equilibrio entre sensibilidad y especificidad, por lo que representa una alternativa diagnóstica confiable, mientras que para resistencia a Rifampicina presenta una alta sensibilidad que es muy útil para países endémicos como el nuestro.

Rapid detection of multidrug-resistant tuberculosis based on allele-specific recombinase polymerase amplification and colorimetric detection.

Multidrug-resistant tuberculosis (MDR-TB) poses a serious threat to TB control. Early diagnosis and proper treatment are essential factors to limit the spread of the disease. The existing molecular tests for MDR-TB usually require specific instruments, steady power supply, and routine maintenance, which might be obstacles for low-resource settings. This study aimed to develop allele-specific isothermal recombinase polymerase amplification (allele-specific RPA) to simultaneously detect the most common mutations in the rpoB gene at codons 516, 526, and 531, which are associated with rifampicin resistance, and in the katG gene at codon 315, which is related to isoniazid resistance. Allele-specific primers targeting four major mutations, rpoB516, rpoB526, rpoB531, and katG315, were constructed and used in individual RPA reactions. The RPA amplicons were endpoints detected by the naked eye immediately after applying SYBR Green I. The optimised RPA assay was evaluated with the Mycobacterium tuberculosis wild-type strain H37Rv and 141 clinical M. tuberculosis isolates. The results revealed that allele-specific RPA combined with SYBR Green I detection (AS-RPA/SYBR) detected these four major mutations with 100% sensitivity and specificity relative to DNA sequencing. The limits of detection for these particular mutations with AS-RPA/SYBR were 5 ng. As a result of the outstanding performance of AS-RPA/SYBR, including its easy setup, speed, lack of a specific instrument requirement, and lack of cross-reaction with other bacteria, this technique may be integrated for the molecular diagnosis of MDR-TB, especially in low-resource settings.

Does Ghana's National Health Insurance Scheme provide financial protection to tuberculosis patients and their households?

Financial barriers are a key limitation to accessing health services, such as tuberculosis (TB) care in resource-poor settings. In Ghana, the National Health Insurance Scheme (NHIS), established in 2003, officially offers free TB care to those enrolled. Using data from the first Ghana's national TB patient cost survey, we address two key questions 1) what are the key determinants of costs and affordability for TB-affected households, and 2) what would be the impact on costs for TB-affected households of expanding NHIS to all TB patients?We reported the level of direct and indirect costs, the proportion of TB-affected households experiencing catastrophic costs (defined as total TB-related costs, i.e., direct and indirect, exceeding 20% of their estimated pre-diagnosis annual household income), and potential determinants of costs, stratified by insurance status. Regression models were used to determine drivers of costs and affordability. The effect of enrolment into NHIS on costs was investigated through Inverse Probability of Treatment Weighting Analysis.Higher levels of education and income, a bigger household size and an multi-drug resistant TB diagnosis were associated with higher direct costs. Being in a low wealth quintile, living in an urban setting, losing one's job and having MDR-TB increased the odds of experiencing catastrophic costs. There was no evidence to suggest that enrolment in NHIS defrayed medical, non-medical, or total costs, nor mitigated income loss. Even if we expanded NHIS to all TB patients, the analyses suggest no evidence for any impact of insurance on medical cost, income loss, or total cost.An expansion of the NHIS programme will not relieve the financial burden for TB-affected households. Social protection schemes require enhancement if they are to protect TB patients from financial catastrophe.