scholarly journals HYBRIDIZATION-BASED NUCLEIC ACID AMPLIFICATION TEST TERHADAP CARTRIDGE-BASED NUCLEIC ACID AMPLIFICATION TEST TERKAIT MULTIDRUG-RESISTANT TUBERCULOSIS (Hybridization-Based Nucleic Acid Amplification Test towards Catridge-Based Nucleic Acid Amplification Test in Multidrug-Resistant Tuberculosis)

Author(s):  
Ivana Agnes Sulianto ◽  
Ida Parwati ◽  
Nina Tristina ◽  
Agnes Rengga I

Indonesia has high burden of multidrug-resistant tuberculosis (MDR-TB). Cartridge-based nucleic acid amplification test (CB-NAAT),which is recommended as a diagnostic method of MDR-TB by World Health Organization, is faster in achieving the result. This methoddetermines MDR-TB only from the rifampisin resistance, by detecting mutations that occur on the 81 bp hot-spot region of the rpoBgene. The isoniazid resistance is not included in the determination of MDR-TB by this method. Hybridization-based NAAT (HB-NAAT)detects MDR-TB not only from the rifampisin resistance (codon 526 and 531 rpoB gene), but also from the isoniazid resistance (codon315 katG gene). The aim of this study was to know the validity of the HB-NAAT in detecting MDR-TB using sputum with CB-NAATas the gold standard in a diagnostic study. All of 51 sputums were collected during June 2013 from patients suspected pulmonaryMDR-TB at Dr. Hasan Sadikin General Hospital. The result of CB-NAAT were 16 MDR-TB, 12 TB non MDR, and 23 non TB. HB-NAATexamination results were 3 MDR-TB, 25 TB non MDR (3 RMR, 6 IMR, 16 susceptible) and 23 non TB. The sensitivity of HB-NAAT was18.75% and specificity 100%. Low sensitivity values may due to the high mutation variations in the samples. So it could not be detectedonly by codons 526 and 531 for rifampisin resistance. For the detection of isoniazid resistance, HB-NAAT have optimal primer at lowconcentrations and it also need more than katG genes to detect isoniazid resistance. Based on this study, it can be conclued, that HBNAAThas low sensitivity but high specificity in the detecting MDR-TB.

Author(s):  
Ivana Agnes Sulianto ◽  
Ida Parwati ◽  
Nina Tristina ◽  
Agnes Rengga I

Indonesia has high burden of multidrug-resistant tuberculosis (MDR-TB). Cartridge-based nucleic acid amplification test (CB-NAAT), which is recommended as a diagnostic method of MDR-TB by World Health Organization, is faster in achieving the result. This method determines MDR-TB only from the rifampisin resistance, by detecting mutations that occur on the 81 bp hot-spot region of the rpoB gene. The isoniazid resistance is not included in the determination of MDR-TB by this method. Hybridization-based NAAT (HB-NAAT) detects MDR-TB not only from the rifampisin resistance (codon 526 and 531 rpoB gene), but also from the isoniazid resistance (codon 315 katG gene). The aim of this study was to know the validity of the HB-NAAT in detecting MDR-TB using sputum with CB-NAAT as the gold standard in a diagnostic study. All of 51 sputums were collected during June 2013 from patients suspected pulmonary MDR-TB at Dr. Hasan Sadikin General Hospital. The result of CB-NAAT were 16 MDR-TB, 12 TB non MDR, and 23 non TB. HB-NAAT examination results were 3 MDR-TB, 25 TB non MDR (3 RMR, 6 IMR, 16 susceptible) and 23 non TB. The sensitivity of HB-NAAT was 18.75% and specificity 100%. Low sensitivity values may due to the high mutation variations in the samples. So it could not be detected only by codons 526 and 531 for rifampisin resistance. For the detection of isoniazid resistance, HB-NAAT have optimal primer at low concentrations and it also need more than katG genes to detect isoniazid resistance. Based on this study, it can be conclued, that HBNAAT has low sensitivity but high specificity in the detecting MDR-TB.


2020 ◽  
Vol 36 (S1) ◽  
pp. 43-43
Author(s):  
Lijun Shen ◽  
Shangshang Gu ◽  
Fan Zhang ◽  
Zhao Liu ◽  
Yuehua Liu

IntroductionChina bears a considerably high burden of multidrug-resistant tuberculosis (MDR-TB). Second-line anti-TB drugs are urgently needed yet domestic MDR-TB drugs are expensive and lack policy support. Patients’ living conditions are closely related to the drug affordability. The national TB prevention programs should play a critical role. The purpose of this study is to measure the cost of treating MDR-TB patients under different treatment schemes and price sources. The results of this study are expected to inform the relevant drug protection policies and provide inputs for further cost-effectiveness analyses.MethodsBased on the treatment plan of China's Multidrug-Resistant Pulmonary Tuberculosis Clinical Path (2012 edition) and the World Health Organization (WHO) Drug-Resistant Tuberculosis Treatment Guide (2018 edition), the treatment costs of MDR-TB were measured under different scenarios. Catastrophic health expenditure was then calculated if the treatment cost exceeds 40 percent of the household's non-subsistence income. National, rural and disposable income per capita in 2018, were used to represent Chinese patients’ affordability.ResultsUnder varied treatment schemes and market price sources in China, the total costs for MDR-TB patients range from 19,401 to 126,703 CNY [2,853 to 18,633 USD] per person. Under current prices, all treatment schemes recommended by the WHO will incur catastrophic costs for Chinese MDR-TB patients. Significant differences were found between rural and urban areas as 52.8 percent of the treatment listed in the 2012 China Guideline would lead to catastrophic cost for rural patients but not urban ones.ConclusionsOur study concludes that the domestic drugs are more expensive than the international purchase price and the treatment of MDR-TB imposes substantial economic burden on patients, especially in the rural areas. The results of the study also indicate that it is urgent for the state to emphasize government responsibility and initiate centralized procurement for price negotiations to reduce the market price of MDR-TB drugs. The urban-rural gap should also be addressed in the design of future policies to ensure the drug affordability for all patients in need.


2019 ◽  
Vol 23 (10) ◽  
pp. 1050-1054
Author(s):  
L. Guglielmetti ◽  
J. Jaffré ◽  
C. Bernard ◽  
F. Brossier ◽  
N. El Helali ◽  
...  

SETTING: The World Health Organization (WHO) recommends that multidrug-resistant tuberculosis (MDR-TB) treatment should be managed in collaboration with multidisciplinary advisory committees (consilia). A formal national Consilium has been established in France since 2005 to provide a centralised advisory service for clinicians managing MDR-TB and extensively drug-resistant (XDR-TB) cases.OBJECTIVE: Review the activity of the French TB Consilium since its establishment.DESIGN: Retrospective description and analysis of the activity of the French TB Consilium.RESULTS: Between 2005 and 2016, 786 TB cases or contacts of TB cases were presented at the French TB Consilium, including respectively 42% and 79% of all the MDR-TB and XDR-TB cases notified in France during this period. Treatment regimens including bedaquiline and/or delamanid were recommended for 42% of the cases presented at the French TB Consilium since 2009. Patients were more likely to be presented at the French TB Consilium if they were born in the WHO Europe Region, had XDR-TB, were diagnosed in the Paris region, or had resistance to additional drugs than those defining XDR-TB.CONCLUSION: The French TB Consilium helped supervise appropriate management of MDR/XDR-TB cases and facilitated implementation of new drugs for MDR/XDR-TB treatment.


2019 ◽  
Vol 6 ◽  
pp. 204993611986473 ◽  
Author(s):  
Julie Huynh ◽  
Ben J. Marais

The World Health Organization estimates that 10 million new cases of tuberculosis (TB) occurred worldwide in 2017, of which 600,000 were rifampicin or multidrug-resistant (RR/MDR) TB. Modelling estimates suggest that 32,000 new cases of MDR-TB occur in children annually, but only a fraction of these are correctly diagnosed and treated. Accurately diagnosing TB in children, who usually have paucibacillary disease, and implementing effective TB prevention and treatment programmes in resource-limited settings remain major challenges. In light of the underappreciated RR/MDR-TB burden in children, and the lack of paediatric data on newer drugs for TB prevention and treatment, we present an overview of new and repurposed TB drugs, describing the available evidence for safety and efficacy in children to assist clinical care and decision-making.


2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Amber Arnold ◽  
Graham S. Cooke ◽  
Onn Min Kon ◽  
Martin Dedicoat ◽  
Marc Lipman ◽  
...  

ABSTRACT The prolonged use of injectable agents in a regimen for the treatment of multidrug-resistant tuberculosis (MDR-TB) is recommended by the World Health Organization, despite its association with ototoxicity and nephrotoxicity. We undertook this study to look at the relative adverse effects of capreomycin and amikacin. We reviewed the case notes of 100 consecutive patients treated at four MDR-TB treatment centers in the United Kingdom. The median total duration of treatment with an injectable agent was 178 days (interquartile range [IQR], 109 to 192 days; n = 73) for those with MDR-TB, 179 days (IQR, 104 to 192 days; n = 12) for those with MDR-TB plus fluoroquinolone resistance, and 558 days (IQR, 324 to 735 days; n = 8) for those with extensively drug-resistant tuberculosis (XDR-TB). Injectable use was longer for those started with capreomycin (183 days; IQR, 123 to 197 days) than those started with amikacin (119 days; IQR, 83 to 177 days) (P = 0.002). Excluding patients with XDR-TB, 51 of 85 (60%) patients were treated with an injectable for over 6 months and 12 of 85 (14%) were treated with an injectable for over 8 months. Forty percent of all patients discontinued the injectable due to hearing loss. Fifty-five percent of patients experienced ototoxicity, which was 5 times (hazard ratio [HR], 5.2; 95% confidence interval [CI], 1.2 to 22.6; P = 0.03) more likely to occur in those started on amikacin than in those treated with capreomycin only. Amikacin was associated with less hypokalemia than capreomycin (odds ratio, 0.28; 95% CI, 0.11 to 0.72), with 5 of 37 (14%) patients stopping capreomycin due to recurrent electrolyte loss. There was no difference in the number of patients experiencing a rise in the creatinine level of >1.5 times the baseline level. Hearing loss is frequent in this cohort, though its incidence is significantly lower in those starting capreomycin, which should be given greater consideration as a first-line agent.


2020 ◽  
Vol 54 (4) ◽  
pp. 208-214
Author(s):  
Deniz Aygün ◽  
Tarık Yıldırım ◽  
Özlem Başoğlu Öner ◽  
Sezer Toprak ◽  
Aylin Babalık ◽  
...  

Objective: Resistance to at least isoniazid and rifampicin, which are the most important drugs in TB treatment, is called multidrug-resistant tuberculosis (MDR-TB). MDR-TB is a life-threatening condition that affects children as well as adults. Material and Methods: The medical records of children diagnosed with MDR-TB between June 2015 and October 2018 were analyzed retrospectively. Results: Seven female (77.8%) and two male (22.2%) patients were included into the study. Their mean age was 11.58 ± 4.23 years (3.75-15 years). Five patients (55.5%) had family members with MDR-TB. All of them had pulmonary tuberculosis. Acid-resistant bacteria (ARB) were observed in three (33.3%) patients, nucleic acid amplification tests were positive in four (44.4%) patients, and positive cultures were observed in seven (77.7%) patients. Seven patients had microbiologically and two patients had clinically confirmed MDR-TB. Five patients (55.5%) had isoniazid and rifampicin resistance, two patients (22.2%) had isoniazid, rifampicin and streptomycin resistance. A treatment protocol consisting of pyrazinamide, ethambutol, amikacin, protionamide and moxifloxacin was started after evaluating the culture results of the patients and family members. Cycloserine was added to the treatment protocol of four (44.4%) patients. The total treatment process was continued for 18 months. Conclusion: Management of childhood MDR-TB is a long and difficult process, but it is a preventable and treatable disease.


Author(s):  
Henny Fauziah ◽  
Aprianti S. ◽  
Handayani I. ◽  
Kadir NA

  The World Health Organization (WHO) recommended microscopic AFB smear examination and culture as follow-ups to the response of MDR TB therapy. Analyzed the results of microscopic AFB smear and culture conversion as well as treatment outcome in Multidrug-Resistant Tuberculosis (MDR-TB) patients with and without Diabetes Mellitus (DM). This is a retrospective study involved 70 MDR-TB patients with (27 patients) with DM and without DM (43 patients) who had microscopic AFB smear and culture results at the start of the follow-up therapy. This research was conducted at Labuang Baji Regional Public Hospital, Makassar, from June to July 2019, used medical records of MDR-TB patients the period of June 2016 to December 2017. The results showed that 52 out of 70 MDR-TB patients had microscopic AFB smear and culture conversion in MDR-TB with DM (21 patients) and without DM (31 patients). The duration of microscopic AFB smear conversion in MDR TB patients with DM (3.33±0.54 months) was longer than patients without DM (2.07±0.05 months), p=0.001. While in culture conversion, there was no significant difference between MDR-TB with DM (1.28±0.64 months) and without DM (1.25±0.59), p=0.648. The recovery outcome between MDR-TB with (48.1%) and without DM (48.8%) was not significantly different. However, the output of treatment failure was greater in DM (11.2%) than without DM (2.3%), although statistically, there was no significant difference (p=0.568). Multidrug-resistant tuberculosis patients with DM experienced slower microscopic AFB smear conversion than MDR-TB patients without DM. However, in culture, there was no significant difference in the conversion period between the two groups. MDR-TB patients, both of with and without DM, had the same chance of recovery.


2016 ◽  
Vol 25 (139) ◽  
pp. 29-35 ◽  
Author(s):  
Riya Moodley ◽  
Thomas R. Godec

Multidrug-resistant (MDR) tuberculosis (TB) is a threat to global TB control, as suboptimal and poorly tolerated treatment options have resulted in largely unfavourable outcomes for these patients. The last of six cohort studies conducted in Bangladesh which assessed a new shorter regimen using currently available TB drugs showed promising results and offered the possibility of a more acceptable and more effective regimen than the one recommended by the World Health Organization (WHO). The aims of stage 1 of the STREAM (Evaluation of a Standardised Treatment Regimen of Anti-tuberculosis Drugs for Patients with Multidrug-resistant Tuberculosis) trial are to evaluate the efficacy and safety of this regimen, compared to the current WHO-recommended standard of care. Stage 2 evaluates two new bedaquiline-containing regimens: one an all-oral regimen and the second a further shortened and simplified version of the stage 1 study regimen, comparing the efficacy and safety of each to that of the stage 1 study regimen and also to the WHO-recommended standard of care. Success of the stage 1 study regimen would in all probability provide a new standard of care for MDR-TB patients, while positive results from the bedaquiline-containing regimens in stage 2 may allow for even greater progress in the management of this difficult population.


2015 ◽  
Vol 53 (12) ◽  
pp. 3876-3880 ◽  
Author(s):  
Andrea M. Cabibbe ◽  
Paolo Miotto ◽  
Raquel Moure ◽  
Fernando Alcaide ◽  
Silke Feuerriegel ◽  
...  

We evaluated the performance of the molecular lab-on-chip-based VerePLEX Biosystem for detection of multidrug-resistant tuberculosis (MDR-TB), obtaining a diagnostic accuracy of more than 97.8% compared to sequencing and MTBDRplusassay forMycobacterium tuberculosiscomplex and rifampin and isoniazid resistance detection on clinical isolates and smear-positive specimens. The speed, user-friendly interface, and versatility make it suitable for routine laboratory use.


2020 ◽  
Vol 52 (4) ◽  
Author(s):  
Linda Choerunnisa ◽  
Ida Parwati ◽  
Coriejati Rita ◽  
Anna Tjandrawati ◽  
Lidya Chaidir

Indonesia is one of the countries with the highest multidrug-resistant tuberculosis cases in the world. Rapid molecular test using the Xpert MTB/RIF assay is one of the detection methods for MDR-TB. Early detection of MDR-TB is crucial for early initiation of treatment. However, Xpert MTB/RIF assay only detects the rpoB gene mutations associated with Rifampicin resistance. Recently, WHO recommends the use of Pyrosequencing, a DNA sequencing method that can detect not only the rpoB gene but also katG and/or inhA gene mutations associated with Isoniazid resistance. The aims of this study were to compare the interpretation between the two methods and to determine the differences in codon mutation position detection of the rpoB gene and mutation detection of the katG and/or inhA gene. This was a cross-sectional comparative observational study on patients ≥18 years old interpreted as RR-TB patients based on Xpert MTB/RIF assay results who had not received MDR-TB drugs at Dr. Hasan Sadikin General Hospital, Bandung, Indonesia. Results showed there were 40 Rifampicin-resistant TB subjects interpreted by Xpert MTB/RIF assay while Pyrosequencing interpreted 30 MDR-TB, 9 RR-TB and one Isoniazid-resistant TB subjects in January - February 2020. The detection of rpoB gene codon mutation position between Xpert MTB/RIF assay and Pyrosequencing methods was not significantly different (p=0.389). Pyrosequencing had detected 27 katG gene mutations, 3 inhA gene mutations, one katG and inhA gene mutation. To conclude, Pyrosequencing can be used for accurate detection of Rifampicin and Isoniazid resistance in MDR-TB.


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