Detection and factors associated with tuberculosis and rifampicin resistance among presumptive patients at the Thailand-Myanmar border

@#Tuberculosis (TB) continues to be a major public health problem in Thailand and many countries. Endemic TB and outbreaks of TB drug resistance in the borderlands are particularly important. The Thailand-Myanmar border has extensive cross-border travel that may accelerate TB’s spread. This cross-sectional study aimed to determine the frequency and factors associated with TB, and rifampicinresistant TB (RR-TB) among presumptive tuberculosis patients in Mae Sot Hospital. Sputum was processed by microscopic examination and Xpert MTB/RIF assay. Laboratory results and socio-demographic characteristics were collected and analyzed. Univariate and multivariate analyses were performed to assess the association of the risk factors with TB and RR-TB. The significant variables at p-values < 0.05 in univariate analysis were selected for multivariate analysis. Of 365 presumptive patients enrolled, 244 (66.85%) were males and 199 (54.52%) were Burmese. Of these, 314 (86.03%) were registered as new cases and 183 (50.14%) worked as laborers. Sputum microscopy was positive in 132 (36.16%) cases. Based on Xpert MTB/RIF, the frequency of TB was 136 (37.26%) and RR-TB was 15 (11.03%). TB was more common in males than females. The majority of the cases belonged to the 26-50-year-old age group and migrant workers. In RR-TB detection, the rpoB mutations covered by probe E were the most frequently observed. Sequencing showed that the most highly mutated codon was codon 531 and Ser531Thr was the most common mutation. For risk factor analysis, working as laborers was significantly (p-value < 0.05) associated with TB (aOR 2.83; 95% CI 1.43-5.63) and previously treated cases were significantly associated with RR-TB (aOR 12.33; 95% CI 2.29-66.49). The high frequency of TB and RR-TB in migrants highlights the problem and factors associated with TB at the border and the need for efforts in TB control programs in this setting.

Tuberculosis con resistencia a rifampicina en Chile / Tuberculosis with resistance to rifampicin in Chile

Resumen El éxito de los tratamientos acortados de la tuberculosis se debe a la asociación de fármacos bactericidas y esterilizantes, principalmente Rifampicina e Isoniazida. Cuando la Rifampicina no puede ser utilizada por resistencia, los tratamientos son más prolongados y el éxito en la curación se reduce. La resistencia a Rifampicina frecuentemente se acompaña de resistencia a Isoniazida (Multidrogoresistencia o MDR). La OMS informa que en 2019 se diagnosticaron sólo el 44% de los casos estimados de tuberculosis con resistencia a Rifampicina (se proyectaba 465.000 casos) y se trató sólo al 38% de los casos estimados, quedando una gran proporción de casos sin diagnosticar y sin tratar. En Chile la vigilancia de la susceptibilidad a fármacos de primera línea en cepas de Mycobacterium tuberculosis se efectúa mediante biología molecular desde 2014, observándose un progresivo incremento de casos resistentes a Rifampicina desde 1% (23 casos) para ese año hasta 2,2% (65 casos) en 2019. La mayoría de casos de resistencia a Rifampicina corresponden a resistencia inicial. En casos con resistencia a Rifampicina realizamos estudio de susceptibilidad a fármacos de segunda línea en el laboratorio de referencia nacional. La terapia de TB-MDR tradicional tiene baja eficacia, con abandonos frecuentes por su largo tiempo de terapia y toxicidad. Nuevos tratamientos sin inyectables y el uso de Clofazimina, Fluorquinolonas, Linezolid y Bedaquilina tienen una mejor tasa de curación. Recientemente, el Programa de Control de la Tuberculosis de Chile dispone de esta terapia más eficaz y de menor duración por vía oral con estos fármacos.

The high success rate of shortened Tuberculosis (TB) treatments has been achieved by the association of bactericidal and sterilizing drugs. The main drugs are Rifampicin and Isoniazide. When Rifampicin cannot be used by resistance, the treatment is prolonged and success in healing is significantly reduced. Resistance to Rifampicin is often accompanied by resistance to Isoniazide (Multidrug resistance or MDR). WHO reports that only 44% of estimated TB cases with resistance to Rifampicin were diagnosed in 2019 (465,000 cases projected) and only 38% of estimated cases were treated, with a large proportion of cases remaining undiagnosed and untreated. In Chile, monitoring of susceptibility to first-line drugs is conducted in strains of Mycobacterium tuberculosis by molecular biology since 2014, observing a progressive increase in cases with Rifampicin resistance from 1% for that year (23 cases) to 2.2% in 2019 (65 cases). Most cases of resistance to Rifampicin correspond to cases of initial resistance. In cases with resistance to Rifampicin we carry out susceptibility study to second-line drugs in a national reference laboratory. MDR-TB therapy has low efficacy, with frequent abandonments for its long therapy time and toxicity. New non-injectable treatments and use of Clofazimine, Fluorquinolones, Linezolid and Bedaquiline are achieving a better cure rate. Recently, Chile's TB Control Program has this most effective and shorter-lasting oral therapy with these drugs.

Population-based molecular epidemiologic study of rifampicin-resistant tuberculosis in rural area of eastern China / 中华流行病学杂志

Objective To describe the drug resistance-related molecular characterization and clustering feature of rifampicin-resistant (RIFr) M.tuberculosis (M.tb) in rural area of eastern China. Methods All patients diagnosed as RIFr M.tb in Deqing and Guanyun county during one year period from 2004 to 2005 were included in the study. By proportion method of drug susceptibility test, 65 isolates were identified resistant to rifampicin and regarded as the studied strains. Hotspots of rpoB gene and katG gene were detected by direct DNA sequencing. Beijing genotype M.tb strains were identified by spoligotyping. IS6110-RFLP (IS6110 restriction fragment length polymorphism) and clustering analysis were performed on all RIFr M.tb isolates available. Results The mutations in 81 bp rifampicin-resistance determination region (RRDR) of the rpoB gene were observed among 60 (92%) RIFr M.tb isolates, with mutation in locus 531 observed in the majority of RIFr isolates (37/65). 49(82%) of the 60 isolates were multidrug resistant TB (MDR-TB), which were referred to as resistant to both RIF and isoniazid (INH). Through spoligotyping, 54(83%) isolates were identified as Beijing genotype strains. In clustering analysis of IS6110-RFLP, 24 isolates were grouped into 11 clusters, suggesting that the recent transmission of M.tb did exist among patients. Regarding the drug resistance profile in clusters, all the isolates in clusters were also MDR-TB. 7 clusters contained isolates carrying different mutations were related to RIF-resistance. Multivariate analysis showed the proportion of new cases in clustered patients is higher than that in the un-clustered patients (new/previously treated: OR=3.342; 95% CI: 1.081-10.32). Conclusion The acquisition of rifampicin resistance in M.tb was more likely to be resulted from the selective growth of RIFr M.tb in the specific drug resistant M.tb such as isoniazid-reisistant M.tb. Previous elongated irregular treatment might favor the epidemic of RIFr M.tb.

Clinical Usefulness of the Line Probe Assay for Rapid Detection of Rifampicin-resistant Tuberculosis / 결핵

BACKGROUND: RpoB gene mutations have been found in about 96-98% of rifampicin (RMP)-resistant Mycobacterium tuberculosis. Recent reports confirm that the in laboratory settings a rpoB gene mutation can be used as a surrogate marker for multi-drug resistant tuberculosis. However, its usefulness in clinical applications has not been evaluated. This study was performed to confirm whether mutation analysis of the rpoB gene of M.tuberculosis is useful in clinical settings. METHODS: The medical records of 33 patients in whom rpoB gene analysis was conducted using an INNOLiPA Rif. TB assay (LiPA) from June, 1998, to July, 2000, at the Asan Medical Center were retrospectively reviewed in 33 patients. the clinical characteristics in addition to the drug susceptibility and LiPA results were analyzed. The drug susceptibility test was considered as a gold standard method for M/ tuberculosis susceptibility and these results were compared with those of the rpoB gene study and sequencing analysis. sequencing analysis of the rpoB gene was done in cases where there was a discrepancy between the results of the drug susceptibility and rpoB gene study. RESULTS: The mean age and sex ratio was 42±18, and 24:9(M:F), respectively. there were 19 RMP susceptible (58%) and 14 RNP-resistant cases (42%) according to the rpoB gene study. The mean time from the request to reporting the results of the rpoB gene study was 5.2±2.6 days. The mean gap from reporting the rpoB gene study to reporting the susceptibility was 56±35 days. Twenty-eight cases (85%) showed identical results compared with the drug susceptibility results, wheres five cases (15%) showed contradictory results. When compared with the sequencing analysis, of the five cases that showed contradictory results, two had LiPA analysis errors and the remaining three were identical to the sequencing results. The rpoB gene study was of assistance in choosing the appropriate drugs in 28 cases (85%). CONCLUSIONS: An rpoB gene study using an LiPA assay was useful in rapidly diagnosing RMP-resistant tuberculosis, which enabled a proper choice of the appropriate drugs in clinical practices. However, an LiPA assay always should be performed in conjunction with microscopy, culture, and susceptibility tests.