ANALISIS MUTASI GEN rpoB MYCOBACTERIUM TUBERCULOSIS Di LUAR REGIO PENENTU RESISTEN RIFAMPISIN : Pada Pasien Sensitif Obat Yang Masih Terdeteksi BTA Saat Pemantauan Kemajuan Pengobatan

Anita Sofia, Prof. dr. Tri Wibawa, Ph.D., Sp.MK(K); Prof. Dra. Sismindari, Apt, SU, Ph.D.

2023 | Tesis | S2 Ilmu Kedokteran Tropis

Background: In 2021, Indonesia is ranked the 3rd highest tuberculosis sufferer in the world after India and China. Based on notification figures for tuberculosis cases from various regions, Kepulauan Riau (Kepri) Province includes 7 regions with the largest number of cases in Indonesia with a notification rate of 179 cases of tuberculosis per 100,000 population. Among seven districts in Kepri Province, the highest number of case findings were located in Batam City. In 2022, the number of cases of pulmonary tuberculosis in Batam City was recorded at 3,501 cases. Diagnosis of tuberculosis in Indonesia, including Batam City, has used Xpert MTB/RIF based on molecular. Besides, testing also aims to detect cases of rifampicin-resistant TB related to mutations in the rpoB gene in the rifampicin resistance determining region (RRDR). Studies in several countries have found that mutation outside RRDR which not detected by this diagnostic due to differences in gene target regions. An increase in tuberculosis cases with poor response to first-line treatment by detected positive sputum smears after two months of treatment indicated the presence of drug-resistant M. tuberculosis that was not detected at diagnosis. Therefore, needs to be tested genetically, whether this increase is related to mutations in the rpoB gene outside the RRDR, such as in studies in several countries.

Purpose: This study aims to determine the presence of mutations in the rpoB gene outside RRDR on M. tuberculosis isolates from tuberculosis patients in Batam that affect treatment progress by detecting positive sputum smears after two months of treatment.

Results: Based on the results of data analysis, there is an increase in cases of tuberculosis that are sensitive to the drug rifampicin from 2020 to 2022. The increase in cases was also followed by an increase in non-conversion cases two months after treatment. The most common cases occur in productive adults, ranging from 15 to 64 years and the highest number of cases occur in men than women. Genetic testing results to look for rpoB gene mutations outside the RRDR that affect treatment progress found that no mutations substituted nucleotide Ile491Phe, likewise other areas in the amplified gene.

Conclusion: Tuberculosis cases have increased from 2020 to 2022 in Batam City, the increase in cases was also followed by an increase in the number of positive sputum smears after two months of treatment. Based on genetic analysis, no rpoB gene mutations were found outside the RRDR, which affected the progress of treatment in Batam City.

Background: In 2021, Indonesia is ranked the 3rd highest tuberculosis sufferer in the world after India and China. Based on notification figures for tuberculosis cases from various regions, Kepulauan Riau (Kepri) Province includes 7 regions with the largest number of cases in Indonesia with a notification rate of 179 cases of tuberculosis per 100,000 population. Among seven districts in Kepri Province the highest number of case findings were located in Batam City. In 2022, the number of cases of pulmonary tuberculosis in Batam City was recorded at 3,501 cases. Diagnosis of tuberculosis in Indonesia, including Batam City, has used Xpert MTB/RIF based on molecular. Besides, testing also aims to detect cases of rifampicin-resistant TB related to mutations in the rpoB gene in the rifampicin resistance determining region (RRDR). Studies in several countries have found that mutation outside RRDR which not detected by this diagnostic due to differences in gene target regions. An increase in tuberculosis cases with poor response to first-line treatment by detected positive sputum smears after two months of treatment indicated the presence of drug-resistant M. tuberculosis that was not detected at diagnosis. Therefore, needs to be tested genetically, whether this increase is related to mutations in the rpoB gene outside the RRDR, such as in studies in several countries.

Purpose: This study aims to determine the presence of mutations in the rpoB gene outside RRDR on M. tuberculosis isolates from tuberculosis patients in Batam that affect treatment progress by detecting positive sputum smear after two months of treatment.

Results: Based on the results of data analysis, there is an increase in cases of tuberculosis that are sensitive to the drug rifampicin from 2020 to 2022. The increase in cases was also followed by an increase in non-conversion cases two months after treatment. The most common cases occur in productive adults, ranging from 15 to 64 years and the highest number of cases occur in men than women. Genetic testing results to look for rpoB gene mutations outside the RRDR that affect treatment progress found that no mutations substituted nucleotide Ile491Phe, likewise other areas in the amplified gene.

Conclusion: Tuberculosis cases have increased from 2020 to 2022 in Batam City, the increase in cases was also followed by an increase in the number of positive sputum smears after two months of treatment. Based on genetic analysis, no rpoB gene mutations were found outside the RRDR, which affected the progress of treatment in Batam City.

Kata Kunci : mutasi gen rpoB, di luar RRDR, BTA positif, kemajuan pengobatan/ rpoB gene mutation, outside RRDR, smear positive, treatment progress