Effectiveness of Xpert MTB/RIF and the Line Probe Assay tests for the rapid detection of drug-resistant tuberculosis in the Central African Republic

Abstract

The Xpert MTB/RIF and Line Probe Assay (LPA) tests are more and more frequently used in mycobacteria testing laboratories for the rapid diagnosis of multi-drug resistance (MDR-TB). In this study, we demonstrate the effectiveness of these tests in the Central African Republic. Rifampicin resistance cases detected by the Xpert MTB/RIF during the year 2020 are also underwent first- and second-line LPA, and a first-line of drug susceptibility testing (DST) on solid medium and we compared these results. 101 rifampicin resistance cases based on the Xpert MTB/RIF were detected. Mean age was 34 years [16–81]. The 20–40 years age group represented 73.2% and the male-to-female sex ratio was 1.9:1. Patient profiles were dominated by treatment failure cases (40.6%) followed by relapsed cases (30.7%) and new cases (18.8%). These 101 rifampicin resistance were also detected with the first-line LPA and were confirmed by the DST. Similarly, the isoniazid results obtained with the first-line LPA, were confirmed by the DST, giving a concordance of 100% for these antibiotics. Rifampicin resistance were for the most part due to the absence of the WT8 sequence (56%) and the presence of the Mut3 mutation (53.4%). The majority of the isoniazid resistance (94.2%) were due to the Mut1 mutation in the katG gene and 4.2% of the cases involved both the katG gene and the inhA gene promoter with the Mut1 mutation. The second-line LPA test no resistance to second-line antibiotics. This study demonstrated the effectiveness of the Xpert MTB/RIF and the LPA tests for the rapid diagnosis of MDR-TB in the Central African Republic. However, due to their high cost, these tests have not been extensively deployed in the country. Public authorities and their TB-partners can help make these molecular tests more accessible to fight MDR-TB in the country.

Molecular characterization of genetic mutations with fitness loss in pulmonary tuberculosis patients associated with HIV co-infection in Northwest Amhara, Ethiopia

“…The most common genetic variant in the rpoB gene associated with high levels of resistance to RIF was found to be at codon S450L (55.6%), followed by H445Y and D435V (22.2%). Our findings in S450L are consistent with the high rates reported in other studies across various regions such as Eastern Ethiopia (59.1%), 34 Northwest Ethiopia (64.0%), 7 Iran (66%), 35 the Central Africa Republic (53.4%), 36 Pakistan (55.6%) 32 and (64.1%), 2 India (58.8%), 9 and China (62.5%) 12 and (58.2%). 37 By contrast, the frequency of mutation at codon S450L in our study was higher than the previous report from Iran (40%) 38 and China (31.25%) 39 but lower than studies conducted in the Tigray region of Ethiopia (70%), 31 Addis Ababa Ethiopia (81.3%), 30 and Pakistan (85%).…”

“…Our results are in line with previous studies conducted in Ethiopia, which also found no isolates with combined mutations in both katG and inhA genes 7,31,34 or triple mutations at the rpoB , katG , and inhA genes from India. 9 By contrast, other studies have shown a higher rate of double mutations at both the katG and inhA genes of INH-mono-resistant isolates in the Central Africa Republic (4.2%), 36 China (13.4%) 11 and (3.4%), 12 Pakistan (14.7%) 40 and (1.1%), 32 South Africa (22.7%), 41 Burkina Faso (14.5%), 33 and India (3.4%). 9 The extent of INH resistance conferred by various mutations may vary depending on the genetic background of the strain.…”

“…32 The KatG S315T1 substitution (100%) was the most frequent specific variant that caused high-level INH resistance in our study. This finding aligns with the previous studies that identified the S315T1 variant as the most common genetic variation in the katG gene in Northwest Ethiopia (70.6%) 6 and (87.8%), 7 Addis Ababa Ethiopia (76.9%), 5 Iran (70%), 35 India (86.3%), 9 China (73.8%), 37 Burkina Faso (77.3%), 33 and Pakistan (78.2%) 32 ; but higher S315T1 mutation reported in Eastern Ethiopia (91.8%), 34 Addis Ababa Ethiopia (100%), 30 India (96.2%), 13 central Africa Republic (94.2%), 36 and Mongolia (99.1%) 42 ; and lower proportions of S315T1 -specific mutations were observed in Northeastern Ethiopia (25%), 4 China (62.9%), 12 Iran (32%), 43 and Pakistan (69.8%). 2 A specific C-15T mutation in the inhA regulatory region was detected in a higher proportion of 100% in our study, which is consistent with previously reported results in Eastern Ethiopia (100), 34 Mongolia (98.0%), 42 and India (88.9%) 9 ; however, lower rates were detected in Northwest Ethiopia (41%) 6 and (3.3%), 7 Addis Ababa Ethiopia (30.8%), 5 Tigray region of Ethiopia (5%), 31 China (5.7%) 12 and (24.6%), 37 South Africa (13.4%), 41 and Pakistan (14.9%) 32 and (5.6%).…”