Title : Drug resistance in tuberculous lymphadenitis: Molecular characterization
Abstract:
Background: Drug-resistant tuberculosis (TB) epidemic in high-TB-incidence countries, particularly Ethiopia, remains a significant challenge. As a result, we investigated the drug resistance, common gene mutation, and molecular characterization of mycobacterial isolates from patients with suspected tuberculous lymphadenitis (TBLN).
Methodology: A cross-sectional study of 218 FNA samples from TBLN patients inoculated on LowensteinJensen media was carried out. The culture isolates were identified as MTB by polymerase chain reaction (PCR) and the difference-9 (RD9) test region. In addition, the GenoType MTBDRplus assay tested the first and second-line MTB drugs, and the spoligotyping strain-dependent polymorphism test was determined.
Results: Among the 50 culture-positive isolates, 14% (7/50) had drug resistance caused by a gene mutation. Out of these, 4 (8%) isolates were mono-resistant to isoniazid drug, which is caused by a gene mutation in katG in the region of interrogated at codon 315 in the amino acid sequence of S315T1, 3 (6%) isolates were resistant to both rifampicin and isoniazid drugs. The mutation was observed for katG (at codon 315 with a change in the sequence of amino acid S315T) and rpoB (at codon 530-533 with a change in the sequence of amino acid S531L (S450L)) genes. The most prevalent spoligotypes were orphan and SIT53 strains.
Conclusion: The predominance of INH mono-resistance poses a critical risk for the potential development of MDR-TB, as INH mono-resistance is a typical pathway to the occurrence of MDR-TB. The Orphan and SIT53 (T) strains were the most common in the study area, and a drug-resistant strain caused by a common gene mutation could indicate the transmission of clonal-resistant strains in the community.
Keywords: M. tuberculosis, Gene mutations, Spoligotyping, MDR-TB, tuberculous lymphadenitis
Audience Take Away:
• Prevalence and Types of Drug Resistance in Tuberculous Lymphadenitis: The audience will learn about the percentage of drug-resistant cases among tuberculous lymphadenitis (TBLN) patients, specifically noting the 14% drug resistance rate observed in the study.
• Common Gene Mutations Linked to Drug Resistance: The presentation will provide details on specific gene mutations responsible for drug resistance, particularly the katG and rpoB gene mutations affecting isoniazid and rifampicin resistance.
• Molecular Characterization Techniques: Attendees will gain insights into the methodologies used for identifying Mycobacterium tuberculosis (MTB) strains and their resistance profiles, including PCR, the RD9 test region, the GenoType MTBDRplus assay, and spoligotyping
• Strain Prevalence and Epidemiology: The presentation will highlight the most prevalent MTB strains found in the study, such as the orphan and SIT53 strains, and discuss their implications for disease transmission within the community
• Implications for Multi-Drug Resistant TB Development: The audience will understand the critical risk posed by INH mono-resistance as a pathway to developing multi-drug resistant TB (MDR-TB), emphasizing the importance of monitoring and addressing INH resistance early
Practical Applications and Benefits Use in Clinical Settings:
• Medical professionals can use the knowledge of prevalent gene mutations and resistance patterns to better inform diagnostic and treatment decisions for TBLN patients, potentially leading to more targeted and effective therapies.
Improved Diagnostic Accuracy:
• The detailed molecular characterization techniques presented can help healthcare providers accurately identify drug-resistant TB strains, leading to more precise and reliable diagnostics.
Research and Teaching Expansion:
• Other faculty and researchers can build on this study to explore further genetic markers of resistance, develop new diagnostic tools, and enhance curricula with up-to-date information on TB resistance mechanisms and molecular diagnostics.
Public Health Strategies:
• Public health officials can use the findings to implement more effective TB control programs, focusing on early detection and prevention of the spread of resistant strains, thus reducing the overall incidence of MDR-TB.
Streamlining Treatment Protocols:
• By understanding the common pathways to drug resistance, clinicians and researchers can devise streamlined treatment protocols that preemptively address potential resistance, thereby increasing treatment efficacy and patient outcomes.
