Identifying MDRTB transmission hotspots using routinely collected data

Manjourides, J., Lin, H.H., Shin, S., Jeffery, C., Contreras, C., Santa Cruz, J., Jave, O., Yagui, M., Asencios, L., Pagano, M. and Cohen, T., 2012. Identifying multidrug resistant tuberculosis transmission hotspots using routinely collected data. Tuberculosis, 92(3), pp.273-279.

Identification of MDRTB transmission hotspots in parts of the study area is crucial.

Resources to interrupt the transmission of resistant disease should be prioritized in these regions.

Further investigation, such as a molecular epidemiological study, might validate these findings and identify causes or specific high-risk locations. See also: https://tbreadingnotes.blogspot.com/2024/08/scientific-advances-and-end-of.html

Possible reasons for higher transmission in these areas:

• Delayed diagnosis and treatment of infectious MDRTB patients
• Higher population density or more respiratory contacts
• Circulation of particularly transmissible MDR strains

Detecting high-risk areas suggests that geographically targeted interventions could be effective.

Programmatically, resources for detecting and treating MDRTB should be concentrated in these areas. See also: https://tuberculosis101.blogspot.com/2024/11/evaluation-of-xpert-mtb-host-response.html

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Wulandari, D.A., Hartati, Y.W., Ibrahim, A.U. and Pitaloka, D.A.E., 2024. Multidrug-resistant tuberculosis. Clinica Chimica Acta, 559, p.119701.

• Multidrug-resistant tuberculosis (MDR-TB) is defined by resistance to at least rifampicin (RIF) and isoniazid (INH).
• MDR-TB arises from inadequate treatment practices, such as incomplete treatment, insufficient drug doses and durations, poor drug quality, and transmission from individuals with drug-resistant TB.
• Resistance in MTB (Mycobacterium tuberculosis) results from spontaneous chromosomal mutations. There are ten gene variants linked to resistance against first-line anti-TB medications, including katG, inhA, ahpC, kasA, and Ndh for INH, and rpoB for RIF.
• Drug resistance occurs primarily through two mechanisms: primary resistance from exposure to a resistant MTB strain and secondary resistance due to poor treatment adherence.

Classification of Drug-Resistant TB

• Mono-resistant TB: Resistant to one first-line anti-TB drug only.
• Isoniazid-resistant TB: Resistant to Isoniazid, but susceptible to Rifampicin.
• Poly-resistant TB: Resistant to more than one first-line anti-TB drug, excluding both Isoniazid and Rifampicin.
• Rifampicin-resistant TB (RR): Resistance to rifampicin detected using phenotypic or genotypic methods, with or without resistance to other anti-TB drugs. Includes mono-resistance, poly-resistance, MDR, or XDR.
• Multidrug-resistant TB (MDR-TB): Resistant to at least both Isoniazid and Rifampicin.
• Pre-extensively drug-resistant TB: Resistant to Rifampicin, Isoniazid, and either Fluoroquinolones or one injectable drug (Amikacin or Kanamycin).
• Extensively drug-resistant TB (XDR-TB): Resistance to any fluoroquinolone, and at least one of three second-line injectable drugs (capreomycin, kanamycin, or amikacin), in addition to being multidrug-resistant.

Rifampicin:

• A lipophilic antibiotic that inhibits RNA synthesis by binding to the β-subunit of DNA-dependent RNA polymerase, blocking RNA transcription.
• Common side effects include hepatotoxicity, immunological allergies, skin syndromes, gastrointestinal issues, influenza-like symptoms, hemolytic anaemia, shock, and acute renal failure.

Isoniazid:

• Requires activation by the mycobacterial enzyme katG to inhibit mycolic acid synthesis essential for the mycobacterial cell wall.
• Side effects include peripheral neuropathy, seizures from overdose, lupus erythematosus, rheumatoid-like syndrome, and various hematological disorders.

Ethambutol:

• Inhibits mycobacterial arabinosyltransferase, crucial for bacterial cell wall biosynthesis.
• It mimics arabinofuranosyl, disrupting the cell wall synthesis process and causing bacterial aggregation and morphological changes.

Pyrazinamide:

• A prodrug activated in acidic conditions to pyrazinoic acid, which inhibits fatty acid synthesis in MTB.

MDR-TB Detection:

• Phenotypic testing: Culture-based method using solid (Lowenstein Jensen) or liquid media (mycobacterium growth indicator tube, MGIT), taking 2-3 months for results.
• Genotypic testing: Faster molecular tests identify mutations causing drug resistance, including probe-based assays and sequence-based assays.
• The GeneXpert test, a NAAT, detects TB and RIF resistance in about 2 hours using real-time PCR with molecular beacons.
• Despite advancements, culture-based methods remain the gold standard for their high identification sensitivity.