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Tuberculosis

Designing molecular diagnostics for current tuberculosis drug regimens

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Article: 2178243 | Received 13 Oct 2022, Accepted 04 Feb 2023, Published online: 27 Feb 2023

Figures & data

Figure 1. Example of a molecular diagnostic cascade for programmatic management of drug-resistant tuberculosis at lower-level healthcare centres.

Note: Lower-level health centres refer to intermediate and peripheral laboratories with limited or minimal infrastructure where technicians with adequate training can perform routine diagnostic testing with molecular tests in 1-2 h [Citation64]. Samples may also be referred to centralized laboratories for additional testing (e.g. additional molecular DST of rifampicin-resistant patients) given rapid and safe transport of specimens from health facilities or lower-level laboratories to the higher-level laboratory, as well as expedient reporting of results back to clinicians. Rapid molecular diagnostic testing of treatment non-responders must also be considered following regimen selection and treatment initiation (e.g. month 2 following treatment initiation) to determine acquired resistance. It should be noted that intermediate centres may also have access to certain instruments such as BD, Abbott or Roche systems, as in . B, bedaquiline; Cfz, clofazimine; E, ethambutol; Eto, ethionamide; H, isoniazid; L, linezolid; Lv, levofloxacin; Pa, pretomanid; R, rifampicin; Z, pyrazinamide.

Figure 1. Example of a molecular diagnostic cascade for programmatic management of drug-resistant tuberculosis at lower-level healthcare centres.Note: Lower-level health centres refer to intermediate and peripheral laboratories with limited or minimal infrastructure where technicians with adequate training can perform routine diagnostic testing with molecular tests in 1-2 h [Citation64]. Samples may also be referred to centralized laboratories for additional testing (e.g. additional molecular DST of rifampicin-resistant patients) given rapid and safe transport of specimens from health facilities or lower-level laboratories to the higher-level laboratory, as well as expedient reporting of results back to clinicians. Rapid molecular diagnostic testing of treatment non-responders must also be considered following regimen selection and treatment initiation (e.g. month 2 following treatment initiation) to determine acquired resistance. It should be noted that intermediate centres may also have access to certain instruments such as BD, Abbott or Roche systems, as in Figure 2. B, bedaquiline; Cfz, clofazimine; E, ethambutol; Eto, ethionamide; H, isoniazid; L, linezolid; Lv, levofloxacin; Pa, pretomanid; R, rifampicin; Z, pyrazinamide.

Figure 2. Example of a molecular diagnostic cascade for higher-level health centres.

Note: Higher-level health centres refer to reference laboratories with sufficient infrastructure as well as well-established laboratory networks and trained personnel to run higher-throughput and complex molecular tests [Citation64]. Rapid molecular diagnostic testing of treatment non-responders must also be considered following regimen selection and treatment initiation (e.g. month 2 following treatment initiation) to determine acquired resistance. The Nipro PZA LPA might also be used at any point along the cascade to evaluate pyrazinamide resistance. B, bedaquiline; Cfz, clofazimine; E, ethambutol; Eto, ethionamide; H, isoniazid; L, linezolid; Lv, levofloxacin; Pa, pretomanid; R, rifampicin; Z, pyrazinamide

Figure 2. Example of a molecular diagnostic cascade for higher-level health centres.Note: Higher-level health centres refer to reference laboratories with sufficient infrastructure as well as well-established laboratory networks and trained personnel to run higher-throughput and complex molecular tests [Citation64]. Rapid molecular diagnostic testing of treatment non-responders must also be considered following regimen selection and treatment initiation (e.g. month 2 following treatment initiation) to determine acquired resistance. The Nipro PZA LPA might also be used at any point along the cascade to evaluate pyrazinamide resistance. B, bedaquiline; Cfz, clofazimine; E, ethambutol; Eto, ethionamide; H, isoniazid; L, linezolid; Lv, levofloxacin; Pa, pretomanid; R, rifampicin; Z, pyrazinamide

Table 1. Current WHO-endorsed diagnostic options and technologies under development or evaluation for tuberculosis drug resistance detection stratified by drug class.

Table 2. Priority molecular diagnostic assays for detection of resistance to new and repurposed compounds in current drug-susceptible and drug-resistant tuberculosis treatment regimens.

Table 3. Current challenges to the design of molecular assays for resistance detection to new and repurposed anti-tuberculosis compounds and research priorities.

Supplemental material

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