A Field Evaluation of the Hardy TB MODS Kit™ for the Rapid Phenotypic Diagnosis of Tuberculosis and Multi-Drug Resistant Tuberculosis

Abstract

BackgroundEven though the WHO-endorsed, non-commercial MODS assay offers rapid, reliable TB liquid culture and phenotypic drug susceptibility testing (DST) at lower cost than any other diagnostic, uptake has been patchy. In part this reflects misperceptions about in-house assay quality assurance, but user convenience of one-stop procurement is also important. A commercial MODS kit was developed by Hardy Diagnostics (Santa Maria, CA, USA) with PATH (Seattle, WA, USA) to facilitate procurement, simplify procedures through readymade media, and enhance safety with a sealing silicone plate lid. Here we report the results from a large-scale field evaluation of the MODS kit in a government service laboratory.Methods & Findings2446 sputum samples were cultured in parallel in Lowenstein-Jensen (LJ), conventional MODS and in the MODS kit. MODS kit DST was compared with conventional MODS (direct) DST and proportion method (indirect) DST. 778 samples (31.8%) were Mycobacterium tuberculosis culture-positive. Compared to conventional MODS the sensitivity, specificity, positive, and negative predictive values (95% confidence intervals) of the MODS Kit were 99.3% (98.3–99.8%), 98.3% (97.5–98.8%), 95.8% (94.0–97.1%), and 99.7% (99.3–99.9%). Median (interquartile ranges) time to culture-positivity (and rifampicin and isoniazid DST) was 10 (9–13) days for conventional MODS and 8.5 (7–11) for MODS Kit (p<0.01). Direct rifampicin and isoniazid DST in MODS kit was almost universally concordant with conventional MODS (97.9% agreement, 665/679 evaluable samples) and reference indirect DST (97.9% agreement, 687/702 evaluable samples).ConclusionsMODS kit delivers performance indistinguishable from conventional MODS and offers a convenient, affordable alternative with enhanced safety from the sealing silicone lid. The availability in the marketplace of this platform, which conforms to European standards (CE-marked), readily repurposed for second-line DST in the near future, provides a fresh opportunity for improving equity of access to TB diagnosis and first and second-line DST in settings where the need is greatest.

Suboptimal specificity of Xpert MTB/RIF among treatment-experienced patients

“…The reference standard for M. tuberculosis detection was a positive result on solid (Löwenstein-Jensen (LJ) media), liquid (BBL™ MGIT™ Mycobacterial Growth Indicator Tubes (Becton Dickinson, Sparks, MD)), or microscopic-observation drug-susceptibility (MODS) culture (TB MODS Kit™, Hardy Diagnostics, Santa Maria, CA USA). [12, 13] Xpert false detection of active TB (“Xpert false-positive”) was defined as Xpert-positivity in absence of any of the three culture modalities being positive. The Biomedical Research and Training Institute (BRTI) Tuberculosis Laboratory within the National Microbiology Reference Laboratory (NMRL) is a centre for Trials of Excellence in Southern Africa (TESA).…”

Performance of microscopic observation drug susceptibility for the rapid diagnosis of tuberculosis and detection of drug resistance in Bamako, Mali

“…The MODS assay is an approved technique that is feasible in a biosafety level 2 laboratory (17). Many published studies have suggested that the MODS assay is an effective and valuable tool for the diagnosis of tuberculosis in limited resources countries (11,18-20).…”

Direct-from-sputum rapid phenotypic drug susceptibility test for mycobacteria

“…If the pathogen in sputum is present, their growth in the liquid medium is observed under an inverted light microscope and morphologically examined for patterns specific to Mtb. This typically takes 7-14 days to observe growth in the wells without drugs and to confirm lack of growth in those with drugs [17] and the cost per test was estimated to be about $5 in a low-resource environment of Peru [18]. Microscopic Observation Drug Susceptibility assay (MODS) has hence been recommended by the WHO as an affordable method for relatively rapid detection and DST.…”

“…Despite its advantages, MODS is not as widely used in resource-limited settings as was initially anticipated due to concerns for biosafety, reliance on the skill of laboratory personnel in interpreting results, and efficiency for handling a large number of samples. While concerns about biosafety can be alleviated using commercially produced kits with sealed wells, such as those produced by hardy Diagnostics [18], and a certain degree of automation can be introduced in the capture of images [19], this method still requires that every well be visually inspected by a well-trained laboratory professional. This puts a requirement of both time and human resources that often make it unfeasible to handle a large number of sputum samples that may need to be tested in high-TB burdened and low-resource settings.…”