Implementation of quality management systems and progress towards accreditation of National Tuberculosis Reference Laboratories in Africa

Background: Laboratory services are essential at all stages of the tuberculosis care cascade, from diagnosis and drug resistance testing to monitoring response to treatment. Enabling access to quality services is a challenge in low-resource settings. Implementation of a strong quality management system (QMS) and laboratory accreditation are key to improving patient care. Objectives: The study objective was to determine the status of QMS implementation and progress towards accreditation of National Tuberculosis Reference Laboratories (NTRLs) in the African Region. Method: An online questionnaire was administered to NTRL managers in 47 World Health Organization Regional Office for Africa member states in the region, between February and April 2015, regarding the knowledge of QMS tools and progress toward implementation to inform strategies for tuberculosis diagnostic services strengthening in the region. Results: A total of 21 laboratories (43.0%) had received SLMTA/TB-SLMTA training, of which 10 had also used the Global Laboratory Initiative accreditation tool. However, only 36.7% of NTRLs had received a laboratory audit, a first step in quality improvement. Most NTRLs participated in acid-fast bacilli microscopy external quality assurance (95.8%), although external quality assurance for other techniques was lower (60.4% for first-line drug susceptibility testing, 25.0% for second-line drug susceptibility testing, and 22.9% for molecular testing). Barriers to accreditation included lack of training and accreditation programmes. Only 28.6%of NTRLs had developed strategic plans and budgets which included accreditation. Conclusion: Good foundations are in place on the continent from which to scale up accreditation efforts. Laboratory audits should be conducted as a first step in developing quality improvement action plans. Political commitment and strong leadership are needed to drive accreditation efforts; advocacy will require clear evidence of patient impact and cost-benefit

Accuracy of Xpert Ultra in Diagnosis of Pulmonary Tuberculosis among Children in Uganda: a Substudy from the SHINE Trial.

Childhood tuberculosis (TB) presents significant diagnostic challenges associated with paucibacillary disease and requires a more sensitive test. We evaluated the diagnostic accuracy of Xpert MTB/RIF Ultra (Ultra) compared to other microbiological tests using respiratory samples from Ugandan children in the SHINE trial. SHINE is a randomized trial evaluating shorter treatment in 1,204 children with minimal TB disease in Africa and India. Among 352 samples and one cervical lymph node fine needle aspirate, one sample was randomly selected per patient and tested with the Xpert MTB/RIF assay (Xpert) and with Lowenstein-Jensen medium (LJ) and liquid mycobacterial growth indicator tube (MGIT) cultures. We selected only uncontaminated stored sample pellets for Ultra testing. We estimated the sensitivity of Xpert and Ultra against culture and a composite microbiological reference standard (any positive result). Of 398 children, 353 (89%) had culture, Xpert, and Ultra results. The median age was 2.8 years (interquartile range [IQR], 1.3 to 5.3); 8.5% (30/353) were HIV infected, and 54.4% (192/353) were male. Of the 353, 31 (9%) were positive by LJ and/or MGIT culture, 36 (10%) by Ultra, and 16 (5%) by Xpert. Sensitivities (95% confidence intervals [CI]) were 58% (39 to 65% [18/31]) for Ultra and 45% (27 to 64% [14/31]) for Xpert against any culture-positive result, with false positives of <1% and 5.5% for Xpert and Ultra. Against a composite microbiological reference, sensitivities were 72% (58 to 84% [36/50]) for Ultra and 32% (20 to 47% [16/50]) for Xpert. However, there were 17 samples that were positive only with Ultra (majority trace). Among children screened for minimal TB in Uganda, Ultra has higher sensitivity than Xpert. This represents an important advance for a condition which has posed a diagnostic challenge for decades

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

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