Policy to practice: impact of GeneXpert MTB/RIF implementation on the TB spectrum of care in Lilongwe, Malawi

While previous research has provided evidence of the diagnostic accuracy of the GeneXpert MTB/RIF (GeneXpert), further information is needed about implementation in the real-world. This study evaluated the impact of the introduction of GeneXpert testing in a tertiary medical center according to the testing algorithm proposed by the National TB Control Program (NTP) guidelines

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Policy to practice: impact of GeneXpert MTB/RIF implementation on the TB spectrum of care in Lilongwe, Malawi

BACKGROUND: While previous research has provided evidence of the diagnostic accuracy of the GeneXpert MTB/RIF (GeneXpert), further information is needed about implementation in the real-world. This study evaluated the impact of the introduction of GeneXpert testing in a tertiary medical center according to the testing algorithm proposed by the National TB Control Program (NTP) guidelines. METHODS: All adult medicine inpatient persons with presumptive TB admitted between November 2013 and March 2014 were eligible for GeneXpert sputum testing and followed to TB treatment initiation status. RESULTS: We identified 932 persons with presumptive TB, of which 307 (32.9%) were GeneXpert tested. Those tested had an average age of 40 years, 49.2% (151) were male, 34.5% (106) were HIV positive, and 84.1% (249) presented with a cough. Of those GeneXpert tested, 28/307 (9.1%) tested positive, a 55.5% increase in detection compared to smear microscopy. However, the majority (44/72, 61%) of TB diagnoses were made by other modalities and not confirmed microbiologically. Of the 58 patients recommended to start treatment and discharged from the hospital, only 23 (40%) were documented to have started treatment at regional directly observed treatment short (DOTS) centers. CONCLUSIONS: GeneXpert contributed minimally to overall TB diagnosis and the cascade of care due to implementation challenges of sputum collection, empiric treatment, and weak linkage to care between inpatient and outpatient settings