Recent Journal Articles by Alaine Nyaruhirira

We describe a novel training programme, the tuberculosis Data Fellowship, designed to build capacity in low- and middle-income countries for tuberculosis data analytics. The programme was piloted in six countries (Bangladesh, Ethiopia, Ghana, Malawi, Mozambique) in July 2018 and Nigeria in September 2018; 20 participants completed the training. A number of key outputs have been achieved, such as improved instrument utilisation rates, decreased error rates, and improved instrument management. The training programme empowers local tuberculosis programme staff to discover and fix critical inefficiencies, provides high-level technical and operational support to the tuberculosis programme, and provides a platform for continued sharing of insights and best practices between countries. It supports the notion that connectivity can increase efficiencies and clinical benefits with better data for decision making, if coupled with commensurate capacity building in data analysis and interpretation.

To describe trends in diagnostic and treatment delays and estimate their effect on  rifampicin-resistant tuberculosis (RR-TB) mortality, we conducted a retrospective analysis of individual-level data including 748 (85.4%) of 876 patients diagnosed with RR-TB notified to the World Health Organization between 1 July 2005 and 31 December 2016 in Rwanda. Logistic regression was used to estimate the effect of diagnostic and therapeutic delays on RR-TB mortality. Between 2006 and 2016, the median diagnostic delay significantly decreased from 88 days to 1 day, and the therapeutic delay from 76 days to 3 days. Simultaneously, RR-TB mortality significantly decreased from 30.8% in 2006 to 6.9% in 2016.

The tuberculosis(TB) control program of Rwanda is currently phasing in light emitting diode-fluorescent microscopy (LED-FM) as an alternative to Ziehl-Neelsen (ZN) smear microscopy. This, alongside the newly introduced Xpert (Cepheid, Sunnyvale, CA, USA) is expected to improve diagnosis of TB and detection of rifampicin resistance in patients at health facilities. We assessed the accuracy of smear microscopy and the incremental sensitivity of Xpert at TB laboratories in Rwanda. This was a cross-sectional study involving four laboratories performing ZN and four laboratories performing LED-FM microscopy. A total of 96 presumptive pulmonary tuberculosis participants were culture positive for M. tuberculosis. The overall incremental sensitivity of Xpert over smear microscopy was 32.3 %; p 

In this opinion paper, we discuss lessons learned from the global scale-up of these laboratory devices and the pathway to tapping the potential of laboratory-generated information in the field of TB by using connectivity. Responding to the demand for connectivity, innovative third-party players have proposed solutions that have been widely adopted by field users of the Xpert® MTB/RIF assay. The experience associated with the utilisation of these systems, which facilitate the monitoring of wide laboratory networks, stressed the need for a more global and comprehensive approach to diagnostic connectivity. In addition to facilitating the reporting of test results, the mobility of digital information allows the sharing of information generated in programme settings. When they become easily accessible, these data can be used to improve patient care, disease surveillance and drug discovery. We list several examples of initiatives that should allow data sources to be combined to improve the understanding of the epidemic, support the operational response and, finally, accelerate TB elimination.

Ethambutol (EMB) resistance can evolve through a multistep process, and mutations in the ubiA (Rv3806c) gene appear to be responsible for high-level EMB resistance in Mycobacterium tuberculosis. We evaluated the prevalence of ubiA and embB (Rv3795) mutations in EMB-resistant strains originating from Africa and South Korea. No differences in embB mutation frequencies were observed between strains from both origins. However, ubiA mutations were present in 45.5% 6.5% of the African EMB-resistant isolates but in only 9.5% 1.5% of the South Korean EMB-resistant isolates. The ubiA mutations associated with EMB resistance were localized to regions encoding the transmembrane domains of the protein, whereas the embB mutations were localized to regions encoding the extramembrane domains. Larger studies are needed to investigate the causes of increased ubiA mutations as a pathway to high-level EMB resistance in African countries, such as extended EMB usage during tuberculosis treatment.

To improve tuberculosis (TB) diagnosis, many national TB programmes have committed to deploying Xpert® MTB/RIF. Implementation of this relatively new technology has suffered from a lack of comprehensive technical assistance, however, including the formulation of policies and plans to address operational issues. While providing technical assistance, we observed numerous operational challenges in the implementation and scale-up of Xpert in five sub-Saharan African countries: low coverage, poor laboratory infrastructure, limited access, poor linkages to treatment, inadequate data on outcomes, problems with specimen transport, diagnostic algorithms that are not aligned with updated World Health Organization recommendations on target patient groups and financing challenges. We recommend better country preparedness and training, laboratory information and quality systems, supply management and referral mechanisms.

Ziehl-Neelsen (ZN) bright-field microscopy is time-consuming, with poor sensitivity, even under optimal conditions. Introduction of Primo Star iLED fluorescent microscopy (FM) may improve TB case finding at referral hospitals in Rwanda. Laboratory technicians demonstrated high acceptance of iLED. The 100% concordance at both demonstration sites during the continuation phase shows technicians' rapid command of the new iLED microscope in a relatively short time. Additionally, fluorescent microscopy reduces the time necessary for examination by more than half. The high level of agreement between iLED and FM during implementation in both sites provides initial evidence for iLED to replace current methods.