Emmanuel André

Connectivity of diagnostic technologies: improving surveillance and accelerating tuberculosis elimination.

In regard to tuberculosis (TB) and other major global epidemics, the use of new diagnostic tests is increasing dramatically, including in resource-limited countries. Although there has never been as much digital information generated, this data source has not been exploited to its full potential. 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. They should therefore be considered as a public health good. We list several examples of concrete 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. With the many opportunities that the pooling of data associated with the TB epidemic can provide, pooling of this information at an international level has become an absolute priority.

Outbreak of multidrug-resistant tuberculosis in South Africa undetected by WHO-endorsed commercial tests: an observational study

BACKGROUNDnGlobal roll-out of rapid molecular assays is revolutionising the diagnosis of rifampicin resistance, predictive of multidrug-resistance, in tuberculosis. However, 30% of the multidrug-resistant (MDR) strains in an eSwatini study harboured the Ile491Phe mutation in the rpoB gene, which is associated with poor rifampicin-based treatment outcomes but is missed by commercial molecular assays or scored as susceptible by phenotypic drug-susceptibility testing deployed in South Africa. We evaluated the presence of Ile491Phe among South African tuberculosis isolates reported as isoniazid-monoresistant according to current national testing algorithms.nnnMETHODSnWe screened records of 37u2008644 Mycobacterium tuberculosis positive cultures from four South African provinces, diagnosed at the National Health Laboratory Service-Dr George Mukhari Tertiary Laboratory, to identify isolates with rifampicin sensitivity and isoniazid resistance according to Xpert MTB/RIF, GenoType MTBDRplus, and BACTEC MGIT 960. Of 1823 isolates that met these criteria, 277 were randomly selected and screened for Ile491Phe with multiplex allele-specific PCR and Sanger sequencing of rpoB. Ile491Phe-positive strains (as well as 17 Ile491Phe-bearing isolates from the eSwatini study) were then tested by Deeplex-MycTB deep sequencing and whole-genome sequencing to evaluate their patterns of extensive resistance, transmission, and evolution.nnnFINDINGSnIle491Phe was identified in 37 (15%) of 249 samples with valid multiplex allele-specific PCR and sequencing results, thus reclassifying them as MDR. All 37 isolates were additionally identified as genotypically resistant to all first-line drugs by Deeplex-MycTB. Six of the South African isolates harboured four distinct mutations potentially associated with decreased bedaquiline sensitivity. Consistent with Deeplex-MycTB genotypic profiles, whole-genome sequencing revealed concurrent silent spread in South Africa of a MDR tuberculosis strain lineage extending from the eSwatini outbreak and at least another independently emerged Ile491Phe-bearing lineage. Whole-genome sequencing further suggested acquisition of mechanisms compensating for the Ile491Phe fitness cost, and of additional bedaquiline resistance following the introduction of this drug in South Africa.nnnINTERPRETATIONnA substantial number of MDR tuberculosis cases harbouring the Ile491Phe mutation in the rpoB gene in South Africa are missed by current diagnostic strategies, resulting in ineffective first-line treatment, continued amplification of drug resistance, and concurrent silent spread in the community.nnnFUNDINGnVLIR-UOS, National Research Foundation (South Africa), and INNOVIRIS.

Tuberculosis contact-tracing among Syrian refugee populations: lessons from Jordan

BackgroundIn response to the influx of displaced Syrians since 2011, the Jordanian National Tuberculosis Program (NTP) implemented a specific Tuberculosis (TB) reduction strategy, including contact-tracing (CT). Contacts of all refugees diagnosed with pulmonary TB (PTB) were registered by the International Organization for Migration and screened for active & latent TB infection (LTBI) in 6 NTP centres.The objectives of this study were to assess prevalence of active TB and LTBI, risk factors for LTBI as well as program performance.MethodsWe performed a retrospective study among contacts (Nu2009=u2009481) of all PTB cases diagnosed between March 2011 and May 2014 (Nu2009=u200976). CT was performed using verbal screening of TB-related symptoms, tuberculin skin test (TST) and chest X-ray.ResultsLTBI was diagnosed in 24.1% of contacts tested with TST while active TB was diagnosed in 2.1% of contacts. Main risk factors for positive TST included smear-positive index case (IC) (OR: 6.33) and previous TB infection in the family (OR: 4.94). Among children, the risk of LTBI was higher when their IC was a care-giving female (OR: 2.83). Prevalence of active TB was two times higher in children under five (U5xa0s) (5.3%) compared to adults (2.5%).ConclusionWe found a high prevalence of active TB and LTBI among contacts of PTB cases in the Syrian refugee population, emphasizing the urgent need for host countries to implement CT strategies for refugees. Our results underscore the vulnerability of U5s and contacts of smear-positive IC highlighting the need for specific actions focusing on those groups.