Abstract

Djibouti is a small country in the Horn of Africa with a high TB incidence (378/100,000 in 2015). Multidrug-resistant TB (MDR-TB) and resistance to second-line agents have been previously identified in the country but the extent of the problem has yet to be quantified. A national survey was conducted to estimate the proportion of MDR-TB among a representative sample of TB patients. Sputum was tested using XpertMTB/RIF and samples positive for MTB and resistant to rifampicin underwent first line phenotypic susceptibility testing. The TB supranational reference laboratory in Milan, Italy, undertook external quality assurance, genotypic testing based on whole genome and targeted-deep sequencing and phylogenetic studies. 301 new and 66 previously treated TB cases were enrolled. MDR-TB was detected in 34 patients: 4.7% of new and 31% of previously treated cases. Resistance to pyrazinamide, aminoglycosides and capreomycin was detected in 68%, 18% and 29% of MDR-TB strains respectively, while resistance to fluoroquinolones was not detected. Cluster analysis identified transmission of MDR-TB as a critical factor fostering drug resistance in the country. Levels of MDR-TB in Djibouti are among the highest on the African continent. High prevalence of resistance to pyrazinamide and second-line injectable agents have important implications for treatment regimens.

Highlights

  • Tuberculosis (TB) strains with multidrug-resistance (MDR-TB; resistance to rifampicin and isoniazid) and extensive drug-resistance (XDR-TB; Multidrug-resistant TB (MDR-TB) with additional resistance to any fluoroquinolone plus one or more of amikacin, kanamycin or capreomycin) represent a major threat for global TB control

  • Prevalence of MDR-TB (4.7% of new and 30.8% of previously treated TB cases) are significantly higher than expected and higher than those reported in neighboring Ethiopia (2.7% of new and 14% of previously treated) and in other countries of the Eastern Mediterranean region[1] but comparable to those detected in Somalia (5.2% of new and 40.8% of previously treated TB cases)[8]

  • Results from genotypic drug susceptibility testing show very high frequencies of mutations associated with resistance to pyrazinamide (68%) and second line injectable agents (18% and 29% of isolates resistant to aminoglycosides and to capreomycin, respectively) among the MDR-TB cases

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Summary

Introduction

Tuberculosis (TB) strains with multidrug-resistance (MDR-TB; resistance to rifampicin and isoniazid) and extensive drug-resistance (XDR-TB; MDR-TB with additional resistance to any fluoroquinolone plus one or more of amikacin, kanamycin or capreomycin) represent a major threat for global TB control. Precise estimates of the prevalence of MDR-TB among new and previously treated TB cases in Djibouti are lacking as the country does not have a continuous drug resistance surveillance system in place and no national drug resistance survey has ever been conducted. We describe the first national TB drug resistance survey conducted by the NTP of Djibouti to estimate the burden of MDR-TB in the country and to provide information about additional resistance to other TB drugs (pyrazinamide, fluoroquinolones and injectable agents). These data help the NTP and its supporting partners with resource prioritization as well as planning and implementation of effective prevention and curative measures

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