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Pulmonary Isolation of Multidrug resistant "Mycobacterium simulans" and Mycobacterium tuberculosis from a patient in the Horn of Africa.

ABSTRACT: In low-income countries of the Horn of Africa, pulmonary infections are usually considered as tuberculosis, which diagnosis relies on clinical data and positive microscopic observation. This strategy allows non-tuberculous mycobacteria to escape detection, facilitating their emergence in populations. A non-tuberculous mycobacterium strain FB-527 was unexpectedly cultured from the sputum of a Djiboutian patient otherwise diagnosed with multi-drug resistant (MDR) tuberculosis. The sequencing of the rpoB and 16S rRNA genes showed that the isolate was identical to strain FI-09026 previously named "Mycobacterium simulans" and reported only once from a Somali patient. Strain FB-527 mimicked Mycobacterium tuberculosis colonies and enzymatic profile using API ZYM strip and was in vitro resistant to rifampicin and isoniazid. Isolation of two MDR mycobacteria complicated the diagnosis and therapeutic management of the patient. We here report on the complete description of strain FB-527 and strain FI-09026 including genome sequencing, finalizing the description of the proposed new species "Mycobacterium simulans".

SUBMITTER: Bouzid F

PROVIDER: S-EPMC6203708 | biostudies-literature | 2018 Oct

REPOSITORIES: biostudies-literature

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Pulmonary Isolation of Multidrug resistant "Mycobacterium simulans" and Mycobacterium tuberculosis from a patient in the Horn of Africa.

Bouzid Fériel F Osman Djaltou Aboubaker DA Baptiste Emeline E Delerce Jeremy J Hassan Mohamed Osman MO Arreh Warsama Ibrahim WI Levasseur Anthony A Garnotel Eric E Drancourt Michel M

Scientific reports 20181026 1

In low-income countries of the Horn of Africa, pulmonary infections are usually considered as tuberculosis, which diagnosis relies on clinical data and positive microscopic observation. This strategy allows non-tuberculous mycobacteria to escape detection, facilitating their emergence in populations. A non-tuberculous mycobacterium strain FB-527 was unexpectedly cultured from the sputum of a Djiboutian patient otherwise diagnosed with multi-drug resistant (MDR) tuberculosis. The sequencing of th ...[more]

PMID: 30367075

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Project description:BackgroundThe risk of tuberculosis outbreaks among people fleeing hardship for refuge in Europe is heightened. We describe the cross-border European response to an outbreak of multidrug-resistant tuberculosis among patients from the Horn of Africa and Sudan.MethodsOn April 29 and May 30, 2016, the Swiss and German National Mycobacterial Reference Laboratories independently triggered an outbreak investigation after four patients were diagnosed with multidrug-resistant tuberculosis. In this molecular epidemiological study, we prospectively defined outbreak cases with 24-locus mycobacterial interspersed repetitive unit-variable number tandem repeat (MIRU-VNTR) profiles; phenotypic resistance to isoniazid, rifampicin, ethambutol, pyrazinamide, and capreomycin; and corresponding drug resistance mutations. We whole-genome sequenced all Mycobacterium tuberculosis isolates and clustered them using a threshold of five single nucleotide polymorphisms (SNPs). We collated epidemiological data from host countries from the European Centre for Disease Prevention and Control.FindingsBetween Feb 12, 2016, and April 19, 2017, 29 patients were diagnosed with multidrug-resistant tuberculosis in seven European countries. All originated from the Horn of Africa or Sudan, with all isolates two SNPs or fewer apart. 22 (76%) patients reported their travel routes, with clear spatiotemporal overlap between routes. We identified a further 29 MIRU-VNTR-linked cases from the Horn of Africa that predated the outbreak, but all were more than five SNPs from the outbreak. However all 58 isolates shared a capreomycin resistance-associated tlyA mutation.InterpretationOur data suggest that source cases are linked to an M tuberculosis clone circulating in northern Somalia or Djibouti and that transmission probably occurred en route before arrival in Europe. We hypothesise that the shared mutation of tlyA is a drug resistance mutation and phylogenetic marker, the first of its kind in M tuberculosis sensu stricto.FundingThe Swiss Federal Office of Public Health, the University of Zurich, the Wellcome Trust, National Institute for Health Research (NIHR) Oxford Biomedical Research Centre (BRC), the Medical Research Council, BELTA-TBnet, the European Union, the German Center for Infection Research, and Leibniz Science Campus Evolutionary Medicine of the Lung (EvoLUNG).

Project description:BackgroundTreatment of multidrug resistant tuberculosis (MDR-TB) is lengthy, toxic, expensive, and has generally poor outcomes. We undertook an individual patient data meta-analysis to assess the impact on outcomes of the type, number, and duration of drugs used to treat MDR-TB.Methods and findingsThree recent systematic reviews were used to identify studies reporting treatment outcomes of microbiologically confirmed MDR-TB. Study authors were contacted to solicit individual patient data including clinical characteristics, treatment given, and outcomes. Random effects multivariable logistic meta-regression was used to estimate adjusted odds of treatment success. Adequate treatment and outcome data were provided for 9,153 patients with MDR-TB from 32 observational studies. Treatment success, compared to failure/relapse, was associated with use of: later generation quinolones, (adjusted odds ratio [aOR]: 2.5 [95% CI 1.1-6.0]), ofloxacin (aOR: 2.5 [1.6-3.9]), ethionamide or prothionamide (aOR: 1.7 [1.3-2.3]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.3 [1.3-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 2.7 [1.7-4.1]). Similar results were seen for the association of treatment success compared to failure/relapse or death: later generation quinolones, (aOR: 2.7 [1.7-4.3]), ofloxacin (aOR: 2.3 [1.3-3.8]), ethionamide or prothionamide (aOR: 1.7 [1.4-2.1]), use of four or more likely effective drugs in the initial intensive phase (aOR: 2.7 [1.9-3.9]), and three or more likely effective drugs in the continuation phase (aOR: 4.5 [3.4-6.0]).ConclusionsIn this individual patient data meta-analysis of observational data, improved MDR-TB treatment success and survival were associated with use of certain fluoroquinolones, ethionamide, or prothionamide, and greater total number of effective drugs. However, randomized trials are urgently needed to optimize MDR-TB treatment. Please see later in the article for the Editors' Summary.

Dataset Information

Pulmonary Isolation of Multidrug resistant "Mycobacterium simulans" and Mycobacterium tuberculosis from a patient in the Horn of Africa.

Publications

Pulmonary Isolation of Multidrug resistant "Mycobacterium simulans" and Mycobacterium tuberculosis from a patient in the Horn of Africa.

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