Mansour Kargarpour Kamakoli1, Ghazaleh Farmanfarmaei1, Morteza Masoumi1, Sharareh Khanipour1, Safoora Gharibzadeh2, Christophe Sola3, Abolfazl Fateh1, Seyed Davar Siadat1, Guislaine Refregier3, Farzam Vaziri4. 1. Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran; Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran. 2. Department of Epidemiology and Biostatistics, Research Center for Emerging and Reemerging Infectious Diseases, Pasteur Institute of Iran, Tehran, Iran. 3. Institut for Integrative Biology of the Cell (I2BC), CEA, CNRS, Univ. Paris Sud, Université Paris-Saclay, Gif-sur-Yvette, France. 4. Department of Mycobacteriology and Pulmonary Research, Pasteur Institute of Iran, Tehran, Iran; Microbiology Research Center (MRC), Pasteur Institute of Iran, Tehran, Iran. Electronic address: farzam_vaziri@yahoo.com.
Abstract
BACKGROUND: Patients with mixed-strain Mycobacterium tuberculosis infections may be at a high risk of poor treatment outcomes. However, the mechanisms through which mixed infections affect the clinical manifestations are not well recognized. Evidence suggests that failure to detect the pathogen diversity within the host can influence the clinical results. We aimed to investigate the effects of different genotypes in mixed infections and determine their relationship with heteroresistance in the treatment of Iranian tuberculosis patients. METHODS: One of the genotypes was identified in the culture and another genotype pattern in the mixed infection was predicted by comparing the pattern of MIRU-VNTR between the clinical specimens and their respective cultures in each patient. For all patients, the drug susceptibility testing was carried out on three single colonies from each clinical sample. The follow-up of patients was carried out during six months of treatment. RESULTS: Based on MIRU-VNTR profiles of clinical samples, we showed that 55.6% (25/45) of the Iranian patients included in the study had mixed infections. Patients with mixed infections had a higher rate of treatment failure, compared to others (P=0.03). By comparing clinical sample profiles to profiles obtained after culture, we were able to distinguish between major and hidden genotypes. Among hidden genotypes, Haarlem (L4.1.2) and Beijing (L2) were associated to treatment failure (6/8 patients). CONCLUSIONS: To conclude, we propose a procedure using the MIRU-VNTR method to identify the different genotypes in mixed infections. The present findings suggest that genotypes with potentially higher pathogenicity may not be detected when performing experimental culture in patients with mixed infections.
BACKGROUND:Patients with mixed-strain Mycobacterium tuberculosis infections may be at a high risk of poor treatment outcomes. However, the mechanisms through which mixed infections affect the clinical manifestations are not well recognized. Evidence suggests that failure to detect the pathogen diversity within the host can influence the clinical results. We aimed to investigate the effects of different genotypes in mixed infections and determine their relationship with heteroresistance in the treatment of Iranian tuberculosispatients. METHODS: One of the genotypes was identified in the culture and another genotype pattern in the mixed infection was predicted by comparing the pattern of MIRU-VNTR between the clinical specimens and their respective cultures in each patient. For all patients, the drug susceptibility testing was carried out on three single colonies from each clinical sample. The follow-up of patients was carried out during six months of treatment. RESULTS: Based on MIRU-VNTR profiles of clinical samples, we showed that 55.6% (25/45) of the Iranian patients included in the study had mixed infections. Patients with mixed infections had a higher rate of treatment failure, compared to others (P=0.03). By comparing clinical sample profiles to profiles obtained after culture, we were able to distinguish between major and hidden genotypes. Among hidden genotypes, Haarlem (L4.1.2) and Beijing (L2) were associated to treatment failure (6/8 patients). CONCLUSIONS: To conclude, we propose a procedure using the MIRU-VNTR method to identify the different genotypes in mixed infections. The present findings suggest that genotypes with potentially higher pathogenicity may not be detected when performing experimental culture in patients with mixed infections.
Authors: Michael Asare-Baah; Marie Nancy Séraphin; LaTweika A T Salmon; Michael Lauzardo Journal: Infect Genet Evol Date: 2020-12-01 Impact factor: 3.342