MDR-TB Outbreak among HIV-Negative Tunisian Patients followed during 11 Years

Dekhil, Naira; Meftahi, Nedra; Mhenni, Besma; Fraj, Saloua Ben; Haltiti, Raja; Belhaj, S.; Mardassi, Helmi

doi:10.1371/journal.pone.0153983

Cited by 8 publications

(14 citation statements)

References 32 publications

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“…cgMLST analysis showed that 65.2% of MDR/XDR strains of M. tuberculosis were clustered, reflecting extensive transmission in Tunisia, particularly of a Haarlem clone. This Haarlem clone showed polymorphisms rpoB Ser450Leu, Val534Met, katG Ser315Thr, embB Met306Ile, and gidB Arg47Trp, and in pncA genes previously identified in a Haarlem MDR TB outbreak in the Bizerte region during 2001–2011 ( 13 , 14 ). As indicated by statistical association, we conclude that this cluster is still spreading in the Bizerte area.…”

Section: Discussionmentioning

confidence: 57%

Whole-Genome Sequencing of Drug-Resistant Mycobacterium tuberculosis Strains, Tunisia, 2012–2016

Bouzouita¹,

Cabibbe²,

Trovato³

et al. 2019

Emerg. Infect. Dis.

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To investigate transmission of drug-resistant strains of Mycobacterium tuberculosis in Tunisia, we performed whole-genome sequencing on 46 multidrug-resistant strains isolated during 2012–2016. Core-genome multilocus sequence typing grouped 30 strains (65.2%) into 3 clusters, indicating extensive recent transmission and Haarlem clone predominance. Whole-genome sequencing might help public health services undertake appropriate control actions.

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Section: Discussionmentioning

confidence: 57%

Whole-Genome Sequencing of Drug-Resistant Mycobacterium tuberculosis Strains, Tunisia, 2012–2016

Bouzouita¹,

Cabibbe²,

Trovato³

et al. 2019

Emerg. Infect. Dis.

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“…Patients with DM have not been specifically studied, although clinical manifestations among patients with TB and DM indicate that patients with DM might have an important role in TB transmission. Moreover, patients with DM have been described as index and secondary cases in TB outbreaks [ 57 , 58 ]. Usage of molecular epidemiologic techniques has previously allowed us to show that increased risk of TB among patients with DM is due to both reactivation and recently transmitted infection [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Genotyping and spatial analysis of pulmonary tuberculosis and diabetes cases in the state of Veracruz, Mexico

et al. 2018

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BackgroundGenotyping and georeferencing in tuberculosis (TB) have been used to characterize the distribution of the disease and occurrence of transmission within specific groups and communities.ObjectiveThe objective of this study was to test the hypothesis that diabetes mellitus (DM) and pulmonary TB may occur in spatial and molecular aggregations.Material and methodsRetrospective cohort study of patients with pulmonary TB. The study area included 12 municipalities in the Sanitary Jurisdiction of Orizaba, Veracruz, México. Patients with acid-fast bacilli in sputum smears and/or Mycobacterium tuberculosis in sputum cultures were recruited from 1995 to 2010. Clinical (standardized questionnaire, physical examination, chest X-ray, blood glucose test and HIV test), microbiological, epidemiological, and molecular evaluations were carried out. Patients were considered “genotype-clustered” if two or more isolates from different patients were identified within 12 months of each other and had six or more IS6110 bands in an identical pattern, or < 6 bands with identical IS6110 RFLP patterns and spoligotype with the same spacer oligonucleotides. Residential and health care centers addresses were georeferenced. We used a Jeep hand GPS. The coordinates were transferred from the GPS files to ArcGIS using ArcMap 9.3. We evaluated global spatial aggregation of patients in IS6110-RFLP/ spoligotype clusters using global Moran´s I. Since global distribution was not random, we evaluated “hotspots” using Getis-Ord Gi* statistic. Using bivariate and multivariate analysis we analyzed sociodemographic, behavioral, clinic and bacteriological conditions associated with “hotspots”. We used STATA® v13.1 for all statistical analysis.ResultsFrom 1995 to 2010, 1,370 patients >20 years were diagnosed with pulmonary TB; 33% had DM. The proportion of isolates that were genotyped was 80.7% (n = 1105), of which 31% (n = 342) were grouped in 91 genotype clusters with 2 to 23 patients each; 65.9% of total clusters were small (2 members) involving 35.08% of patients. Twenty three (22.7) percent of cases were classified as recent transmission. Moran`s I indicated that distribution of patients in IS6110-RFLP/spoligotype clusters was not random (Moran`s I = 0.035468, Z value = 7.0, p = 0.00). Local spatial analysis showed statistically significant spatial aggregation of patients in IS6110-RFLP/spoligotype clusters identifying “hotspots” and “coldspots”. GI* statistic showed that the hotspot for spatial clustering was located in Camerino Z. Mendoza municipality; 14.6% (50/342) of patients in genotype clusters were located in a hotspot; of these, 60% (30/50) lived with DM. Using logistic regression the statistically significant variables associated with hotspots were: DM [adjusted Odds Ratio (aOR) 7.04, 95% Confidence interval (CI) 3.03–16.38] and attending the health center in Camerino Z. Mendoza (aOR18.04, 95% CI 7.35–44.28).ConclusionsThe combination of molecular and epidemiological information with geospatial data allowed us to identify the concurrenc...

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“…However, the occurrence of exogenous reinfection in one-fifth of the cases suggested that exogenous TB reinfection in DM patients might be due to nosocomial TB transmission occurring as a result of DM patients attending clinics where there is a high prevalence of diagnosed and undiagnosed TB, as has been described for HIV infected patients [ 74 ]. Patients with DM have been described as index and secondary cases in TB outbreaks [ 75 , 76 ]. Therefore, there are grounds to hypothesize that patients with DM and TBP may have a greater likelihood of recent transmission than TBP patients without DM.…”

Section: Discussionmentioning

confidence: 99%

Molecular clustering of patients with diabetes and pulmonary tuberculosis: A systematic review and meta-analysis

et al. 2017

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IntroductionMany studies have explored the relationship between diabetes mellitus (DM) and tuberculosis (TB) demonstrating increased risk of TB among patients with DM and poor prognosis of patients suffering from the association of DM/TB. Owing to a paucity of studies addressing this question, it remains unclear whether patients with DM and TB are more likely than TB patients without DM to be grouped into molecular clusters defined according to the genotype of the infecting Mycobacterium tuberculosis bacillus. That is, whether there is convincing molecular epidemiological evidence for TB transmission among DM patients. Objective: We performed a systematic review and meta-analysis to quantitatively evaluate the propensity for patients with DM and pulmonary TB (PTB) to cluster according to the genotype of the infecting M. tuberculosis bacillus.Materials and methodsWe conducted a systematic search in MEDLINE and LILACS from 1990 to June, 2016 with the following combinations of key words “tuberculosis AND transmission” OR “tuberculosis diabetes mellitus” OR “Mycobacterium tuberculosis molecular epidemiology” OR “RFLP-IS6110” OR “Spoligotyping” OR “MIRU-VNTR”. Studies were included if they met the following criteria: (i) studies based on populations from defined geographical areas; (ii) use of genotyping by IS6110- restriction fragment length polymorphism (RFLP) analysis and spoligotyping or mycobacterial interspersed repetitive unit-variable number of tandem repeats (MIRU-VNTR) or other amplification methods to identify molecular clustering; (iii) genotyping and analysis of 50 or more cases of PTB; (iv) study duration of 11 months or more; (v) identification of quantitative risk factors for molecular clustering including DM; (vi) > 60% coverage of the study population; and (vii) patients with PTB confirmed bacteriologically. The exclusion criteria were: (i) Extrapulmonary TB; (ii) TB caused by nontuberculous mycobacteria; (iii) patients with PTB and HIV; (iv) pediatric PTB patients; (v) TB in closed environments (e.g. prisons, elderly homes, etc.); (vi) diabetes insipidus and (vii) outbreak reports. Hartung-Knapp-Sidik-Jonkman method was used to estimate the odds ratio (OR) of the association between DM with molecular clustering of cases with TB. In order to evaluate the degree of heterogeneity a statistical Q test was done. The publication bias was examined with Begg and Egger tests. Review Manager 5.3.5 CMA v.3 and Biostat and Software package R were used.ResultsSelection criteria were met by six articles which included 4076 patients with PTB of which 13% had DM. Twenty seven percent of the cases were clustered. The majority of cases (48%) were reported in a study in China with 31% clustering. The highest incidence of TB occurred in two studies from China. The global OR for molecular clustering was 0.84 (IC 95% 0.40–1.72). The heterogeneity between studies was moderate (I2 = 55%, p = 0.05), although there was no publication bias (Beggs test p = 0.353 and Eggers p = 0.429).ConclusionThere were very few studies meeti...

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MDR-TB Outbreak among HIV-Negative Tunisian Patients followed during 11 Years

Cited by 8 publications

References 32 publications

Whole-Genome Sequencing of Drug-Resistant Mycobacterium tuberculosis Strains, Tunisia, 2012–2016

Whole-Genome Sequencing of Drug-Resistant Mycobacterium tuberculosis Strains, Tunisia, 2012–2016

Genotyping and spatial analysis of pulmonary tuberculosis and diabetes cases in the state of Veracruz, Mexico

Molecular clustering of patients with diabetes and pulmonary tuberculosis: A systematic review and meta-analysis

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