A 10-year survey on prevalence and occurrence rate of multi-drug resistant Mycobacterium tuberculosis in Latin American and Mediterranean Families : A Systematic review and meta-analysis

Introduction: Latin American and Mediterranean (LAM) is a family of Mycobacterium tuberculosis (M. tuberculosis). Drug resistant in M. tuberculosis LAM family is a major problem in the world population. Our objective of this study was to determine the prevalence of M. tuberculosis LAM family with multi-drug resistant (MDR) in the worldwide by a metaanalysis and systematic review. Materials and methods: Data sources of this study were 68 original articles (2001-2012) which were published in different databases. Research articles with full text in English were selected. Review articles, congress abstracts, studies that were reported in languages other than English and also studies that were not available for us in abstract or full text were excluded. Data that were obtained from prevalence and occurrence rate of MDR M. tuberculosis LAM family were analyzed using meta-analysis random effects models with software package Meta R, Version 2.13 (P < 0.10). Results: During 10 years, lowest rate of prevalence was observed in 2010 and 2006 (95% CI: 5.91%-6.95%) and highest prevalence rate was in 2006 (95% CI: 17.48%24.05%). prevalence of MDRM. tuberculosis analysis showed positive MDR between them (95% CI: 10.30%11.23%). Prevalence for negative MDR was 9.22% (95% CI: 8.3%10.2%). Conclusion: Our study showed that M. tuberculosis LAM family is prevalent in Europian countries. LAM sub lineage was a major focus of studies that carried out in different countries. The proper technique for prevention of transmission of M. tuberculosis is necessary.


Introduction
Tuberculosis (TB) is a bacterial infectious disease caused by Mycobacterium tuberculosis (M.tuberculosis).It is still an important cause of morbidity and mortality (1,2).TB can be seen in various forms including pulmonary and extra pulmonary (3).Epidemiological estimates in 2011 showed 1.4 million deaths and 8.7 million new cases of TB in world (4).For example, reports in Moscow showed M. tuberculosis morbidity about 50 cases per 100,000 people in 2008 (5).The best way to treat TB is antibiotic treatment.Antibiotics used to treat including first-line drugs (isoniazid, rifampin, ethambutol, and streptomycin) and second-line drugs (aminoglycosides, kanamycin, amikacin, and fluoroquinolones) (6)(7)(8)(9).The dramatic rise and the increasing emergence of drugresistant M. tuberculosis isolates are causes for concern attention to this disease (10)(11)(12)(13).Many reports presented multi-drug resistance (MDR) -M.tuberculosis that resistant to at least both isoniazid and rifampin.This problem cause TB, increasing treatment period, rising health care costs, and mortality rates (14-16).Also studies showed that transmission of different M. tuberculosis families are associated with drug resistance in worldwide populations.The main genotype families of M. tuberculosis are beijing, haarlem, east-african-indian(EAI), latinamerican and mediterranean(LAM), U and T strains (9,10).LAM is one of M. tuberculosis phylogenetic family and its name is derived from the geographical area which was isolated.LAM sub lineage was a major focus of studies in different area of Americas, Europe, Africa and Russia (11

Data
Sources: For prevalence determination of M. tuberculosis LAM family with MDR and occurrence rate in the worldwide population, literature databases (PubMed, Science Direct, Google Scholar, ISI Web of Science, and Biological Abstracts) and original articles were considered between 2001-2012 years in English language.Key words for search in databases were M. tuberculosis, TB, LAM family and MDR.Study Selection: Process for selecting the studies: the data includes number of cases, websites, author, study place, year of the research, sample size, and prevalence of LAM and MDR association.Inclusion criteria were: (1) research articles with full text, (2) articles with abstract in English.Excluded studies were: (1) review articles, (2) congress abstracts, (3) studies that reported in languages other than English, (4) studies that were not available for us in abstract or full text, (5) studies that their sampling location was uncertain, (6) studies that locations of sampling was performed at the same time, and (7) studies that their data were not clear (see Flowchart 1).
Data Extraction: In our study 106 articles were selected.The variance of prevalence was computed using binomial distribution and meta-analysis with the random effect model which was applied to combine the prevalence among the studies.There was sensitivity and heterogeneity among the studies.
Inconsistency (I²), (95% confidence interval, CI) and Cochran Q (P<0.10)statistical tests were used to check out this heterogeneity.Meta R Version 2.13 software package for Meta-analysis was applied.

Discussion
Studies proved that MDR in patients with TB is related with high mortality (1).for MDR-TB different rates in studies.Also genetic variation is related to prevalence and spread of drug-resistant strains.So genotyping is an important tool for detection of origin and transmission patterns of drug-resistant strains (72).There are several methods for molecular typing of M. tuberculosis such as: Spoligotyping, RFLP typing based on the IS6110 and VNTR (6 -8).Spoligotyping is a major technical for molecular typing of M. tuberculosis (70).This typing method is based on DNA presence of polymorphism at one particular chromosomal locus, the "Direct Repeat" (DR) region, which is in M. tuberculosis complex bacteria (7).The DR locus consists of conserved direct repeatations interspersed with unique spacer sequences (8)

Figure 1 .
Figure 1.Results of publication bias for M. tuberculosis LAM family in worldwide population based on year (CI: 95%).

Table 1 ) Prevalence of M. tuberculosis LAM family in Worldwide Population Based on Years of Study: The
).According to the countries and the years, the highest prevalence rate of M. tuberculosis LAM family was in Venezuela in 2006 and the lowest rate was in Pakistan and Iran in 2010 and 2006 (both 0.2 %), respectively Also patients with MDR -TB were observed in these studies (data for 10 groups were analyzed during 2001-2012.The lowest rate of prevalence was observed in 2010 and 2006 [6.42% (95% CI: 5.91%-6.95%)].Highest prevalence rate was in 2012 [20.62% (95% CI: 17.48%-24.05%)].

Table 1 .
Data that were extracted from published documents about country, year, and prevalence of M. tuberculosis Latin American and Mediterranean (LAM) family and multi-drug resistant (MDR).

Table 2 .
Pooled sensitivity (CI: 95%) and heterogeneity for M. tuberculosis LAM family in worldwide population based on year.