Publications by authors named "Lucia Barrera"

27 Publications

  • Page 1 of 1

The Toxic Food Environment Around Elementary Schools and Childhood Obesity in Mexican Cities.

Am J Prev Med 2016 08 1;51(2):264-270. Epub 2016 Apr 1.

Department of Environmental Health, Harvard TH Chan School of Public Health, Boston, Massachusetts. Electronic address:

Introduction: The childhood obesity epidemic is a global concern. There is limited evidence in Mexico linking the local food environment to obesity. The purpose of this study is to describe the links between the local food environment around elementary schools and schoolchildren's BMI in two Mexican cities.

Methods: Cross-sectional surveys were conducted in 60 elementary schools in two Mexican cities (i.e., Cuernavaca and Guadalajara) in 2012-2013. Anthropometric measurements on schoolchildren were collected, as well as environmental direct audits and observations in a 100-m buffer around schools. Children's BMI was evaluated according to WHO-recommended procedures. In BMI models, the explanatory variable was the number of retail food sources. These models were adjusted for child's characteristics, schools' socioeconomic background, compliance with federal guidelines concerning unhealthy foods within schools' facilities, and corresponding city. Analysis was conducted in 2014.

Results: The number of mobile food vendors was higher around public schools than outside private schools (p<0.05). Linear regression procedures showed a significant positive statistical association between children's BMI and the number of mobile food vendors around schools. Schoolchildren from the highest tertile of mobile food vendors showed 6.8% higher BMI units than those from the lowest tertile. Children attending schools within the highest tertile of food stores also had 4.7% higher BMI units than children from schools in the lowest tertile.

Conclusions: Health policy in Mexico should target the obesogenic environment surrounding elementary schools, where children may be more exposed to unhealthy foods.
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http://dx.doi.org/10.1016/j.amepre.2016.02.021DOI Listing
August 2016

Outbreaks of Mycobacterium tuberculosis MDR strains differentially induce neutrophil respiratory burst involving lipid rafts, p38 MAPK and Syk.

BMC Infect Dis 2014 May 16;14:262. Epub 2014 May 16.

Inmunologia de enfermedades respiratorias, IMEX-CONTICET-ANM, Buenos Aires, Argentina.

Background: Neutrophils (PMN) are the first cells to infiltrate the lung after infection, and they play a significant protective role in the elimination of pathogen, by releasing preformed oxidants and proteolytic enzymes from granules and generating ROS, thus limiting inflammation by succumbing to apoptosis. In a previous study, we found marked differences in ROS-induced apoptosis between two Mycobacterium tuberculosis (Mtb) strains, M and Ra, representative of widespread Mtb families in South America, i.e. Haarlem and Latin-American Mediterranean (LAM), being strain M able to generate further drug resistance and to disseminate aggressively.

Methods: In this study we evaluate the nature of bacteria-PMN interaction by assessing ROS production, apoptosis, lipid raft coalescence, and phagocytosis induced by Mtb strains.

Results: Dectin-1 and TLR2 participate in Mtb-induced ROS generation and apoptosis in PMN involving p38 MAPK and Syk activation with the participation of a TLR2-dependent coalescence of lipid rafts. Further, ROS production occurs during the phagocytosis of non-opsonized bacteria and involves α-glucans on the capsule. In contrast, strain M lacks the ability to induce ROS because of: 1) a reduced phagocytosis and 2) a failure in coalescence of lipid raft.

Conclusions: The differences in wall composition could explain the success of some strains which stay unnoticed by the host through inhibition of apoptosis and ROS but making possible its replication inside PMN as a potential evasion mechanism. Innate immune responses elicited by Mtb strain-to-strain variations need to be considered in TB vaccine development.
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http://dx.doi.org/10.1186/1471-2334-14-262DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4049492PMC
May 2014

Genotypes of Mycobacterium tuberculosis in patients at risk of drug resistance in Bolivia.

Infect Genet Evol 2013 Jul 17;17:195-201. Epub 2013 Apr 17.

Instituto Nacional de Enfermedades Infecciosas ANLIS Carlos G Malbrán, Vélez Sarsfield 563, 1281 Buenos Aires, Argentina.

Bolivia ranks among the 10 Latin American countries with the highest rates of tuberculosis (TB) and multidrug resistant (MDR) TB. In view of this, and of the lacking information on the population structure of Mycobacterium tuberculosis in the country, we explored genotype associations with drug resistance and clustering by analyzing isolates collected in 2010 from 100 consecutive TB patients at risk of drug resistance in seven of the nine departments in which Bolivia is divided. Fourteen isolates were MDR, 29 had other drug resistance profiles, and 57 were pansusceptible. Spoligotype family distribution was: Haarlem 39.4%, LAM 26.3%, T 22.2%, S 2.0%, X 1.0%, orphan 9.1%, with very low intra-family diversity and absence of Beijing genotypes. We found 66 different MIRU-VNTR patterns; the most frequent corresponded to Multiple Locus Variable Analysis (MLVA) MtbC15 patterns 860, 372 and 873. Twelve clusters, each with identical MIRU-VNTR and spoligotypes, gathered 35 patients. We found no association of genotype with drug resistant or MDR-TB. Clustering associated with SIT 50 and the H3 subfamily to which it belongs (p<0.0001). The largest cluster involved isolates from three departments and displayed a genotype (SIT 50/MLVA 860) previously identified in Bolivian migrants into Spain and Argentina suggesting that this genotype is widespread among Bolivian patients. Our study presents a first overview of M. tuberculosis genotypes at risk of drug resistance circulating in Bolivia. However, results should be taken cautiously because the sample is small and includes a particular subset of M. tuberculosis population.
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http://dx.doi.org/10.1016/j.meegid.2013.04.010DOI Listing
July 2013

Two genetically-related multidrug-resistant Mycobacterium tuberculosis strains induce divergent outcomes of infection in two human macrophage models.

Infect Genet Evol 2013 Jun 24;16:151-6. Epub 2013 Jan 24.

Instituto de Medicina Experimental (IMEX) - CONICET, Academia Nacional de Medicina, Pacheco de Melo 3081, (C1425ASU) Buenos Aires, Argentina.

Mycobacterium tuberculosis has a considerable degree of genetic variability resulting in different epidemiology and disease outcomes. We evaluated the pathogen-host cell interaction of two genetically closely-related multidrug-resistant M. tuberculosis strains of the Haarlem family, namely the strain M, responsible for an extensive multidrug-resistant tuberculosis outbreak, and its kin strain 410 which caused a single case in two decades. Intracellular growth and cytokine responses were evaluated in human monocyte-derived macrophages and dU937 macrophage-like cells. In monocyte-derived macrophages, strain M grew more slowly and induced lower levels of TNF-α and IL-10 than 410, contrasting with previous studies with other strains, where a direct correlation was observed between increased intracellular growth and epidemiological success. On the other hand, in dU937 cells, no difference in growth was observed between both strains, and strain M induced significantly higher TNF-α levels than strain 410. We found that both cell models differed critically in the expression of receptors for M. tuberculosis entry, which might explain the different infection outcomes. Our results in monocyte-derived macrophages suggest that strain M relies on a modest replication rate and cytokine induction, keeping a state of quiescence and remaining rather unnoticed by the host. Collectively, our results underscore the impact of M. tuberculosis intra-species variations on the outcome of host cell infection and show that results can differ depending on the in vitro infection model.
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http://dx.doi.org/10.1016/j.meegid.2013.01.007DOI Listing
June 2013

HIV infection and geographically bound transmission of drug-resistant tuberculosis, Argentina.

Emerg Infect Dis 2012 Nov;18(11):1802-10

Instituto Nacional de Enfermedades Infecciosas ANLIS Dr. Carlos G. Malbrán Buenos Aires, Argentina.

During 2003-2009, the National Tuberculosis (TB) Laboratory Network in Argentina gave 830 patients a new diagnosis of multidrug-resistant (MDR) TB and 53 a diagnosis of extensively drug- resistant (XDR) TB. HIV co-infection was involved in nearly one third of these cases. Strain genotyping showed that 7 major clusters gathered 56% of patients within restricted geographic areas. The 3 largest clusters corresponded to epidemic MDR TB strains that have been undergoing transmission for >10 years. The indigenous M strain accounted for 29% and 40% of MDR and XDR TB cases, respectively. Drug-resistant TB trends in Argentina are driven by spread of a few strains in hotspots where the rate of HIV infection is high. To curb transmission, the national TB program is focusing stringent interventions in these areas by strengthening infection control in large hospitals and prisons, expediting drug resistance detection, and streamlining information-sharing systems between HIV and TB programs.
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http://dx.doi.org/10.3201/eid1811.120126DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3559153PMC
November 2012

Differential induction of macrophage cell death by antigens of a clustered and a non-clustered multidrug-resistant Mycobacterium tuberculosis strain from Haarlem family.

FEMS Immunol Med Microbiol 2012 Dec 10;66(3):363-71. Epub 2012 Sep 10.

Instituto de Medicina Experimental-CONICET, Buenos Aires, Argentina.

Some multidrug-resistant (MDR) Mycobacterium tuberculosis (Mtb) genotypes are the cause of large outbreaks, including strain M identified in Argentina. In contrast, its kin strain 410 has only caused a single case to date. Cell wall antigens from Mtb were associated with the modulation of macrophage (MΦ) cell death, and the ability to inhibit of MΦ apoptosis is considered a virulence mechanism. In this study, the ability these two clinical isolates with divergent epidemiology to induce MΦ cell death was evaluated using whole inactivated bacteria. We showed that gamma-irradiated (I-) strains induced MΦ necrosis, the strongest inducer being I-410. Cell death biased towards apoptosis with the heat-killed (hk) strains, both hk-MDR strains being poorer inducers of MΦ apoptosis than was H37Rv. These effects were partly due to their ability to induce anti-apoptotic mechanisms which were not related to the lack of tumor necrosis factor alpha induction or a compensatory effect of interleukin-10. The most noticeable difference between strain M and strain 410 was the ability shown by hk-M to interfere with apoptosis induced by hk-H37Rv. Thus, heat-stable and heat-labile antigens from these epidemiologically divergent Mtb strains differ in their ability to manipulate MΦ death.
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http://dx.doi.org/10.1111/j.1574-695X.2012.01024.xDOI Listing
December 2012

Clinical isolates of Mycobacterium tuberculosis differ in their ability to induce respiratory burst and apoptosis in neutrophils as a possible mechanism of immune escape.

Clin Dev Immunol 2012 21;2012:152546. Epub 2012 Jun 21.

IMEX-CONICET-ANM, Academia Nacional de Medicina, 1425 Buenos Aires, Argentina.

Tuberculosis pathogenesis was earlier thought to be mainly related to the host but now it appears to be clear that bacterial factors are also involved. Genetic variability of Mycobacterium tuberculosis (Mtb) could be slight but it may lead to sharp phenotypic differences. We have previously reported that nonopsonized Mtb H37Rv induce apoptosis of polymorphonuclear neutrophils (PMNs) by a mechanism that involves the p38 pathway. Here we evaluated the capability to induce PMN apoptosis of two prevalent Mtb lineages in Argentina, the Latin America and Mediterranean (LAM), and Haarlem, using the H37Rv as a reference strain. Results showed that LAM strains strongly induced apoptosis of PMN which correlated with the induction of reactive oxygen species (ROS) production and p38 activation. Interestingly, the highly prosperous multidrug-resistant M strain, belonging to the Haarlem lineage, lacked the ability to activate and to induce PMN apoptosis as a consequence of (1) a weak ROS production and (2) the contribution of antiapoptotic mechanisms mediated at least by ERK. Although with less skill, M is able to enter the PMN so that phenotypic differences could lead PMN to be a reservoir allowing some pathogens to prevail and persist over other strains in the community.
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http://dx.doi.org/10.1155/2012/152546DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3388301PMC
October 2012

Outbreaks of mycobacterium tuberculosis MDR strains induce high IL-17 T-cell response in patients with MDR tuberculosis that is closely associated with high antigen load.

J Infect Dis 2011 Oct;204(7):1054-64

Instituto de Investigaciones Hematológicas Mariano R. Castex, Academia Nacional de Medicina, Buenos Aires, Argentina.

Background: The proinflammatory cytokine interleukin 17 (IL-17) plays an important role in immune responses but it is also associated with tissue-damaging inflammation. So, we evaluated the ability of Mycobacterium tuberculosis clinical isolates to induce IL-17 in tuberculosis (TB) patients and in healthy human tuberculin reactors (PPD(+)HD).

Methods: IL-17, interferon γ (IFN-γ), and interleukin 23 (IL-23) receptor expression were evaluated ex vivo and cultured peripheral blood mononuclear cells from TB and PPD(+)HD stimulated with irradiated clinical isolates from multidrug resistant (MDR) outbreaks M (Haarlem family) and Ra (Latin American-Mediterranean family), as well as drug-susceptible isolates belonging to the same families and laboratory strain H37Rv for 48 hours in T-cell subsets by flow cytometry.

Results: We observed that: (1) MDR strains M and Ra are stronger IL-17 inducers than drug-susceptible Mtb strains of the Haarlem and Latin American-Mediterranean families, (2) MDR-TB patients show the highest IL-17 expression that is independent on the strain, (3) IL-17 expression is dependent on CD4(+) and CD8(+) T cells associates with persistently high antigen load.

Conclusions: IL-17--producing T cells could play an immunopathological role in MDR-TB promoting severe tissue damage, which may be associated with the low effectiveness of the second-line drugs employed in the treatment.
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http://dx.doi.org/10.1093/infdis/jir460DOI Listing
October 2011

Conspicuous multidrug-resistant Mycobacterium tuberculosis cluster strains do not trespass country borders in Latin America and Spain.

Infect Genet Evol 2012 Jun 21;12(4):711-7. Epub 2011 Jun 21.

Instituto Nacional de Enfermedades Infecciosas ANLIS Carlos Malbrán, Vélez Sarsfield 563, 1281 Buenos Aires, Argentina.

Multidrug-resistant Mycobacterium tuberculosis strain diversity in Ibero-America was examined by comparing extant genotype collections in national or state tuberculosis networks. To this end, genotypes from over 1000 patients with multidrug-resistant tuberculosis diagnosed from 2004 through 2008 in Argentina, Brazil, Chile, Colombia, Venezuela and Spain were compared in a database constructed ad hoc. Most of the 116 clusters identified by IS6110 restriction fragment length polymorphism were small and restricted to individual countries. The three largest clusters, of 116, 49 and 25 patients, were found in Argentina and corresponded to previously documented locally-epidemic strains. Only 13 small clusters involved more than one country, altogether accounting for 41 patients, of whom 13 were, in turn, immigrants from Latin American countries different from those participating in the study (Peru, Ecuador and Bolivia). Most of these international clusters belonged either to the emerging RD(Rio) LAM lineage or to the Haarlem family of M. tuberculosis and four were further split by country when analyzed with spoligotyping and rifampin resistance-conferring mutations, suggesting that they did not represent ongoing transnational transmission events. The Beijing genotype accounted for 1.3% and 10.2% of patients with multidrug-resistant tuberculosis in Latin America and Spain, respectively, including one international cluster of two cases. In brief, Euro-American genotypes were widely predominant among multidrug-resistant M. tuberculosis strains in Ibero-America, reflecting closely their predominance in the general M. tuberculosis population in the region, and no evidence was found of acknowledged outbreak strains trespassing country borders.
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http://dx.doi.org/10.1016/j.meegid.2011.06.006DOI Listing
June 2012

Biomarkers and diagnostics for tuberculosis.

Lancet 2010 Nov;376(9752):1539-40; author reply 1540

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http://dx.doi.org/10.1016/S0140-6736(10)62027-2DOI Listing
November 2010

[Disease due to Mycobacterium simiae and "Mycobacterium sherrisii" in Argentina].

Medicina (B Aires) 2010 ;70(4):343-6

INEI, ANLIS Dr Carlos G. Malbrán.

A revision of mycobacterial disease due to M simiae (n = 4) and "M. sherrisii" (n = 6) identified during an eight-year period is presented. Cases occurred among patients with AIDS (n = 6), previous history of silicosis (n = 2) or tuberculosis (n = 2). One case was lost to follow-up and the remaining nine responded poorly to chemotherapy based on clarithromycin, ethambutol and fluoroquinolones. Five patients died of whom four were HIV-positive, three remained chronic and one was cured. These microorganisms originated 2.1% of mycobacterioses cases detected in an eight-year period. Timely identification of this group of uncommon mycobacteria by molecular methods seems to be clinically relevant in order to warn of difficulties inherent to the treatment. However, the distinction between both closely related microorganisms might not be crucial for case management as no distinctive characteristics were evident among patients affected by M. simiae or "M. sherrisii".
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October 2011

Patients with multidrug-resistant tuberculosis display impaired Th1 responses and enhanced regulatory T-cell levels in response to an outbreak of multidrug-resistant Mycobacterium tuberculosis M and Ra strains.

Infect Immun 2009 Nov 31;77(11):5025-34. Epub 2009 Aug 31.

Instituto de Investigaciones Hematológicas Mariano R Castex, Academia Nacional de Medicina, Pacheco de Melo 3081, 1425 Buenos Aires, Argentina.

In Argentina, multidrug-resistant tuberculosis (MDR-TB) outbreaks emerged among hospitalized patients with AIDS in the early 1990s and thereafter disseminated to the immunocompetent community. Epidemiological, bacteriological, and genotyping data allowed the identification of certain MDR Mycobacterium tuberculosis outbreak strains, such as the so-called strain M of the Haarlem lineage and strain Ra of the Latin America and Mediterranean lineage. In the current study, we evaluated the immune responses induced by strains M and Ra in peripheral blood mononuclear cells from patients with active MDR-TB or fully drug-susceptible tuberculosis (S-TB) and in purified protein derivative-positive healthy controls (group N). Our results demonstrated that strain M was a weaker gamma interferon (IFN-gamma) inducer than H37Rv for group N. Strain M induced the highest interleukin-4 expression in CD4+ and CD8+ T cells from MDR- and S-TB patients, along with the lowest cytotoxic T-lymphocyte (CTL) activity in patients and controls. Hence, impairment of CTL activity is a hallmark of strain M and could be an evasion mechanism employed by this strain to avoid the killing of macrophages by M-specific CTL effectors. In addition, MDR-TB patients had an increased proportion of circulating regulatory T cells (Treg cells), and these cells were further expanded upon in vitro M. tuberculosis stimulation. Experimental Treg cell depletion increased IFN-gamma expression and CTL activity in TB patients, with M- and Ra-induced CTL responses remaining low in MDR-TB patients. Altogether, these results suggest that immunity to MDR strains might depend upon a balance between the individual host response and the ability of different M. tuberculosis genotypes to drive Th1 or Th2 profiles.
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http://dx.doi.org/10.1128/IAI.00224-09DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2772532PMC
November 2009

Epidemiology of antituberculosis drug resistance 2002-07: an updated analysis of the Global Project on Anti-Tuberculosis Drug Resistance Surveillance.

Lancet 2009 May 15;373(9678):1861-73. Epub 2009 Apr 15.

Stop TB Department, WHO, Geneva, Switzerland.

Background: The Global Project on Anti-Tuberculosis Drug Resistance has been gathering data since 1994. This study provides the latest data on the extent of drug resistance worldwide.

Methods: Data for drug susceptibility were gathered from 90 726 patients in 83 countries and territories between 2002 and 2007. Standardised collection of results enabled comparison both between and within countries. Where possible, data for HIV status and resistance to second-line drugs were also obtained. Laboratory data were quality assured by the Supranational Tuberculosis Reference Laboratory Network.

Findings: The median prevalence of resistance to any drug in new cases of tuberculosis was 11.1% (IQR 7.0-22.3). The prevalence of multidrug resistance in new tuberculosis cases ranged from 0% in eight countries to 7% in two provinces in China, 11.1% in Northern Mariana Islands (although reporting only two cases), and between 6.8% and 22.3% in nine countries of the former Soviet Union, including 19.4% in Moldova and 22.3% in Baku, Azerbaijan (median for countries surveyed 1.6%, IQR 0.6-3.9). Trend analysis showed that between 1994 and 2007, the prevalence of multidrug-resistant (MDR) tuberculosis in new cases increased substantially in South Korea and in Tomsk Oblast and Orel Oblast, Russia, but was stable in Estonia and Latvia. The prevalence of MDR tuberculosis in all tuberculosis cases decreased in Hong Kong and the USA. 37 countries and territories reported representative data on extensively drug-resistant (XDR) tuberculosis. Five countries, all from the former Soviet Union, reported 25 cases or more of XDR tuberculosis each, with prevalence among MDR-tuberculosis cases ranging between 6.6% and 23.7%.

Interpretation: MDR tuberculosis remains a threat to tuberculosis control in provinces in China and countries of the former Soviet Union. Data on drug resistance are unavailable in many countries, especially in Africa, emphasising the need to develop easier methods for surveillance of resistance in tuberculosis.

Funding: Global Project: United States Agency for International Development and Eli Lilly and Company. Drug resistance surveys: national tuberculosis programmes, the Government of the Netherlands, the Global Fund to Fight AIDS, Tuberculosis and Malaria, Japan International Cooperation Agency, and Kreditanstalt für Wiederaufbau.
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http://dx.doi.org/10.1016/S0140-6736(09)60331-7DOI Listing
May 2009

Mycobacterium tuberculosis strains of the Beijing genotype are rarely observed in tuberculosis patients in South America.

Mem Inst Oswaldo Cruz 2008 Aug;103(5):489-92

Instituto Nacional de Enfermedades Infecciosas ANLIS Carlos Malbrá, Buenos Aires, Argentina.

The frequency of the Beijing genotype of Mycobacterium tuberculosis as a cause of tuberculosis (TB) in South America was determined by analyzing genotypes of strains isolated from patients that had been diagnosed with the disease between 1997 and 2003 in seven countries of the subcontinent. In total, 19 of the 1,202 (1.6%) TB cases carried Beijing isolates, including 11 of the 185 patients from Peru (5.9%), five of the 512 patients from Argentina (1.0%), two of the 252 Brazilian cases (0.8%), one of the 166 patients from Paraguay (0.6%) and none of the samples obtained from Chile (35), Colombia (36) and Ecuador (16). Except for two patients that were East Asian immigrants, all cases with Beijing strains were native South Americans. No association was found between carrying a strain with the Beijing genotype and having drug or multi-drug resistant disease. Our data show that presently transmission of M. tuberculosis strains of the Beijing genotype is not frequent in Latin America. In addition, the lack of association of drug resistant TB and infection with M. tuberculosis of the Beijing genotype observed presently demands efforts to define better the contribution of the virulence and lack of response to treatment to the growing spread of Beijing strains observed in other parts of the world.
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http://dx.doi.org/10.1590/s0074-02762008000500014DOI Listing
August 2008

Mutations in DNA repair genes are associated with the Haarlem lineage of Mycobacterium tuberculosis independently of their antibiotic resistance.

Tuberculosis (Edinb) 2007 Nov 4;87(6):502-8. Epub 2007 Oct 4.

Corporación Corpogen, Carrera 5 No. 66A-34, Bogotá, Colombia.

The analysis of the DNA repair genes ogt and ung was carried out in 117 Mycobacterium tuberculosis clinical isolates from Argentina and Colombia in order to explore correlation between mutations in these genes and multi-drug resistance. With the exception of two Beijing family isolates, the rest of the strains harbored either two wild-type or two mutant alleles with identical single nucleotide polymorphisms (SNPs) in each gene (ogt44 and ung501). These ogt44 and ung501 mutations were not associated with multi-drug resistance and occurred simultaneously in circulating Haarlem genotype M. tuberculosis strains. We therefore propose the use of these markers as tools in phylogenetic and epidemiologic studies.
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http://dx.doi.org/10.1016/j.tube.2007.05.011DOI Listing
November 2007

First insight into Mycobacterium tuberculosis genetic diversity in Paraguay.

BMC Microbiol 2007 Aug 8;7:75. Epub 2007 Aug 8.

Departamento de Biología Molecular, Instituto de Investigaciones en Ciencias de la Salud (IICS), Universidad Nacional de Asunción, Asunción, Paraguay.

Background: We present a picture of the biodiversity of Mycobacterium tuberculosis in Paraguay, an inland South American country harboring 5 million inhabitants with a tuberculosis notification rate of 38/100,000.

Results: A total of 220 strains collected throughout the country in 2003 were classified by spoligotyping into 79 different patterns. Spoligopatterns of 173 strains matched 51 shared international types (SITs) already present in an updated version of SpolDB4, the global spoligotype database at Pasteur Institute, Guadeloupe. Our study contributed to the database 13 new SITs and 15 orphan spoligopatterns. Frequencies of major M. tuberculosis spoligotype lineages in our sample were as follows: Latin-American & Mediterranean (LAM) 52.3%, Haarlem 18.2%, S clade 9.5%, T superfamily 8.6%, X clade 0.9% and Beijing clade 0.5%. Concordant clustering by IS6110 restriction fragment length polymorphism (RFLP) and spoligotyping identified transmission in specific settings such as the Tacumbu jail in Asuncion and aboriginal communities in the Chaco. LAM genotypes were ubiquitous and predominated among both RFLP clusters and new patterns, suggesting ongoing transmission and adaptative evolution in Paraguay. We describe a new and successfully evolving clone of the Haarlem 3 sub-lineage, SIT2643, which is thus far restricted to Paraguay. We confirmed its clonality by RFLP and mycobacterial interspersed repetitive unit (MIRU) typing; we named it "Tacumbu" after the jail where it was found to be spreading. One-fifth of the spoligopatterns in our study are rarely or never seen outside Paraguay and one-tenth do not fit within any of the major phylogenetic clades in SpolDB4.

Conclusion: Lineages currently thriving in Paraguay may reflect local host-pathogen adaptation of strains introduced during past migrations from Europe.
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http://dx.doi.org/10.1186/1471-2180-7-75DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1988809PMC
August 2007

[False diagnosis of tuberculosis by culture].

Medicina (B Aires) 2007 ;67(3):287-94

Agencia de Promoción Científicas, SeCyT, beca PICT 9978, Instituto Nacional de Enfermedades Infecciosas INEI ANLIS Carlos G. Malbrán, Buenos Aires, Argentina.

A remarkable input to the epidemiology of tuberculosis was not the only benefit of the molecular tools developed in the early nineties for Mycobacterium tuberculosis intra-species differentiation. These genotyping methods served also to unveil specimen cross-contamination, which was until then overlooked in laboratories culturing mycobacteria. This error consists in the accidental carry-over of bacilli from a specimen with high bacterial load to that, or those, processed subsequently. The ensuing detection of falsely positive cultures can result in a wrong diagnosis of tuberculosis and the initiation of a long-lasting treatment with potentially toxic drugs. This series of errors implies the mismanagement of patients, the distraction of public health system resources, and the distortion of epidemiological data. M. tuberculosis laboratory cross-contamination was detected wherever investigated systematically, with a median rate of 3% of all positive cultures. The confirmation of this error requires a critical appraisal of bacteriological, clinical, epidemiological and genotyping results. We present here a review of national and international information on laboratory cross-contamination and describe measures recommended for minimizing the risk, surveying the occurrence, and avoiding clinical consequences of this laboratory error that raises a question on the reliability of a positive culture.
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July 2008

Susceptibility tests to second line drugs and re-treatment of tuberculosis revisiting early experiences.

Medicina (B Aires) 2007 ;67(3):231-7

Panel de Consultores en Tuberculosis, OMS, Buenos Aires.

The value of susceptibility tests in guiding antituberculous therapy with second-line drugs remains controversial. We reanalyzed three reports regarding the relationship between in vitro susceptibility of Mycobacterium tuberculosis and the clinical outcome of in-patients treated with these drugs at the Muñiz Hospital, Buenos Aires, during the sixties. These patients had been irregularly treated with a standard regimen consisting of isoniazid, streptomycin and PAS; they developed resistance to at least the first two drugs and persisted culture-positive. Susceptibility testing to ethionamide, cycloserine and kanamycin were performed by the proportion method on Löwenstein Jensen medium. Some level of resistance was detected among isolates from patients not previously treated with these drugs, that could be due to cross resistance with previously administered first line structural analogs. However, the studies evidenced significant association between resistance to ethionamide and cycloserine and prior treatment with these drugs. Increased resistance to all three drugs was detected within the first three months of treatment. In vitro resistance to ethionamide emerged earlier and was the most frequent followed by resistance to cycloserine and kanamycin. The low frequency of resistance to kanamycin could be related to the low dosage of this drug used at that time. Simultaneous resistance to the three agents, but not to two or one drug, appeared to be a marker of treatment failure. An apparent reversion of drug resistance was observed in near 6% of patients, for whom susceptibility tests were repeated on subsequent isolates, indicating this percentage of inconsistency in reproducibility of test results.
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July 2008

Worldwide emergence of extensively drug-resistant tuberculosis.

Emerg Infect Dis 2007 Mar;13(3):380-7

Centers for Disease Control and Prevention, Atlanta, Georgia, USA.

Mycobacterium tuberculosis strains that are resistant to an increasing number of second-line drugs used to treat multidrug-resistant tuberculosis (MDR TB) are becoming a threat to public health worldwide. We surveyed the Network of Supranational Reference Laboratories for M. tuberculosis isolates that were resistant to second-line anti-TB drugs during 2000-2004. We defined extensively drug-resistant TB (XDR TB) as MDR TB with further resistance to > or = 3 of the 6 classes of second-line drugs. Of 23 eligible laboratories, 14 (61%) contributed data on 17,690 isolates, which reflected drug susceptibility results from 48 countries. Of 3,520 (19.9%) MDR TB isolates, 347 (9.9%) met criteria for XDR TB. Further investigation of population-based trends and expanded efforts to prevent drug resistance and effectively treat patients with MDR TB are crucial for protection of public health and control of TB.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2725916PMC
http://dx.doi.org/10.3201/eid1303.061400DOI Listing
March 2007

[New diagnosis tools for tuberculosis laboratory network in Latin America].

Rev Cubana Med Trop 2007 May-Aug;59(2):82-9

Instituto Nacional De Enfermedades Infecciosas Dr. Carlos G. Malbran, Buenos Aires, Argentina.

Feasibility of rapid and sustainable diagnostic methods that provide useful and timely results to guide the clinical control of tuberculosis patients was analyzed. However, policies guiding the insertion of new diagnostics in the laboratory services that support the tuberculosis control are lacking in developing countries. The introduction of these methods in developing countries laboratories requires rational policies guiding the application of these technologies. In the last few years, some automated systems for culture and molecular testing in laboratory services for tuberculosis diagnosis, which offered accuracy and speed, have been reported. However, their implementation is restricted because of costly resources, logistics and infrastructure. Recently, various economically feasible tests have demonstrated to be applicable in poor-resource labs. The detection of adenosine desaminase (ADA) in pleural fluid is a valuable low-cost approach to the diagnosis of tuberculosis. On the other hand, the microscopic detection of Mycobacterium tuberculosis using thin layer agar is a moderate cost alternative method. Drug susceptibility testing to antituberculous drugs can be expedited by the nitrate reduction assay in tuberculosis laboratories using routine procedures for tuberculosis diagnosis.
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April 2013

Multicenter evaluation of the nitrate reductase assay for drug resistance detection of Mycobacterium tuberculosis.

J Microbiol Methods 2005 Nov;63(2):145-50

Mycobacteriology Unit, Institute of Tropical Medicine, Nationalestraat, 155, Antwerp, B-2000, Belgium.

The performance of the nitrate reductase assay was evaluated in a multicenter laboratory study to detect resistance of Mycobacterium tuberculosis to the first-line anti-tuberculosis drugs rifampicin, isoniazid, ethambutol and streptomycin using a set of coded isolates. Compared with the gold standard proportion method on Löwenstein-Jensen medium, the assay was highly accurate in detecting resistance to rifampicin, isoniazid and ethambutol with an accuracy of 98%, 96.6% and 97.9%, respectively. For streptomycin, discrepant results were obtained with an overall accuracy of 85.3%. The assay proved easy to be implemented in countries with limited laboratory facilities.
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http://dx.doi.org/10.1016/j.mimet.2005.03.004DOI Listing
November 2005

Multicenter evaluation of mycobacteria identification by PCR restriction enzyme analysis in laboratories from Latin America and the Caribbean.

J Microbiol Methods 2005 May 25;61(2):193-9. Epub 2004 Dec 25.

Departamento de Microbiologia, Imunologia e Parasitologia, Universidade Federal de São Paulo-Escola Paulista de Medicina, Rua Botucatu, 862 3 degrees andar, São Paulo 04023-062, Brazil.

The identification of mycobacterial species in clinical isolates is essential for making patient care decisions. Polymerase chain reaction (PCR) restriction enzyme analysis (PRA) is a simple and rapid identification method, based on amplification of 441 bp of the hsp65 gene and restriction with BstEII and HaeIII. As a contribution to the validation of PRA, a multicenter study was performed in eight laboratories located in Argentina, Brazil, Colombia, Chile, and Guadeloupe. Each laboratory received 18 coded isolates from the collection of the Institute of Tropical Medicine (Antwerp, Belgium), representing duplicates of nine laboratory strains: Mycobacterium terrae CIPT 140320001, Mycobacterium scrofulaceum CIPT 140220031, Mycobacterium flavescens ATCC 14474, Mycobacterium triviale ATCC 23292, Mycobacterium nonchromogenicum ATCC 19530, Mycobacterium chitae ATCC 19627, Mycobacterium abscessus ATCC 19977, Mycobacterium kansasii ATCC 12478, and Mycobacterium peregrinum ATCC 14467. A detailed protocol including amplification, enzymatic digestion, and gel preparation was provided to each laboratory. Two laboratories identified correctly all 18 (100%) isolates, one identified correctly 17 (94.5%), two identified 14 (77.7%), one identified 11 (61%), and two identified 8 (44.4%) isolates. Errors detected in laboratories with more than 77% accuracy were associated with electrophoresis running conditions and an unspecific amplicon produced by a single strain. Lower accuracy was mainly related to inappropriate use of DNA markers and insufficient training in interpretation of patterns. In conclusion, the PRA method was readily implemented in some Latin American and Caribbean laboratories of mycobacteria, but improvements in critical points, as gel running conditions and training in interpretiation of patterns, are needed in order to improve accuracy. In others, improvement in critical points is still necessary.
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http://dx.doi.org/10.1016/j.mimet.2004.11.015DOI Listing
May 2005

In-house phage amplification assay is a sound alternative for detecting rifampin-resistant Mycobacterium tuberculosis in low-resource settings.

Antimicrob Agents Chemother 2005 Jan;49(1):425-7

INEI-ANLIS "Carlos G. Malbrán," Av. Vélez Sarsfield 563, 1281 Buenos Aires, Argentina.

An in-house mycobacteriophage amplification assay for detecting rifampin-resistant Mycobacterium tuberculosis showed 100% sensitivity, 97.7% specificity, and 95.2% predictive value for resistance in a test of 129 isolates from a hot spot area of multidrug-resistant M. tuberculosis. The applicability of the test was demonstrated in the routine work flow of a low-resource reference laboratory.
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http://dx.doi.org/10.1128/AAC.49.1.425-427.2005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC538913PMC
January 2005

[Distribution of PRA patterns of clinical isolates of the Mycobacterium avium complex from Spain and South America].

Biomedica 2004 Jun;24 Supp 1:60-4

Departamento de Medicina Preventiva, Facultad de Medicina, Universidad Autónoma, Madrid, España.

Mycobacterium avium complex (MAC) infections are the most frequent systemic infections associated with advanced AIDS. DNA probes for accurate identification of mycobacteria are available but are very expensive in many Latin American settings. Consequently, most Latin American diagnostic laboratories employ inaccurate and outdated tests for mycobacteria identification. Therefore, PCR restriction analysis (PRA) of the hsp65 gene was evaluated for the identification of 163 MAC human isolates originated from Spain and South America. The predominant PRA type in each country was: M. avium type I in Argentina (23/42, 55%) and Brazil (48/72, 67%), M. avium type II in Spain (18/26, 69%) and M. avium type III in Colombia (10/23, 43%). The Colombia frequency is noteworthy, since the PRA type III was quite infrequent in the other three countries. Furthermore, its presence has not been reported outside the Americas. The advantages and disadvantages of PRA in diagnostic mycobacteriology are discussed.
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June 2004

Multidrug-resistant tuberculosis in HIV-negative patients, Buenos Aires, Argentina.

Emerg Infect Dis 2003 Aug;9(8):965-9

Hospital F. J. Muñiz, Buenos Aires, Argentina.

Initial multidrug-resistant (MDR) tuberculosis (TB) in HIV-negative patients treated at a Buenos Aires referral hospital from 1991 to 2000 was examined by using molecular clustering of available isolates. Of 291 HIV-negative MDRTB patients, 79 were initially MDR. We observed an ascending trend of initial MDRTB during this decade (p=0.0033). The M strain, which was responsible for an institutional AIDS-associated outbreak that peaked in 1995 to 1997, caused 24 of the 49 initial MDRTB cases available for restriction fragment length polymorphism. Of those, 21 were diagnosed in 1997 or later. Hospital exposure increased the risk of acquiring M strain-associated MDRTB by approximately two and a half times. The emergence of initial MDRTB among HIV-negative patients after 1997 was apparently a sequel of the AIDS-related outbreak. Because the prevalence of M strain-associated disease in the study population did not level out by the end of the decade, further expansion of this disease is possible.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3020598PMC
http://dx.doi.org/10.3201/eid0908.020474DOI Listing
August 2003
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