Mauricio Beltrán

Serological response to Helicobacter pylori infection among Latin American populations with contrasting risks of gastric cancer

Gastric cancer is a rare outcome of chronic Helicobacter pylori infection. Serologic profiles may reveal bacterial, environmental and/or host factors associated with cancer risk. We therefore compared specific anti‐H. pylori antibodies among populations with at least twofold differences in gastric cancer mortality from Mexico, Colombia and Chile. Our study included 1,776 adults (mean age 42 years) from three nationally representative surveys, equally divided between residents of high‐ and low‐risk areas. Antibodies to 15 immunogenic H. pylori antigens were measured by fluorescent bead‐based multiplex assays; results were summarized to identify overall H. pylori seropositivity. We used logistic regression to model associations between antibody seroreactivity and regional cancer risk (high vs. low), adjusting for country, age and sex. Both risk areas had similar H. pylori seroprevalence. Residents in high‐ and low‐risk areas were seroreactive to a similar number of antigens (means 8.2 vs. 7.9, respectively; adjusted odds ratio, OR: 1.02, p = 0.05). Seroreactivities to Catalase and the known virulence proteins CagA and VacA were each significantly (p < 0.05) associated with residence in high‐risk areas, but ORs were moderate (1.26, 1.42 and 1.41, respectively) and their discriminatory power was low (area under the curve < 0.6). The association of Catalase was independent from effects of either CagA or VacA. Sensitivity analyses for antibody associations restricted to H. pylori‐seropositive individuals generally replicated significant associations. Our findings suggest that humoral responses to H. pylori are insufficient to distinguish high and low gastric cancer risk in Latin America. Factors determining population variation of gastric cancer burden remain to be identified.

Genomic Epidemiology of NDM-1-Encoding Plasmids in Latin American Clinical Isolates Reveals Insights into the Evolution of Multidrug Resistance

Abstract Bacteria that produce the broad-spectrum Carbapenem antibiotic New Delhi Metallo-β-lactamase (NDM) place a burden on health care systems worldwide, due to the limited treatment options for infections caused by them and the rapid global spread of this antibiotic resistance mechanism. Although it is believed that the associated resistance gene blaNDM-1 originated in Acinetobacter spp., the role of Enterobacteriaceae in its dissemination remains unclear. In this study, we used whole genome sequencing to investigate the dissemination dynamics of blaNDM-1-positive plasmids in a set of 21 clinical NDM-1-positive isolates from Colombia and Mexico (Providencia rettgeri, Klebsiella pneumoniae, and Acinetobacter baumannii) as well as six representative NDM-1-positive Escherichia coli transconjugants. Additionally, the plasmids from three representative P. rettgeri isolates were sequenced by PacBio sequencing and finished. Our results demonstrate the presence of previously reported plasmids from K. pneumoniae and A. baumannii in different genetic backgrounds and geographically distant locations in Colombia. Three new previously unclassified plasmids were also identified in P. rettgeri from Colombia and Mexico, plus an interesting genetic link between NDM-1-positive P. rettgeri from distant geographic locations (Canada, Mexico, Colombia, and Israel) without any reported epidemiological links was discovered. Finally, we detected a relationship between plasmids present in P. rettgeri and plasmids from A. baumannii and K. pneumoniae. Overall, our findings suggest a Russian doll model for the dissemination of blaNDM-1 in Latin America, with P. rettgeri playing a central role in this process, and reveal new insights into the evolution and dissemination of plasmids carrying such antibiotic resistance genes.

First Complete Providencia rettgeri Genome Sequence, the NDM-1-Producing Clinical Strain RB151

ABSTRACT Providencia rettgeri is an opportunistic bacterial pathogen of clinical significance due to its association with urinary tract infections and multidrug resistance. Here, we report the first complete genome sequence of P. rettgeri. The genome of strain RB151 consists of a 4.8-Mbp chromosome and a 108-kbp blaNDM-1-positive plasmid.

Genomic and Molecular Characterization of Clinical Isolates of Enterobacteriaceae Harboring mcr-1 in Colombia, 2002 to 2016

ABSTRACT Polymyxins are last-resort antimicrobial agents used to treat infections caused by carbapenem-resistant Enterobacteriaceae. Due to the worldwide dissemination of polymyxin resistance in animal and human isolates, we aimed to characterize polymyxin resistance associated with the presence of mcr-1 in Enterobacteriaceae and nonfermenter Gram-negative bacilli, using isolates collected retrospectively in Colombia from 2002 to 2016. A total of 5,887 Gram-negative clinical isolates were studied, and 513 were found to be resistant to the polymyxins. Susceptibility to colistin was confirmed by broth microdilution for all mcr-1-positive isolates, and these were further subjected to whole-genome sequencing (WGS). The localization of mcr-1 was confirmed by S1 pulsed-field gel electrophoresis (S1-PFGE) and CeuI-PFGE hybridization. Transferability was evaluated by mating assays. A total of 12 colistin-resistant isolates recovered after 2013 harbored mcr-1, including 8 Escherichia coli, 3 Salmonella enterica serovar Typhimurium, and 1 Klebsiella pneumoniae isolate. E. coli isolates were unrelated by PFGE and belonged to 7 different sequence types (STs) and phylogroups. S. Typhimurium and K. pneumoniae isolates belonged to ST34 and ST307, respectively. The mcr-1 gene was plasmid borne in all isolates but two E. coli isolates which harbored it on the chromosome. Conjugation of mcr-1 was successful in 8 of 10 isolates (8.2 × 10−5 to 2.07 × 10−1 cell per recipient). Plasmid sequences showed that the mcr-1 plasmids belonged to four different Inc groups (a new IncP-1 variant and the IncFII, IncHI1, and IncH families). Our results indicate that mcr-1 is circulating in clinical isolates of colistin-resistant Enterobacteriaceae in Colombia and is mainly harbored in transferable plasmids.

Molecular Epidemiology of Candida auris in Colombia Reveals a Highly Related, Countrywide Colonization With Regional Patterns in Amphotericin B Resistance

Background Candida auris is a multidrug-resistant yeast associated with hospital outbreaks worldwide. During 2015-2016, multiple outbreaks were reported in Colombia. We aimed to understand the extent of contamination in healthcare settings and to characterize the molecular epidemiology of C. auris in Colombia. Methods We sampled patients, patient contacts, healthcare workers, and the environment in 4 hospitals with recent C. auris outbreaks. Using standardized protocols, people were swabbed at different body sites. Patient and procedure rooms were sectioned into 4 zones and surfaces were swabbed. We performed whole-genome sequencing (WGS) and antifungal susceptibility testing (AFST) on all isolates. Results Seven of the 17 (41%) people swabbed were found to be colonized. Candida auris was isolated from 37 of 322 (11%) environmental samples. These were collected from a variety of items in all 4 zones. WGS and AFST revealed that although isolates were similar throughout the country, isolates from the northern region were genetically distinct and more resistant to amphotericin B (AmB) than the isolates from central Colombia. Four novel nonsynonymous mutations were found to be significantly associated with AmB resistance. Conclusions Our results show that extensive C. auris contamination can occur and highlight the importance of adherence to appropriate infection control practices and disinfection strategies. Observed genetic diversity supports healthcare transmission and a recent expansion of C. auris within Colombia with divergent AmB susceptibility.

Absence of occult hepatitis B in Colombian blood donors

INTRODUCTION In Colombian blood banks, screening for the surface antigen of hepatitis B is mandatory in all units collected. Testing of antibody against core antigens is not administered, although this method may be useful to detect donors infected with the hepatitis B virus. OBJECTIVE The prevalence of occult hepatitis B was determined by applying a full-serological profile of hepatitis B virus to blood samples of blood donors. MATERIALS AND METHODS Between April 2008 and October 2009, a prospective cross sectional study was conducted using 628 samples from donors to blood banks located in four Colombian cities. Prevalence for hepatitis B had been previously recorded for these cities. Serological screening was performed for the complete virus; then nucleic acid amplification was tested in sera that were anti-HBc reactive and with a titer of anti-HBs ≤30 mUI/ml. RESULTS Of the 628 samples tested, 129 met the serological criteria established to be tested nucleic acid amplification. None of them demonstrated evidence of nucleic acid amplification of hepatitis B virus. CONCLUSIONS This is the first study in Colombia to detect the presence of blood donors that may be occult hepatitis B carriers. None was detected.

Resultados de la vigilancia nacional de la resistencia antimicrobiana de enterobacterias y bacilos Gram negativos no fermentadores en infecciones asociadas a la atención de salud, Colombia, 2012-2014

INTRODUCTION The Colombian National Antimicrobial Resistance Monitoring System for the surveillance of healthcare-associated infections was set up to meet this problem in the third quarter of 2012. OBJECTIVE To describe resistance profiles and laboratory-based surveillance based on the information collected by the System. MATERIALS AND METHODS We conducted a retrospective and descriptive study of the information notified to the Colombian Public Health Surveillance System (Sivigila), and in the Whonet databases covering the period from July 2012 to December 2014 provided by the primary data-generating units in the country, as well as laboratory surveillance results from 1,642 phenotypic and genotypic tests on carbapenemase isolates (927 from Enterobacteriaceae, 614 from Pseudomonas spp. and 101 from Acinetobacter spp.). RESULTS There was a significant increase in Escherichia coli resistance to third-generation cephalosporins (reaching 26.3% in ICUs and 22.5% in other hospital wards), and Klebsiella pneumoniae resistance to ertapenem also increased (reaching 14.6% in ICUs). Acinetobacter baumannii carbapenem resistance exceeded 50% in ICUs whereas Pseudomonas aeruginosa had lower carbapenem resistance (38.8%). KPC (n = 574) and NDM (n=57) were the most frequently occurring carbapenemases in Enterobacteriaceae, VIM (n=229) and KPC (n=114) in P. aeruginosa, and OXA-23 in A. baumannii (n=87); several carbapenemase combinations were identified, KPC + VIM being the most common in Pseudomonas spp. and Enterobacteriaceae. CONCLUSION The data from the surveillance of healthcare-associated infections revealed significant carbapenem resistance profiles and antimicrobial resistance mechanisms circulating in Colombian healthcare institutions.

Detección de anticuerpos contra Trypanosoma cruzi en pacientes multitransfundidos, Colombia

INTRODUCTION Chagas disease is a public health problem in Latin America. Even though vector-borne infection is the most important transmission mode for this disease, other modes such as transfusions require evaluation. OBJECTIVE To describe the prevalence of T. cruzi infection in multitransfused patients. MATERIALS AND METHODS We detected IgG antibodies against T. cruzi by two immunoassays in samples from multitransfused patients in four hospitals located in Bogotá and Medellín, Colombia. We analyzed the association with known risk factors, and we calculated the odds ratios (OR) with 95% confidence intervals using Stata 11™ statistical software. RESULTS In total, 479 samples were tested. Overall, T. cruzi antibody prevalence was 1.88% (nine patients). Five were onco-hematological patients, two were hemodialyzed, one had thalassemia, and one had suffered acute blood loss. We found no hemophilia patients. There was no association between known risk factors for transfusion-transmitted infection (such as the number of transfusion events, number of blood units and type of blood component) and the presence of anti-T. cruzi antibodies in this study. Only the hepatitis C virus infection showed a positive association with the presence of anti-T. cruzi antibodies (OR=5.68, 95% CI: 1.36-23.63). CONCLUSIONS The results of this study showed a low frequency of T. cruzi infection in multitransfused patients, suggesting that the risk of transfusion infection in Colombia is low. Known risk factors for transfusion-related infection were not associated with the presence of anti-T. cruzi antibodies.

Enfermedad de Chagas y su seroprevalencia en tres departamentos de la Amazonia colombiana

Objetivo. Determinar la seroprevalencia de la enfermedad de Chagas en poblacion general procedente de tres departamentos de la Amazonia colombiana: Vaupes, Amazonas y Guaviare y analizar variables de riesgo para la enfermedad. Metodos. Para determinar la seropositividad se analizaron 3429 muestras de suero obtenidas mediante previo consentimiento informado durante los anos 2009 y 2010 a traves de un muestreo probabilistico, de conglomerados, estratificado y trietapico para cada departamento, con probabilidades finales desiguales. Fueron analizadas en el Laboratorio de Parasitologia del Instituto Nacional de Salud de Bogota mediante dos tecnicas de diagnostico, Inmunoensayo enzimatico (Elisa) e Inmunofluorescencia indirecta (IFI) empleando como antigeno una cepa de Trypanosoma cruzi colombiana previamente caracterizada como linaje T cI. Resultados. Se encontro una seroprevalencia general de 0,99%, 2,07% para el departamento del Guaviare, 0,79% para el departamento de Vaupes y 0,09% para el departamento de Amazonas. Estos resultados permitiran establecer una linea de base epidemiologica que contribuya a las estrategias de control de la enfermedad en esta zona.