title: Acute Chagas outbreaks: molecular and biological features of Trypanosoma cruzi isolates, and clinical aspects of acute cases in Santander, Colombia.
abstract: BACKGROUND
  Outbreaks of acute Chagas disease associated with oral transmission are easily detected nowadays with trained health personnel in areas of low endemicity, or in which the vector transmission has been interrupted. Given the biological and genetic diversity of Trypanosoma cruzi, the high morbidity, mortality, and the observed therapeutic failure, new characteristics of these outbreaks need to be addressed at different levels, both in Trypanosoma cruzi as in patient response. The aim of this work was to evaluate the patient's features involved in six outbreaks of acute Chagas disease which occurred in Santander, Colombia, and the characteristics of Trypanosoma cruzi clones isolated from these patients, to establish the potential relationship between the etiologic agent features with host behavior.
  
  
  METHODS
  The clinical, pathological and epidemiological aspects of outbreaks were analyzed. In addition, Trypanosoma cruzi clones were biologically characterized both in vitro and in vivo, and the susceptibility to the classical trypanocidal drugs nifurtimox and benznidazole was evaluated. Trypanosoma cruzi clones were genotyped by means of mini-exon intergenic spacer and cytochrome b genes sequencing.
  
  
  RESULTS
  All clones were DTU I, and based on the mini-exon intergenic spacer, belong to two genotypes: G2 related with sub-urban, and G11 with rural outbreaks. Girón outbreak clones with higher susceptibility to drugs presented G2 genotype and C/T transition in Cyt b. The outbreaks affected mainly young population (±25.9 years), and the mortality rate was 10 %. The cardiac tissue showed intense inflammatory infiltrate, myocardial necrosis and abundant amastigote nests. However, although the gastrointestinal tissue was congestive, no inflammation or parasites were observed.
  
  
  CONCLUSIONS
  Although all clones belong to DTU I, two intra-DTU genotypes were found with the sequencing of the mini-exon intergenic spacer, however there is no strict correlation between genetic groups, the cycles of the parasite or the clinical forms of the disease. Trypanosoma cruzi clones from Girón with higher sensitivity to nifurtimox presented a particular G2 genotype and C/T transition in Cyt b. When the diagnosis was early, the patients responded well to antichagasic treatment, which highlights the importance of diagnosis and treatment early to prevent fatal outcomes associated with these acute episodes.
authors.affiliation: Grupo de Inmunología y Epidemiología Molecular (GIEM), Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia. mdiazgalvis@yahoo.com.
authors.forename: Martha Lucía
authors.initials: ML
authors.lastname: Díaz
authors.affiliation: Grupo de Investigación en Enfermedades Tropicales (CINTROP), Departamento de Ciencias Básicas, Escuela de Medicina, Universidad Industrial de Santander, Bucaramanga, Colombia. sandramilena20@gmail.com.
authors.forename: Sandra
authors.initials: S
authors.lastname: Leal
authors.affiliation: Grupo de Inmunología y Epidemiología Molecular (GIEM), Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia. jcmlaboratorio@gmail.com.
authors.forename: Julio César
authors.initials: JC
authors.lastname: Mantilla
authors.affiliation: Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. amolinaberrios@u.uchile.cl.|Present address: Laboratorio de Farmacología y Farmacogenética, Instituto de Investigación en Ciencias Odontológicas (ICOD), Facultad de Odontología, Universidad de Chile, Santiago, Chile. amolinaberrios@u.uchile.cl.
authors.forename: Alfredo
authors.initials: A
authors.lastname: Molina-Berríos
authors.affiliation: Programa de Farmacología Molecular y Clínica, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. rodlopez@u.uchile.cl.|Present address: Instituto de Farmacología y Morfofisiología, Facultad de Ciencias Veterinarias, Universidad Austral de Chile, Valdivia, Chile. rodlopez@u.uchile.cl.
authors.forename: Rodrigo
authors.initials: R
authors.lastname: López-Muñoz
authors.affiliation: Programa de Biología Celular y Molecular, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile. asolari@med.uchile.cl.
authors.forename: Aldo
authors.initials: A
authors.lastname: Solari
authors.affiliation: Grupo de Investigación en Enfermedades Tropicales (CINTROP), Departamento de Ciencias Básicas, Escuela de Medicina, Universidad Industrial de Santander, Bucaramanga, Colombia. pescobarwww@yahoo.co.uk.
authors.forename: Patricia
authors.initials: P
authors.lastname: Escobar
authors.affiliation: Grupo de Inmunología y Epidemiología Molecular (GIEM), Facultad de Salud, Universidad Industrial de Santander, Bucaramanga, Colombia. cig@uis.edu.co.|Escuela de Microbiología, Facultad de Salud, Carrera 32 #29-31, Oficina 419, Universidad Industrial de Santander, Bucaramanga, Colombia. cig@uis.edu.co.
authors.forename: Clara Isabel
authors.initials: CI
authors.lastname: González Rugeles
mesh_terms: D000208:Acute Disease; D000818:Animals; D001483:Base Sequence; D014355:Chagas Disease / Q000453:epidemiology* / Q000469:parasitology; D003105:Colombia / Q000453:epidemiology; D016054:DNA, Protozoan / Q000737:chemistry / Q000235:genetics; D004196:Disease Outbreaks; D005091:Exons / Q000235:genetics; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009547:Nifurtimox / Q000494:pharmacology; D009593:Nitroimidazoles / Q000494:pharmacology; D017422:Sequence Analysis, DNA; D014344:Trypanocidal Agents / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000235:genetics* / Q000302:isolation & purification
chemical_list: D016054:DNA, Protozoan; D009593:Nitroimidazoles; D014344:Trypanocidal Agents; D009547:Nifurtimox; C009999:benzonidazole