Carmen Larrañaga

Publications (12)30.78 Total impact

• Article: Respiratory syncytial virus infection and recurrent wheezing in Chilean infants: a genetic background?

  Lorena I Tapia, Sandra Ampuero, M Angélica Palomino, Vivian Luchsinger, Nelson Aguilar, Eliana Ayarza, Rossana Mamani, Carmen Larrañaga
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  ABSTRACT: Respiratory syncytial virus (RSV) infection has been associated to recurrent wheezing, but pathogenic mechanisms are unclear. Interleukin-4/Interleukin-13 (IL-4/IL-13) pathway is involved in both conditions. A common host genetic susceptibility may exist in patients whom RSV will trigger severe illness and those who develop recurrent wheezing. Objective: To assess, by a candidate-gene approach, whether genetic polymorphisms in IL-4/IL-13 pathway are associated with RSV infection severity and its outcome in Chilean children. A cohort of 118 RSV-infected infants was analyzed and followed for one year. Severity of acute infection and later recurrent wheezing were characterized. Alleles and genotypes frequencies were determined for two SNP in each of the genes IL-4, IL-13 and IL-4Rα. Association tests and interaction analyses were performed. Enrollment included 60 moderate and 58 severe cases. Two SNP were found associated to severity during acute infection in IL-4Rα gene (Gln551Arg, Ile50Val). The follow up was completed in 71% of patients (84/118). Later recurrent wheezing was 54% in severe group, versus 31% in moderate cases (p=0.035). In relation to outcome, allele Ile50 in IL-4Rα was more frequent in patients with moderate disease and no wheezing outcome. A common protector genotype is proposed for Chilean children: IL-4Rα Ile/Ile. Conclusion: Genetic variations in the host are associated to infection severity and outcome. A common genetic background might be influencing both pathologies.
  Infection, genetics and evolution: journal of molecular epidemiology and evolutionary genetics in infectious diseases 01/2013; · 3.22 Impact Factor
• Article: [Clinical guideline. Acquired immunodeficiency virus infection. Part III. Antiretroviral treatment for children and adolescents].

  Elba Wu, Carmen Larrañaga, Gloria Berríos, Edith Ortiz, Anibal Hurtado, Anamaría Peña, Isabel Galaz
  Revista chilena de infectologia: organo oficial de la Sociedad Chilena de Infectologia 10/2010; 27(5):449-75. · 0.45 Impact Factor
• Article: Impaired immune response in severe human lower tract respiratory infection by respiratory syncytial virus.

  Carmen L Larrañaga, Sandra L Ampuero, Vivian F Luchsinger, Flavio A Carrión, Nelson V Aguilar, Pamela R Morales, María Angélica M Palomino, Lorena F Tapia, Luis F Avendaño
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  ABSTRACT: Respiratory syncytial virus (RSV) is a major cause of acute lower respiratory infection in infants. The immune response plays a leading role in the severity of the disease. We hypothesized that severe RSV disease is associated with an impaired immune response characterized by low circulating T lymphocytes and plasma cytokine concentrations. We evaluate the in vivo immune responses of previously healthy infants with their first proven RSV-acute lower respiratory infection that required hospitalization. According to the clinical severity, defined by using a strict scoring system, the in vivo immune response was compared through the analysis of plasma cytokine values and the phenotyping of peripheral blood lymphocyte and natural killer (NK) cells. Absolute blood cell counts of CD4+, CD8+, and CD19+ lymphocytes and NK cells were lower in subjects with RSV than in control infants. Lowest cell counts were observed in more severe RSV-infected infants. Significant low values were obtained in CD8+ lymphocytes (P = 0.03) and nonactive NK cells, that express CD94 antigen (P = 0.046). In contrast, activated NK cells that do not express CD94 molecules were significantly higher in RSV infected infants than in healthy controls (% of cells: P = 0.004). The interferon-gamma and tumor necrosis factor-alpha values in RSV infected patients were lower than in controls subjects. Interleukin-17 cytokine was not detected in healthy infants and the largest concentration was found in moderately ill patients as compared with severe cases (P = 0.033). RSV infection showed significantly higher interleukin-8 chemokine than in control infants (P = 0.024). We propose that severe RSV infection in very young infants is associated with poor blood proinflammatory cytokine production, low counts of CD8+ T cells and with a greater activity of a group of NK cells, that are independent of the major histocompatibility complex class Ib recognition system.
  The Pediatric Infectious Disease Journal 10/2009; 28(10):867-73. · 3.58 Impact Factor
• Article: Parvovirus B19 infection in Chile: markers of infection and immunity in patients with clinical symptoms.

  Carmen Larrañaga, Oscar León, Patricia Díaz, Marta Miranda, Ximena Norambuena, Marcela Pérez, Aldo Gaggero
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  ABSTRACT: Parvovirus B19 infection is associated with a wide variety of symptoms and signs, and given that some clinical features, such as anemia, arthropathy and rash may be attributable to other causes, laboratory diagnosis of B19 markers is necessary. The principal aims were to study the behavior of B19 infection-associated diseases in the Chilean population and to compare B19 markers for recent or active infection and for immunity status in patients with clinical symptoms suspicious of B19 infection and control individuals. Sera from a total of 267 patients with diverse clinical manifestations associated with B19 and from 69 healthy controls were tested for B19 DNA using PCR and for specific IgM and immunoglobulin G (IgG) by enzyme-linked immunosorbent assay (ELISA). Out of 267 patients examined, 89 had B19-associated disease markers: 43 had B19 DNA without IgM, 25 had IgM without B19 DNA, and 21 had both B19 DNA and IgM. Also 49 patients were positive only for IgG without B19 DNA or IgM. Out of the 69 healthy controls, only 2 had B19 DNA without IgM and 30 had IgG without B19 DNA and/or IgM. The distribution of the clinical diagnoses associated with recent B19 infection, tested by B19 DNA and/or IgM, included 38.5% with hematological illnesses, 23.4% with rheumatic diseases, 45.7% with infectious diseases, 33.3% with indications of prenatal infection, 32.3% with conditions that induce immunodeficiency, and 15.8% with other miscellaneous conditions. The use of both markers, DNA and IgM, allows a more adequate diagnosis of infection by this virus.
  Journal of Medical Virology 01/2008; 79(12):1927-34. · 2.82 Impact Factor
• Article: [Cytomegalovirus disease in HIV-1 infected Chilean children].

  Anamaría Peña, Carmen Larrañaga, Vivian Luchsinger, Julia Villarroel, Ana Chávez, Elba Wu
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  ABSTRACT: Cytomegalovirus (CMV) is a frequent opportunistic infection in human immunodeficiency virus type 1 (HIV-1) infected children associated with significant morbidity and mortality. The aim of this study was to determine the frequency and impact of CMV disease in a prospective ly followed cohort of HIV-1 infected Chilean children. CMV disease was diagnosed in 28 out of 222 HIV infected children (12.6%); 92% of them were classified in category C and 61% in category 3 (CDC, 1994). Lung disease was the most common manifestation (25 children). Samples were obtained from the respiratory tract, blood, urine and tissue biopsies. Shell vial for CMV early antigen detection was the most commonly used diagnostic technique (20/ 28). All patients were treated with iv.ganciclovir and two children died during the CMV episode. The mean survival time for the remaining children is currently 42 months. Conclusion: CMV disease was frequent and caused mortality in HIV-1 infected Chilean children. Early diagnosis and treatment are key for clinical success.
  Revista chilena de infectologia: organo oficial de la Sociedad Chilena de Infectologia 01/2008; 24(6):477-84. · 0.45 Impact Factor
• Article: Molecular characterization of hospital-acquired adenovirus infantile respiratory infection in Chile using species-specific PCR assays.

  Carmen Larrañaga, Jorge Martínez H, Angélica Palomino M, Mónica Peña C, Flavio Carrión A, Luís Fidel Avendaño C
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  ABSTRACT: Adenovirus serotypes 7, 2 and 1 are the second most common cause of viral acute lower respiratory tract infection (ALRI) requiring hospitalization in Chile. Nosocomial outbreaks have high secondary attack and lethality rates, and call for rapid and specific diagnosis. We compared the results obtained on ALRI specimens by immunofluorescence (IFA) and virus isolation, plus restriction enzyme digestion (RFLP) typing, with universal, species-specific and 7h-specific PCR typing of adenovirus. A second objective was to determine the type of adenovirus implicated in nosocomial infection and nosocomial cross-infection rates. Infants hospitalized for ALRI in the Roberto del Río Children's Hospital (Santiago, Chile) in 1995-1996 had nasopharyngeal aspirates obtained at admission and tested by IFA and virus isolation. Adenovirus isolates were identified by RFLP. When an index case was identified, samples were collected from contacts for 2 consecutive days and twice weekly thereafter for 2 weeks. Further typing of adenovirus isolates was undertaken with universal, species-specific and 7h-specific PCR performed in 2003 on the stored frozen samples. Fifteen index cases of adenovirus and their 65 contacts were identified. The nosocomial secondary attack rate using PCR was estimated as 46%. PCR had a higher sensitivity (98.7%) compared to virus isolation (90%) and IFA (50%) and facilitated identification of adenovirus strains more easily and accurately than RFLP (91.6% versus 55.8%). Fifty-three percent of the contacts had severe outcomes. The case fatality rate was 16.6% and was associated with adenovirus 7h. Prompt, rapid and sensitive methods to identify adenovirus infection are necessary, especially for hospital-acquired adenovirus infections, because of their ease of spread and high fatality rate.
  Journal of Clinical Virology 08/2007; 39(3):175-81. · 3.97 Impact Factor
• Article: Parvovirus B19 may have a role in the pathogenesis of juvenile idiopathic arthritis.

  Benito Gonzalez, Carmen Larrañaga, Oscar León, Patricia Díaz, Marta Miranda, Marcelo Barría, Aldo Gaggero
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  ABSTRACT: To determine the prevalence of human parvovirus B19 infection in patients with juvenile idiopathic arthritis (JIA) by detection of specific IgM, IgG, and viral DNA. Serum samples of 50 patients with diagnosis of JIA and 39 healthy controls were analyzed by ELISA to detect IgG and IgM anti-B19-specific antibodies. The parvovirus B19 genome was detected by nested polymerase chain reaction (PCR). The average age of the patients was 9.6 years (2-14 yrs); 30 were female (60%) and 20 male (40%). The definitive diagnoses of these patients corresponded to 19 systemic forms (38%), 11 to the oligoarticular variety (22%) and 20 to the polyarticular (40%). The average age of the control group was 7.8 years (2-16 yrs); the distribution by sex was 25 females (64%) and 14 males (36%). IgM against parvovirus B19 was detected in 20% of the cases (10 patients) and B19 DNA genome by PCR in 48% (24 patients); in 10% of the cases (5 patients), both markers were detected. IgG was found in 32% (16 patients). In the control group neither IgM nor the viral genome was detected. However, 43.5% of the controls (17/39) had IgG against parvovirus B19, indicating past infection by the virus. Our study confirms recent observations regarding a high prevalence of viral DNA in JIA patients and a possible role of this viral infection in JIA pathogenesis.
  The Journal of Rheumatology 07/2007; 34(6):1336-40. · 3.69 Impact Factor
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  Available from: uchile.cl

  Article: Adenovirus and respiratory syncytial virus-adenovirus mixed acute lower respiratory infections in Chilean infants.

  María Angélica Palomino, Carmen Larrañaga, Eliecer Villagra, Jorge Camacho, Luis F Avendaño
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  ABSTRACT: In Chile respiratory syncytial virus (RSV) and adenovirus (AD) are the principal viruses detected in acute lower respiratory infections (ALRI) in infants. An overview of AD pneumonia in Chile to detect annual trends and to compare the severity of single AD or mixed RSV-AD infections is presented. Surveillance in 4927 infants hospitalized for ALRI has been performed from 1989 to 2001 using immunofluorescence assay (IFA) and viral isolation. Clinical features in 117 infants with single genotyped AD and 81 infants with mixed RSV-AD infections were analyzed. Adenovirus cases declined from 20% annually in the early 1990s to approximately 5% in the 2000 decade. Genotype 7h showed increasing prevalence in hospitalized cases. The mean annual burden of hospitalizations caused by AD in Santiago was estimated to be 0.6%. No difference was observed in duration of fever, oxygen requirement and hospital stay between groups. Lung consolidation was more frequent in AD cases than mixed cases (P < 0.01); interstitial pattern and hyperinflation prevailed in the mixed cases (P < 0.01). No child died. AD diagnosis was confirmed on admission by IFA in 17% of cases of RSV-AD and in 43% of cases of single AD ALRI. AD cases diagnosed early by IFA had worse clinical outcome than those diagnosed later by virus isolation (P < 0.05). AD cases declined since 1989. Mixed RSV-AD infections were not more severe than single AD etiology. AD cases admitted with positive IFA had worse prognoses than AD infections diagnosed later by virus isolation.
  The Pediatric Infectious Disease Journal 04/2004; 23(4):337-41. · 3.58 Impact Factor
• Article: Surveillance for respiratory syncytial virus in infants hospitalized for acute lower respiratory infection in Chile (1989 to 2000).

  Luis F Avendaño, María Angélica Palomino, Carmen Larrañaga
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  ABSTRACT: Hospitalized infants (4,618) were studied for lower respiratory infections from 1989 through 2000 by routine immunofluorescence assay and viral isolation. The hospitalization rate for respiratory syncytial virus (RSV) averaged 2% per year. The fatality rate was 0.1%. Monthly RSV detection varied from 14 to 88%, and epidemics lasted 3.5 to 6 months. From 1994 high-early versus low-late epidemic patterns alternately were observed, the first influenced by a group B strain.
  Journal of Clinical Microbiology 11/2003; 41(10):4879-82. · 4.15 Impact Factor
• Article: [Digestive pathology in children infected with the human immunodeficiency virus (HIV), in Santiago de Chile].

  Renzo Tassara, Teresa Alarcón, Carmen Larrañaga, Elba Wu, Ana M Alvarez
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  ABSTRACT: Human immunodeficiency virus (HIV) epidemiology has changed, affecting an increasing number of children. As in adults, the disease predominantly affects the digestive and respiratory systems. To report the gastrointestinal problems in HIV infected pediatric patients. Twenty four HIV infected children (nine male, aged 1 to 12 years old, followed for 1 to 170 months), are reported. This group has been under care by a multiprofessional team. Oral candidiasis was present in 21 (88%), esophagic candidiasis in 3 (13%), oral ulcers in 4 (17%). Diarrhea was observed in 18 children (75%) and in eight, it had a chronic evolution. Cryptosporidium parvum was the most frequent agent found in six cases (1 with acute and 5 with chronic diarrhea). Schlerosing cholangiopathy was observed in one case, with a fatal outcome, in association to microsporidiosis. Upper endoscopy was done in 11 patients, demonstrating microscopic inflammatory changes in esophagic, gastric and duodenal epithelia in all. Digestive problems are common in HIV infected pediatric patients. They must be always sought actively. Endoscopy is a valuable tool for the early diagnosis of these problems.
  Revista medica de Chile 02/2003; 131(1):19-24. · 0.33 Impact Factor
• Article: Genome type analysis of chilean adenovirus strains isolated in a children's hospital between 1988 and 1990

  Adriana E. Kajon, Carmen Larrañaga, Mónica Suárez, Göran Wadell, Luis F. Avendaño
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  ABSTRACT: In a study designed to evaluate the genetic variability of adenovirus strains associated with infantile cases of respiratory disease requiring hospitalization, a collection of 136 adenovirus isolates obtained in the Roberto del Rio Children's Hospital of Santiago, Chile between June 1988 and November 1990 was studied by restriction enzyme analysis. Nasopharyngeal aspirates were obtained on admission from children under 2 years. During the study period a total of 227 adenovirus respiratory infections (ARI) were diagnosed at the ward for ARI by immunofluorescence, representing 23% of all admissions. Fifty percent of the 136 typed strains were found to belong to subgenus B, and the other 50% corresponded to subgenus C. Digestion with a set of seven enzymes allowed the identification of nine different genome types of subgenus C, three of which had not been previously described, exhibiting novel restriction patterns with either Bgl II or BstEII. Ad7h, identified in 66 isolates, was the predominant genome type and was associated with the nine cases requiring mechanical respiratory assistance and with the two fatalities recorded during the 29 months. No differences were found between the age and sex distribution of subgenus B and C genomic variants, but the mean length of hospital stay (X ± 2 SE) recorded among patients infected with subgenus B types was significantly higher (17.72 + 4.52 days (n = 55) vs. 7.54 + 1.70 days (n = 53); F = 17.22; P < 0.0001) © 1994 Wiiey-Liss, Inc.
  Journal of Medical Virology 12/1993; 42(1):16 - 21. · 2.82 Impact Factor
• Article: Plasma interferon-gamma, interleukin-10 and soluble markers of immune activation in infants with primary adenovirus (ADV) and respiratory syncytial virus (RSV) infection.

  J Alonso Fernández, Lorena Tapia, M Angélica Palomino, Carmen Larrañaga, Mónica Peña, Héctor Jaramillo
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  ABSTRACT: Adenovirus (ADV) and respiratory syncytial virus (RSV) are etiological agents of acute respiratory tract infection in infants. Long-term prognosis of ADV infection includes severe lung damage, bronchiectasis and hyperlucent lung, while RSV infection is associated with development of recurrent wheezing and subsequent asthma. These differences may be related to differences in the primary immune responses elicited by these viruses. In this paper, we investigated the type of cytokine responses and the magnitude of immune activation in ADV and RSV infections in infants. We examined plasma concentrations of interferon-gamma (IFN-gamma), interleukin-10 (IL-10), soluble interleukin-2 receptor (sCD25) and soluble tumor necrosis factor receptor II (sTNFR-II) in previously healthy infants during the acute phase of primary ADV infection (n = 21) and RSV infection (n = 68), and in uninfected controls (n = 44). In ADV-infected infants, IFN-gamma plasma levels were significantly higher than those observed in RSV cases and the control group (p < 0.05). RSV cases did not show any differences in IFN-gamma plasma levels compared to the other groups. sCD25 levels were significantly higher in ADV- and RSV-infected infants than in controls (p < 0.0001), and higher in ADV than in RSV cases (p < 0.05). sTNFR-II levels were significantly higher in RSV- and ADV-infected infants than in controls (p < 0.0001, p < 0.05, respectively), and higher in RSV than in ADV infection (p < 0.05). No significant differences were observed in IL-10 plasma concentrations between the three groups. These results indicate that ADV and RSV infections in infants differ significantly with regard to the magnitude of production of interferon-gamma and soluble immune activation markers sCD25 and sTNFR-II. These immunological differences may be involved in the different clinical outcomes associated with these viral infections.
  European cytokine network 16(1):35-40. · 1.73 Impact Factor