Carmen Larrañaga

Adenovirus surveillance on children hospitalized for acute lower respiratory infections in Chile (1988–1996)

Adenoviruses (Ad) play an important role in the etiology of acute lower respiratory tract infections (ALRI) in young children in Chile. Our aim was to correlate the clinical severity of the infections with the Ad strains isolated during surveillance over 8 years. From 1988 through 1996, nasopharyngeal aspirates (NPA) were obtained for viral isolation and immunofluorescence assay (IFA) from children under 2 years of age hospitalized for ALRI; Ad isolates were further studied by restriction enzyme analysis of genomic DNA. Of 3,097 cases enrolled, the Ad isolation rate was 12.6%. The most common admission diagnoses among Ad‐positive cases were pneumonia and wheezing bronchitis (69.8%). Duration of Ad shedding was studied in 74 cases by IFA. Children excreting Ad for 4 or more days had a longer hospital stay than those shedding for 1–3 days (mean: 16.8 and 7.2 days, respectively; P < .01). Viral shedding for more than 3 days was associated with more severe outcomes. Genome typing of 221 out of 390 Ad isolates resulted in 87 subgenus C and 134 subgenus B strains, including 123 Ad genome type 7h (55.6%, P < .01). The IFA from the NPA was more sensitive for the detection of subgenus B (51.5%) than subgenus C infections (24.1%, P < .01). Children shedding Ad 7h had longer hospital stays (P < .01), a higher frequency of rectal temperatures over 39°C (P < .01), and greater need for additional oxygen (P < .02) than subgenus C cases. Four cases requiring mechanical ventilation were associated with Ad 7h infections. The data presented show that, in children hospitalized for ALRI, the genome type 7h was associated with a more severe clinical outcome. J. Med. Virol. 60:342–346, 2000.

Surveillance for Respiratory Syncytial Virus in Infants Hospitalized for Acute Lower Respiratory Infection in Chile (1989 to 2000)

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.

Treatment of respiratory syncytial virus infection with vitamin A: a randomized, placebo-controlled trial in Santiago, Chile.

BACKGROUND Treatment with high dose vitamin A reduces complications and duration of hospitalization for children with measles. In respiratory syncytial virus (RSV) infection, as with measles, low serum vitamin A concentrations correlate with increased severity of illness. METHODS To determine whether high dose vitamin A treatment is also effective for treating RSV disease, we conducted a randomized, double blind, placebo-controlled trial among 180 RSV-infected children between 1 month and 6 years of age at three hospitals in Santiago, Chile. Children with nasal washes positive for RSV antigen were given oral vitamin A (50,000 to 200,000 IU of retinyl palmitate, doses according to age; n = 89) or placebo (n = 91) within 2 days of admission. RESULTS There was no significant benefit from vitamin A treatment for the overall group in duration of hospitalization, need for supplemental oxygen or time to resolve hypoxemia. For the subgroup of children with significant hypoxemia on admission (room air oxygen saturation level < or = 90%), those given vitamin A had more rapid resolution of tachypnea (P = 0.01) and a shorter duration of hospitalization (5.5 vs. 9.3 days, P = 0.09). No toxicities were seen, including excess vomiting or bulging fontanel. CONCLUSIONS If vitamin A has a beneficial effect on the course of RSV disease, it may be seen only in more severely ill children.

Community- and hospital-acquired respiratory syncytial virus infections in Chile.

Nasopharyngeal aspirates were obtained on admission from 614 patients younger than 2 years of age who were hospitalized in a ward for acute respiratory infections from June 1988 through October, 1989, in Santiago, Chile. Patients in two rooms were followed during the cold seasons by sampling aspirates every other day during the childs entire hospital stay. Clinical features were recorded daily. Indirect monoclonal immunofluorescent assay and isolation in HEp-2 were used for respiratory syncytial virus (RSV) diagnosis. The mean RSV detection rate was 39% at the time of admission, ranging from 8% in April, 1989, to 62% in July, 1988. During the cold months 43 of 288 (15%) nosocomial RSV cases were detected. Pneumonia and wheezing bronchitis were the principal diagnoses of both groups admitted, whether they were shedding RSV or not. It is concluded that RSV plays a major role in admissions for acute respiratory infections, as well as in nosocomial infections, in Santiago. Because clinical features do not allow one to differentiate viral from bacterial acute respiratory infections, the importance of rapid viral diagnosis is emphasized.

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

Background. 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. Methods. 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. Results. Adenovirus cases declined from 20% annually in the early 1990s to ~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). Conclusions. 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.

Hospital-acquired adenovirus 7h infantile respiratory infection in Chile.

Background. Adenoviruses are the second most common cause of viral acute lower respiratory tract infection (ALRI) requiring hospitalization in Chile. Little information is available with respect to nosocomial infection rate by adenovirus. This issue is important because of its potential severity and long term sequelae. Methods. Infants hospitalized for ALRI were studied to determine the rate of nosocomial cross‐infection with respiratory adenovirus and its corresponding genome type. The group studied included all cases younger than 2 years of age admitted to a seven crib ward in the Roberto del Río Childrens Hospital (Santiago, Chile) between May, 1995, and October, 1996. Nasopharyngeal aspirates for immunofluorescence assay and viral isolation were obtained on admission and the next day. On identification of a positive case for adenovirus, samples were obtained from contacts for 2 consecutive days and twice weekly thereafter for 2 weeks. Results. Fifteen index positive cases for adenovirus and their 65 contacts were identified. Secondary attack rate for adenoviral cross‐infection was 55%, most of which were diagnosed by viral isolation. Mortality occurred in 4 cases; 3 had underlying diseases. Four secondary cases presented mild respiratory infection after acquiring the cross‐infection, and 16 patients developed a moderate and severe ALRI. Twelve patients required supplemental oxygen and 4 needed mechanical respiratory support. Genome types for the 10 index cases and 19 contacts were obtained. All of these corresponded to adenovirus 7h. Conclusions. The high secondary attack rate observed, stresses the importance of adequate isolation of patients and the need for rapid and sensitive viral diagnosis.

Comparison of virological profiles of respiratory syncytial virus and rhinovirus in acute lower tract respiratory infections in very young Chilean infants, according to their clinical outcome

Abstract Background Respiratory syncytial virus (RSV) and rhinovirus (HRV) are the main cause of acute lower respiratory tract infections (ALRTIs) in infants. Viral and host-related risk factors for severe disease have also not been clearly established. Objective To assess whether certain viral features of RSV and, or HRV are associated with severe ALRTI. Study design RSV and HRV were studied in nasopharyngeal samples of infants by immunofluorescence, Luminex® and/or real-time RT-PCR assays. Quantitation and genotyping of RSV and HRV by PCR were done. Results Of 124 virus positive specimens, 74 (59.7%) had RSV; 22 (17.7%) HRV and 28 (22.6%) RSV-HRV co-infection. Hospitalization was required in 57/74 RSV infants (77.0%); in 10/22 HRV cases (45.5%) (p =0.006) and in 15/28 co-infected by both viruses (53.6%) (p =0.003). Severe cases were 33/74 (44.6%) RSV infections, 2/22 HRV cases (9.1%), (p <0.002) and 6/28 (21.4%) patients co-infected by RSV–HRV (p <0.026). Three genotypes (NA1, B7, B9) of RSV circulated during the study. In 33 severe infants, NA1 was detected in 19 cases (57.6%); B7 in 13 (39.4%) and B9 in 1 (3.0%) (p <0.01; OR=10.0). RSV loads were similar between outpatients and hospitalized infants (p =0.7) and among different severities (p =0.7). NA1 loads were higher than other strains (p =0.049). Three geno-groups of HRV circulated homogeneously. Conclusion In very young infants, RSV cause more severe disease than HRV. Co-infection does not increase the severity of illness. NA1 RSV genotype was associated with major frequency of hospitalization, severe respiratory disease and higher viral load.

SP-A1, SP-A2 and SP-D gene polymorphisms in severe acute respiratory syncytial infection in Chilean infants.

Respiratory syncytial virus (RSV) is the principal pathogen that causes acute lower respiratory tract infection (ALRI) in infants. Severe RSV-ALRI has been associated with the host genetic susceptibility. To assess whether severe RSV disease in infants is associated with certain single nucleotide polymorphism (SNP) into the gene of SP-A1, SP-A2 and SP-D, a prospective study was performed among blood donors and RSV-infected infants aged <or=6 months, considering their severity, according to a strict scoring system. Allele and genotype frequencies were compared using χ(2)-test. Association studies and haplotype analysis were tested by using Armitagës trend test and Unphased 3.0 program. A total of 118 RSV-infected infants and 104 blood donors were enrolled into the study; 59 infants had a severe respiratory disease, 34 children developed a moderate illness and 25 had a mild disease. There was no difference in the allelic and genotypic frequencies of SP-A1, but intragenic haplotypes showed significant differences among infected infants and blood donors (p=0.0021). 1A(0) variant of SP-A2 was the most frequent allele in all groups. Thr(11) allele of SP-D is significantly higher in RSV infants (p=0.028), as given by its higher frequency in severe disease (p=0.046). Heterozygous Thr(11)/Met(11) was significantly more common in infected infants (p=0.037), because it has higher frequency in critically ill children (p=0.017). Thr(160) allele was significantly higher in severe infants compared with blood donors (p=0.046) and infants with mild disease (p=0.018). Thr(11)-Thr(160)-Ser(270) haplotype was significantly more common in RSV-infants, due to severe (p=0.00000034) and moderate disease (p=0.000009). Differences were also found among severe and mild disease (p=0.026). Differences found with other authors, indicate the need for local studies to identify genetic biomarkers of severity.

Seroprevalencia de anticuerpos IgG contra parvovirus B19 en donantes de sangre de hospitales en Santiago, Chile

BACKGROUND Parvovirus B19 (B19) is associated with a wide range of disease manifestations, whose severity depends on the immunological and hematological status of the host. Infection with B19 has been reported worldwide and the prevalence of immunoglobulin G antibodies against B19 increases with age and varies by location and time of the last B19 epidemic. AIM To evaluate the prevalence of IgG antibodies against Parvavirus B19 virus in a population of volunteer blood donors at two hospital blood banks in Santiago, Chile. MATERIAL AND METHODS A total of 400 serum samples from blood donors aged 18 to 65 years, were examined for the presence of IgG antibodies against Parvovirus B19. RESULTS The overall prevalence of IgG antibodies was 54.8%. No significant difference was found between men and women (57.6% and 49.3%, respectively). CONCLUSIONS IgG antibody seroprevalence against Parvovirus B19, was 55% in this sample of Chilean blood donors. This figure is in agreement with previous reports from abroad.

Respiratory syncytial virus infection and recurrent wheezing in Chilean infants: A genetic background?

UNLABELLED 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.