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.

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.

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.

Molecular characterization of hospital-acquired adenovirus infantile respiratory infection in Chile using species-specific PCR assays.

BACKGROUND: 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. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Definición / Definition

Asma es la enfermedad inflamatoria crónica más frecuente en la edad pediátrica; sin embargo, es frecuente encontrar diversas definiciones en torno a una misma enfermedad. Los aspectos clínicos de ella, descansan sobre un sustrato fisiopatológico inflamatorio que en la práctica, no siempre puede ser objetivado y mucho menos medido; mas aún, los criterios epidemiológicos definidos y aceptados mundialmente, son inespecíficos. En el presente trabajo se comentan algunos aspectos relevantes en torno a esta frecuente condición.

Plasma interferon-gamma, interleukin-10 and soluble markers of immune activation in infants with primary adenovirus (ADV) and respiratory syncytial virus (RSV) infection.

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.

Diagnóstico de infección por adenovirus y virus respiratorio sincicial en lactantes: comparación entre aislamiento e inmunofluorescencia indirecta / Diagnosis of adenovirus and respiratory sintitial virus infection in infants: compararison among isolation and indirect immunofluorescence

Con el objeto de comparar el rendimiento del aislamiento en cultivo celular y de la inmunofluorescencia indirecta (IFI) para la detección de adenovirus y VRS, se analizaron 390 muestras de aspirado nasofaríngeo provenientes de 256 lactantes menores de dos años ingresados al Hospital Roberto del Río, Santiago. Se inocularon células HEp-2 y se hizo IFI para VRS y adenovirus con anticuerpos monoclonales. Los efectos citopáticos observados se confirmaron con IFI. Se detectaron 100/390 (25,6%) cultivos positivos: 40 VRS, 43 adenovirus y 17 ambos virus. Con IFI hubo 145/390 (37,2%) muestras positivas: 116 VRS, 9 adenovirus y 20 ambos virus. En total se detectaron 136 muestras positivas para VRS: 96 por IFI, 13 por cultivo y 27 por ambas técnicas. Del total de 57 adenovirus diagnosticados, 14 lo fueron por IFI, 39 por aislamiento y 4 por ambos métodos. El análisis de los casos dio cifras semejantes a la relatada para las muestras. Se concluye que en nuestro medio la IFI es más sensible que el cultivo celular para detección de VRS. Por el contrario, el aislamiento viral en HEp-2 tiene mejor rendimiento que la IFI para detectar adenovirus