Cyclovirus detection in Chilean adults with and without community-acquired pneumonia.

Cycloviruses (CyV) (genus Cyclovirus, family Circoviridae) are nonenveloped DNA viruses. The first report in humans was in 2010 and research has focused only on disease-associated human sample detection. The only HuACyV (CyCV-ChileNPA1, HuACyV10) reported in the Chilean population was in children (3.3%) with an acute respiratory infection. Its detection in respiratory samples from adults, with/without respiratory disease remains unknown. The aim of this study was to detect HuACyV10 in adults with and without respiratory disease. HuACyV10 was studied in nasopharyngeal swabs from 105 hospitalized adults with community-acquired pneumonia (CAP) and 104 adults without respiratory symptoms. Total nucleic acids were extracted, and viral rep and cp gene fragments were amplified by real-time polymerase chain reaction. HuACyV10 was detected in 19.05% adults with CAP and in 0.96% asymptomatic adults, being significantly higher in adult CAP than asymptomatic (n = 1) ones (p = 0.0001). C t values were between 26.7 and 39.6, and the median was 34.1 for rep and 33.8 for the CAP in adults CAP (p = 0.68), and 35.7 and 36.0, respectively, in the asymptomatic case. HuACyV10 detection in CAP adults concentrated in the Autumn-Winter season of the Southern hemisphere. The only asymptomatic adult with HuACyV10 was detected in the Spring-Summer period. In this first report of HuACyV10 in respiratory samples from adults, detection was significantly higher in CAP than in asymptomatic adults. As the sensitivity of both rep and cp genes was similar, both can be applied for detecting HuACyV10. It would be advisable to investigate the pathogenic role of HuACyV10 in adult respiratory infections. ​.

[Yield of two mortality predictors in immunocompetent patients with community acquired pneumonia]. / Rendimiento de dos índices predictores de mortalidad (PSI y CURB-65) en pacientes adultos inmunocompetentes hospitalizados por neumonía adquirida en la comunidad.

BACKGROUND: The severity of community acquired pneumonia (CAP) can be evaluated by the PSI and CURB-65 scales. However, it is unknown whether their predictive capacity varies according to the etiology of the disease. AIM: To compare the performance of these scales in adults with viral, bacterial, mixed, and no agent detected CAP. MATERIAL AND METHODS: We studied 725 patients hospitalized for CAP aged 18 to 95 years (47% females) Urinary S. pneumoniae and Legionella antigens were detected by immuno-chromatography (Binax®). Respiratory viruses and bacteria were detected by PCR in nasopharyngeal smears. The proportions of deaths, admission to the intensive care unit (ICU), and oxygen therapy were compared between mild and non-severe patients defined by PSI (I/II and I-III) and CURB-65 (1 and 1-2), according to the causative agent. RESULTS: Ten percent of patients died. A causative agent was detected in 65%. The proportion of mild and non-severe patients according to PSI and CURB-65, and of deceased patients, admitted to the ICU and with oxygen therapy was similar in the four categories per agent. There were no deaths among non-severe patients with bacterial CAP. However, 6% of patients with CAP caused by virus or without causative agents, died. No deaths occurred among mild patients with bacterial CAP. In viral CAP, no deaths occurred among patients classified as mild only by PSI. The yields of PSI were greater than those of CURB-65 in non-severe patients who died and were admitted to the ICU with bacterial and viral CAP (5 and 14%; 7 and 12% respectively, p = 0.04). CONCLUSIONS: The prognostic performance of PSI in CAP varies according to the causative agent in adults. It is higher in non-severe bacterial cases, and superior to CURB-65.

Comparison of Luminex xTAG® RVP fast assay and real time RT-PCR for the detection of respiratory viruses in adults with community-acquired pneumonia.

Community-acquired pneumonia (CAP) is the third cause of death worldwide. Viruses are frequently detected in adult CAP. Highly sensitive diagnostic techniques should be used due to poor viral shedding. Different sampling methods can affect viral detection, being necessary to establish the optimal type of sample for identifying respiratory viruses in adults. The detection rates of respiratory viruses by Luminex xTAG® RVP fast assay, real time RT-PCR (rtRT-PCR) (Sacace®), and immunofluorescence assay (IFA) in adult CAP were performed in nasopharyngeal swabs (NPS) and aspirates (NPA) from 179 hospitalized adults. Positivity was 47.5% for Luminex®, 42.5% for rtRT-PCR (P = 0.3), and 2.7% for IFA (2.7%) (P < 0.0). The sensitivity, specificity, and kappa coefficient of xTAG® RVP compared with rtRT-PCR were 84.2%, 79.6%, and 0.62%, respectively. Luminex® and rtRT-PCR detected 65 (58.0%) and 57 (50.9%) viruses in 112 NPA and 35 (34.3%) and 31 (30.4%) in 102 NPS, respectively (P < 0.01). xTAG® RVP is appropriate for detecting respiratory viruses in CAP adults. Both molecular techniques yielded better results with nasopharyngeal aspirate than swabs.

Cyclovirus in nasopharyngeal aspirates of Chilean children with respiratory infections.

Some respiratory tract infections remain unexplained despite extensive testing for common pathogens. Nasopharyngeal aspirates (NPAs) from 120 Chilean infants from Santiago with acute lower respiratory tract infections were analysed by viral metagenomics, revealing the presence of nucleic acids from anelloviruses, adenovirus-associated virus and 12 known respiratory viral pathogens. A single sequence read showed translated protein similarity to cycloviruses. We used inverse PCR to amplify the complete circular ssDNA genome of a novel cyclovirus we named CyCV-ChileNPA1. Closely related variants were detected using PCR in the NPAs of three other affected children that also contained anelloviruses. This report increases the current knowledge of the genetic diversity of cycloviruses whose detection in multiple NPAs may reflect a tropism for human respiratory tissues.

Community-acquired pneumonia in Chile: the clinical relevance in the detection of viruses and atypical bacteria.

BACKGROUND: Adult community-acquired pneumonia (CAP) is a relevant worldwide cause of morbidity and mortality, however the aetiology often remains uncertain and the therapy is empirical. We applied conventional and molecular diagnostics to identify viruses and atypical bacteria associated with CAP in Chile. METHODS: We used sputum and blood cultures, IgG/IgM serology and molecular diagnostic techniques (PCR, reverse transcriptase PCR) for detection of classical and atypical bacteria (Mycoplasma pneumoniae, Chlamydia pneumoniae, Legionella pneumoniae) and respiratory viruses (adenovirus, respiratory syncytial virus (RSV), human metapneumovirus, influenza virus, parainfluenzavirus, rhinovirus, coronavirus) in adults >18 years old presenting with CAP in Santiago from February 2005 to September 2007. Severity was qualified at admission by Fine's pneumonia severity index. RESULTS: Overall detection in 356 enrolled adults were 92 (26%) cases of a single bacterial pathogen, 80 (22%) cases of a single viral pathogen, 60 (17%) cases with mixed bacterial and viral infection and 124 (35%) cases with no identified pathogen. Streptococcus pneumoniae and RSV were the most common bacterial and viral pathogens identified. Infectious agent detection by PCR provided greater sensitivity than conventional techniques. To our surprise, no relationship was observed between clinical severity and sole or coinfections. CONCLUSIONS: The use of molecular diagnostics expanded the detection of viruses and atypical bacteria in adults with CAP, as unique or coinfections. Clinical severity and outcome were independent of the aetiological agents detected.

Relationship between severity of adult community-acquired pneumonia and impairment of the antioxidant defense system.

Oxidant/antioxidant imbalance has been reported in some infectious diseases, including community-acquired pneumonia (CAP). The aim was to assess the antioxidant status in adults with CAP and its relationship with clinical severity at admission. Fifty-nine patients with CAP were enrolled and categorized at admission by the FINE score, from July 2010 to October 2012. In the same period 61 controls were enrolled. Plasma samples were obtained at admission for determination of the ferric reducing ability of plasma (FRAP) and lipid peroxidation (8-isoprostane). Erythrocyte reduced (GSH)/oxidized (GSSG) glutathione, malondialdehyde (MDA) and antioxidant enzyme activity were assessed. Antioxidant status in adults with CAP represented by FRAP and the GSH/GSSG ratio were 16.8% (p=0.03) and 39.7% (p=0.04) lower than control values, respectively. In addition, FRAP values showed a positive correlation with GSH/GSSG ratio (r=0.852; p<0.02; n=59). The CAP group showed greater lipid peroxidation in both plasma and erythrocytes. The FINE score correlated negatively with FRAP (r= -0.718; p<0.05; n=59) and positively with MDA and F2 isoprostane levels (r=0.673; p<0.05; n=59; r=0.892; p<0.01; n=59, respectively). Antioxidant status alterations correlated with clinical severity. The FRAP assay and lipid peroxidation biomarkers may provide a useful parameter for estimating the severity and the clinical outcome of patients with CAP.

Role of neutralizing antibodies in adults with community-acquired pneumonia by respiratory syncytial virus.

BACKGROUND: Respiratory syncytial virus (RSV) has been implicated in the etiology of adult community-acquired pneumonia (CAP). We investigated RSV infection in Chilean adults with CAP using direct viral detection, real-time reverse-transcription polymerase chain reaction (rtRT-PCR), and serology (microneutralization assay). METHODS: RSV, other respiratory viruses, and bacteria were studied by conventional and molecular techniques in adults aged ≥18 years presenting with CAP to the healthcare facilities in Santiago, Chile from February 2005 through December 2007. RESULTS: All 356 adults with CAP enrolled had an acute blood sample collected at enrollment, and 184 had a convalescent blood sample. RSV was detected in 48 cases (13.4%). Immunofluorescence assay and viral isolation each detected only 1 infection (0.2%), whereas rtRT-PCR was positive in 32 (8.9%) cases and serology was positive in 20 (10.8%) cases. CAP clinical characteristics were similar in RSV-infected and non-RSV-infected cases. RSV-specific geometric mean serum-neutralizing antibody titer (GMST) was significantly lower at admission in the 48 RSV-infected cases compared with 308 non-RSV-infected adults (GMST in log(2): RSV/A 8.1 vs 8.9, and RSV/B 9.3 vs 10.4; P < .02). CONCLUSIONS: RSV infection is frequent in Chilean adults with CAP. Microneutralization assay was as sensitive as rtRT-PCR in detecting RSV infection and is a good adjunct assay for diagnostic research. High RSV-specific serum-neutralizing antibody levels were associated with protection against common and severe infection. The development of a vaccine could prevent RSV-related CAP in adults.

IL-7/IL7R axis dysfunction in adults with severe community-acquired pneumonia (CAP): a cross-sectional study.

Community-acquired pneumonia (CAP) is a worldwide leading cause of death. Recognized risk factors in some severe cases have not been identified. Lymphocytopenia has been frequently described in CAP. Since IL-7, membrane-bound receptor (IL7Rα;CD127) and soluble IL7Rα (sIL7R) are critical in lymphocytes homeostasis, in this work we aimed to evaluate the involvement of the IL-7/IL7Rα axis in the severity of adult CAP, since it has not been explored. The IL7Rα SNPs rs6897932, rs987106, and rs3194051 SNPs in IL7α were genotyped, the systemic expression of the IL7R gene, sIL7R, IL-7, and levels of peripheral IL7Rα+ T lymphocytes were quantified in 202 hospitalized CAP cases. rs3194051GG was more frequent in non-survivors than in survivors; rs987106TT was more frequent and rs3194051AA less frequent in patients at intensive care unit (ICU) than in those not admitted to ICU. IL7Rα gene expression was lower in non-survivors than in survivors, and in severe than in mild cases. CD3+CD127+ lymphocytes were lower in severe than in mild cases; in non-survivors than in survivors and in ICU than in non- ICU admitted cases. sIL7Rα plasmatic levels were higher in non-survivors than in survivors, and in severe than in mild cases. rs6897932CC, rs987106AA and rs3194051GG carriers showed the highest while rs6897932TT showed the lowest sIL7Rα levels. The AUC of sIL7Rα levels predicting 30-day mortality was 0.71. Plasma IL-7 levels were lower in ICU-admitted than in not ICU-admitted and in non-survivors than in survivors. No additional association was detected. In conclusion, rs3194051GG and rs987106TT IL7R genotypes were associated with a poorer prognosis. A significant association between sIL7R levels and SNPs of the IL7R gene is described for the first time in adult CAP. Increased plasmatic sIL7R could contribute to identifying adult CAP cases at risk of death.

Immunoglobulins concentration and B cell counts as severity markers in adult community-acquired pneumonia: Cross sectional study.

Community-acquired pneumonia (CAP) is a worldwide cause of morbidity and mortality. Immunoglobulins (Igs) and B cells quantification studies in CAP are few and show discrepancies. Serum IgA acts as a powerful natural anti-inflammatory factor, but its role in the CAP has not yet been defined. The highly sensitive xMAP Luminex technique allows better immunoglobulins quantification. The aim of this study was to analyze the relation between clinical severity and circulating Igs and B cells in adults with CAP.Igs (M, A, G1, G2, G3, and G4) and B cells were quantified in peripheral blood of 190 Chilean patients ≥18 years old hospitalized for CAP and in 21 adults without respiratory disease, using xMAP Luminex and flow cytometry, respectively. Clinical history was recorded and PSI and CURB-65 scores were calculated for evaluation of clinical severity.The total IgM, IgG2 and total IgG levels were lower in CAP than in asymptomatic adults (P < .05). No significant differences of Igs levels were found between patients classified as severe and mild by PSI and CURB-65 scores. Fatal cases had higher levels of IgA (P < .05). No differences in CD19 B cells frequency was found between CAP and asymptomatic adults (P = .40). In PSI severe cases, CD19 B cells were significantly lower than in mild cases (P = .008). No differences were found in CURB-65 severe and mild groups (P = .11). In fatal cases (11/82) group, CD19 B cells frequency was lower than in 71 survivors (P = .2). No differences in memory B lymphocytes were detected between asymptomatic and CAP adults, severe and mild patients, survivors and fatal cases (P > .05).Serum IgA levels were significantly higher in fatal CAP cases, raising it as a potential biomarker for severe disease considering its relatively universal availability. In PSI severe patients, B cells showed lower levels and could have a role on its physiopathology. Finding new markers rooted in physiopathology could improve the possibility of scoring severe CAP cases. Luminex technology showed promising quantification serum Igs.

Genetic variability of human metapneumovirus isolated from Chilean children, 2003-2004.

Human metapneumovirus (hMPV) is a significant cause of acute lower respiratory tract infection in all age groups, particularly in children. Two genetic groups and four subgroups of hMPV have been described. They co-circulate during an epidemic in variable proportions. The aims were to characterize the genotypes of hMPV recovered from children hospitalized for acute lower respiratory tract infection and to establish the molecular epidemiology of strains circulating in Santiago of Chile during a 2-year period. The detection of the N gene by reverse-transcription polymerase chain reaction was carried out for screening 545 infants hospitalized for acute lower respiratory tract infection in Santiago during 2003-2004. The genetic typing of hMPV was performed by analyzing the fusion gene sequences. hMPV was detected in 10.2% (56/545 cases). Phylogenetic analysis of F gene sequences from 39 Chilean hMPV strains identified the two groups and four subgroups previously described. Strains clustered into group A were split further into the sub lineages A1, A2, and A3. Most Chilean strains clustered into the proposed novel A3 sub lineage (59%). A3 viruses were present in both years, while A1 and A2 circulated just in 1 year. In conclusion, hMPV is a relevant cause of acute lower respiratory infection in Chilean children and the potential novel cluster of group A emphasize the need for further regional genetic variability studies.

Human respiratory syncytial virus genomic and antigenic variants isolated in two hospitals during one epidemic, in Santiago, Chile.

BACKGROUND: Human respiratory syncytial virus (HRSV) is a major cause of severe lower respiratory tract infection (LRI) in children. Distinct variants of the viruses have been described. OBJECTIVE: The objective was to compare the antigenic and genetic variability of HRSV strains recovered from infants admitted to two hospitals during one epidemic in a big city. STUDY DESIGN: We analyzed nasopharyngeal aspirates from 201 infants admitted for LRI to two hospitals during 2002 in Santiago, Chile. The analyses were carried out using a panel of monoclonal antibodies against G glycoprotein epitopes (EIA) and RFLP for N and G genes. RESULTS: No differences in HRSV groups A/B and in N patterns distribution were observed among both hospitals. On the contrary, antigenic and genetic G patterns displayed a wide diversity of strains circulating during one epidemic, in one big city. CONCLUSIONS: RSV variability assessment depended rather on the tool used for analysis than on the geographical location.

Detection of Mycoplasma pneumoniae in adult community-acquired pneumonia by PCR and serology.

Diagnosis of pneumonia caused by Mycoplasma pneumoniae in adults is hampered by a lack of rapid and standardized tests for detection. This prospective study was conducted to compare the diagnostic values of an indirect immunofluorescence assay and a 16S rRNA gene PCR for the diagnosis of M. pneumoniae pneumonia in adults. From February 2005 to January 2008, 357 patients (53.8 % males, median age 63 years, range 18-94) admitted for community-acquired pneumonia (CAP) to two hospitals in Santiago, Chile, were enrolled in the study. Thirty-two patients (9.0 %) met the criteria of current or recent M. pneumoniae infection, and laboratory diagnosis was definitive in 26 cases (81.2 %) and presumptive in six cases (18.8 %). Among the 32 M. pneumoniae infections, the PCR assay was positive in 23 (71.9 %) and the serology in 27 (84.4 %) of the cases. IgM was positive in acute-phase serum specimens in 13 cases (40.6 %) of M. pneumoniae infections. Using serology as the gold standard, the sensitivity, specificity, and positive and negative predictive values of the PCR were 66.7, 98.5, 78.3 and 97.3 %, respectively, whereas the global agreement of the methods was 343/357 (96.1 %). The frequency of M. pneumoniae CAP cases declined significantly during the second year of study, suggesting the end of an epidemic period. In conclusion, although good global agreement was found between PCR and serology, the lower sensitivity of the PCR leads us to recommend the use of both procedures in parallel to confirm M. pneumoniae in CAP in adults.

[Cytomegalovirus disease in HIV-1 infected Chilean children]. / Enfermedad por citomegalovirus en niños chilenos infectados por el virus de la inmunodeficiencia humana-1.

UNLABELLED: 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.

Recomendación del Comité Asesor de Vacunas y Estrategias de Inmunización (CAVEI) sobre vacunación contra viruela símica en Chile

La viruela del mono fue declarada emergencia de salud pública de importancia internacional por la Organización Mundial de la Salud el año 2022. En Chile, hasta septiembre se han confirmado sobre 450 enfermos, mayoritariamente hombres jóvenes. Este poxvirus zoonótico se transmite entre humanos por contacto estrecho; la enfermedad es autolimitada y puede ser fatal en inmunocomprometidos. La prevención mediante inmunización es importante. MVA-BN es una de las tres vacunas disponibles, de 3° generación, contiene el virus vaccinia atenuado, no replicante por lo que se puede administrar a pacientes inmunocomprometidos y mujeres embarazadas y está aprobada para viruela símica en personas > 18 años. La información disponible sobre eficacia y efectividad es limitada. El CAVEI recomienda incorporar esta vacuna para interrumpir la cadena de transmisión y reducir el riesgo de enfermedad grave, en dos dosis separadas por 28 días, por vía subcutánea, priorizando el uso post-exposición para contactos estrechos con riesgo de enfermedad grave, idealmente en los primeros 4 días y hasta 14 días post contacto de riesgo y en ausencia de síntomas. Cuando el suministro de vacunas lo permita, se recomienda prevención pre-exposición para personas con alto riesgo ocupacional o por prácticas sexuales. Esta recomendación podría modificarse según la epidemiología, el suministro de vacunas y nueva información científica.

Monkeypox was declared a public health emergency of international concern by the World Health Organization during 2022. In Chile, over 450 patients have been confirmed until September, mostly young men. This zoonotic poxvirus is transmitted from humans to humans through close contact; it is a self-limiting disease and can be fatal in people with immunodeficiency. Prevention by immunization is important. MVA-BN, one of the three vaccines available, it is a third generation vaccine, based on non-replicating modified vaccinia virus, therefore can be administered to immunocompromised patients and pregnant women and it has been approved for monkeypox in people over 18 years of age. The available information on efficacy and effectiveness is limited. The CAVEI recommends incorporating this vaccine to interrupt the chain of transmission and reduce the risk of severe disease, administered subcutaneously in two doses, 28 days apart, prioritizing post exposure use for close contacts of confirmed cases with risk of severe disease, ideally within 4 days of exposure and it can be used up to 14 days after exposure and in the absence of symptoms. When the vaccine supply allows it, its application is recommended as pre-exposure prevention for people with high-risk sexual practices or with occupational risk. This recommendation could be modified according to epidemiology, vaccines supply and new scientific information.

Rendimiento de dos índices predictores de mortalidad (PSI y CURB-65) en pacientes adultos inmunocompetentes hospitalizados por neumonía adquirida en la comunidad / Yield of two mortality predictors in immunocompetent patients with community acquired pneumonia

Background: The severity of community acquired pneumonia (CAP) can be evaluated by the PSI and CURB-65 scales. However, it is unknown whether their predictive capacity varies according to the etiology of the disease. Aim: To compare the performance of these scales in adults with viral, bacterial, mixed, and no agent detected CAP. Material and Methods: We studied 725 patients hospitalized for CAP aged 18 to 95 years (47% females) Urinary S. pneumoniae and Legionella antigens were detected by immuno-chromatography (Binax®). Respiratory viruses and bacteria were detected by PCR in nasopharyngeal smears. The proportions of deaths, admission to the intensive care unit (ICU), and oxygen therapy were compared between mild and non-severe patients defined by PSI (I/II and I-III) and CURB-65 (1 and 1-2), according to the causative agent. Results: Ten percent of patients died. A causative agent was detected in 65%. The proportion of mild and non-severe patients according to PSI and CURB-65, and of deceased patients, admitted to the ICU and with oxygen therapy was similar in the four categories per agent. There were no deaths among non-severe patients with bacterial CAP. However, 6% of patients with CAP caused by virus or without causative agents, died. No deaths occurred among mild patients with bacterial CAP. In viral CAP, no deaths occurred among patients classified as mild only by PSI. The yields of PSI were greater than those of CURB-65 in non-severe patients who died and were admitted to the ICU with bacterial and viral CAP (5 and 14%; 7 and 12% respectively, p = 0.04). Conclusions: The prognostic performance of PSI in CAP varies according to the causative agent in adults. It is higher in non-severe bacterial cases, and superior to CURB-65.

[Influenza: the reemergence of an ancient disease and its risk of pandemia]. / Influenza: reemergencia de una antigua enfermedad y el potencial riesgo de una nueva pandemia.

Influenza is a seasonally, acute respiratory disease, highly transmissible. The diversity of the natural reservoirs of influenza A virus and its faculty of reassortment increase the risk of a new pandemia. Prevention strategies during the outbreaks include vaccination indicated to risk population as infants between 6 to 2 years old, persons above 65 years old, pregnant women and patients with underlying diseases. Antiviral prophylaxis is useful to control small outbreaks and to be used in household contacts of risk population who have not been vaccinated. Antiviral drugs as a treatment should be considered in persons with severe disease. During a pandemia these prevention measures must be reinforced and rational use of antiviral drugs and vaccine with the pandemic strain should be emphasized.

[Antigenemia and real time polymerase chain reaction for diagnosis of cytomegalovirus disease in HIV infected adults]. / Antigenemia y reacción de polimerasa en cadena en tiempo real en el diagnóstico de enfermedad por citomegalovirus en adultos con virus de inmunodeficiencia adquirida.

BACKGROUND: Cytomegalovirus (CMV) infection is frequent in HIV adults. It is unknown usefulness of quantitative methods for diagnosing the CMV disease in Chilean patients. AIM: To determine the performance of antigenemia and real time polymerase chain reaction (rtPCR) in the diagnosis of CMV disease in Chilean HIV adults. METHOD: Detection of CMV by viral isolation (AVR), antigenemia and quantitative rtPCR in HIV adults. RESULTS: The 102 adults with suspected CMV disease had lower LTCD4 count and higher HIV viral load than 77 patients without suspicion (p < 0.05). Antigenemia and PCR were positive in 47 (46.1%) and 37 (36.3%) adults with clinical suspicion and in 2 (2.6%) and 4 (5.2%) of 77 without suspicion. The sensitivity, specificity, positive and negative predictive value of antigenemia and RPCtr were 92%, 80%, 72% and 95% and 72%, 95%, 92% and 80%, respectively. The cutoff values were ≥ lcell (+) and ≥ 5.5 log10 copies/2 x 10(6) cells. CMV was isolated in 6/179 patients (3.4%), all symptomatic. CONCLUSION: Positivity of antigenemia and rtPCR are similar for diagnosing CMV disease in Chilean HIV adults. AVR is inappropriate as a gold standard for its low performance.

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.