Otávio A. L. Cintra

Severe lower respiratory tract infection in infants and toddlers from a non-affluent population: viral etiology and co-detection as risk factors

BackgroundLower respiratory tract infection (LRTI) is a major cause of pediatric morbidity and mortality, especially among non-affluent communities. In this study we determine the impact of respiratory viruses and how viral co-detections/infections can affect clinical LRTI severity in children in a hospital setting.MethodsPatients younger than 3 years of age admitted to a tertiary hospital in Brazil during the months of high prevalence of respiratory viruses had samples collected from nasopharyngeal aspiration. These samples were tested for 13 different respiratory viruses through real-time PCR (rt-PCR). Patients were followed during hospitalization, and clinical data and population characteristics were collected during that period and at discharge to evaluate severity markers, especially length of hospital stay and oxygen use. Univariate regression analyses identified potential risk factors and multivariate logistic regressions were used to determine the impact of specific viral detections as well as viral co-detections in relation to clinical outcomes.ResultsWe analyzed 260 episodes of LRTI with a viral detection rate of 85% (n = 222). Co-detection was observed in 65% of all virus-positive episodes. The most prevalent virus was Respiratory Syncytial Virus (RSV) (54%), followed by Human Metapneumovirus (hMPV) (32%) and Human Rhinovirus (HRV) (21%). In the multivariate models, infants with co-detection of HRV + RSV stayed 4.5 extra days (p = 0.004), when compared to infants without the co-detection. The same trends were observed for the outcome of days of supplemental oxygen use.ConclusionsAlthough RSV remains as the main cause of LRTI in infants our study indicates an increase in the length of hospital stay and oxygen use in infants with HRV detected by RT-PCR compared to those without HRV. Moreover, one can speculate that when HRV is detected simultaneously with RSV there is an additive effect that may be reflected in more severe clinical outcome. Also, our study identified a significant number of children infected by recently identified viruses, such as hMPV and Human Bocavirus (HBov), and this is a novel finding for poor communities from developing countries.

Detection of Human Bocavirus mRNA in Respiratory Secretions Correlates with High Viral Load and Concurrent Diarrhea

Human bocavirus (HBoV) is a parvovirus recently identified in association with acute respiratory infections (ARI). Despite its worldwide occurrence, little is known on the pathogenesis of HBoV infections. In addition, few systematic studies of HBoV in ARI have been conducted in Latin America. Therefore, in order to test whether active viral replication of human bocavirus is associated with respiratory diseases and to understand the clinical impact of this virus in patients with these diseases, we performed a 3-year retrospective hospital-based study of HBoV in outpatients and inpatients with symptoms of Acute Respiratory Infections (ARI) in Brazil. Nasopharyngeal aspirates (NPAs) from 1015 patients with respiratory symptoms were tested for HBoV DNA by PCR. All samples positive for HBoV were tested by PCR for all other respiratory viruses, had HBoV viral loads determined by quantitative real time PCR and, when possible, were tested by RT-PCR for HBoV VP1 mRNA, as evidence of active viral replication. HBoV was detected in 4.8% of patients, with annual rates of 10.0%, 3.0% and 3.0% in 2005, 2006 and 2007, respectively. The range of respiratory symptoms was similar between HBoV-positive and HBoV-negative ARI patients. However, a higher rate of diarrhea was observed in HBoV-positive patients. High HBoV viral loads (>108 copies/mL) and diarrhea were significantly more frequent in patients with exclusive infection by HBoV and in patients with detection of HBoV VP1 mRNA than in patients with viral co-infection, detected in 72.9% of patients with HBoV. In summary, our data demonstrated that active HBoV replication was detected in a small percentage of patients with ARI and was correlated with concurrent diarrhea and lack of other viral co-infections.

Human bocavirus respiratory infections in children.

Human bocavirus (HBoV) was recently identified in respiratory samples from patients with acute respiratory infections and has been reported in different regions of the world. To the best of our knowledge, HBoV has never been reported in respiratory infections in Brazil. Nasopharyngeal aspirates were collected from patients aged <5 years hospitalized in 2005 with respiratory infections in Ribeirão Preto, southeast Brazil, and tested by polymerase chain reaction (PCR) for HBoV. HBoV-positive samples were further tested by PCR for human respiratory syncytial virus, human metapneumovirus, human coronaviruses 229E and OC43, human influenza viruses A and B, human parainfluenza viruses 1, 2 and 3, human rhinovirus and human adenovirus. HBoV was detected in 26/248 (10.5%) children of which 21 (81%) also tested positive for other respiratory viruses. Despite the high rates of co-infections, no significant differences were found between HBoV-positive patients with and without co-infections with regard to symptoms.

Nasopharyngeal colonization with Streptococcus pneumoniae in children infected with human immunodeficiency virus

OBJECTIVES To determine the prevalence of pneumococcus colonization among HIV-infected outpatients aged 0 to 18 years. To determine the resistance to penicillin of the microorganisms observed, to identify their serotypes, and to determine whether there are associations between known risk factors and colonization in this group. MATERIAL AND METHOD This was an observational and cross-sectional study in which nasopharynx swabs were collected from 112 children on the occasion of their monthly appointments and a questionnaire applied to the mothers. The material collected was processed at the microbiology laboratory of the hospital in accordance with National Committee for Clinical Laboratory Standards (NCCLS) regulations and serotyping was performed at the Centers for Diseases Control and Prevention (CDC). Data were analyzed statistically using the chi-square test and with univariate and multivariate analysis with multiple logistic regression. RESULTS The prevalence rate of nasopharyngeal colonization by pneumococci was 28.6%, with a 15.6% rate of resistance to penicillin (6.2% intermediate resistance and 9.4% full resistance). The serotypes identified were 6A, 6B, 7C, 9V, 11A, 13, 14, 15A, 16F, 18C, 19B, 19F, 23B, 23F, and 34. In this population there were no associations between pneumococcal colonization and the risk factors studied. CONCLUSIONS The prevalence of pneumococcal colonization among HIV-infected children at our service was not higher than prevalence rates observed in healthy children and reported in the literature.

Colonização nasofaríngea por Streptococcus pneumoniae em crianças com infecção pelo vírus da imunodeficiência humana

OBJECTIVE: To determine the prevalence of pneumococcus colonization among HIV-infected outpatients aged 0 to 18 years. To determine the resistance to penicillin of the microorganisms observed, to identify their serotypes, and to determine whether there are associations between known risk factors and colonization in this group. MATERIAL AND METHOD: This was an observational and cross-sectional study in which nasopharynx swabs were collected from 112 children on the occasion of their monthly appointments and a questionnaire applied to the mothers. The material collected was processed at the microbiology laboratory of the hospital in accordance with National Committee for Clinical Laboratory Standards (NCCLS) regulations and serotyping was performed at the Centers for Diseases Control and Prevention (CDC). Data were analyzed statistically using the chi-square test and with univariate and multivariate analysis with multiple logistic regression. RESULTS: The prevalence rate of nasopharyngeal colonization by pneumococci was 28.6%, with a 15.6% rate of resistance to penicillin (6.2% intermediate resistance and 9.4% full resistance). The serotypes identified were 6A, 6B, 7C, 9V, 11A, 13, 14, 15A, 16F, 18C, 19B, 19F, 23B, 23F, and 34. In this population there were no associations between pneumococcal colonization and the risk factors studied. CONCLUSIONS: The prevalence of pneumococcal colonization among HIV-infected children at our service was not higher than prevalence rates observed in healthy children and reported in the literature.

Safety, immunogenicity and efficacy of influenza vaccine in children.

OBJECTIVES To review the immunogenicity, safety and efficacy of inactivated and attenuated trivalent influenza vaccines in children. SOURCES OF DATA Database search of the medical literature indexed on MEDLINE, LILACS and in the Cochrane Library. Review articles, clinical trials and epidemiological studies published from 1990 to 2006 were selected for analysis. SUMMARY OF THE FINDINGS Influenza is an infectious disease that is both universal and seasonal, with incidence in all age groups and annual epidemics characterized by excessive morbidity and mortality. The elderly and people with comorbidity are high risk groups for severe influenza. It has recently been proven that healthy infants suffer similar morbidity to other risk groups, and therefore vaccination against influenza is indicated for them too, as being the most effective means of preventing infection by the influenza virus. The safety of influenza vaccines in children appears adequate, with the most often observed adverse effects being local reactions or fever. Immunogenicity in children varies from 30 to 90%, being directly proportional to age. Efficacy depends on the primary objective and can range from levels comparable with placebo to up to 91% efficacy against confirmed influenza A infection. Schoolchildren play an important role in the dissemination of the influenza virus, and population studies have demonstrated herd immunity. CONCLUSIONS Trivalent influenza vaccines, whether inactivated or attenuated, have low reactogenicity and offer variable immunogenicity and efficacy in children. Vaccination is effective for prevention of infections by the influenza virus and for reducing morbidity. More powerful studies of efficacy and safety in infants are still required.

Concurrent detection of other respiratory viruses in children shedding viable human respiratory syncytial virus.

Human respiratory syncytial virus (HRSV) is an important cause of respiratory disease. The majority of studies addressing the importance of virus co‐infections to the HRSV‐disease have been based on the detection of HRSV by RT‐PCR, which may not distinguish current replication from prolonged shedding of remnant RNA from previous HRSV infections. To assess whether co‐detections of other common respiratory viruses are associated with increased severity of HRSV illnesses from patients who were shedding viable‐HRSV, nasopharyngeal aspirates from children younger than 5 years who sought medical care for respiratory infections in Ribeirão Preto (Brazil) were tested for HRSV by immunofluorescence, RT‐PCR and virus isolation in cell culture. All samples with viable‐HRSV were tested further by PCR for other respiratory viruses. HRSV‐disease severity was assessed by a clinical score scale. A total of 266 samples from 247 children were collected and 111 (42%) were HRSV‐positive. HRSV was isolated from 70 (63%), and 52 (74%) of them were positive for at least one additional virus. HRSV‐positive diseases were more severe than HRSV‐negative ones, but there was no difference in disease severity between patients with viable‐HRSV and those HRSV‐positives by RT‐PCR. Co‐detection of other viruses did not correlate with increased disease severity. HRSV isolation in cell culture does not seem to be superior to RT‐PCR to distinguish infections associated with HRSV replication in studies of clinical impact of HRSV. A high rate of co‐detection of other respiratory viruses was found in samples with viable‐HRSV, but this was not associated with more severe HRSV infection. J Med. Virol. 85:1852–1859, 2013.

[Vaccination and the respiratory tract--what should we know?].

Objective: this article aims at presenting a review of the main vaccines used in the pediatric population with direct impact on the prevention of infectious processes of the respiratory tract in children. Sources: data from articles published in national and international scientific journals. The data were selected by means of direct search or search in the Lilacs and Medline databases. Summary of the findings: this article was structured in topics, presenting issues related to immunization against frequent pathogens of the respiratory tract in human beings: Haemophilus influenza, influenza virus, respiratory syncytial virus and Streptococcus pneumoniae. Conclusions: the prevention of respiratory diseases through immunization is one of the main measures for the control of respiratory infection. These new vaccines, especially against Haemophilus influenza, have been available for some years with acknowledged efficacy. Now, the vaccine against Streptococcus pneumoniae (heptavalent vaccine) leads to a new perspective towards the management of respiratory diseases in children. In risk populations, the control of viral diseases through immunization, actively against the influenza virus and passively against the syncytial respiratory virus, is also an efficient measure to reduce respiratory disease.

Segurança, imunogenicidade e eficácia da vacina contra o vírus influenza em crianças

OBJECTIVES:To review the immunogenicity, safety and efficacy of inactivated and attenuated trivalent influenza vaccines in children. SOURCES OF DATA: Database search of the medical literature indexed on MEDLINE, LILACS and in the Cochrane Library. Review articles, clinical trials and epidemiological studies published from 1990 to 2006 were selected for analysis. SUMMARY OF THE FINDINGS: Influenza is an infectious disease that is both universal and seasonal, with incidence in all age groups and annual epidemics characterized by excessive morbidity and mortality. The elderly and people with comorbidity are high risk groups for severe influenza. It has recently been proven that healthy infants suffer similar morbidity to other risk groups, and therefore vaccination against influenza is indicated for them too, as being the most effective means of preventing infection by the influenza virus. The safety of influenza vaccines in children appears adequate, with the most often observed adverse effects being local reactions or fever. Immunogenicity in children varies from 30 to 90%, being directly proportional to age. Efficacy depends on the primary objective and can range from levels comparable with placebo to up to 91% efficacy against confirmed influenza A infection. Schoolchildren play an important role in the dissemination of the influenza virus, and population studies have demonstrated herd immunity. CONCLUSIONS: Trivalent influenza vaccines, whether inactivated or attenuated, have low reactogenicity and offer variable immunogenicity and efficacy in children. Vaccination is effective for prevention of infections by the influenza virus and for reducing morbidity. More powerful studies of efficacy and safety in infants are still required.