Pediatric Acute Respiratory Infections Research Articles

PIX-6 Detection of BK-JC viruses in immunocompromised patients using real-time PCR in a university hospital, Ankara, Turkey

Acute respiratory tract infections (ARI) present a significant morbidity and pose a global health burden. Patients are frequently treated with antibiotics although ARI are most commonly caused by virus, strengthening the need for improved diagnostic methods.Detect viral and bacterial RNA in nasopharyngeal aspirates (NPA) from children aged 6–23 months with ARI using nCounter.A custom-designed nCounter probeset containing viral and bacterial targets was tested in NPA of ARI patients.Initially, spiked control viral RNAs were detectable in ≥6.25 ng input RNA, indicating absence of inhibitors in NPA. nCounter applied to a larger NPA sample (n = 61) enabled the multiplex detection of different pathogens: RNA viruses Parainfluenza virus (PIV 1–3) and RSV A-B in 21%, Human metapneumovirus (hMPV) in 5%, Bocavirus (BoV), CoV, Influenza virus (IV) A in 3% and, Rhinovirus (RV) in 2% of samples, respectively. RSV A-B was confirmed by Real Time PCR (86.2–96.9% agreement). DNA virus (AV) was detected at RNA level, reflecting viral replication, in 10% of samples. Bacterial transcripts from Staphylococcus aureus, Haemophilus influenzae, Streptococcus pneumoniae, Moraxella catarrhalis, Mycoplasma pneumoniae and Chlamydophila pneumoniae were detected in 77, 69, 26, 8, 3 and 2% of samples, respectively.nCounter is robust and sensitive for the simultaneous detection of viral (both RNA and DNA) and bacterial transcripts in NPA with low RNA input (<10 ng). This medium-throughput technique will increase our understanding of ARI pathogenesis and may provide an evidence-based approach for the targeted and rational use of antibiotics in pediatric ARI.

Antibiotics and paediatric acute respiratory infections in rural Vietnam: health‐care providers’ knowledge, practical competence and reported practice

To assess knowledge, practical competence and reported practices among health-care providers about antibiotics to treat acute respiratory infections in children under five in rural Vietnam. Health-care providers prescribing or dispensing western drugs for children self-completed a structured questionnaire. Recommendations concerning antibiotic use from WHO and national guidelines were used to assess the appropriateness of reported treatment of acute respiratory infections. Ninety-six per cent of 409 eligible health care providers participated. Only 27% demonstrated correct knowledge regarding the consequences of resistance. Seventy-nine per cent would use antibiotics for common colds with fever, and 21% in cases with no fever. Nineteen per cent had overall knowledge compliant with recommended guidelines. Stated antibiotic use in written scenarios for common colds (81%) was not significantly different from that for non-referral cases of pneumonia (87%). The proportion of antibiotic use in the common cold scenario was significantly lower among health-care providers who had the correct overall knowledge. According to reported symptoms from the most recent encounter with a sick child, the diseases seen were 62% mild acute respiratory infections, 19% severe, and 19% non-respiratory infections. Among those, antibiotics, most commonly beta-lactams, were used in 90%, 87% and 78% of cases, respectively. Antibiotics are often prescribed or dispensed to treat common colds. Interventions to change prescribing and dispensing practices should be developed and implemented in collaboration with local and national paediatricians. Continuous training of health-care providers, particularly drug sellers, is important.

Frequent detection of human rhinoviruses, paramyxoviruses, coronaviruses, and bocavirus during acute respiratory tract infections

Viruses are the major cause of pediatric acute respiratory tract infection (ARTI) and yet many suspected cases of infection remain uncharacterized. We employed 17 PCR assays and retrospectively screened 315 specimens selected by season from a predominantly pediatric hospital‐based population. Before the Brisbane respiratory virus research study commenced, one or more predominantly viral pathogens had been detected in 15.2% (n = 48) of all specimens. The Brisbane study made an additional 206 viral detections, resulting in the identification of a microbe in 67.0% of specimens. After our study, the majority of microbes detected were RNA viruses (89.9%). Overall, human rhinoviruses (HRVs) were the most frequently identified target (n = 140) followed by human adenoviruses (HAdVs; n = 25), human metapneumovirus (HMPV; n = 18), human bocavirus (HBoV; n = 15), human respiratory syncytial virus (HRSV; n = 12), human coronaviruses (HCoVs; n = 11), and human herpesvirus‐6 (n = 11). HRVs were the sole microbe detected in 37.8% (n = 31) of patients with suspected lower respiratory tract infection (LRTI). Genotyping of the HRV VP4/VP2 region resulted in a proposed subdivision of HRV type A into sublineages A1 and A2. Most of the genotyped HAdV strains were found to be type C. This study describes the high microbial burden imposed by HRVs, HMPV, HRSV, HCoVs, and the newly identified virus, HBoV on a predominantly paediatric hospital population with suspected acute respiratory tract infections and proposes a new formulation of viral targets for future diagnostic research studies. J. Med. Virol. 78:1232–1240, 2006. © 2006 Wiley‐Liss, Inc.

Effects of Nonstructural Proteins NS1 and NS2 of Human Respiratory Syncytial Virus on Interferon Regulatory Factor 3, NF-κB, and Proinflammatory Cytokines

Human respiratory syncytial virus (HRSV) is the leading cause of serious pediatric acute respiratory tract infections, and a better understanding is needed of the host response to HRSV and its attenuated vaccine derivatives. It has been shown previously that HRSV nonstructural proteins 1 and 2 (NS1 and NS2) inhibit the induction of alpha/beta interferon (IFN-alpha/beta) in A549 cells and human macrophages. Two principal transcription factors for the early IFN-beta and -alpha1 response are interferon regulatory factor 3 (IRF-3) and nuclear factor kappaB (NF-kappaB). At early times postinfection, wild-type HRSV and the NS1/NS2 deletion mutants were very similar in the ability to activate IRF-3. However, once NS1 and NS2 were expressed significantly, they acted cooperatively to suppress activation and nuclear translocation of IRF-3. Since these viruses differed greatly in the induction of IFN-alpha/beta, NF-kappaB activation was evaluated in Vero cells, which lack the structural genes for IFN-alpha/beta and would preclude confounding effects of IFN-alpha/beta. This showed that deletion of the NS2 gene sharply reduced the ability of HRSV to induce activation of NF-kappaB. Since recombinant HRSVs from which the NS1 or NS2 genes have been deleted are being developed as vaccine candidates, we investigated whether the changes in activation of host transcription factors and increased IFN-alpha/beta production had an effect on the epithelial production of proinflammatory factors. Viruses lacking NS1 and/or NS2 stimulated modestly lower production of RANTES (Regulated on Activation Normal T-cell Expressed and Secreted), interleukin 8, and tumor necrosis factor alpha compared to wild-type recombinant RSV, supporting their use as attenuated vaccine candidates.

Outdoor air pollution and acute respiratory infections among children in developing countries.

Acute respiratory infections (ARIs) are the most common cause of illness and death in children in the developing world. This review focuses on outdoor air pollutants associated with pediatric ARI mortality and morbidity. Studies were identified using MEDLINE and other electronic databases. Four studies showed an increase in infant mortality in relation to outdoor air pollution. Short-term follow-up and time-series studies suggest that air pollutants act as risk factors for respiratory infection. Air pollution exposure increases the incidence of upper- and lower-respiratory infections in children. Because complex pollution mixtures are present in the studied urban areas, pollutant levels at which ARI risk would be expected to increase cannot be determined. Children may be at greater risk, given the poor environmental and nutritional conditions prevalent in developing countries.