Multilevel analysis of childhood nonviral gastroenteritis associated with environmental risk factors in Quebec, 1999-2006.

Childhood nonviral gastroenteritis is a priority for various public health authorities. Given that waterborne transmission is sometimes incriminated during investigation of gastroenteritis outbreaks, the authors hypothesized that watershed characteristics may influence the occurrence of this disease and could contribute additional insights for better prevention and control. The study described here aimed to investigate watershed characteristics in relation to nonviral gastroenteritis and specifically three bacterial and parasitic forms of childhood gastroenteritis to assess their relative importance in the province of Quebec, Canada. Information on children aged 0-4 years with bacterial or parasitic enteric infections reported through ongoing surveillance between 1999 and 2006 in the province of Quebec was collected. Factors measured at the municipal and watershed levels were analyzed using multilevel models with a Poisson distribution and log link function. Childhood nonviral gastroenteritis, giardiasis, and campylobacteriosis were positively associated with small ruminants and cattle density. Childhood salmonellosis was positively associated with cattle density. Also, childhood campylobacteriosis incidence was positively associated with larger watershed agricultural surface. In addition to local agroenvironmental factors, this analysis revealed an important watershed effect.

Molecular evolution of respiratory syncytial virus fusion gene, Canada, 2006-2010.

To assess molecular evolution of the respiratory syncytial virus (RSV) fusion gene, we analyzed RSV-positive specimens from 123 children in Canada who did or did not receive RSV immunoprophylaxis (palivizumab) during 2006-2010. Resistance-conferring mutations within the palivizumab binding site occurred in 8.7% of palivizumab recipients and none of the nonrecipients.

Molecular characterization of rotavirus isolates from select Canadian pediatric hospitals.

BACKGROUND: We report the first multi-site rotavirus genotype analysis in Canada. Prior to this study, there was a dearth of rotavirus G and P genotyping data in Canada. Publically funded universal rotavirus vaccination in Canada started in 2011 and has been introduced by four provinces to date. Uptake of rotavirus vaccines in Canada prior to 2012 has been very limited. The aim of this study was to describe the genotypes of rotavirus strains circulating in Canada prior to widespread implementation of rotavirus vaccine by genotyping samples collected from selected paediatric hospitals. Secondly we identified rotavirus strains that differed genetically from those included in the vaccines and which could affect vaccine effectiveness. METHODS: Stool specimens were collected by opportunity sampling of children with gastroenteritis who presented to emergency departments. Samples were genotyped for G (VP7) genotypes and P (VP4) genotypes by hemi-nested multiplex PCR methods. Phylogenetic analysis was carried out on Canadian G9 strains to investigate their relationship to G9 strains that have circulated in other regions of the world. RESULTS: 348 samples were collected, of which 259 samples were rotavirus positive and genotyped. There were 34 rotavirus antigen immunoassay negative samples genotyped using PCR-based methods. Over the four rotavirus seasons, 174 samples were G1P[8], 45 were G3P[8], 22 were G2P[4], 13 were G9P[8], 3 were G4P[8] and 2 were G9P[4]. Sequence analysis showed that all Canadian G9 isolates are within lineage III. CONCLUSIONS: Although a limited number of samples were obtained from a median of 4 centres during the 4 years of the study, it appears that currently approved rotavirus vaccines are well matched to the rotavirus genotypes identified at these hospitals. Further surveillance to monitor the emergence of rotavirus genotypes in Canada is warranted.

Antibiotic use in children is not influenced by the result of rapid antigen detection test for the respiratory syncytial virus.

BACKGROUND: Rapid antigen detection test (RADT) for respiratory syncytial virus (RSV) is widely used in children hospitalized with acute respiratory tract infection (ARTI), but its influence on antibiotic (AB) use is uncertain. OBJECTIVE: To evaluate if confirmation of RSV infection by RADT modified AB use and elucidate others factors associated with the continuation of antibiotics. STUDY DESIGN: Charts of children hospitalized with viral ARTI aged 0-35 months were reviewed. Modification of antibiotics according to RSV RADT results was compared using Kaplan-Meier estimates and multivariate Cox regression. RESULTS: Of children receiving antibiotics when the RSV RADT result was available, RSV RADT was positive in 144 and negative in 54. Positive RSV RADT results did not lead to modification of antibiotic use. Factors independently associated with cessation of intravenous antibiotics were age > or = 3 months (HR 2.44 [1.41-4.21]) and absence of pneumonia (HR 1.50 [1.03-2.19]). Absence of otitis was associated with cessation of oral antibiotics (HR 9.16 [95% CI, 2.35-35.76]). CONCLUSION: Confirmed presence of RSV by RADT did not influence antibiotic use in young children with ARTI. Except with pneumonia, the risk of bacterial superinfection of RSV infected children is minimal and confirmation of RSV infection should prompt treating physicians to interrupt antibiotics.

Infections by human coronavirus-NL in hospitalized children.

BACKGROUND: A new human coronavirus (HCoV), HCoV-NL, was recently reported for Dutch patients with acute respiratory tract infections (ARTI). Little information is available on the incidence, clinical manifestations and epidemiologic features of HCoV-NL infections. METHODS: We performed a prospective study of symptomatic (case subjects with ARTI) and asymptomatic (control subjects undergoing elective surgery) children,

Invasive Haemophilus influenzae type b infections in vaccinated and unvaccinated children in Canada, 2001-2003.

BACKGROUND: Although vaccination of infants against Haemophilus influenzae type b (Hib) invasive infections is effective and has been routinely available in Canada since 1992, cases of the disease continue to occur. We were interested in determining whether recent cases of Hib infection reflected progressive loss of protection with time since vaccination, increasing nonacceptance of vaccination or a deleterious effect of coadministration of recently introduced vaccines such as those for pneumococcal and meningococcal conjugates and hepatitis B. We report on the causes of Hib infections among vaccinated and unvaccinated children between 2001 and 2003 in Canada. METHODS: Through our established network of 12 pediatric tertiary care hospitals we actively searched for cases in each centre by reviewing daily admissions and laboratory reports, visiting the wards and checking discharge diagnosis codes. Culture-confirmed cases were summarized by nurse monitors using a standardized reporting system. RESULTS: We identified 29 cases during the 3 years: 16 in 2001, 10 in 2002 and 3 in 2003. Half of the 29 patients had meningitis. Hib infection was more common among children less than 6 months of age (11 cases) and in boys (20 cases). Two deaths occurred (7% case-fatality ratio). A total of 20 children had received no or incomplete primary vaccination because of parental refusal (7 cases), because they were too young to have completed the primary series (11 cases, including 1 in which parental refusal was also a factor) or because of delays in completing the primary series (2 cases); the vaccination history was uncertain in the remaining case. Infection despite primary vaccination occurred in 9 children: 2 previously healthy children and 7 who were immunocompromised or who had a predisposing condition. None of the cases identified in 2003 involved children who had received any of the newly introduced vaccines. INTERPRETATION: Invasive Hib infections remain rare in Canada, with most cases occurring in children too young to have completed the primary series. Protection after vaccination appears to extend into later childhood and does not appear to be diminished by coadministration of newer infant vaccines.

Mutation of rpiA in Enterobacter cloacae decreases seed and root colonization and biocontrol of damping-off caused by Pythium ultimum on cucumber.

Strains of Enterobacter cloacae show promise as biocontrol agents for Pythium ultimum-induced damping-off on cucumber and other crops. E. cloacae A145 is a mini-Tn5 Km transposon mutant of strain 501R3 that was significantly reduced in suppression of damping-off on cucumber caused by P. ultimum. Strain A145 was deficient in colonization of cucumber, sunflower, and wheat seeds and significantly reduced in colonization of corn and cowpea seeds relative to strain 501R3. Populations of strain A145 were also significantly lower than those of strain 501R3 at all sampling times in cucumber, wheat, and sunflower rhizosphere. Populations of strain A145 were not detectable in any rhizosphere after 42 days, while populations of strain 501R3 remained at substantial levels throughout all experiments. Molecular characterization of strain A145 indicated mini-Tn5 Km was inserted in a region of the E. cloacae genome with a high degree of DNA and amino acid sequence similarity to rpiA, which encodes ribose-5-phosphate isomerase. In Escherichia coli, RpiA catalyzes the interconversion of ribose-5-phosphate and ribulose-5-phosphate and is a key enzyme in the pentose phosphate pathway. Ribose-5-phosphate isomerase activity in cell lysates from strain A145 was approximately 3.5% of that from strain 501R3. In addition, strain A145 was a ribose auxotroph, as expected for an rpiA mutant. Introduction of a 1.0-kb DNA fragment containing only the rpiA homologue into strain A145 restored ribose phosphate isomerase activity, prototrophy, seedling colonization, and disease suppression to levels similar to those associated with strain 501R3. Experiments reported here indicate a key role for rpiA and possibly the pentose phosphate pathway in suppression of damping-off and colonization of subterranean portions of plants by E. cloacae.

Hospitalizations for diarrhea in Quebec children from 1985 to 1998: estimates of rotavirus-associated diarrhea.

OBJECTIVE: To characterize the incidence and duration of hospitalization due to diarrhea and to assess the proportion of hospitalizations that are attributed to rotavirus-associated diarrhea. DESIGN: Retrospective study of hospitalization data. SETTING: Hospitals located in Quebec. POPULATION STUDIED: Children from one to 59 months of age who were discharged from hospital from April 1, 1985 to March 31, 1998. MAIN RESULTS: There were 63,827 hospitalizations for diarrhea over the study period, for an average of 4910 hospitalizations/year. The epidemic curve showed a periodicity with regular alternation of high and low annual peaks. The number of hospitalizations for rotavirus-associated diarrhea was estimated according to three different methods. The estimates varied between 1353 and 1849 hospitalizations due to rotavirus-associated diarrhea/year over the 13-year period, with good agreement between the results of the three methods for a one-month to five years of age incidence of 320 hospitalizations for rotavirus-associated diarrhea/100,000 children. The average duration of hospital stay decreased from 5.2 days in 1985 to 3.3 days in 1998. CONCLUSIONS: The present article shows the importance of diarrhea hospitalizations among children and the alternating peak-year periodicity.

The hidden costs and characteristics of childhood rotavirus emergency visits in Canada.

BACKGROUND: Administrative databases are often used to determine burden of rotavirus disease in emergency departments (EDs). Our objective was to describe rotavirus ED visits to include healthcare utilization pre- and postvisit to estimate true societal costs. METHODS: During rotavirus seasons in 2007, 2008, and 2009, a convenience sample of children <3 years of age with vomiting and/or diarrhea and rotavirus in stool samples at ED visits was identified at 5 pediatric hospitals in Canada. Interviews took place within 24 hours and 2 weeks after diagnosis, and ED charts were reviewed. Using unit costs for all resources, healthcare and societal costs were determined in Canadian dollars. RESULTS: A total of 199 children (mean age, 16 months; range, 1-35 months) had rotavirus and had a completed initial questionnaire on record. Prior healthcare provider visits had occurred in 104 (52.3%) before and 50/172 (29.1%) children 2 weeks after the ED visit. The mean healthcare cost of the ED visit alone was $218.10 (95% confidence interval [CI]: $198, $238), and the mean societal cost was $261.40 (95% CI: $240, $283). Including both total healthcare and parental costs, this increased to a mean total societal cost of $674.80 (95% CI: $578, $771) per episode of rotavirus infection. CONCLUSIONS: Both the pre- and postvisit costs contribute substantially to the societal costs associated with an ED visit for rotavirus infection. In Canada, we estimate that the annual healthcare cost for children requiring a rotavirus ED visit ranges from $4.5 to $9.3 million, but when parental costs are included, the total societal cost ranges from $8.9 to $18.4 million.

A descriptive review of selected nonviral enteric illnesses reported in children in Quebec between 1999 and 2006.

OBJECTIVE: To review the epidemiology of selected nonviral enteric illnesses reported in children in Quebec between 1999 and 2006. METHODS: Incidence rates were calculated to describe age, sex, temporal and geographical characteristics of the selected nonviral enteric cases reported in children who were between zero and four years of age. Standard descriptive methods were used to analyze the temporal and geographical distributions of the incidence rates. RESULTS: A total of 5068 cases were reported. Of these, three pathogens accounted for the majority of the infections: Giardia (32.52%), Salmonella (30.98%) and Campylobacter (30.82%). Salmonella was most frequent in children younger than one year of age, whereas comparable incidence rates for the three pathogens were calculated for children between one and four years of age. For Giardia, the geographical distributions showed that the highest rates were in areas with more than 100,000 inhabitants (except Montreal, Quebec); for Salmonella, the highest rates were in Montreal; and for Campylobacter, the highest rates were in areas with fewer than 10,000 inhabitants. No detectable trends were seen over the study period for the three pathogens. Seasonal summer peaks were noted for Salmonella and Campylobacter, contrasting with late summer to early autumn peaks for Giardia. CONCLUSION: Findings suggest that Giardia, Salmonella and Campylobacter were the most common causes of nonviral enteric illnesses reported in children in Quebec. Giardia cases seemed to arise from different sources and transmission routes than the other two pathogens. Characteristics specific to Campylobacter infections in children, namely its predominance in areas with low population densities, and to Salmonella infections, namely predominance in the Greater Montreal area, should be further investigated to better guide prevention and control measures.

Current trends in nontuberculous mycobacteria infections in Canadian children: A pediatric investigators collaborative network on infections in Canada (PICNIC) study.

BACKGROUND: Nontuberculous mycobacteria (NTM) infections appear to be increasing in number and severity in developed countries worldwide. Surgical excision has been considered the standard treatment for NTM lymphadenitis, but the use of medical therapy seems to be increasing. OBJECTIVE: To determine the disease characteristics as well as the current therapeutic management of NTM infections in Canadian children. METHODS: Cases of definite or probable NTM infections were identified prospectively in children up to 18 years of age seen in 10 Canadian paediatric tertiary care centres from September 2005 to August 2006. Clinical, microbiological and pathological data were collected. RESULTS: A total of 60 cases were identified. Data were complete for 45 patients, including 34 cases of lymphadenitis, four cases of skin and soft tissue infection, and seven cases of pulmonary NTM infection. Seventy-nine per cent of children (27 of 34) with lymphadenitis had an unsuccessful course of antibiotics before diagnosis. Sixty-eight per cent of purified protein derivative tests (15 of 22) were positive. NTM was detected in 76% of samples (29 of 38), of which 62% were Mycobacterium avium complex. All patients with lymphadenitis underwent surgical therapy and most patients (74%) also received antimicrobials. CONCLUSIONS: Current trends indicate that the majority of the study centres are using medical therapy with variable regimen and duration as an adjunct to surgical excision in the treatment of NTM lymphadenitis. Larger numbers and longer follow-up times are needed to better evaluate the efficacy of medical therapy and outcome of disease. A randomized controlled study comparing surgical therapy alone and chemotherapy for NTM lymphadenitis is required.

Distribution and clinical impact of human respiratory syncytial virus genotypes in hospitalized children over 2 winter seasons.

Sequencing studies of the glycoprotein G gene were performed in human respiratory syncytial virus (hRSV) strains detected by reverse-transcription polymerase chain reaction directly from nasopharyngeal aspirates of hospitalized children < or =3 years old over 2 winters. Clinical data were compared between 106 children infected with group A hRSV (96 GA2 genotypes) and 94 children infected with hRSV group B (62 GB3 genotypes). A severity index was defined by assigning 1 point each for the use of >30% supplemental oxygen, admission to an intensive-care unit, and duration of hospital stay of >5 days. Group A and genotype GA2 strains were associated with greater severity of hRSV disease than were group B strains.

Surveillance for influenza admissions among children hospitalized in Canadian immunization monitoring program active centers, 2003-2004.

OBJECTIVES: Influenza is a common childhood infection that may result in hospitalization. Our objectives were to (1) determine characteristics of children hospitalized for influenza and disease manifestations and (2) obtain baseline data before implementation of new recommendations for routine immunization of young children and their caretakers against influenza. METHODS: All of the children hospitalized with laboratory-confirmed influenza at 9 Canadian tertiary care hospitals during the 2003-2004 influenza season were identified from virology laboratory reports, and their charts were reviewed. RESULTS: There were 505 children admitted because of influenza. Fifty-seven percent were < 2 years old. Previously healthy children accounted for 58% of all of the cases. Pulmonary and neurologic disorders were the most common underlying chronic conditions. Fever and cough were the most frequent manifestations. Seizures occurred in 9% of cases. Serious complications included myocarditis (2), encephalopathy (6), and meningitis (1). There were 3 influenza-related deaths. Mean duration of hospitalization was 5.3 days. Twelve percent of children required ICU admission, and 6% required mechanical ventilation. Antibiotic therapy was administered in 77% of cases, and 7% received anti-influenza drugs. Information on influenza vaccination was available for 84 of 154 children identified as vaccine candidates. Twenty two had received vaccine, but only 7 children had been fully immunized > 14 days before the onset of illness. CONCLUSIONS: Healthy young children and children with chronic conditions are at risk for serious illness with influenza. Ongoing surveillance is needed to evaluate the impact of changing immunization recommendations on the burden of influenza illness in children.

Respiratory tract reinfections by the new human Metapneumovirus in an immunocompromised child.

The human Metapneumovirus (HMPV), a new member of the Paramyxoviridae family, has been recently associated with respiratory tract infections in young children. We report the case of a young, immunocompromised child who had severe lower respiratory tract infections during two consecutive winter seasons caused by genetically distinct HMPV strains.

Multiplex real-time PCR assay for detection of influenza and human respiratory syncytial viruses.

A multiplex real-time PCR assay was developed with a LightCycler instrument for detection of influenza viruses A and B and the human respiratory syncytial virus (HRSV). Detection of each viral product and of an internal control was based on determination of specific melting temperatures by the LightCycler software. The lower limit of detection in the multiplex PCR assay was found to be 50 copies for each viral target. In an evaluation of nasopharyngeal samples collected from hospitalized children (ages, 0 to 3 years) with acute respiratory tract infections during the winter of 2001 to 2002, a viral pathogen was detected by the multiplex PCR test in 139 (66.8%) of 208 cases, including 45 (21.6%) influenza A virus infections, no (0%) influenza B virus infections, 106 (51%) HRSV infections, and 12 (5.8%) coinfections. The multiplex PCR test was compared to rapid antigen detection assays for influenza viruses A and B (Directigen; Becton Dickinson, Sparks, Md.) and HRSV (RSV TestPack; Abbott Laboratories, Abbott Park, Ill.) in 172 and 204 samples, respectively. After resolution of discrepant test results by use of additional PCR assays targeting other viral genes, the sensitivity (Se) and specificity (Sp) of the multiplex PCR assay for influenza A virus were 100 and 97.7% compared to 43.6 and 98.5% for the antigenic test. Similarly, the Se and Sp of the multiplex PCR assay for HRSV were 94.5 and 98.9% compared to 81.6 and 94.7% for the antigenic test. In conclusion, our multiplex real-time PCR assay combines both rapidity and sensitivity for detecting the most important respiratory viral pathogens in children.

Human metapneumovirus infections in hospitalized children.

We evaluated the percentage of hospitalizations for acute respiratory tract infections in children < or =3 years of age attributable to human metapneumovirus (HMPV) and other respiratory viruses in a prospective study during winter and spring 2002. We used real-time polymerase chain assays and other conventional diagnostic methods to detect HMPV, human respiratory syncytial virus (HRSV), and influenza viruses in nasopharyngeal aspirates of children. HMPV was detected in 12 (6%) of the 208 children hospitalized for acute respiratory tract infections, HRSV in 118 (57%), and influenza A in 49 (24%). Bronchiolitis was diagnosed in 8 (68%) and pneumonitis in 2 (17%) of HMPV-infected children; of those with HRSV infection, bronchiolitiss was diagnosed in 99 (84%) and pneumonitis in 30 (25%). None of the HMPV-infected children was admitted to an intensive-care unit, whereas 15% of those with HRSV or influenza A infections were admitted. HMPV is an important cause of illness in young children with a similar, although less severe, clinical presentation to that of HRSV.