Viral And Atypical Bacterial Etiology Of593Hospitalized Children With Community Acquired Pneumonia

BackgroundCommunity-acquired pneumonia (CAP) is the most common childhood infectiousdiseases, with high morbidity and mortality in the world. Presently, pneumonia isfigured as one of five major causes of pediatric death in China, there were21.1million new cases of pneumonia in children under five years of age in China annually(0.22episodes/person-year), compared to0.026episodes per child year in developedcountry. Determining the causative agent of pneumonia is a major problem, as manyinvestigators have conducted clinical approach built on patient’s history, clinical signsand symptoms, laboratory tests and radiograph findings, yet, none of them have beenfound to be sufficiently reliable in differential diagnosis between etiology ofpneumonia.In contrast to extensive reports on the management of hospitalized CAP patients,about80%of patients with CAP is still treated empirically. When patients receive adiagnosis of CAP, the therapeutic decision does not acknowledge whether to treat ornot with antibiotics and even in patients who have prescription, it does not reflect theappropriate antibiotic choice related to etiology rather than formed on experience inmost clinical setting. Most CAPs cases are treated with antibiotics withoutconsidering the probable viral etiology in which unnecessary and ineffective antibiotictreatment could be discouraged, as atypical bacteria such as chlamydia pneumoniaeand mycoplasma pneumoniae require specific antibiotic coverage becauseconventional antibiotics used against typical organisms are not effective. Inadequacyof epidemiologic data to help clinicians decide on proper treatment resulting in theincrease of antimicrobial-resistant CAP pathogens, which lead to another worldwide health problem. For above reasons, understanding the epidemiology and clinicalfeatures of CAP in daily clinical practice is essential to improve the diagnosis,management, and prevention of these infections which can reduce the economicburden as a consequence of an excessive and inappropriate antibiotic prescriptions, aswell as decreasing mortality related CAP.Objectives1. To investigate the etiology of CAP-associated respiratory viruses;2. To determine the age distribution and seasonal variation of viral and atypicalbacterial pathogens;3. To identify pathogen-specific clinical characteristics.Methods1. Study populationWe conducted a prospective study of593hospitalized CAP children between1month and≤14years of age. Patients were divided into3groups: infants (1-12months)286patients (48.2%), preschool-aged children (>12months–5years)259patients (43.7%), and school-aged children (>5years–14years)48patients (8.1%).2. Data collection, evaluation and analysisPeripheral blood sample (2ml) was obtained from all patients within the first24hours of admission for routine blood test, blood chemistry tests of liver, cardiac,kidney function, and for detection of inflammation markers. Throat swabs for viraland atypical bacteriological studies were also prospectively collected24hoursfollowing admission for all cases and detection of pathogens was performed inparallel, using multiplex quantitative PCR assays. A positive case was defined as thepresence of any pathogen detected in specimen of a given patient. A patient wasconsidered to have a single infection if only one pathogen was detected in one testedspecimen. In case more than one pathogen detected, patients were considered to haveco-infections. Following admission, information supplemented from a standardizedwritten questionnaire was filled out from each child and during hospitalization, theresults of detailed physical examination of respiratory apparatus, any changes inclinical symptoms, laboratory parameters, complications, and treatment given wererecorded daily for clinical data collection. Day of discharge was recorded to calculatethe length of hospital stay. Pediatric LRTI clinical score for assesment of disease severity including respiratory rate, using of accessory muscle, auscultatory findings,skin color and general condition.Results1. Patients ranged in age between1month and≤14years old with median age of14months. There were67%males and33%females (ratio M:F=2:1). Median agedid not differ significantly between male and female (U=35112, P>0.05). Themedian onset of symptoms before admission was seven days (range from1-160days). The median duration of hospitalization was seven days (range from2-36days).2. Among593CAP patients,367(61.9%) were positive for any respiratorypathogens. A single pathogen was identified in289(48.7%) of593samples andmultiple pathogens in78(13.2%) samples. The most commonly identifiedpathogen was RSV which accounted for133(22.4%) of the whole analyzedpatients. Other pathogens detected were (in descending order of frequency): Inf A(56,9.4%), EV (52,8.8%), ADV (40,6.7%), Mpp (39,6.6%), hCoV (32,5.4%),hBoV (31,5.2%), PIV (29,4.9%), hMPV (25,4.2%), Inf B (24,4%), and Cp (7,1.2%). No specific etiological pathogen was found in another226(38.1%)pneumonia patients. Among593CAP patients,318(53.6%) patients had viralinfection with or without coinfecting other viruses,31(5.2%) patients had soleatypical bacterial infection (including Mpp or Cp) and18(3.0%) of cases wereevidenced as mixed viral/atypical bacterial infection.3. Among289single-infected pathogen patients, the commonest pathogens wereRSV in91cases (15.3%), Inf A in32(5.4%), ADV in30(5.1%), Mpp in28(4.7%). Of78patients with multiple pathogens infections, two pathogens weredetected in57(9.6%) patients, three pathogens in20(3.4%) patients, and onepatient contained five pathogens. The commonest pathogens in coinfected sampleswere RSV (42cases,7.1%), EV (31cases,5.2%), and Inf A (24cases,4%), withcombination of RSV+EV for15cases, RSV+Inf A9cases, and RSV+hCoV5cases.4. The distribution of pathogens in the different age groups: RSV was primarilyresponsible for CAPs (33.6%) in infants under1year of age. Inf A, Inf B, hBoV,hCoV and hMPV predominated in the children between1and5years of age, incontrast to PIV which was more prevalent in infants. ADV and Mpp were the most frequent pathogens in children older than5years, whereas EV infection wasdetected in all age groups with nearly equal proportion.5. The monthly distributions of detected pathogens: RSV peak was detected inFebruary, followed by smaller peak in September. The largest number of reportsof hMPV increased during late winter. Inf A activity was more reported duringautumn and late winter, while Inf B was less frequent with peak in January andFebruary. hCoV and EV infections were detected throughout the study period, butEV had highest peak in May and September, whereas hCoV was relativelyconstant every month. hBoV was more prevalent during summer and peaked inJuly. PIV and ADV had no definite seasonal patterns, but ADV showed higherpeak at August-September. Mpp infection was most frequently reported duringsummer months of July and August, later peaked in September. The proportion ofremaining Cp was insufficient to detect seasonal pattern. Records of infectedpatients with unidentified pathogen were maintained throughout the year. Theoverall number of coinfection was higher during early autumn and winter months.6. Distribution of disease severity categories in593patients:358(60.4%) patientshad mild disease,141(23.8%) had moderate disease and94(15.9%) had severedisease. Distribution of disease severity categories within age groups hadstatistically significant difference (χ~2=36.682, P <0.001). Severe disease wasmore common in infants, while mild disease was highly observed in school-agedchildren.7. Clinical characteristic of single pathogen infections, multipathogen infections andpathogen-negative cases: tachypnea was highly observed in single pathogen-infected patients than in pathogen-negative patients (χ~2=12.876, P <0.001).Mucoid sputum, fine moist rales, wheezing, chest retraction, bronchodilatortherapy and intravenous corticosteroid were observed more frequently in singlepathogen-infected and multipathogen-infected patients than in pathogen-negativepatients (P <0.05for all comparisons). Hepatomegaly was observed morefrequently in multipathogen-infected patients than in single pathogen-infectedpatients (χ~2=5.817, P <0.05) and pathogen-negative patients (χ~2=7.745, P <0.05).8. Distribution of disease severity categories according to infection types hadstatistically significant difference (χ~2=53.805, P <0.001). Most of mild diseasewas seen in pathogen-negative patients, while moderate to severe disease was more frequently observed in single pathogen-infected or multipathogen-infectedpatients. Both age and duration of hospital stay of patients either with provenpathogen infections or those without detectable pathogen had significantrelationship with disease severity. Clinical score of single pathogen infections,multipathogen infections, and pathogen-negative patients had statisticallysignificant negative correlation with age (P <0.05); clinical score of singlepathogen infections and pathogen-negative patients had statistically significantpositive correlation with duration of hospitalization (P <0.05).9. Clinical characteristics of patients with single RSV, Inf A, ADV, hBoV, hMPV,Mpp and not otherwise specified (NOS) pathogen infections: median age of RSV-infected patients was lower than other pathogen-infected groups (χ~2=87.120, P <0.05). Wheezing, tachypnea, chest retraction were frequently observed in RSVinfection than in Inf A, ADV, Mpp, hBoV, NOS, multipathogen infections andpathogen-negative cases (P <0.05for all comparisons). Bronchodilator andcorticosteroid were more frequently prescribed for RSV infection than for otherpathogen infections (P <0.05). Fever was more frequently observed in ADV-infected patients than in RSV-, NOS-, multipathogen-infected patients andpathogen-negative cases (P <0.001for all comparisons). High hsCRP and ESRlevel were more frequently found in ADV infection than the rest of cohort (P <0.05for all comparisons), but no differences compare with Mpp and Inf Ainfections (P>0.05). RSV and ADV infections were responsible for more severedisease than other pathogens (χ~2=128.975, P <0.001).10. Clinical characteristics of patients with single RSV infection and mixed RSVinfection: duration of fever lasted longer in mixed RSV infections than in singleRSV infections (U=472, P <0.05). Wheezing, tachypnea, and rhinorrhea werestatistically more frequent in single RSV infections than in mixed RSV infections(P <0.05). Hepatomegaly and high ESR level were statistically more frequent inmixed RSV infections than in single RSV infections (χ~2=4.855, P=0.03; χ~2=6.67, P=0.01).11. Distribution of disease severity categories between single RSV infection andmixed RSV infection had statistically significant difference (χ~2=6.617, P <0.05).Single-RSV infected patients prone to moderate-severe disease, whereas mixedRSV-infected patients more commonly had mild disease. Among single RSV- infected patients, distribution of disease severity categories within age groups hadstatistically significant difference (χ~2=6.8, P <0.05); clinical score of single-RSVinfected patients had statisically significant positive correlation with duration ofhospital stay (ρ=0.213, P <0.05). Among mixed RSV-infected patients,distribution of disease severity categories had no statistically significant differenceamong age groups (χ~2=4.178, P>0.05); clinical score of mixed-RSV infectedpatients had no statisically significant correlation with duration of hospital stay (ρ=-0.004, P>0.05).12. There was statistically significant positive correlation between viral load of RSVinfection and clinical score (ρ=0.499, P <0.001) but showing no significantcorrelation with duration of hospital stay (ρ=-0.013, P>0.05).Conclusions1. Hospitalized children with community acquired pneumonia in Guangzhoubetween2010-2011were mostly infants less than1year of age and predominatedin boys. Positive detection rate of viral pathogens was highest in infants group.2. RSV-infected patients were significantly younger than other pathogen-infectedpatients. RSV was the leading cause of community acquired pneumonia in infants,whereas ADV and Mpp were responsible for infection in older children. Amongpatients with severe pneumonia, RSV and ADV were frequently detected.3. RSV viral titer had positive correlation with disease severity; coinfection with otherpathogens did not increase RSV disease severity.4. Age had negative correlation with disease severity; duration of hospitalization hadpositive correlation with disease severity.5. RSV was most prominent between late winter and early spring, with smaller peakin autumn. hBoV and Mpp were prevalent during summer months; PIV and ADVhad no definite seasonal patterns; the rest of pathogens were detected frequentlyduring autumn-winter months.6. Wheezing, tachypnea, chest retraction, prescription of bronchodilator andcorticosteroid were frequently found in RSV and hMPV infections; fever, highhsCRP and high ESR level were significantly found in ADV and Mpp infections.