Cord Blood Vitamin D Deficiency Is Associated With Respiratory Syncytial Virus Bronchiolitis Five-year cohort study of hospitalization for respiratory syncytial virus associated lower respiratory tract infection in African children. Economic impact of community-acquired and nosocomial lower respiratory tract infections in young children in Germany High Human Bocavirus Viral Load Is Associated with Disease Severity in Children under Five Years of Age Early Administration of Azithromycin and Prevention of Severe Lower Respiratory Tract Illnesses in Preschool Children With a History of Such Illnesses: A Randomized Clinical Trial. Lower respiratory tract illness and RSV prophylaxis in very premature infants Respiratory Syncytial Virus and Other Viral Infections among Children under Two Years Old in Southern Vietnam 2009-2010: Clinical Characteristics and Disease Severity Respiratory syncytial virus (RSV) infection in preterm infants and the protective effects of RSV immune globulin (RSVIG). Respiratory Syncytial Virus Immune Globulin Study Group. Respiratory syncytial virus: co-infection and paediatric lower respiratory tract infections
BACKGROUND : Respiratory syncytial virus ( RSV ) is the most important pathogen causing severe lower respiratory tract infection ( LRTI ) in infants . Epidemiologic and basic studies suggest that vitamin D may protect against RSV LRTI . OBJECTIVE : To determine the association between plasma vitamin D concentrations at birth and the subsequent risk of RSV LRTI . DESIGN : A prospect i ve birth cohort study was performed in healthy term neonates . Concentrations of 25-hydroxyvitamin D ( 25-OHD ) in cord blood plasma were related to RSV LRTI in the first year of life , defined as parent-reported LRTI symptoms in a daily log and simultaneous presence of RSV RNA in a nose-throat specimen . RESULTS : The study population included 156 neonates . Eighteen ( 12 % ) developed RSV LRTI . The mean plasma 25-OHD concentration was 82 nmol/L. Overall , 27 % of neonates had 25-OHD concentrations < 50 nmol/L , 27 % had 50 - 74 nmol/L and only 46 % had 25-OHD 75 nmol/L. Cord blood 25-OHD concentrations were strongly associated with maternal vitamin D3 supplementation during pregnancy . Concentrations of 25-OHD were lower in neonates who subsequently developed RSV LRTI compared with those who did not ( 65 nmol/L versus 84 nmol/L , P = .009 ) . Neonates born with 25-OHD concentrations < 50 nmol/L had a sixfold ( 95 % confidence interval : 1.6 - 24.9 ; P = .01 ) increased risk of RSV LRTI in the first year of life compared with those with 25-OHD concentrations ≥75 nmol/L. CONCLUSIONS : Vitamin D deficiency in healthy neonates is associated with increased risk of RSV LRTI in the first year of life . Intensified routine vitamin D supplementation during pregnancy may be a useful strategy to prevent RSV LRTI during infancy OBJECTIVES To describe the epidemiology of respiratory syncytial virus ( RSV ) associated lower respiratory tract infection ( RSV-LRTI ) hospitalizations in South African children over a 5-year period , and determine the impact of gestational age ( GA ) on the incidence of RSV-LRTI hospitalization . STUDY DESIGN A cohort of 39,836 children , 6.47 % of whom were HIV infected , enrolled into a phase 3 trial were prospect ively studied for respiratory viruses when hospitalized for LRTI . RESULTS The incidence of hospitalization for RSV-LRTI was 19.4 per 1000 in HIV uninfected children and 2.5-fold ( 95 % CI 2.04 - 3.03 ) greater in HIV infected children ( 45.0 per 1000 ) . The incidence of RSV-LRTI was 4.9-fold greater ( 95 % CI 3.9 - 6.8 ) in children born at < 36 weeks of gestational age ( GA ) and repeat hospitalizations for RSV-LRTI was 3.7-fold ( 95 % CI 1.4 - 9.4 ) more likely in these children ( 7.3 % ) than children born at > or = 36 weeks of GA ( 1.9 % ) . The burden of RSV-LRTI was greater in children born at < 32 weeks of GA than those born at 32 - 35 weeks of GA between 6 - 12 months ( P=0.008 ) and 12 - 24 months of age ( P=0.001 ) . The RSV epidemic occurred at the end of the rainy season and peaked when the monthly temperatures were at its lowest each year Data on the economic burden of lower respiratory tract infections ( LRTI ) in young children are lacking in Germany . The objective of the cost-of-illness study was to estimate the economic impact of community-acquired LRTI and nosocomial LRTI as well as of infections due to respiratory syncytial virus ( RSV ) , parainfluenza viruses ( PIV ) and influenza viruses ( IV ) . The economic analysis is part of the PRI.DE study , a prospect i ve , multi-centre , population -based epidemiological study on the impact of LRTI in children aged 0 to 36 months in Germany . The analysis includes children with community-acquired infections ( 1329 cases treated as out patients , 2039 cases treated as in patients ) and nosocomial infections ( 90 cases ) .  Medical services consumed were generated by chart abstract ion and parental expenses data by telephone interviews within four weeks after physician visit or hospitalisation . Costs were evaluated from following perspectives : third party payer , parent and society . Total costs for outpatient treatment are € 123 per LRTI case . Stratified by virus type , total costs per case are € 163 ( RSV ) , € 100 ( PIV ) and € 223 ( IV ) . Total costs per hospitalised LRTI case amount to € 2579 . Stratified by virus type , total costs per case are € 2772 ( RSV ) , € 2374 ( PIV ) and € 2597 ( IV ) . Total costs per nosocomial case are € 2814 . Economic burden due to LRTI is € 213 million annually . It is concluded that treatment of LRTI in children up to age three causes a considerable economic burden in Germany . Presented results are the first data describing the economic burden of LRTI in young children assessed by means of the incidence data for Germany . This cost-of-illness study provides basic data for further decision-making , focusing on the economic assessment of preventive strategies for RSV , PIV and IV infections Human bocavirus ( HBoV ) is a parvovirus and detected worldwide in lower respiratory tract infections ( LRTIs ) , but its pathogenic role in respiratory illness is still debatable due to high incidence of co-infection with other respiratory viruses . To determine the prevalence of HBoV infection in patients with LRTI in Shanghai and its correlation with disease severity , we performed a 3-year prospect i ve study of HBoV in healthy controls , out patients and in patients under five years of age with X-ray diagnosed LRTIs .  Nasopharyngeal aspirates were tested by PCR for common respiratory viruses and by real time PCR for HBoV subtypes 1–4 . Nasopharyngeal swabs from healthy controls and serum sample s and stools from in patients were also tested for HBoV1 - 4 by real time PCR .  Viral loads were determined by quantitative real time PCR in all HBoV positive sample s. HBoV1 was detected in 7.0 % of in patients , with annual rates of 5.1 % , 8.0 % and 4.8 % in 2010 , 2011 and 2012 , respectively . Respiratory syncytial virus ( RSV ) subtype A was the most frequent co-infection detected ; HBoV1 and RSVA appeared to co-circulate with similar seasonal variations . High HBoV viral loads ( > 106 copies/ml ) were significantly more frequent in in patients and out patients than in healthy controls . There was a direct correlation of high viral load with increasing disease severity in patients co-infected with HBoV1 and at least one other respiratory virus . In summary , our data suggest that HBoV1 can cause LRTIs , but symptomatic HBoV infection is only observed in the context of high viral load IMPORTANCE Many preschool children develop recurrent , severe episodes of lower respiratory tract illness ( LRTI ) . Although viral infections are often present , bacteria may also contribute to illness pathogenesis . Strategies that effectively attenuate such episodes are needed . OBJECTIVE To evaluate if early administration of azithromycin , started prior to the onset of severe LRTI symptoms , in preschool children with recurrent severe LRTIs can prevent the progression of these episodes . DESIGN , SETTING , AND PARTICIPANTS A r and omized , double-blind , placebo-controlled , parallel-group trial conducted across 9 academic US medical centers in the National Heart , Lung , and Blood Institute 's AsthmaNet network , with enrollment starting in April 2011 and follow-up complete by December 2014 . Participants were 607 children aged 12 through 71 months with histories of recurrent , severe LRTIs and minimal day-to-day impairment . INTERVENTION Participants were r and omly assigned to receive azithromycin ( 12 mg/kg/d for 5 days ; n = 307 ) or matching placebo ( n = 300 ) , started early during each predefined RTI ( child 's signs or symptoms prior to development of LRTI ) , based on individualized action plans , over a 12- through 18-month period . MAIN OUTCOMES AND MEASURES The primary outcome measure was the number of RTIs not progressing to a severe LRTI , measured at the level of the RTI , that would in clinical practice trigger the prescription of oral corticosteroids . Presence of azithromycin-resistant organisms in oropharyngeal sample s , along with adverse events , were among the secondary outcome measures . RESULTS A total of 937 treated RTIs ( azithromycin group , 473 ; placebo group , 464 ) were experienced by 443 children  ( azithromycin group , 223 ; placebo group , 220 ) , including 92 severe LRTIs ( azithromycin group , 35 ; placebo group , 57 ) . Azithromycin significantly reduced the risk of progressing to severe LRTI relative to placebo ( hazard ratio , 0.64 [ 95 % CI , 0.41 - 0.98 ] , P = .04 ; absolute risk for first RTI : 0.05 for azithromycin , 0.08 for placebo ; risk difference , 0.03 [ 95 % CI , 0.00 - 0.06 ] ) . Induction of azithromycin-resistant organisms and adverse events were infrequently observed . CONCLUSIONS AND RELEVANCE Among young children with histories of recurrent severe LRTIs , the use of azithromycin early during an apparent RTI compared with placebo reduced the likelihood of severe LRTI . More information is needed on the development of antibiotic-resistant pathogens with this strategy . TRIAL REGISTRATION clinical trials.gov Identifier : NCT01272635 Aims : To determine the frequency of and the risk factors for readmissions for any lower respiratory tract illness ( LRTI ) and for respiratory syncytial virus ( RSV ) documented LRTI in children born very prematurely who had or had not received RSV prophylaxis . Methods : Multicentre prospect i ve longitudinal cohort study of 2813 infants , born between April 2000 and December 2000 at less than 33 weeks of gestational age , and followed until the end of the epidemic season . Results : Among the 2256 children who had no bronchopulmonary dysplasia at 36 weeks of postmenstrual age and were not su bmi tted to RSV prophylaxis  , 27.4 % were readmitted at least once for any reason during the epidemic season ; 15.1 % and 7.2 % were readmitted at least once for any LRTI and RSV related LRTI , respectively . Children born at less than 31 weeks ’ gestation , having an intrauterine growth restriction , or living in a single mother family were at a significantly higher risk of readmission for LRTI in general as well as for RSV related LRTI . Of the 376 children su bmi tted to prophylaxis , 28.2 % were readmitted at least once for any LRTI and 6.1 % for RSV related LRTI . Conclusion : One out of four children who had received no prophylaxis , was born very prematurely , and was without bronchopulmonary dysplasia at 36 weeks of postmenstrual age , was readmitted at least once for any reason . Roughly 50 % and 20 % of these readmissions were related to a LRTI and an RSV infection , respectively . Further epidemiological studies are warranted to assess the aetiology and impact of other respiratory pathogens on post-discharge readmission and respiratory morbidity in this population Background Despite a high burden of respiratory syncytial virus ( RSV ) infections among children , data on demographic and clinical characteristics of RSV are scarce in low and middle income countries . This study aims to describe the viral etiologies , the demographic , epidemiological , and clinical characteristics of children under two years of age who were hospitalized with a lower respiratory tract infections ( LRTI ) , focusing on RSV ( prevalence , seasonality , subgroups , viral load ) and its association with disease severity . Methods A prospect i ve study among children under two years of age , hospitalized with LRTI was conducted in two referral pediatric hospitals in Ho Chi Minh City , Vietnam , from May 2009 to December 2010 . Socio-demographic , clinical data and nasopharyngeal swabs were collected on enrolment and discharge . Multiplex real-time RT-PCR ( 13 viruses ) and quantitative RSV RT-PCR were used to identify viral pathogens , RSV load and subgroups . Results Among 632 cases , 48 % were RSV positive . RSV infections occurred at younger age than three other leading viral infections i.e rhinovirus ( RV ) , metapneumovirus ( MPV ) , parainfluenza virus ( PIV-3 ) and were significantly more frequent in the first 6 months of life . Clinical severity score of RSV infection was significantly higher than PIV-3 but not for RV or MPV . In multivariate analysis , RV infection was significantly associated with severity while RSV infection was not . Among RSV infections , neither viral load nor viral co-infections were significantly associated with severity . Young age and having fever at admission were significantly associated with both RSV and LRTI severity . A shift in RSV subgroup predominance was observed during two consecutive rainy seasons but was not associated with severity . Conclusion We report etiologies , the epidemiological and clinical characteristics of LRTI among hospitalized children under two years of age and risk factors of RSV and LRTI severity OBJECTIVE To evaluate the safety and efficacy of respiratory syncytial virus immune globulin ( RSVIG ) in the prevention of severe respiratory syncytial virus ( RSV ) lower respiratory tract infection ( LRTI ) in infants born prematurely with or without bronchopulmonary dysplasia ( BPD ) . METHODS Data from a prospect i ve , blinded , r and omized , multicenter trial during three consecutive RSV seasons involving 249 children . This analysis comprises 162 preterm children , of whom 102 had BPD . The 87 children with congenital heart disease ( CHD ) were excluded from this analysis . Children were r and omized to receive monthly infusions of RSVIG 750 mg/kg ( high dose ) , RSVIG 150 mg/kg ( low dose ) , or no RSVIG : Results from the preterm infants with and without BPD who received RSVIG 750 mg/kg are contrasted with control infants who did not receive RSVIG : RESULTS As compared with controls , high-dose RSVIG administration significantly reduced the incidences of RSV LRTI ( P = .01 ) and moderate-to-severe LRTI ( P = .006 ) . RSV-associated hospitalization also was decreased ( P = .06 ) as well as were total RSV-associated days in the intensive care unit ( P = .05 ) . Significantly fewer preterm infants developed severe RSV LRTI in the RSVIG group compared with controls ( 4/58 [ 7 % ] vs 14/58 [ 24 % ] , respectively ; P = .01 ) . Adverse reactions occurred in 5 % of RSVIG infusions . These were generally mild and included reversible fluid overload , transient fever , and decreases in oxygen saturation . There was one death unrelated to either RSV or RSVIG administration . CONCLUSIONS Prophylaxis with RSVIG is safe and is currently the only effective means to prevent severe RSV LRTI in high-risk preterm infants Comprehensive population -based data on the role of respiratory viruses in the development of lower respiratory tract infections ( LRTIs ) remain unclear . We investigated the incidence and effect of single and multiple infections with respiratory viruses on the risk of  LRTIs in Vietnam .  Population -based prospect i ve surveillance and a case – control study of hospitalised paediatric patients with acute respiratory infection ( ARI ) were conducted from April 2007 through to March 2010 . Healthy controls were r and omly recruited from the same community .  Nasopharyngeal sample s were collected and tested for 13 respiratory viruses using multiplex PCRs .  1992 hospitalised ARI episodes , including 397 ( 19.9 % ) with LRTIs , were enrolled .  Incidence of hospitalised LRTIs among children aged < 24 months was 2171.9 per 100 000 ( 95 % CI 1947.9–2419.7 ) . The majority of ARI cases ( 60.9 % ) were positive for at least one virus . Human rhinovirus ( 24.2 % ) , respiratory syncytial virus ( 20.1 % ) and influenza A virus ( 12.0 % ) were the most common and 9.5 % had multiple-viral infections . Respiratory syncytial virus and human metapneumovirus infections independently increased the risk of LRTIs . Respiratory syncytial virus further increased the risk , when co-infected with human rhinovirus , human metapneumovirus and parainfluenza virus-3 but not with influenza A virus . The case – control analysis revealed that respiratory syncytial virus and influenza A virus increased the risk of ARI hospitalisation but not human rhinovirus . Respiratory syncytial virus is the leading pathogen associated with risk of ARI hospitalisation and LRTIs in Vietnam
Children with LRTI were found to have significantly lower mean vitamin D levels as compared to controls There was likewise a correlation between vitamin D levels and incidence and severity of LRTI .
Studies related to vitamin D deficiency and lower respiratory tract infections ( LRTI ) in children have inconsistent findings .
The objective of this systematic review was to assess the prevalence of vitamin D deficiency in children with LRTI , and to evaluate the correlation between vitamin D levels and the incidence and severity of LRTI .