“PREVALENCE AND CLINICAL FEATURES OF RESPIRATORY SYNCYTIAL VIRUS INFECTION IN
CHILDREN LESS THAN 60 MONTHS OF AGE HOSPITALIZED WITH SEVERE PNEUMONIA IN A TERTIARY CARE REFERRAL HOSPITAL – A CROSS-
SECTIONAL AND ANALYTICAL STUDY”
Dissertation submitted for
M.D., DEGREE EXAMINATION BRANCH VII PEDIATRIC MEDICINE
THE TAMIL NADU DR.M.G.R MEDICAL UNIVERSITY CHENNAI
INSTITUTE OF CHILD HEALTH AND HOSPITAL FOR CHILDREN
MADRAS MEDICAL COLLEGE CHENNAI
APRIL 2017
CERTIFICATE
This is to certify that the dissertation “Prevalence and clinical features of respiratory syncytial virus infection in children less than 60 months of age hospitalized with severe pneumonia in a tertiary care referral hospital – A cross- sectional and analytical study”submitted by DR SUGANYA.M to the Faculty of Pediatrics, THE TAMILNADU DR.M.G.R. MEDICAL UNIVERSITY, CHENNAI in partial fulfillment of the requirements for the award of M.D., DEGREE (PEDIATRICS) is a bonafide research work carried out by him under our direct supervision and guidance.
PROF.DR.M.K.MURALITHARAN, M.S., M.Ch (Neurosurgery)
The DEAN,
Madras Medical College &
Rajiv Gandhi Govt. General Hospital, Chennai – 600 003.
PROF.DR.D.SAMINATHAN, MD., DCH.,
Director & Superintendent, Institute of Child Health &
Hospital for Children, Chennai – 600 008.
PROF.DR.T.RAVICHANDRAN, MD.,DCH, Professor of Pediatrics,
Institute of child health &
Hospital for children, Chennai- 600 008.
DECLARATION
I DR.SUGANYA.M solemnly declare that the dissertation titled
“Prevalence and clinical features of respiratory syncytial virus infection in children less than 60 months of age hospitalized with severe pneumonia in a tertiary care referral hospital – A cross- sectional and analytical study”
has been prepared by me.
This is submitted to the Tamil Nadu DR.M.G.R Medical University, in partial fulfillment of the rules and regulations for the M.D Degree examination in Pediatrics.
Place : Chennai DR.SUGANYA.M
Date :
SPECIAL ACKNOWLEDGEMENT
My sincere thanks to PROF. DR. M.K.MURALITHARAN, M.S., M.Ch, Dean, Madras Medical College, for allowing me to do this dissertation, utilizing the institutional facilities.
ACKNOWLEDGEMENT
It is with immense pleasure and privilege, I express my heartfelt gratitude, admiration and sincere thanks to PROF. DR. D. SAMINATHAN, M.D., DCH.,Professor and Head of the Department of Pediatrics, for his guidance and support during this study.
I am greatly indebted to my guide and teacher, PROF. DR.T.RAVICHANDRAN, M.D., DCH.,Professor of Pediatrics for his supervision, guidance and encouragement while undertaking this study.
I would like to thank to my Assistant Professors DR.S.STALIN, MD., DCH., DR.V.PRABHU, M.D.,DCH., DR.D.KAVITHA M.D, DR.V.ARUNAGIRI MD.,for their valuable suggestions and support.
I thank PROF DR.S.EZHILARASI,MD.,DCH.,
DR S.KALPANA MD.,DR S.SARATH BALAJI MD., Dept. of Paediatric PULMONOLOGY, for their valuable support and suggestions.
I also thank all the members of the Dissertation Committee for their valuable suggestions.
I gratefully acknowledge the help and guidance received from Dr. S.SRINIVASAN, DCH.,Registrar at every stage of this study.
I also express my gratitude to all my fellow postgraduates for their kind cooperation in carrying out this study and for their critical analysis.
I thank the Dean and the members of Ethical Committee, Rajiv Gandhi Government General Hospital and Madras Medical College, Chennai for permitting me to perform this study.
I thank all the parents and children who have ungrudgingly lent themselves to undergo this study without whom, this study would not have seen the light of the day.
ABBREVIATION RSV - Respiratory Syncytial Virus
WHO - World Health Organisation
LTRI - Lower Respiratory Tract Infection SGA - Small for Gestational Age
AGA - Appropriate for Gestational Age CHD - Congenital Heart Disease
DFA - Direct Immunofluorescence Assay
EIA - Enzyme Immunosorbent Assay
CIA - Chromatographic Immuno Assay
RT PCR - Reverse Transcriptase Polymerase Chain Reaction
IV fluids - Intravenous fluids
CONTENTS
S.NO TITLE PAGE
NOS.
1 INTRODUCTION 1
2 REVIEW OF LITERATURE 19
3 STUDY JUSTIFICATION , AIMS & OBJECTIVES 24, 25
4 MATERIALS & METHODS 26
5 STATISTICAL ANALYSIS 36
6 OBSERVATION & RESULTS 37
7 DISCUSSION 63
8 CONCLUSION 72
9 LIMITATIONS 74
10 BIBLIOGRAPHY
11
ANNEXURES PROFORMA
PATIENT CONSENT FORM MASTER CHART
1
INTRODUCTION
Acute respiratory tract infections are a leading cause of morbidity and mortality in paediatric age group worldwide(1). Viruses are common pathogens of acute lower respiratory tract infection (ALRTI) in children(2).The most common viral pathogens are Respiratory syncytial virus, Influenza virus, Parainfluenza virus, Human Metapneumo virus and Adeno virus.(3). Among these RSV was the most frequent agent causing acute respiratory infection,with greater association with bronchiolitis(4).
Fig 1 :Etiology of respiratory infections in Children
The World Health Organisation (WHO) has estimated the global RSV disease burden to be 64 million cases annually and that 160,000 deaths occur
2
due to RSV infection every year(5). The infection rate in children is as high as 60 % in the first year of life and by the end of second year of life almost all are infected. Clinical manifestations of RSV infection may vary from mild disease of upper respiratory tract to severe lower respiratory infection including bronchiolitis and bronchopneumonia(6).Risk factors for RSV infection include premature birth, chronic lung disease, congenital heart disease and immunosuppression,overcrowding and smokers in the house(7).
RSV is a highly contagious pathogen. The lower respiratory tract infection caused by RSV is almost confined to children less than 3 years,especially during the first 6 months of age where it is more severe.
Reinfections can occur within short intervals and through out the life(8).
Specific treatment options are not available for children infected with RSV.We need to understand the prevalence and clinical profile of RSV infection in order to plan specific prevention and treatment strategies.This would lead to better management of the disease and avoid unnecessary use of antibiotics thereby preventing the emergence of resistant organism.
HISTORY
A cytopathogenic agent producing acute respiratory illness in chimpanzees and in humans was identified by Morris et al in 1956.
3
At the Walter Reed Army institute in October 1955,a respiratory illness with features of sneeze, cough, mucopurulent discharge occurred in chimpanzees. The causative agent was named as chimpanzee coryza agent.
Later, when the virus was grown in cell culture, a characteristic effect of formation of large multinucleated cells (giant syncytia) was identified and the virus was renamed as "respiratory syncytial virus"(10).
VIROLOGY
CLASSIFICATION
Order Mononegavirales Family Paramyzoviridae Subfamily Pneumovirinae Genus Pneumovirus VIRAL GENOME
RSV contains 2 major antigenic groups – groups A and B. These antigenic groups differed in many structural proteins with the major difference occurring in the F and G proteins.
4
Fig 2 RSV viral genome and RSV virion
RSV contains single strand of unsegmented negative sense RNA.RSV genome consists of 10 genes encoding 11 proteins(11).These genes (with corresponding proteins) include N (nucleoprotein), L(RNA polymerase), P (Phosphoprotein cofactor for L), G (glycoprotein), F (fusion protein), SH(small hydrophobic protein), M (Matrix protein),non-structural proteins NS1 and NS2 (type I interferon inhibitors) and M2 (required for transcription). G, F and SH proteins are transmembrane surface proteins. Viral nucleocapsid is formed by the association of N,L and P proteins.(11)
5 RSV VIRION
Fig 3 :RSV virion
RSV Virion are pleomorphic spherical particles with an lipid envelope covering a nucleocapsid that contains a single stranded RNA (12). Once the RSV binds to cell surface glycosoaminoglycans, by the process of membrane fusion the nucleocapsid enters into the cytoplasm of the cell. In the cytoplasm of the cell viral gene expression and replication occurs. The virions by budding through the plasma membrane acquire a lipid envelope.
The envelope contains spike like projections spaced at 6-10 nm interval and are approximately 11-20 nm in length.(13,14,15).
6 EPIDEMIOLOGY
RSV is an important cause of acute respiratory tract infection in infants and young children(2).The most common age of infection is the first 6 months of life, with about half of these occurring in the first 6 to 12 weeks of life(16).Most studies have showed RSV infection to have a male preponderance . As per the World Health Organisation estimate, the annual global burden of RSV disease is 64 million cases and the number of deaths attributable to RSV infection every year is 160,000(17).
RSV outbreaks show seasonality. In tropical countries RSV epidemics occur during rainy seasons and in temperate countries they occur during winter and spring seasons.
RISK FACTORS MALE SEX:
Male sex is identified as a risk factor for severe RSV bronchiolitis . The male to female risk ratio is 1.425:1(18). The anatomical nature of the airways of boys being shorter and narrower is the reason behind this sex predominance.
They are more prone to develop bronchial obstruction once infected with RSV.
7 PREMATURE BIRTH :
In children born at<35 weeks of gestational age the main reason for rehospitalisation following discharge from NICU was RSV infection.(19).Preterm born infants had an higher rate of hospitalisation, ICU admission, need for mechanical ventilation and prolonged hospital stay when compared to infants born at term.(20). A study was done to assess the RSV immunoglobulin levels in preterm versus term infants. Preterm infants less than 28 weeks had a significantly lower level of RSV specific immunoglobulins when compared to term infants. Infants born more than 29 weeks of gestation has RSV specific immunoglobulin levels similar to term infants.(21).
SMALL FOR GESTATION AT BIRTH :
The Canadian PICNIC study has shown low birth weight as an independent risk factor for RSV infection associated hospitalisation.(22).
Intrauterine growth restriction was identified as a significant risk factor for death due to RSV disease in another study done in developing countries (23) CONGENITAL HEART DISEASE :
Navas, et al from the PICNIC Study Group in Canada found an incidence of 16.4 % for congenital heart disease in children with RSV infection. The oxygen requirement of these children with underlying cardiac disease was for a prolonged duration when compared with the children without underlying heart disease. They were also found to have a significantly higher
8
mortalitiy rate (3.4%).Hemodynamically significant heart disease, cardiomyopathy and Down syndrome were reported as predictors of RSV hospitalisation in a Danish study.(24)
CHRONIC LUNG DISEASE :
Several studies such as the IMPACT and the PREVENT study found a high correlation between chronic lung disease, Bronchopulmonary dysplasia and the mortality associated with RSV infection. Carbonell- Estrany et al in his study reported 15 % RSV rehospitalisation rate in children with chronic lung disease(25)
IMMUNODEFICIENCY :
Children who had immunodeficiency were highly susceptible for severe and persistent RSV infection.They also had prolonged viral shedding . Significantly higher mortality and morbidity rates were associated with RSV infection in children with immunodeficiency(26). A study was done on 608 children who were hospitalised for RSV infection. This study concluded that immunodeficiency was a significant risk factor for RSV hospitalisation and was associated with increased morbidity and mortality.(27).
9 FAMILY H/O ALLERGY :
Family history of allergy was a significant risk factor for children to acquire RSV infection. Following a first episode of severe RSV LRTI, the incidence of wheezing and asthma was increased in future. In a study conducted on 206 hospitalised infants less than 1 year of age with first episode of RSV bronchiolitis , 45 % of infants had atleast one first degree relative with history of atopy and 43 % had a first degree relative with h/o asthma.(28)
OTHER RISK FACTORS :
Other risk factors include bronchopulmonary dysplasia,children with neuromuscular impairement, downsyndrome,low socioeconomic status, crowded living conditions.
MODE OF TRANSMISSION
The routes of transmission of RSV are 1. Through large particles or droplets
This occurs by close contact with infected secretions followed by inoculation into nose or eyes.
2. By small particle aerosol
This mode of transmission does not require close contact with the source.
3. Self inoculation after touching contaminated surfaces(fomites).
This mode requires environmental surface contamination with
10
infected secretions and transmission by contact with these sources such as with fomites.(29)
Day care setting and schools are the most ideal setting for RSV transmission to susceptible children
PATHOGENESIS
The incubation period for RSV is 3 - 6 days, may vary from 2 - 8 days.
Mode of entry is through the eyes ,nose or mouth . The virus spreads along the respiratory epithelium through cell to cell transfer and produces Bronchiolitis and or Pneumonia. Peribronchiolar inflammation with lymphocytes occur early in the course of Bronchiolitis.This inflammation leads to the characteristic necrosis followed by sloughing of the bronchiolar epithelium.
The bronchioles may get plugged by the sloughed material thereby obstructing the airflow, the hallmark of bronchiolitis. Initially air traping occurs distal to the obstruction causing hyperinflation, then resorption occurs causing focal areas of atelectasis(30).In RSV pneumonia, mononuclear cell infiltration of the interstitial tissue is also seen.
11
Fig 4 : Pathogenesis of RSV infection CLINICAL FEATURES
The spectrum of clinical manifestations of RSV infection ranges from mild upper respiratory illness, croup to pneumonia and bronchiolitis.In infants and young children RSV infection initially presents as upper respiratory symptoms such as running nose,cough and nasal block with or without fever gradually progressing to the lower respiratory tract in more than half of the children.RSV can present as apnea in preterm infants.(31)
IMMUNITY
Protection against and recovery from RSV infection are mediated largely by the host immune system; secretory antibodies, serum antibodies, major histocompatibility complex, class I-restricted cytotoxic T lymphocytes
12
(CTLs).Both humoral and cell mediated immunity are requirement for infection containment and termination.Secretory antibodies prevent infection of upper respiratory tract whereas serum antibodies protect against infection of the lower respiratory tract. In the very young, maternally derived antibodies act as specific effectors.(32). Humoral neutralizing antibodies correlate with resistance to RSV reinfection. But this protection is of short duration and incomplete,hence reinfection can occur throughout life(32).
LABORATORY DIAGNOSIS
The specific diagnosis of RSV infection is made by virus isolation or by detecting viral antigens or virus specific nucleic acid sequences in respiratory secretions. Nasal wash or a nasopharyngeal aspirate has been demonstrated to be more sensitive than a nasopharyngeal swab specimen(33)
Laboratory methods currently available for the detection of RSV are Virus isolation in tissue culture, detection of viral antigens by Direct or Indirect Immunofluorescent (IF) staining (DFA/IFA) or by Enzyme-linked Immunosorbent assays (ELISAs), serology by demonstration of RSV-specific serum IgM antibody and the detection of viral nucleic acids by amplification assays, predominantly reverse transcription polymerase chain reaction (RT- PCR).
13 VIRAL CULTURE :
Virus isolation by tissue culture was considered as gold standard, but it needs technical expertise and average time of 3 to 6 days for viral cytopathic effect to appear. Shell vial centrifugation cultures followed by DFA or immunoperoxidase staining significantly increases the sensitivity and shortens the turn around time for virus identification to 1 to 2 days (34,35,36).The need for technical expertise and the cost involved makes viral culture unsuitable for large scale screening and in office practise.
ANTIGEN DETECTION :
Antigen detection assays include Direct immunofluorescence assays (DFA), Enzyme Immunosorbent Assays (EIA), Chromatographic and optical Immunoassays.
In DFA fluorescein-labelled antibodies bind to RSV antigen in the respiratory secretions.In DFA the immunofluorescence pattern of the infected cells can be seen directly under microscope providing additional specificity.
Sensitivity and specificity of DFA, when compared to RT-PCR, were found to be 93% and 97% respectively(37)
In the EIA, RSV antigen is bound by RSV specific antibodies. This bound complex will then be detected using a second antibody linked to an enzyme. Studies have found IFA to be slightly more accurate than ELISA.
14
In Lateral flow immunoassay RSV is immobilized using mouse monoclonal anti-RSV antibody and specially selected antibodies are used as detector materials. Lateral flow immunoassay is for rapid antigen detection in nasopharyngeal aspirate samples. When a CIA was compared with DFA for RSV antigen detection in a study, it was found that the sensitivity and specificity of CIA were 92% and 98%, respectively, with a diagnostic efficiency of 95%(38) . It is a rapid, easy, handy, cost effective method for RSV detection.The limiting factor for CIA is that it’s a non quantitative test.
SEROLOGY :
Although humoral immunity plays an important role in the containment and termination of RSV infection, the rise in RSV specific IgM antibody titres varies significantly with age.Virus specific antibody testing is not effective in diagnosis.Despite severe RSV infection,serologic response is not commonly detected in infants (32).In the presence of maternally derived antibodiesthe infant’s own antibody response is barely detectable (39).
NUCLEIC ACID TESTS :
Reverse Transcription Polymerase Chain Reaction (RT PCR) is the most widely used nucleic acid amplification test.It is a rapid method as results are available within 3 to 5 hours .In a study done on 80 culture positive samples from young children the sensitivity of RT PCR was found to be 97.5 %(40).In another study the overall RT PCR specificity was found to be 99 %(41).
15 TREATMENT
Treatment of RSV is largely supportive as specific drugs are very limited in number and efficacy. Antiviral drugs, Fusion inhibitors, Nanoparticles, Antisense therapy, Ethnobotanicals are some of the drugs being tried or under trial.
Fig 5 :Mechanism of action of Anti viral drugs
16
Table 1:Anti viral drugs
Drug Mechanism Example remark
Anti viral drugs Replication inhibition Mutation
Inhibitor of inosine monophosphate dehydrogenase Immunostimulatory effects
RSV 604
Ribavirin,viramidine, merimepodib
Ribavirin,mycophenolate, mizoribine
Ribavirin
Effective against RSV, but adverse effect on the host
Fusion inhibitors
Inhibiting fusion protein attachment to cell
Peptide-HR121,HR212,RhoA Chemical-
BMS-433771, RFI-641
Peptide fusion inhibitors promising anti-RSV drug.
Nanoparticles Inhibiting
attachment to cell
Silver nanoparticles, gold nanoparticles
Emerging field, conclusive studies required Antisense
therapy
RNA interference siRNA-ALN-RSV01 Phosphoro diamidate morpholino oligomers
Effective and safe;
ALN- RSV01 completed phase IIb clinical trails Ethnobotanicals Probably fusion
inhibitors,
anti-inflammatory
Plant extracts. Promising
but
conclusive studies required
17
Anti-viral drug Ribavirin is the only recognised specific treatment for RSV infection(42). Ribavirin not only inhibits replication of RSV and causes mutation in the virus, but also has immunostimulatory effects on the host(42).Studies failed to show a decrease in the length of ICU stay , need for mechanical ventilation and mortality rates(43).Howeverfew studies have shown a possible decrease in long-term wheezing (44).The AAP recommends the use of ribavirin to be based on patient factors and risks, clinical circumstances and used in those ‘with severe disease or those at risk for severe disease, such as hemodynamically significant cardiopulmonary disease and immunosuppression.(45)
RSV IMMUNOGLOBULIN
Many trials evaluated the use of RSV immunoglobulins for treatment of RSV infection, but found no benefit(46)
IMMUNOPROPHYLAXIS
Palivizumab is a humanized mouse monoclonal antibody. Palivizumab attaches to the F protein and neutralises it hence fusion of the virus to the epithelial cell is inhibited. The Impact-RSV trial evaluated Palivizumab and found that it reduced hospitalization from 10.6 % in placebo group to 4.8% in palivizumab group. The ICU admissions were reduced by 57%,length of hospital stay was reduced by 42% and days on oxygen was redeuced by 40
%(47).FDA has approved Palivizumab for high risk children.
18 RSV VACCINE
FORMALIN INACTIVATED AND BOVINE VACCINE
These vaccines were developed but they failed to induce protection in children against RSV.
GENETICALLY ENGINEERED VACCINE
Recently a chimeric DNA (Cdna) vaccine has been developed which when administered intranasally to rhesus monkeys induced robust immune response. This vaccine is under clinical trials(48). Subunit vaccines using fusion proteins and nanovaccines (encapsulating DNA Vaccine into polymer to increase its retention and efficacy) are under investigation and trial.
19
REVIEW OF LITERATURE
Soham Gupta et al studied 77 children with respiratory infection for RSV by direct fluorescent antigen testing and found 17 (22.1 %) children to be positive for RSV. The mean age group was 8.24±7.21 months with male female ratio of 1.8:1.one child had an history of prematurity and 3 had underlying congenital heart disease. This study concluded that RSV was a significant cause of morbidity and moratility in children presenting with acute respiratory infection in southern india.(49).
Harish nair et al in his study estimated the incidence of RSV acute respiratory infection in children less than 5 years of age using data from systematic review of studies published between January 1995 and June 2009 and ten unpublished studies. An estimated 33.8 million new cases of RSV infection occurred worldwide during the year 2005.(22% of all acute lower respiratory tract infections). This study also brought out the mortality rate of RSV which was estimated to be around 66000 – 1,99,000 children.99 percent of these deaths occurred in developing countries.(50)
Vefik Africa et al studied 112 patients, less than 24 months. The mean age of children with RSV positivity was 4.4 ± 2.8 months and RSV negative was 6.1 ± 4.7 months.31 children were RSV positive and 81 were RSV negative. Among the positive children 14 were female and 17 were male. 8 were born preterm. Running nose was seen in all children with RSV positive
20
and 75.3 % of RSV negative children. No significant difference between the 2 group was seen with respect to other clinical findings such as fever,cough,vomiting,dyspnea,apnea,conjunctivitis and hyperemia of the tympanic membrane. No significant difference was noticed between the groups.
In the above study the mean period of hospitalisation in the RSV positive group was 6.7 ± 10.1 days and 3 ± 4.2 days. No statistical difference between the groups was observed in terms of hospital admission and stay duration.There was statistically significant difference between the 2 groups in terms of admission to intensive care unit and ventilator support.(51)
Siddhartha shah et al conducted a study among hospitalised children in the rural community of northern india.505 children were enrolled for the study ,82 tested positive for RSV. Hospitalisation related to RSV infection per 1000 children per annum was found highest in children aged 0-5 months followed by 6-23 months and lowest incidence among children 24 – 59 months.Based on bivariate comparison the clinical features like wheezing,crepitations,tacypnea,chestindrawing were more common in the RSV positive group.Compared to the estimated hospitalisation rates,the WHO ARI definition captured 86 % of RSV incidence in contrast to 50 – 60 % with other case definitions like ILI and SARI. The study concluded that the WHO case definition because of its high sensitivity appears to be the most sensitive screening definition for RSV surveillance.(52).
21
Lamarao et al in his study obtained 1,050 nasopharyngeal aspirates in children less than 3 years. Out of these 243 (23.1 %) were RSV positive. The mean age of RSV positive children was 12.1 months versus 15.5 months in the RSV negative group. No statistically significant difference in gender distribution was identified in this study.Nasal obstruction and Rhinorrhea were predominant in the RSV positive group.(53)
Nokes et almonitored 635 children until each experienced 3 RSV epidemics. A total of 409 infections were observed with 365 primary and 82 repeat episodes. This study mainly brought out the risks of reinfection withRSV.The study concluded that the risk of reinfection remained significant beyond the first year of life following a primary symptomatic episode. They also identified that one quarter of all the reinfections were associated with lower respiratory tract infection.(54).
Susan E Robertson et al carried out study on children less than 5 years to find out the incidence of RSV in 2 states.The incidence per 1000 child years were 94 in Nigeria, 34 in Indonesia. The incidence of severe RSV associated LRTI per 1000 child years was 10 in Indonesia , 5 in Mozambique , and 9 in South Africa. (55).
Loscertales et al studied 5635 children less than 1 year presenting to outpatient department with cough or nasal secretion and 1307 children hospitalised with LRTI.The incidence of RSVinfection was found to be 8.6 % in out patient children and 10.6 % in children hospitalised with lower
22
respiratory tract infection.Cough,increased respiratory rate and chest indrawing were independently related to RSV infection.Wheezing was found to be infrequent in this study.(56)
Lianghulu et al found the incidence of RSV to be 20.74 %. He analysed 1803 hospitalised infants.Compared to RSV negative group, children in RSV positive group had higher rates of tachypnea,moistrales and chest x ray abnormality. These children also had increased requirements of oxygen support and prolonged hospitalisations.(57)
Hall et al in their study found that the rate of hospitalisation due to RSV infection was 3 three times higher than that with influenza or parainfluenzaviruses.This study estimated that around 2 million children under 5 years of age need care for RSV illness per annum. Characteristics that were significantly associated with RSV hospitalisation were young age and prematurity.This study had estimated that 1 out of 334 hospitalisations in children less than 5 years of age was due to RSV infection and 1 out of 38 visits to an emergency department was due to RSV.(58)
William et al conducted a study to update the clinical profile of children with RSV infection.They retrospectively analysed case records of 246 children with RSV positivity admitted to a tertiary care hospital. The common admitting diagnosis were bronchiolitis in 34.7 % of admissions, Pneumonia 32.5 % and possible septicaemia in 13 %. The mean age was found to be 3 months. Male to female sex ratio was 1.4: 1, median length of
23
hospital stay was 3 days.Children with underlying cardiac disease required intensive care (50 %) more than those without cardiac disease.They also had more complications and prolonged hospital stay. Death among the study group was 3 (1.2 %) and all 3 were children with underlying cardiac disease.Common risk factors identified were young age, male sex, chronic cardiopulmonary disease and family history of atopy.This study also brought out septic syndrome as a clinical diagnosis in addition to the typical diagnosis of bronchiolitis and pneumonia in RSV infected children.(59)
24
STUDY JUSTIFICATION
This study aims to estimate the exact prevalence of RSV infection in children less than 60 months who are admitted with severe pneumonia.Enumerating the clinical profile of the children in the study group leads to a better understanding of the nature of viral infections while treating a child with respiratory infection. Effective management strategies can be implemented thereby avoiding unnecessary use of antibiotics in children with respiratory infection.Understanding the burden of RSV infection in terms of morbidity and mortality can motivate research activities into effective treatment protocol and vaccine development for RSV respiratory infection.
25
AIMS AND OBJECTIVES
To estimate the prevalence of Respiratory Syncytial Virus in children less than 60 months of age hospitalized for severe pneumonia
To describe the clinical features of the Respiratory Syncytial Virus in children less than 60 months of age hospitalized for severe pneumonia
26
MATERIALS AND METHODS
STUDY CENTRE
This study was conducted at the INSTITUTE OF CHILD HEALTH AND HOSPITAL FOR CHILDREN, Egmore, Chennai – 8. This is a tertiary care referral centre in Tamil nadu.
STUDY POPULATION
Children less than 60 months admitted with severe pneumonia in the general medical wards in The Institute of child health and hospital for children during the study period and who satisfied the following criteria were included in the study
INCLUSION CRITERIA
1. Physician-diagnosed severe pneumonia with one or more of the following features,
Fast breathing (as defined in WHO classification)
≥ 60 breaths/min for children aged ≤ 2 months
≥ 50 breaths/min for children aged 2-11 months
≥ 40 breaths/min for children aged 12-60 months
Lower chest wall indrawing
2. Respiratory symptoms for less than 14 days duration.
27 EXCLUSION CRITERIA :
1. History of foreign body aspiration.
2. History of recurrent aspiration like children with developmental delay.
3. Any contraindication for nasopharyngeal aspiration like recent nasopharyngeal surgery
STUDY DURATION 6 months
STUDY DESIGN
Cross-sectional and analytical study STUDY POPULATION
100 children admitted with acute lower respiratory infection satisfying the above criteria were recruited for the study.
ETHICAL APPROVAL AND INFORMED CONSENT
The study protocol was approved by the Institution Ethics Committee.
Informed consent was obtained from the parent or the legal guardian of the study subjects after explaining to them in detail about the nature of the study.
CONFLICT OF INTEREST None
28 FINANCIAL SUPPORT
None
METHODOLOGY
Pre-structured proforma will be used to record the relevant information from individual patient selected for the study.The following data will be recorded,
Demographic factors such as age, gender, weight .
Risk factors for RSV infection such as premature birth (born at <37 weeks of gestation), birth weight small for gestational age, congenital heart disease, chronic lung disease , immunodeficiency and family history of allergy (including asthma).
Presence or absence of symptoms like running nose,
Cough, fever, hurried breathing, vomiting and loose stools were recorded.
Presence or absence of signs like tachypnea, chest indrawing, wheeze, crackles and hypoxia in room air.
Chest x ray findings
Management strategies such as need for oxygen, iv fluids, and mechanical ventilation
RSV detection will be done using RT PCR on the nasopharyngeal aspirate sample.
Duration of hospital stay will be recorded at the time of discharge of the patient.
29 METHOD OF SAMPLE COLLECTION
Appropriate sized naso gastric tube was inserted into nasopharynx of the child,1-2 ml of normal saline was instilled into the naso gastric tube and 2 ml was aspirated through the tube immediately using a sterile syringe.The aspirate was immediately transferred into a sterile transport medium provided by the lab at Institute of basic medical sciences,Taramani.The samples were immediately sent to the labatory at Institute of basic medical sciences ,Taramani for RNA extraction and processing..
ASSAY PROCEDURE
The samples were transported in 2 ml of viral transport medium (Himedia, India) at 4°C to laboratory on the same day for processing.
RNA EXTRACTION:
Viral RNA in nasal swab was extracted using Macherey-Nagel Viral RNA isolation Kit (MN, Germany), according to the below instruction.
LYSIS OF VIRUSES
600 µl of buffer RAV1 (Lysis buffer) containing carrier RNA and Guanidiumthiocyanate was added to 150µl of sample and mixed well for 5 mins at 70°c.
30 BINDING CONDITIONS
To the clear lysis solution 600 µl and mixed for 10-15 seconds.
Nucleospin RNA virus column in collection tube (2 ml) was taken and 700µl of lysed sample was loaded and centrifuged at 1 min at 8000rpm. .
WASHING AND DRYING OF SILICA MEMBRANE 1ST WASH
To the virus column 500 µl of buffer RAW was added .This was centrifuged for 1 min at 8000rpm. The flow through was discarded.
2ND WASH
600µl of buffer RAV3 was added to the RNA virus column and centrifuged for 1 min at 8000rpm.
3RD WASH
The RNA virus column was placed in a new collection tube (2 ml) and 200µl of buffer RAV3 was added. The sample is centrifuged for 2-5 minutes at 11,000rpm to remove the ethanol buffer completely.
31 ELUTION
50µl of RNase free water was added to the RNA column. It is then centrifuged at 11000rpm for 1 minute. The process of elution removes the unwashed components and purifies the RNA.
cDNA CONVERSION
cDNA was synthesized using a cDNA synthesis kit (Revert AidKit, Fermentas, Canada) according to the manufacturer’s instructions. Briefly, cDNA synthesis was carried out in a reaction volume of 20 μl, which contained nuclease free water, 2μl RNA, 4 μl of reaction buffer, 1 μl of ribolock inhibitor (20units/μl) 2 μl of 10 mMdNTPs, 1x RT buffer, 1 μl random primers and 1 μl of revertaid reverse transcriptase (200units/ μl). The following cycling conditions were used for cDNA synthesis: 5 min at 25 °C, followed by 60 min at 42 °C, and 5 min at 70 °C.
REALTIME RT PCR
Primers and probes mentioned in the Table was used for the real time PCR. Thermo cycling conditions were 95 °C for 10 mins; and 40 cycles of 94
°C, 15 s, and 60 °C, 2 min. Appropriate positive and negative controls were included in the study. Samples were considered positive if the Ct (Cycle threshold) value is ≥ 0.2 with an appropriate amplification curve shape.
32
Primers and Probe used for the detection of RSV
Oligo Primer/probe
Forward 5′ GCTCTTAGCAAAGTCAAGTTGAATGA 3′
Reverse 5′ AACATGCCACATAACTTATTGAT 3′
Probe 5′ FAM-ACACTCAACAAAGATCAACTTCTGTCATCCAGC-
TAMRA 3′
33
Fig : 6 RTPCR Technique
34 STUDY END POINTS
The outcomes measured include:
Prevalence of RSV infection
Risk factors for RSV infection in the RSV positive group
Association of symptoms such as fever, cough , running nose, hurried breathing, vomiting, loose stools
Association of signs such as wheezing, crackles, and hypoxia in room air.
Chest x ray findings
Requirement of oxygen support
Requirement of mechanical ventilation
Requirement of Intravenous fluids.
Duration of hospital stay
Whether the child was discharged or expired in the hospital
35 SAMPLE SIZE : 100 Patients
MANEUVRE :
Pre-structured proforma will be used to record the relevant information from individual patient selected for the study.The following data will be recorded,
Demographic factors such as age, gender, weight .
Risk factors for RSV infection such as premature birth (born at
<37 weeks of gestation),
Birthweight small for gestational age, chronic lung disease, congenital Heart disease, Immunodeficiency and family history of allergy (including asthma).
Presence or absence of symptoms like running nose, cough, fever, hurried breathing, vomiting and loose stools was recorded.
Presence or absence of signs like wheeze, crackles and hypoxia in room air.
RSV detection will be done using RT-PCR on the nasopharyngeal aspirate sample.
Duration of hospital stay and details of treatment underwent will be recorded at the time of discharge of the patient.
36
STATISTICAL ANALYSIS
The data collected from the patients were entered in the Microsoft excel sheet and analysed using SPSS version 23. Descriptive statatistics were expressed as mean for continuous variable and frequencies for categorical variables. The test of significance usd for continuous variables and categorical variables were unpaired student (t) test and Chi square test respectively. A “p”
value of <0.05 was taken as being of significance for all statistical tests.
37
32%
31%
35%
2%
0-6 months 7-12 months 13-24 months 25-60 months
OBSERVATION AND RESULTS
Our study was conducted at the “INSTITUTE OF CHID HEALTH AND HOSPITAL FOR CHILDREN”, a tertiary care referral hospital in Chennai, Tamilnadu.Nasopharyngeal aspirate were collected from 100 children less than 60 months of age satisfying the inclusion criteria for the study.
DEMOGRAPHY OF THE STUDY POPULATION AGE
Table 2 :Age distribution of the study population`
Age group Number Percentage
0 – 6 months 25 25%
7 – 12 months 24 24 %
13 – 24 months 27 27 %
25 – 60 months 24 24 %
CHART 1
Of the 100 children constituting the study population,25 children were in the age group less than 6 months,24 were between 7 to 12 months,27 were between 13 to 24 months and 24 were between 25 to 60 months.
38
sex distribution
Boys Girls
GENDER
` Table 3 :Gender distribution of the study population
Gender Number Percentage
Male 70 70 %
Female 30 30 %
CHART 2
Of the 100 children in the study population 70 were boys and 30 were girls.
39
PREVALENCE
RSV positive RSV negative
PREVALENCE CHART 3
Table 4 :Frequency of RSV positivity
Total no of patients 100
RSV positive 30
RSV negative 70
Percentage of RSV positivity 30 %
In our study the prevalenceof RSV among children aged less than 60 months of age is 30 percent (30 children out of 100)
40 STATISTICAL ANALYSIS OF DATA AGE
Table 5 : statistical analysis of age of the study population
Age distribution
Diagnostic test
No. of patients
n (%)
p value Positive
n (%)
Negative n (%)
0 – 6 6 (20.0) 19 (27.1) 25 (25.0)
0.199 7 – 12 10 (33.3) 14 (20.0) 24 (24.0)
19 – 24 10 (33.3) 17 (24.3) 27 (27.0) 25 – 60 4 (13.3) 20 (28.6) 24 (24.0)
Table6 : Association between Mean Age and RSV infected patients among the study population (n=100)
Age (months)
Diagnostic test
p value Positive
n
Negative n
Mean 11.0 22.6
0.0006
Standard Deviation 8.9 16.9
Standard Error or
mean 1.625 2.020
41
20
33.3 33.3
13.3
27.1 20 24.3 28.6
0 10 20 30 40 50 60 70 80 90 100
0 – 6 7 – 12 19 – 24 25 – 60
Percentage
Age (in months)
Age distribution of the study population (n=100)
RSV Positive RVS Negative
CHART 4
The mean age of children in the RSV positive group was 11 months whereas the mean age of children in the RSV negative group was 22.6 months.hence the mean age of children with RSV infection was less than the RSV negative group.
42
83.3
16.7 64.3
35.7
0 10 20 30 40 50 60 70 80 90
Male Female
Percentage
Gender
Association between Sex and RSV infected patients among the study population (n=100)
RSV Positive RSV Negative
GENDER
Table 7 : Sex distribution of the study population (n=100)
Sex
Diagnostic test
No. of patients
n (%)
p value Positive
n (%)
Negative n (%)
Male 25 (83.3) 45 (64.3) 70 (70.0)
0.062 Female 5 (16.7) 25 (35.7) 30 (30.0)
CHART 5
43
Of the study population 70 were boys and 30 were girls.In the RSV positive group (n = 30),25(83.3%) were boys and 5(16.7%) were girls.Among RSV negative group(n=70),45(64.3%) were boys and 25(35.7%) were girls.This was statistically significant i.e in the RSV positive group boys significantly outnumbered girls.(p<0.05).
44
Preterm birth
Preterm term
RISK FACTORS AND RSV INFECTION
We compared RSV positive and RSV negative group based on the presence or absence of risk factors such as premature birth, birth weight small for gestation, congenital heart disease, family h/o asthma.
PRETERM BIRTH
CHART 6 – Total number of preterm birth in the study population
45
Table 8 : Association between RSV infection & Prematuriy
CHART 7
In the RSV positive group, 4(13%) children were born premature, when compared to 11(15%) in the RSV negative group. However, this difference was not statistically significant.
Diagnostic test
p value Positive
n
Negative N
Preterm 4 11
1.000
Term 26 59
Total 30 70
0 5 10 15 20 25 30 35 40 45 50 55 60
Preterm Term
RSV positive RSV negative
46
Birth weight small for gestation
SGA AGA
BIRTH WEIGHT SMALL FOR GESTATIONAL AGE CHART 8 – Birth weight SGA in the study population
Table 9 : Association between LBW and RSV infected patients among the study population (n=100)
LBW
Diagnostic test
p value Positive
n
Negative n
Yes 10 22
1.000
No 20 48
Total 30 70
47
0 5 10 15 20 25 30 35 40 45 50 55 60
SGA AGA
RSV positive RSV negative
CHART 9
In RSV positive group 10(33 %) children and in RSV negative group 22(31 %) children were small for gestation at birth. This was not statistically significant.
48
CHD
CHD PRESENT CHD ABSENT
CONGENITAL HEART DISEASE
CHART 10 – CHD in the study population
Table 10 : Association between CHD and RSV infected patients among the study population (n=100)
CHD
Diagnostic test
p value Positive
n
Negative n
Present 3 1
0.045
Absent 27 69
Total 30 70
49
0 10 20 30 40 50 60 70
CHD NO CHD
RSV positive RSV negative
CHART 11
3 (10 %) of children in the RSV positive group and 1 (1.4%) in the RSV negative group had an underlying congenital heart disease. The p value was less than 0.05 and this difference between the 2 groups were statistically significant.
50
Family history of allergy
Family h/o allergy No Family h/o allergy
FAMILY HISTORY OF ALLERGY (INCLUDING ASTHMA) CHART 12 – Family history of allergy in the study population
Table 11 :Association between F/H/O ALLERGY and RSV infected patients among the study population (n=100)
F/H/O Asthma
Diagnostic test
p value Positive
n
Negative n
Yes 5 3
0.036
No 25 67
Total 30 70
51
0 10 20 30 40 50 60 70 80
Family h/o allergy No family h/o allergy
RSV positive RSV negative
CHART 13
5 Children among RSV positive group and 3 children among RSV negative group had family h/o asthma. The p value was less than 0.05 and it was statistically significant.
52 SYMPTOMS
The symptoms like fever,runningnose,vomiting,loose stools and hurried breathing were compared between RSV positive and RSV negative group.
CHART 14 – Symptoms of the Study population
Among the symptoms fever was seen in 26 (87%) of RSV positive children 37 (53%) in RSV negative children. This was statistically significant as the p value was <.05. Cough was seen in 24 (80%) of RSV positive and 66 (94%) RSV negative children. This was statistically significant. Running nose was seen in 25 (83%) children in RSV positive group and 41 (58%) children in RSV negative group which was statistically significant. Vomiting was seen in 9 (30%) children in RSV positive group and 9 (13%) children in RSV negative group which was also statistically significant. There was no statistical significance in the incidence of hurried breathing and loose stools between the groups.
SYMPTOMS
FEVER COUGH RUNNING NOSE HURRIED BREATHING VOMITING
LOOSE STOOLS
53
0 10 20 30 40 50 60 70 80 90 100
Fever Cough Running nose
Hurried breathing
Vomiting loose stools
RSV POSITIVE RSV NEGATIVE
Table 12 : Association between the various Clinical features and RSV infected patients among the study population (n=100)
Clinical feature
Diagnostic test
Total p value Positive
n (%)
Negative n (%)
Fever Present 26(87) 37(53) 63
0.001*
Absent 4(13) 33(47) 37
Cough Present 24(80) 66(94) 90
0.039*
Absent 6(20) 4(6) 10
Running nose Present 25(83) 41(58) 66
0.013*
Absent 5(17) 29(42) 34
Hurried breathing
Present 24(80) 51(73) 75
0.312
Absent 6(20) 19(27) 25
Vomiting Present 9(30) 9(13) 18
0.040*
Absent 21(70) 61(87) 82
Loose stools
Present 5(17) 7(10) 12
0.266
Absent 25(83) 63(90) 88
CHART 15
54 SIGNS
The clinical signs in the RSV positive group were compared with RSV negative group and were assessed for significance. Signs like wheeze, crackles and hypoxia in room air were taken into consideration.
CHART 16 – Signs in the Study population
SIGNS
WHEEZING CRACKLES
HYPOXIA IN ROOM AIR
55
0 10 20 30 40 50 60 70 80 90 100
Wheeze Crackles Hypoxia in room air
RSV POSITIVE RSV NEGATIVE
Table 13 : Statistical analysis of signs of ALRI
Clinical feature
Diagnostic test
Total p value Positive
n
Negative n
Wheeze Present 26 46 72
0.032
Absent 24 28
Crackles Present 22 57 79
0.256
Absent 8 13 21
Hypoxia in room
Air
Present 2 1 3
0.159
Absent 28 69 97
CHART 17
56
Among the clinical signs wheeze was present in 26(86%) of RSV positive children and 46(66 %) of RSV negative children.As the p value was less than 0.05 this difference was statistically significant..
On auscultation crackles was present in 22 (73%) and 57 (81%) of RSV positive and RSV negative group respectively. This difference was not statistically significant.
Hypoxia in room air was present in 2 (7 %) children of RSV positive group and in 1(1%) child in RSV negative group . The p value was 0.159 and this was not statistically significant.
57
CLINICAL DIAGNOSIS BASED ON CHEST XRAY
Table 14 :Distribution Of RSV Positive Samples
CLINICAL DIAGNOSIS
BASED ON CHEST X RAY
RSV POSITIVE
RSV NEGATIVE
CHI SQUARE
VALUE
P VALUE
BRONCHIOLITIS 22 36 4.136 0.041
PNEUMONIA 7 30 3.434 0.063
NORMAL 1 4 - -
CHART 18
0 5 10 15 20 25 30 35 40
Bronchilitis Pneumonia Normal
RSV Positive RSV negative
58 CHART 19
Based upon chest x ray findings it was found that 22 (73 %) children in the RSV positive group had a diagnosis of Bronchiolitis and 36 (51 %) children in the RSV negative group had a diagnosis of Bronchiolitis. This difference was statistically sigfnificant.7 (23 %) children in the RSV positive group had chest x ray findings of Pneumonia and 30 (43 %) children in the RSV negative group had an chest x ray finding of pneumonia. This difference was not statistically significant.
Distribution of study population
Bronchiolitis Pneumonia Normal
59
oxygen
oxygen needed NO OXYGEN SUPPORT
MANAGEMENT
Variables such as the requirement for oxygen support by hood or mask,need for mechanical ventilation and iv fluids were assessed for significance between the RSV positive and RSV negative group.
CHART 20
60 CHART 21
Table 15 : statistical analysis of management
Variable
Diagnostic test
Total p value Positive
n
Negative n Oxygen
requirements
yes 23 45 68
0.0252
No 7 25
32
Mechanical Ventilation
Yes 2 nil
2
0.088
No 28 70
98
Iv fluids
Yes 21 45 66
0.650
No 9 25 34
IV FLUIDS
IV FLUIDS NO IV FLUIDS
61
0 0.5 1 1.5 2 2.5 3 3.5 4 4.5 5
Oxygen Mechanical ventilation IV Fluids
RSV POSITIVE RSV NEGATIVE
CHART 22
In our study 23(77 %) of children among RSV positive group and 45 (64 %) of children among RSV negative group required oxygen support.This difference in oxygen requirement between the two groups were not significant.
Similarly the IV fluid requirement between the 2 groups were 21 (70 %) and 45 (64 %) in RSV positive and RSV negative children respectively.This difference was also not statistically significant.2 out of 30 children tested positive for RSV needed mechanical ventilation whereas none of the children tested RSV negative in our study group were in need of mechanical ventilator support.
62 OUTCOME
Table 16 :Statistical analysis of outcome
Min Max Mean S.D S.E
Hosp stay
3 14 5.04 1.70 .170
In our study there was no death among the study population. The mean duration of hospital stay among our study population was 5.04 days.
63
DISCUSSION
PREVALENCE
Our study included 100 children less than 60 months with clinical features of severe pneumonia.Out of 100 children 30 tested posiive for RSV by RT-PCR method. Thus the prevalence of RSV in our study was 30 percent in children less than 60 months of age.
In a cross sectional study conducted in Brazil on children hospitalised for community acquired pneumonia, the prevalence of RSV was 23.1 percent.(60).In another study published in the LANCET journal the prevalence of RSV in children less than 5 years of age was estimated to be 22 percent.(61).In a study conducted over 32 centres in Italy over a 6 month period RSV was detected in 40.6 percent of hospitalised children by Immune enzymatic technique.(62)
AGE
The mean age of children in RSV positive group in our study was 11 months and in the RSV negative group was 22.6 months.Hence in our study significantly more number of children in the RSV positive group were younger than the RSV negative group.
64
Many studies across the world have proven that RSV is more common in children less than 1 year of age, particularly in the first 6 months of age.
Studies carried out in vellore, New delhi and chandigarh also found out that RSV infection is more common in children less than 12 months of age.(63,64,65). A study done in Brazil found out that the mean age in RSV infected children was 12.1 months which was significantly lower than the mean age in RSV negative children which was 15.5 months.(60). Khuri-Bulos et al found that 83.4% of children infected with RSV were less than 1 year of age(66).
SEX
In our study the prevalence of RSV in male children was 83.3 percent and in female children was 16.7 percent.Thus boys with RSV significantly out numbered girls .
Many studies identified male sex as a risk factor for RSV infection.
65
In a study conducted in China to define the risk factors for RSV infection in children the male female ratio was found to be 1.9 : 1.(67).Canadian PICNIC (Paediatric Investigators Collaborative Network on Infections in Canada) study identified male sex as a significant risk factor for RSV Infection.(23).Analysis of representative studies over 30 years found the male to female sex ratio in RSV infection as 1.425 : 1.(68). However there are few studies with varied results.In a study conducted in Brazil gender was not found to be significant risk factor.(60). The Spanish FLIP study also reported than male sex was not a significant risk factor for RSV infection.(69)
66 RISK FACTORS
PREMATURE BIRTH
In our study the number of children with premature birth in RSV positive group was not significantly higher than in the RSV negative group.
Though premature birth was identified as a significant risk factor for RSV infection in many studies there are certain other studies showing results similar to our study. Boyce et al in their study showed that hospitalisation due to RSV infection was not significantly higher in preterm infants than in term infants.(70).In a study conducted in Nepal, preterm infants less than 32 weeks had an higher incidence of RSV infection.(71).In another study conducted on pre mature infants ,babies less than 35 weeks were at higher risk for hospitalisation due to RSV infection.
BIRTH WEIGHT SMALL FOR GESTATIONAL AGE
In our study 33 percent children among RSV positive group and 31 percent among RSV negative group were small for gestation age at birth.This difference between two groups were not statistically significant.
67
Results similar to ours was obtained in the Spanish FLIP study which showed that birth weight was not a significant risk factor for the development of RSV respiratory infection.In a study published in the European Journal of Paediatrics,low birth weight was found to be a significant risk factor for RSV infection.(72). The Canadian PICNIC study also identified birth weight small for geststional age as an independent risk factor for RSV hospitalisation.(23).
CONGENITAL HEART DISEASE
In our study there was statistical difference in the incidence of congenital heart disease between RSV positive and RSV negative group.
Congenital heart disease was shown as a significant risk factor in many studies. In a study conducted at Korea, children with congenital heart disease was found to be significantly at higher risk for morbitity from RSV infection.(73). Mc Donald et al in his study reported that children with congenital heart disease were at risk for severe illness from RSV infection.(74).Navas et al from the PICNIC study group in Canada showed increased oxygen requirement and prolonged hospital stay among children with CHD infected with RSV.
68 FAMILY H/O ALLERGY
In our study significantly more number of children in the RSV positive group had an underlying family history of asthma than in the RSV negative group.
Many studies found family history of allergy including asthma to be a significant risk factor for RSV infection. The Spanish FLIP study also reported the family history of wheezing as a significant risk factor for RSV infection.(75).Bradley JP et al in their study on children with RSV infection found that 45 percen of these children had atleast one first degree relative with family h/o asthma,27 percent had atleast one first degree relative with a family h/o eczema and 21 percent had a first degree relative with hay fever. This study reported family h/o allergy as a significant risk factor for RSV infection.(76) SYMPTOMS
In our study fever,cough,runningnose,vomiting were found to be significantly high in the RSV positive group than in the RSV negative group.
69
Several other studies have also shown similar results.Martinslamarao et al showed that Rhinorrhea and nasal obstruction were significantly high in RSV infected children.(53) .Another study done in Jordan also found post tussive vomiting more common in RSV infected children.(77).Similarly running nose and vomiting were also found to be significantly higher in RSV infected children in an study done on RSV infected children.(78).
SIGNS
In our study presence of wheeze in RSV positive group was significantly higher than in RSV negative group.
Many studies have found higher incidence of respiratory distress and wheeze in children with RSV than in children without RSV.
The combination of wheezing, cough and retractions were found to be predictors of RSV infection in children in a study done to identify the clinical predictors of RSV infection in children.(79).Many other studies have shown wheezing to be significantly more frequent in children with RSV infection.(45),(80),(78).
