1. RSV Infection
Disease overview
DR/ AHMED OKASHA
JAHRA NICU

2. RSV- Definition
Respiratory syncytial (sin-SISH-uhl) virus, or RSV, is a member of the Pneumovirus
genus, of the family Paramyxoviridae . The virus is an enveloped, non-segmented virus
containing a single negative-strand of RNA. The viral genome encodes ten proteins
including two envelope proteins, F and G. The G protein mediates the attachment of
the virus to the host cells and the F protein is involved in cell penetration and promotes
cell to cell transmission through the formation of syncytia. 1,2,3
RSV Overview

3. 3

4. RSV- Clinical Features
• RSV is the most common virus causing respiratory infections in children and
almost all will have been infected with RSV by the age of 2 years. 1
• Primary RSV symptoms include fever, runny nose, cough and wheezing. In 2540% of cases symptoms progress to bronchiolitis or pneumonia. 2
• Risk factors for RSV include premature birth, CHD, BPD/CLD and a
compromised immune system and RSV poses greater risk to children with
underlying vulnerability 3
• Severe RSV infection can lead to long-term complications including the
development of wheezing and asthma later in life.3
• RSV is also associated with a high mortality rate, and in infants under 1 year it
is the most common cause of viral death . 4

5. EPIDEMIOLOGY OF SEVERE RSV INFECTION
Diagnosis & Transmission
Diagnosis
When suspected, infection with RSV may be confirmed using
a number of diagnostic methods such as viral culture, rapid
antigen detection tests (enzyme immunoassay, EIA) and
reverse-transcriptase polymerase chain reaction (RT-PCR). 1,2
Transmission
Severe RSV infection is easily spread,
particularly in environments such as hospitals,
day care, schools and large families. 3
RSV is spread via direct contact with
contaminated hands, surfaces, and respiratory
secretions, as well as unprotected coughing and
sneezing. 4
Annual outbreaks are consistent and seasonal
The RSV season occurs in the winter months. However, the overall length of the season
varies greatly between countries. 1
Overview of RSV annual seasons in different countries. 2,3,4,5

6. EPIDEMIOLOGY OF SEVERE RSV INFECTION
Seasonality
RSV-infection in (almost) all children
It has been estimated that RSV causes as much as 90% of all childhood bronchiolitis and up to 40%
of all paediatric pneumonias.
Approximately two thirds of all infants are infected with RSV during their first year; about one third of
those infected develop LRTI, 2.5% are hospitalised and 0.1% die.
By 2 years, 95% of infants have been infected with RSV at least once and 36% at least twice.27, 77
Peak rates of severe RSV infection occur in infants aged 6 weeks to 6 months.

7. EPIDEMIOLOGY OF SEVERE RSV INFECTION
Re-Infection
Re-infection is common
re-infection occurs because infection does not provide complete longlasting immunity: between 40% and 70% of preschool-age children are
re-infected with RSV, and approximately 20% of school-age children,
adolescents and adults are re-infected.1
RSV is the only pathogen of its kind to have such a high rate of reinfection and a high viral load is thought to be related to risk of
recurrence . 2
Severe RSV infection does not provide complete immunity that may lead
to re-infection 1
However, RSV re-infection can be severe in high-risk patients such as
those born prematurely, those with chronic lung disease (CLD) and those
with congenital heart disease (CHD) . 3
RSV Overview

8. POPULATION AT HIGH RISK
RSV infection in preterm infants
Preterm infants with immature lungs will suffer greater damage to their airways and
respiratory system compared to full term infants. 1
<29 Weeks Gestational Age
29 – 32 Weeks Gestational Age
The highest between the high risk
32 – 35 Weeks Gestational Age
Congenital Heart Disease (<2years at the beginning of the season)
Chronic Lung Disease (<2years at the beginning of the season)
RSV Overview

9. GROUPS AT HIGHEST RISK OF SEVERE RSV
DISEASE
The risk factors listed in Below Table have been shown to increase the risk and severity of
severe RSV infection.
1,2,3,4,5,6,7,8,9
RSV Overview

10. GROUPS AT HIGHEST RISK OF SEVERE
RSV DISEASE
Multiple risk factors associated with severe RSV infection
There are several risk factors for severe RSV infection and premature infants or
infants with BPD/CLD or CHD are particularly vulnerable. 1
Risk factors associated with severe RSV infection in late preterms
These include inadequate housing, socioeconomic status and a poor standard of
hospital care.2
Other social factors such as teenage mothers and unmarried mothers of infants are
also considered to be potential factors in RSV hospitalisation, as well as medical
factors including a NICU stay and/or ventilator assistance at birth. 3
Tobacco smoke has also been linked to an increased risk of RSV hospitalisation but is
also seen as a factor that can be controlled in the home. 1
RSV Overview

11. High Risk Infants Have a Greater Risk of RSV
Hospitalization Relative to Healthy, Term infants
• Retrospective cohort study from the Tennessee Medicaid program (USA) collected
between 1989 and 1993
• 47% of all RSV hospitalizations occurred in babies born prematurely
562
11
1. Boyce et al. J Pediatr 2000;

12. Once Hospitalized, RSV Disease Tends to be
more Severe in High Risk Infant Populations
Patients hospitalized with RSV LRTIs at seven centres in Canada were prospectively
followed (n=689)
Wang EEL, et al. J Peds. 1995:126(2):212–219.
12
RSV Overview

13. RSV Hospitalized CLD Babies Incur Significant
Resource-Use During the First 2 Years of Life
A retrospective chart review in CLD babies <32wGA. Infants that were re-admitted for a proven RSV
infection were compared with infants with non-respiratory re-admission or no re-admission
Mean health resource utilization
*P<0.001
**P<0.01
***P<0.05
**
*
Greenough et al. Arch Dis Child. 2001 (UK study)
***
*
*
13

14. Chronic lung disease and severe RSV infection
BPD/CLD infants have a reduced response to severe RSV infection due to
reduced oxygenation and a poor response to inflammation 2
The burden of RSV in children with BPD/CLD was initially described prospectively in a
cohort of 30 infants <2 years of age at the onset of RSV season who were receiving
home oxygen therapy. During the 4-month study, 27 children had one or more acute
respiratory illnesses and RSV was responsible for 16/27 (59%). Of the 16 children with
RSV, 11 (69%) required hospitalisation. The hospital course was prolonged and
complicated. Seven of the 11 children were hospitalised for more than 1 week; four
were admitted to the intensive care unit and two needed mechanical ventilation. No
children died.3
1.Baraldi E, Flippone M. Chronic Lung Disease after premature birth. N Engl J Med. 2007;357:1946-55
2.Stenmark K. International Congress on Respiratory Viruses 2003. (CONFERENCE PRESENTATION) .
3.Groothuis JR, Gutierrez KM, Lauer BA. Respiratory syncytial virus infection in children with bronchopulmonary dysplasia. Pediatrics. 1988;82(2):199-203.
RSV Overview

15. Congenital heart disease and RSV infection
Congenital heart disease (CHD): CHD refers to heart defects present from birth.
Physical signs of heart disease include tachypnea, hyperpnea and tachycardia. There
are many types of heart defects, e.g. stenotic valve lesions 1
Cyanotic heart disease patients have lower than normal oxygen saturation levels
1
Acyanotic heart disease patients have normal oxygen levels but blood is abnormally
pumped around the body1
CHD patients have increased hospitalisation rates for RSV due to a compromised
cardiovascular function.2
RSV Overview

16. Outcomes in CHD children with RSV compared
to children without CHD

17. BURDEN OF DISEASE
Acute Bronchiolitis is one of the major causes of morbidity in
infants under 12 months who have severe RSV infection with up
to 80 percent of acute bronchiolitis cases are associated with
RSV infection.1
RSV and global rates of acute lower respiratory infections (ALRI)
This equates to 22% of all ALRIs. At least 3.4 million of these were severe cases
requiring hospital admission. 2
RSV burden compared to influenza
In children <1 year, deaths associated with RSV are higher than those caused by
influenza 1

18. BURDEN OF DISEASE
Bronchiolitis Associated Hospitalisation
Severe RSV infection is still the leading cause of bronchiolitis associated hospitalisation
42-45% of LRTI hospitalisations in children under 2 years of age are caused by RSV .
1
67% of children under 2 years hospitalised for bronchiolitis in the US in 2007 were RSV positive . 2
Percentage of bronchiolitis hospitalisations which are RSV-related .
2

19. BURDEN OF DISEASE
RSV Vs Influenza
Rate of emergency department visits per 1000 patients for infants with Influenza or RSV.
Bourgeois F, Valim C, McAdam A, Mandl K. Relative impact of influenza and respiratory syncytial virus in young children.
Pediatrics. 2009;124(6):e1072-e80.

20. BURDEN OF DISEASE
Emergency and Clinic Visits
Rate of RSV emergency department visits and office visits per 1000 patients for infants 0-59
months.
all C, et al. The Burden of Respiratory Syncytial Virus Infection in Young Children. N Engl J Med. 2009;360(6):588-98.

21. BURDEN OF DISEASE
RSV Resource Utilization
Healthcare resource utilization in RSV-bronchiolitus hospitalisations versus non-RSV
bronchiolitis hospitalisations.
Garcia JJ et al. 47th Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC) and the Infectious Disease Society of America (IDSA).
Washington DC, USA; October 2008.
RSV Overview

22. BURDEN OF DISEASE
RSV Intensive/Complex Resource Utilization
Resource intensive and complex hospitalisations in
high-risk infants
Hospitalisation rates, length of stay and rates of mechanical ventilation are
higher in infants with risk factors for RSV infection, especially in infants with 3+
risk factors 1
A US study of 684 infants (≤1 year) hospitalised with bronchiolitis or RSV pneumonia
states that 76% of high-risk patients are managed in PICU due to the increased risk of
respiratory complications once hospitalised. Complications are associated with a
longer length of stay and increased costs. 2
1.Thorburn K. Pre-existing disease is associated with a significantly higher risk of death in severe respiratory syncytial virus infection. ArchDisChild. 2009;94(2):99103. 2.Willson DF, Landrigan CP, Horn SD, Smout RJ. Complications in infants hospitalized for bronchiolitis or respiratory syncytial virus pneumonia. J Pediatr.
2003;143(5):142-9
RSV Overview

23. BURDEN OF DISEASE
Increased risk of Childhood Asthma
Long-term outcomes of severe RSV disease
Greater severity of RSV bronchiolitis is associated with an increased risk of developing
childhood asthma .
Proportion of patients in each severity group diagnosed with asthma.
Carroll K, Wu P, Gebretsadik T, Griffin M, Dupont W, Mitchel E, et al. Season of infant bronchiolitis and estimates of subsequent risk and burden of early
childhood asthma. J Allergy Clin Immunol. 2009;123(4):964-6.
RSV Overview

24. BURDEN OF DISEASE
Increased risk of Childhood Asthma/Wheezing
Severe RSV bronchiolitis is associated with asthma and wheezing throughout childhood.
RSV LRTI in early childhood is an independent risk factor for the subsequent development
of wheezing up to age 18 years .
Current prevalence (%) of asthma in RSV-infected children and controls by age at follow-up .
Sigurs N, Aljassim F, Kjellmann B. Asthma and allergy patterns over 18 years after severe RSV bronchiolitis in the first year of life. THORAX. 2010.
RSV Overview

25. BURDEN OF DISEASE
Quality of Life
Quality of life in high-risk infants and parents
According to a prospective study conducted in the US, RSV-related hospitalisation
causes significant distress for children.Children’s health and functional status during
hospitalisation for severe RSV infection as assessed by the caregiver was significantly
poorer than that of age-matched controls (the control group were hospitalisations of
premature infants who had no history of RSV, RSV-related illness or RSV prophylaxis).
Caregivers continued to report significantly poorer child health in the RSV group as
long as 60 days after hospital discharge.
Hospitalisation for severe RSV infection results in
significant, lasting consequences for the child
Leidy N, Margolis M, Marcin J, Flynn J, Frankel L, Johnson S, et al. The impact of severe respiratory syncytial virus on the child, caregiver, and family during hospitalization and
recovery. Pediatrics. 2005;115(6):1536-46.
RSV Overview

26. BURDEN OF DISEASE
Severe RSV disease may be fatal
Using US mortality data from the National Center for Health Statistics, Thompson and
colleagues developed a statistical model to estimate the age-specific number of deaths
attributable to RSV and influenza. The results show that, during the period 1990–1999,
RSV was the leading cause of viral death in infants, (mean mortality rates for
underlying respiratory and circulatory deaths) with nearly nine times the mortality
associated with influenza in infants less than 1 year old (5.3 deaths per 100,000
person-years vs 0.6 attributed to influenza).
Thompson WW, Shay DK, Weintraub E, Brammer L, Cox N, Anderson LJ, et al. Mortality associated with influenza and respiratory syncytial virus in the United
States. JAMA. 2003;289(2):179-86.
RSV Overview

27. BURDEN OF DISEASE
Co Morbidity Leading to Fatality
Co morbidity
RSV Case-Fatality Rate Range
High-Risk Infants are at Greater Risk of RSV-Related Death
Chronic Lung Disease (CLD)
3.5%–23%
Congenital Heart Disease (CHD)
2%–37%
Preterm (≤36 wGA)
0%–6.1%
Nosocomial RSV Infection
0%–12.2%
No Comorbidity or Risk Factors
<1%
Table: review of literature identified from a structured literature search (1966–2009)
Mortality specifically attributed to RSV can be difficult to
determine as most pediatric patients do not undergo postmortem
examination to determine cause of death
Welliver, et al. Curr Med Res Opin. 2010
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RSV Overview

28. BURDEN OF DISEASE
Mortality
Mortality in high-risk infants
Hospitalisation for RSV is associated with greater mortality risk in the two years following
discharge
Sampalis JS. Morbidity and mortality after RSV-associated hospitalizations among premature Canadian infants. J Pediatr. 2003;143(5 Suppl):S150-S6.
RSV Overview

29. CURRENT CLINICAL PRACTICE
Treatment
Treatment for Severe RSV Infection is Limited to Supportive Care
Severe RSV disease can be managed using:
• Hospitalization
• Oxygen supplementation
• Mechanical ventilation
• Pediatric intensive care
Other treatment options include:
• Antibiotics – given for suspected bacterial
infection; NOT for Tx of RSV
• Bronchodilators
• Nebulized hypertonic saline
• Ribavirin is the only approved drug for the
treatment of severe RSV.
However, due to conflicting data and limitations of
the drug, use of ribavirin is controversial.
1. Krilow, Expert Rev. Anti Infect. Ther, 2011
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RSV Overview

30. CURRENT CLINICAL PRACTICE
Prevention
Synagis® (palivizumab)1 Is the Only Available Effective Option for
Prevention of Severe RSV Infection
• Humanized monoclonal antibody that
provides effective prophylaxis against
severe disease caused by RSV infection
• Injected intramuscularly once monthly
during periods of active RSV circulation
• Binds the F protein of the RS virus
• Blocks fusion of RSV to host cell
membrane and fusion of infected
host cells (“syncytial formation”)
• The F protein does not change in RSV subtypes; palivizumab provide protection
against subtypes of RSV2,3
1.Synagis® (palivizumab) [package insert], Abbott Laboratories
2.Johnson S, et al. J Infect Dis. 1997;176:1215–1224.
3.Williams JV, et al. In: Richman DD, et al, eds.Clinical Virology. 3rd ed
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RSV Overview

31. CURRENT CLINICAL PRACTICE
Prevention
Prevention Is the Only Viable Strategy to Reduce the Risk of Acquiring an RSV
Infection1
• RSV transmission can be minimized
through a number of different ways:
- Routine hand washing
- Careful handling of contaminated materials
- Cohort infected individuals
- Limit contact with hospital visitors, especially
young children
- Passive immunization with Synagis®
(palivizumab)2
1.Hall et al. J Pediatr. 1981
2.Allen et al. Am J Infect Control. 1990.
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RSV Overview