RSV, MPV

Question 1

Paramyxoviridae classification

Answer 1

Subfamily- Paramyxovirinae : respivirus (PArainfl 1 and 3), rubulavirus (Parainf 2,4, mumps), morbilivirus (measles), henipa (nipah, hendra)

Subfamily- Pneumovirinae: Pneumovirus- RSV, metapneumovirus - MPV

Question 1

Homology between RSV and MPV; homology between genotypes of MPV

Answer 1

40%
80-90%; max varaition with G and SH

Question 2

Genome of MPV vs RSV

Answer 2

MPV: F, G, SH, M, M2-1- transcription elongation factor, M2-2 RNA synthesiss regulatory factor, NP, P, L

RSV: extra NS

Question 3

MPV- fusion and attachment by; receptor

Answer 3

The heptad repeat domain A in the F protein appears to be critical for fusogenecity,

G protein helps tether virus particles to the cell surface and confers optimal infectivity but is not critical for viral attachment.

Type 2 alveolar and bronchiolar epithelial - proteo- glycan, integrin, and C-type lectin receptors

Question 4

Genotypes of MPV

Answer 4

two major geno- types (A and B) and five subgroups with two sublineages (A1, A2a, A2b, B1, and B2). - based on F and G

Question 5

MPV vs RSV

Answer 5

1) hMPV lacks two nonstructural proteins found in RSV that are known to inhibit host interferon production, and likely uses other mechanisms to subvert innate immune responses.32,33 In human volunteers, peripheral blood mononuclear cells stimulated with hMPV produce a stronger innate and weaker adaptive cytokine response than RSV.

2) pre and postfusion F- same neutralising epitopes

3)omewhat older than for RSV infection, with highest rates noted between 6 and 11 months of age

4) febrile seizures, ataxia, and encephalitis appear to be approximately 10 times more common in children with hMPV compared to those infected with RSV.92

5) fever more common

6) generally peaking
1 to 2 months later than RSV.

Question 6

MPV- ab against (immunogenic); neutralising ones

Answer 6

F>G, SH; F

Question 7

Reinfection in RSV and MPV is possible because

Answer 7

reinfections
occur throughout life in part due to poor development of T- and B-cell
immunity.

Lymphopenia and receipt of cytotoxic therapy
are risk factors for severe hMPV disease, suggesting that cellular immunity
is important for hMPV illness resolution.

Question 8

MPV- age group; seropositivity; % for hospitalisation

Answer 8

ubiquitous pathogen that affects all age groups. Seroprevalence studies indicate that by age 5 years, most children

2% to 3% of all symptomatic respiratory infections among children in the first 5 years

13% of hospitalizations in children
2% of acute respiratory illnesses in the general adult population are due to hMPV.

Question 9

coinfection and seasonality of MPV

Answer 9

winter seasonality of hMPV, coinfection with other viral and bacterial respiratory pathogens ranges from 5% to 60%

Streptococcus pneumoniae,

The presence of the neuraminidases of influenza virus appears to promote the adherence of bacteria to the respiratory epithelium, whereas replication of hMPV is required to increase superinfection of pneumococcus in the respiratory tract.58 In addition, hMPV infection appears to impair neutrophil recruitment to the airways,
leading to delayed bacterial clearance.

Question 10

MPV- seasonality

Answer 10

temperate climates, the virus circulates
predominantly in the late winter and spring months, - Low temperature and
vapor pressure and increased wind speed a

Question 11

MPV- clinical features

Answer 11

mild upper respiratory infection to bronchiolitis and severe pneumonia

most infections are symptomatic.

incubation period of about 5 to 6 days

Most young children with hMPV infection exhibit fever, cough, sore throat, and rhinorrhea

seizures, ataxia, and encephalitis

pharyngitis, conjunctivitis, maculopapular rash - less common

bronchiolitis (47%–84%), asthma (common in childdren younger than 3 yrs- older rhinovirus) (11%–25%), and pneumonia (11%–17%); croup

perihilar infiltrates (87%), hyperinflation (69%), patchy opacities, and atelectasis

risk factors: emale sex, prematurity, esophageal reflux, underlying heart and lung disease, lack of breastfeeding, vitamin D deficiency, and household crowding.

Adult: Healthy adults generally present with mild influenza-like illness and common cold syndromes, with some remaining asymptomatic.36,50,115 In addition to respiratory illnesses, a mononucleosis-like syndrome due to hMPV ; COPD, asthma worsening

Question 12

Diagnosis of MPV

Answer 12

RT-PCR: conserved regions of the F and N genes; sputum, BAL> Nasal washes and nasopharyngeal swabs; PCR may occur for up to 4 weeks in children with primary infection,

IFA: less sensitive than RT-PCR, (low load)

Serology: against F; fourfold rise in antibody titer or seroconver- sion, and thus clinical utility is limited.

Viral culture: rhesus monkey kidney (LLC-MK2) cells in medium containing trypsin. small, round, granular, and refringent cells without large syncytia,

Question 13

Treatment of MPV

Answer 13

supportive

careful of glucocorticoids - antiinflammatory benefits may be offset by the blunting of immune responses that control viral replication.
enhanced hMPV replication in human primary bronchial epithelial cells and reduced viral apoptosis. The effect was suppressed by the use of adjuvant recombinant interferon therapy, raising potential therapeutic strategies.

Ribavarin, favipravir, DAS181 - in studies

Question 14

Spread of MPV

Answer 14

direct contact with infected secretions through fomites or large-particle aerosols (droplet)

Question 15

RSV: aka, hosts

Answer 15

chimpanzee coryza agent (CCA). humans and chimpanzee

Question 16

RSV: ab against; neutralisation; binding by whom; receptor; cells

Answer 16

G and F; prefusion F has more epitopes

G and F; G- CX3C, F- nucleolin in resp epi cell

resp epi cells - cilliated columnar, type I and II pneumocytes, RSV can also infect macrophages, dendritic cells, and T and B cells.

Question 17

Seeasonality of rsv

Answer 17

RSV infections are ubiquitous

In temperate climates, outbreaks occur primarily in late fall through early spring and spread across the United States over 20 or more weeks, generally from October to May. In warmer climates, RSV activity may be more prolonged or even present throughout the year.

Question 18

Genotypes of RSV and homology

Answer 18

2- a and b

81% - most diversity in G protein

Question 19

CF of RSV - infants; types and course

Answer 19

rarely asymptomatic

40% to 90% of bronchiolitis (both expiratory and inspiratory obstruction may be evident, rapid variability in the presence and intensity of physical findings, marked transient swings in oxygen saturation )

up to 50% of pneumonia admissions

tracheobronchitis cases, 10% to 30%

2% to 10% of croup

The highest hospitalization rates (25.9/1000) were in infants 1 month of age, slowly decreasing thereafter. - max before 6 months - all before 5 years

However, severe disease rarely occurs after primary infection in healthy children.

RSV usually starts with upper respiratory tract illness with nasal congestion and cough. Low-grade fever lasting 2 to 4 days occurs in most infants early in the illness. fever is frequently absent by the time of lower respiratory tract involvement. cough may become more prominent and productive, followed by increased respiratory rate, dyspnea, and retractions of intercostal muscles.

Question 20

RSV: IP and viral shedding

Answer 20

an incuba- tion period of 2 to 5 days.

Shedding duration is typically 7 to 10 days, but virus can occasionally be detected for 30 days.85 Increased viral load has been associated with greater disease severity.

Question 21

Main pathogenesis of RSV causing bronchiolitis - why infants more?

Answer 21

characteristic proliferation and necrosis of the epi- thelium of the bronchioles develop. Small airways become obstructed from sloughed epithelium and increased mucus secretion. partial obstruction - hyperinflation, complete obstruction - atelectasis

1) smaller airway- more resistance
2) young infants are at increased risk for developing atelectasis because collateral channels that maintain alveolar expansion in the presence of airway obstruction are not yet well developed.
3) Despite a relatively short half-life of 28 to 40 days, maternally derived antibodies have been correlated with protection in some, but not all, studies.
4)neutralizing antibody responses are blunted in infants younger than 6 months of age owing to a dampening effect of maternal antibody.
5) Infants infected in the first several months of life have higher levels of Th2-type cytokines in nasal secretions than older infants - IL-4 and IL-13 also augment isotype switching to IgE, and a Th2-biased response has been correlated with wheezing, more severe disease, and greater cellular inflammation and eosinophilia in the lung.

Question 22

rationale for maternal vaccination in rsv

Answer 22

26% reduction in hospitalization during the first 6 months of life for every twofold increase in cord blood neutralizing antibody.115 In addition, a study found that higher levels of antibody to prefusion-F and G proteins of RSV and neutralizing antibody were associated with less severe disease in the first few months of life.

Question 23

Serological diagnosis of RSV

Answer 23

IgM) antibody appears within several days but is transient and detectable usually only for a few weeks.95 IgG antibody appears during the second week, peaks in the fourth week, and begins to decline after 1 to 2 months.

against F

Adult: Following natural infection, 75% of adults demonstrate a fourfold or greater decrease in titer, returning to preinfec- tion titers within 2 years in most cases.

Question 24

cf of RSV in children > 1yr of age

Answer 24

Acute otitis media is a common complication of

74% had RSV detected in middle ear fluid.

Acute otitis media usually develops about 5 days after the onset of the respiratory illness and is more common among children older than 1 year - 2-22% bacterial superinfection

Question 25

RSV in older children

Answer 25

75% and 65% develop infection during their second and third years, respectively, using serologic and viral detection methods.53 Recurrent infections commonly are upper respiratory tract illnesses, but 20% to 50% of recurrent infections among preschool-aged children involve the lower respiratory tract, - wheeze

Question 25

RSV in elderly- y

Answer 25

typically manifests with upper respiratory symptoms,

severe illness are frail elderly patients; patients with underlying cardio-
pulmonary disease, especially chronic obstructive pulmonary disease and CHF;
and severely immunocompromised patients;

similar to influenza: 28% of the incidence
of influenza hospitalizations.
RSV mortality
in The Netherlands was 64% of that attributable to influenza (bacterial coinf- 30% similar to infl)

comorbiditess; pulmonary age related decline; age related immune function

Question 26

difference between infl and rsv

Answer 26

earache, sinus pain, persistent productive cough, and wheezing were significantly more common with RSV

Question 27

Risk factors for infants, Immunocomp

Answer 27

premature infants and children with underlying chronic lung disease, cyanotic or complicated congenital heart disease- non surgically treaetd, immunosuppressive conditions, or other chronic diseases that affect the handling of respiratory secretions such as neuromuscular disease.

SOT, HSCT

Question 28

Complication of RSV in infants

Answer 28

Up to 20% of infants hospitalized with RSV infection have been admitted with apnea.

BActerial superinf

bronchiolitis obliterans syndrome

Recurrent wheezing - 30-50%

Question 29

Diagnostic modalities

Answer 29

PCR (nasopharyngeal wash> nasal swab)
IFA
Culture - HEp2- in 3-5 days- synctitium 24 hrs later

Question 30

treatment of RSV

Answer 30

supportive- neither bronchodilators nor corticosteroids are effective for RSV disease or bronchiolitis of unspecified cause among previously

Ribavirin - only in immunocomp- inhalational - teratogenic - so not in pregnant; Others- siRNA, presatovir - fusion inhibtior

Question 31

precautions in rsv

Answer 31

contact + droplet

Question 32

prophylaxis for rsv: infant

Answer 32

Nirsevimab > pavilizumab (if nir not available)

100-fold potency in vitro compared with palivizumab

extended half-life due to a 3–amino acid mutation in the Fc region enhancing binding within the lysosome and preventing antibody degradation and increasing recirculation to the cell surface.

single dose
in all babies born oct to march
in all babies <8 months of age before season (oct- mar) in maternal not vaccinated or born <14 days of maternal vaccine (despite vccine in decreased transplacental antibody transfer such as premature infants or infants born to mothers with decreased maternal antibody transfer due to HIV infection or maternal hypergammaglobulinemia)

in babies 8m-19 months- immunocomp , underlying lung, cf, american indian

Pavilizumab: till 1 year: prematurity (<29 weeks’ gestation), chronic lung disease, functionally important cardiac disease that has not been surgically corrected, and chronic conditions that interfere with the handling of respiratory secretions.

second year of life except for preterm children who required at least 28 days of supplemental oxygen at birth and continue to require supplemental oxygen, long-term systemic steroid therapy, or diuretic therapy within 6 months

Question 33

RSV prevention adult and pregnancy

Answer 33

see notes