Epidemiology and prevention of respiratory syncytial virus infections in children in Italy

Chiara Azzari, Eugenio Baraldi, Paolo Bonanni, Elena Bozzola, Alessandra Coscia, Marcello Lanari, Paolo Manzoni, Teresa Mazzone, Fabrizio Sandri, Giovanni Checcucci Lisi, Salvatore Parisi, Giorgio Piacentini, Fabio Mosca, Chiara Azzari, Eugenio Baraldi, Paolo Bonanni, Elena Bozzola, Alessandra Coscia, Marcello Lanari, Paolo Manzoni, Teresa Mazzone, Fabrizio Sandri, Giovanni Checcucci Lisi, Salvatore Parisi, Giorgio Piacentini, Fabio Mosca

Abstract

Respiratory syncytial virus (RSV) is the leading global cause of respiratory infections in infants and the second most frequent cause of death during the first year of life. This highly contagious seasonal virus is responsible for approximately 3 million hospitalizations and 120,000 deaths annually among children under the age of 5 years. Bronchiolitis is the most common severe manifestation; however, RSV infections are associated with an increased long-term risk for recurring wheezing and the development of asthma. There is an unmet need for new agents and a universal strategy to prevent RSV infections starting at the time of birth. RSV is active between November and April in Italy, and prevention strategies must ensure that all neonates and infants under 1 year of age are protected during the endemic season, regardless of gestational age at birth and timing of birth relative to the epidemic season. Approaches under development include maternal vaccines to protect neonates during their first months, monoclonal antibodies to provide immediate protection lasting up to 5 months, and pediatric vaccines for longer-lasting protection. Meanwhile, improvements are needed in infection surveillance and reporting to improve case identification and better characterize seasonal trends in infections along the Italian peninsula. Rapid diagnostic tests and confirmatory laboratory testing should be used for the differential diagnosis of respiratory pathogens in children. Stakeholders and policymakers must develop access pathways once new agents are available to reduce the burden of infections and hospitalizations.

Keywords: LRTI; Monoclonal antibodies; RSV; RSV epidemiology; RSV pediatric burden; RSV prevention; RSV vaccines; Respiratory syncytial virus.

Conflict of interest statement

All authors have been participants at advisory boards and/or have been speakers at symposia and/or lecture sponsored by Sanofi and/or AbbVie. G Checcucci Lisi and S Parisi are employees of Sanofi Pasteur, working at the Medical Affairs Department, and may hold shares/stock options as part of remuneration package.

© 2021. The Author(s).

Figures

Fig. 1
Fig. 1
Number of respiratory samples sent by sentinel physicians and number of samples testing positive for influenza virus, SARS-COV-2, and RSV; 2020–2021 season, Lombardy (updated January 27, 2021). SARS-COV-2 was the only virus detected in tested influenza-like illness samples. RSV respiratory syncytial virus [12]
Fig. 2
Fig. 2
Structure of RSV. RSV respiratory syncytial virus. Modified from [16]
Fig. 3
Fig. 3
Number of RSV-positive and RSV-negative samples and ILI incidence per 1000 residents per week in four consecutive seasons. ILI influenza-like illness; RSV respiratory syncytial virus. Modified from [37, 39]
Fig. 4
Fig. 4
Seasonal trend of pediatric hospitalizations due to respiratory infections from RSV in Tuscany, 2015–2019. RSV respiratory syncytial virus [1]
Fig. 5
Fig. 5
Periods of potential protection from RSV infection using different prevention strategies, based on RSV seasonality in Italy. RSV respiratory syncytial virus. Modified from [5]

References

    1. Barbati F, Moriondo M, Pisano L, Calistri E, Lodi L, Ricci S, Giovannini M, Canessa C, Indolfi G, Azzari C. Epidemiology of respiratory syncytial virus-related hospitalization over a 5-year period in Italy: evaluation of seasonality and age distribution before vaccine introduction. Vaccines (Basel) 2020;8(1):15. doi: 10.3390/vaccines8010015.
    1. Public Health England . Respiratory syncytial virus (RSV): symptoms, transmission, prevention, treatment. 2008.
    1. Centers for Disease Control and Prevention . RSV in infants and young children. 2020.
    1. Cutrera R, Wolfler A, Picone S, Rossi GA, Gualberti G, Merolla R, del Vecchio A, Villani A, Midulla F, Dotta A. Impact of the 2014 American Academy of Pediatrics recommendation and of the resulting limited financial coverage by the Italian Medicines Agency for palivizumab prophylaxis on the RSV-associated hospitalizations in preterm infants during the 2016-2017 epidemic season: a systematic review of seven Italian reports. Ital J Pediatr. 2019;45(1):139. doi: 10.1186/s13052-019-0736-5.
    1. Janet S, Broad J, Snape MD. Respiratory syncytial virus seasonality and its implications on prevention strategies. Hum Vaccin Immunother. 2018;14(1):234–244. doi: 10.1080/21645515.2017.1403707.
    1. Mazur NI, Martinón-Torres F, Baraldi E, Fauroux B, Greenough A, Heikkinen T, Manzoni P, Mejias A, Nair H, Papadopoulos NG, Polack FP, Ramilo O, Sharland M, Stein R, Madhi SA, Bont L, Respiratory Syncytial Virus Network (ReSViNET) Lower respiratory tract infection caused by respiratory syncytial virus: current management and new therapeutics. Lancet Respir Med. 2015;3(11):888–900. doi: 10.1016/S2213-2600(15)00255-6.
    1. Shi T, McAllister DA, O'Brien KL, Simoes EAF, Madhi SA, Gessner BD, Polack FP, Balsells E, Acacio S, Aguayo C, Alassani I, Ali A, Antonio M, Awasthi S, Awori JO, Azziz-Baumgartner E, Baggett HC, Baillie VL, Balmaseda A, Barahona A, Basnet S, Bassat Q, Basualdo W, Bigogo G, Bont L, Breiman RF, Brooks WA, Broor S, Bruce N, Bruden D, Buchy P, Campbell S, Carosone-Link P, Chadha M, Chipeta J, Chou M, Clara W, Cohen C, de Cuellar E, Dang DA, Dash-Yandag B, Deloria-Knoll M, Dherani M, Eap T, Ebruke BE, Echavarria M, de Freitas Lázaro Emediato CC, Fasce RA, Feikin DR, Feng L, Gentile A, Gordon A, Goswami D, Goyet S, Groome M, Halasa N, Hirve S, Homaira N, Howie SRC, Jara J, Jroundi I, Kartasasmita CB, Khuri-Bulos N, Kotloff KL, Krishnan A, Libster R, Lopez O, Lucero MG, Lucion F, Lupisan SP, Marcone DN, McCracken J, Mejia M, Moisi JC, Montgomery JM, Moore DP, Moraleda C, Moyes J, Munywoki P, Mutyara K, Nicol MP, Nokes DJ, Nymadawa P, da Costa Oliveira MT, Oshitani H, Pandey N, Paranhos-Baccalà G, Phillips LN, Picot VS, Rahman M, Rakoto-Andrianarivelo M, Rasmussen ZA, Rath BA, Robinson A, Romero C, Russomando G, Salimi V, Sawatwong P, Scheltema N, Schweiger B, Scott JAG, Seidenberg P, Shen K, Singleton R, Sotomayor V, Strand TA, Sutanto A, Sylla M, Tapia MD, Thamthitiwat S, Thomas ED, Tokarz R, Turner C, Venter M, Waicharoen S, Wang J, Watthanaworawit W, Yoshida LM, Yu H, Zar HJ, Campbell H, Nair H, RSV Global Epidemiology Network Global, regional, and national disease burden estimates of acute lower respiratory infections due to respiratory syncytial virus in young children in 2015: a systematic review and modelling study. Lancet. 2017;390(10098):946–958. doi: 10.1016/S0140-6736(17)30938-8.
    1. Bont L, Checchia PA, Fauroux B, Figueras-Aloy J, Manzoni P, Paes B, Simões EAF, Carbonell-Estrany X. Defining the epidemiology and burden of severe respiratory syncytial virus infection among infants and children in Western countries. Infect Dis Ther. 2016;5(3):271–298. doi: 10.1007/s40121-016-0123-0.
    1. Murray J, Bottle A, Sharland M, Modi N, Aylin P, Majeed A, Saxena S, On behalf of the Medicines for Neonates Investigator Group Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study. PLoS One. 2014;9(2):e89186. doi: 10.1371/journal.pone.0089186.
    1. Lanari M, Prinelli F, Adorni F, Di Santo S, Vandini S, Silvestri M, et al. Risk factors for bronchiolitis hospitalization during the first year of life in a multicenter Italian birth cohort. Ital J Pediatr. 2015;41(1):40. doi: 10.1186/s13052-015-0149-z.
    1. Ministero della Salute, Istituto Superiore di Sanità . Sistema di Sorveglianza InfluNet. 2020.
    1. Lombardia R. Influnews: Informazioni settimanali sull’influenza. 2021.
    1. Ghirardo S, Ullmann N, Ciofi Degli Atti ML, Raponi M, Cutrera R. Delayed season’s onset and reduction of incidence of bronchiolitis during COVID-19 pandemic. Pediatr Pulmonol. 2021;56(8):2780–2781. doi: 10.1002/ppul.25461.
    1. Britton PN, Hu N, Saravanos G, Shrapnel J, Davis J, Snelling T, Dalby-Payne J, Kesson AM, Wood N, Macartney K, McCullagh C, Lingam R. COVID-19 public health measures and respiratory syncytial virus. Lancet Child Adolesc Health. 2020;4(11):e42–e43. doi: 10.1016/S2352-4642(20)30307-2.
    1. Australia NSW. COVID-19 weekly surveillance. 2021.
    1. Foley DA, Yeoh DK, Martin AC, Mace AO, Sikazwe CT, et al. The interseasonal resurgence of respiratory syncytial virus in Australian children following the reduction of coronavirus disease 2019–related public health measures. Clin Infect Dis. 2021;17:ciaa1906. doi: 10.1093/cid/ciaa1906.
    1. Aranda SS, Polack FP. Prevention of pediatric respiratory syncytial virus lower respiratory tract illness: perspectives for the next decade. Front Immunol. 2019;10:1006. doi: 10.3389/fimmu.2019.01006.
    1. Drysdale SB, Barr RS, Rollier CS, Green CA, Pollard AJ, Sande CJ. Priorities for developing respiratory syncytial virus vaccines in different target populations. Sci Transl Med. 2020;12(535):eaax2466. doi: 10.1126/scitranslmed.aax2466.
    1. Bergeron HC, Tripp RA. Emerging small and large molecule therapeutics for respiratory syncytial virus. Expert Opin Investig Drugs. 2020;29(3):285–294. doi: 10.1080/13543784.2020.1735349.
    1. Barr R, Green CA, Sande CJ, Drysdale SB. Respiratory syncytial virus: diagnosis, prevention and management. Ther Adv Infect Dis. 2019;6:2049936119865798. doi: 10.1177/2049936119865798.
    1. Takeyama A, Hashimoto K, Sato M, Sato T, Tomita Y, Maeda R, Ito M, Katayose M, Kawasaki Y, Hosoya M. Clinical and epidemiologic factors related to subsequent wheezing after virus-induced lower respiratory tract infections in hospitalized pediatric patients younger than 3 years. Eur J Pediatr. 2014;173(7):959–966. doi: 10.1007/s00431-014-2277-7.
    1. Baraldi E, Bonadies L, Manzoni P. Evidence on the link between respiratory syncytial virus infection in early life and chronic obstructive lung diseases. Am J Perinatol. 2020;37(Suppl 2):S26–S30. doi: 10.1055/s-0040-1714345.
    1. Coutts J, Fullarton J, Morris C, Grubb E, Buchan S, Rodgers-Gray B, Thwaites R. Association between respiratory syncytial virus hospitalization in infancy and childhood asthma. Pediatr Pulmonol. 2020;55(5):1104–1110. doi: 10.1002/ppul.24676.
    1. Driscoll AJ, Arshad SH, Bont L, Brunwasser SM, Cherian T, Englund JA, Fell DB, Hammitt LL, Hartert TV, Innis BL, Karron RA, Langley GE, Mulholland EK, Munywoki PK, Nair H, Ortiz JR, Savitz DA, Scheltema NM, Simões EAF, Smith PG, Were F, Zar HJ, Feikin DR. Does respiratory syncytial virus lower respiratory illness in early life cause recurrent wheeze of early childhood and asthma? Critical review of the evidence and guidance for future studies from a World Health Organization-sponsored meeting. Vaccine. 2020;38(11):2435–2448. doi: 10.1016/j.vaccine.2020.01.020.
    1. Ralston SL, Lieberthal AS, Meissner HC, Alverson BK, Baley JE, Gadomski AM, Johnson DW, Light MJ, Maraqa NF, Mendonca EA, Phelan KJ, Zorc JJ, Stanko-Lopp D, Brown MA, Nathanson I, Rosenblum E, Sayles S, 3rd, Hernandez-Cancio S, American Academy of Pediatrics Clinical practice guideline: the diagnosis, management, and prevention of bronchiolitis. Pediatrics. 2014;134(5):e1474–e1502. doi: 10.1542/peds.2014-2742.
    1. Baraldi E, Lanari M, Manzoni P, Rossi GA, Vandini S, Rimini A, Romagnoli C, Colonna P, Biondi A, Biban P, Chiamenti G, Bernardini R, Picca M, Cappa M, Magazzù G, Catassi C, Urbino AF, Memo L, Donzelli G, Minetti C, Paravati F, di Mauro G, Festini F, Esposito S, Corsello G. Inter-society consensus document on treatment and prevention of bronchiolitis in newborns and infants. Ital J Pediatr. 2014;40(1):65. doi: 10.1186/1824-7288-40-65.
    1. European Medicines Agency. Synagis, INN-palivizumab. Summary of product characteristics. . Accessed 23 Feb 2021.
    1. Agenzia Italiana del Farmaco. Determina 2 Novembre 2017. . 2017. Accessed 23 Feb 2021.
    1. Variazione del Piano Terapeutico Palivizumab, in base alla Determina AIFA DG/1836/2017, pubblicata sulla G.U. del 9/11/2017 n. 262. . 2017. Accessed 23 Feb 2021.
    1. Bollani L, Baraldi E, Chirico G, Dotta A, Lanari M, Del Vecchio A, et al. Revised recommendations concerning palivizumab prophylaxis for respiratory syncytial virus. Ital J Pediatr. 2015;41(1):97. doi: 10.1186/s13052-015-0203-x.
    1. Higgins D, Trujillo C, Keech C. Advances in RSV vaccine research and development – a global agenda. Vaccine. 2016;34(26):2870–2875. doi: 10.1016/j.vaccine.2016.03.109.
    1. World Health Organization. RSV vaccine research and development. . Accessed 23 Feb 2021.
    1. Rocca A, Biagi C, Scarpini S, Dondi A, Vandini S, Pierantoni L, Lanari M. Passive immunoprophylaxis against respiratory syncytial virus in children: where are we now? Int J Mol Sci. 2021;22(7):3703. doi: 10.3390/ijms22073703.
    1. NITAG, Ministero della Salute. Piano nazionale Vaccini. Ecco le indicazioni degli esperti del Ministero della Salute del Nitag. Quotidinano Sanità, 15/09/2020. . Accessed 23 Feb 2021.
    1. NITAG, Ministero della Salute. Il PNPV 2020–2022: raccomandazioni del nucleo strategico del NITAG. Available at: . Accessed 23 Feb 2021.
    1. World Health Organization. WHO Global Respiratory Syncytial Virus Surveillance. Outcomes from phase 1. . Accessed 23 Feb 2021.
    1. World Health Organization. WHO RSV Surveillance phase-2 (2019–2021). . Accessed 23 Feb 2021.
    1. World Health Organization. RSV surveillance case definitions. . Accessed 23 Feb 2021.
    1. Sistema di Sorveglianza Sentinella dell'Influenza, InfluNet. Protocollo operativo. Stagione 2019–20. . 2019. Accessed 23 Feb 2021.
    1. Sistema di Sorveglianza Sentinella dell’Influenza, InfluNet. Stagione influenzale 2020–2021: il “Protocollo operativo InfluNet & CovidNet”. . 2020. Accessed 23 Feb 2021.
    1. Pellegrinelli L, Galli C, Bubba L, Cereda D, Anselmi G, Binda S, Gramegna M, Pariani E. Respiratory syncytial virus in influenza-like illness cases: epidemiology and molecular analyses of four consecutive winter seasons (2014–2015/2017–2018) in Lombardy (northern Italy) J Med Virol. 2020;92(12):2999–3006. doi: 10.1002/jmv.25917.
    1. Calderaro A, De Conto F, Buttrini M, Piccolo G, Montecchini S, Maccari C, et al. Human respiratory viruses, including SARS-CoV-2, circulating in the winter season 2019–2020 in Parma. Northern Italy Int J Infect Dis. 2021;102:79–84. doi: 10.1016/j.ijid.2020.09.1473.
    1. Kuhdari P, Brosio F, Malaventura C, Stefanati A, Orsi A, Icardi G, Gabutti G. Human respiratory syncytial virus and hospitalization in young children in Italy. Ital J Pediatr. 2018;44(1):50. doi: 10.1186/s13052-018-0492-y.
    1. Ciarlitto C, Vittucci AC, Villani A, Concato C, Di Camillo C, Zangari P, et al. Respiratory syncityal virus a and B: three bronchiolitis seasons in a third level hospital in Italy. Ital J Pediatr. 2019;45(1):115. doi: 10.1186/s13052-019-0704-0.
    1. Wrotek A, Czajkowska M, Jackowska T. Nosocomial infections in patients hospitalized with respiratory syncytial virus: a practice review. Adv Exp Med Biol. 2020;1271:1–10. doi: 10.1007/5584_2020_483.
    1. Bozzola E, Ciarlitto C, Guolo S, Brusco C, Cerone G, Antilici L, Schettini L, Piscitelli AL, Chiara Vittucci A, Cutrera R, Raponi M, Villani A. Respiratory syncytial virus bronchiolitis in infancy: the acute hospitalization cost. Front Pediatr. 2021;8:594898. doi: 10.3389/fped.2020.594898.
    1. Biagi C, Dondi A, Scarpini S, Rocca A, Vandini S, Poletti G, Lanari M. Current state and challenges in developing respiratory syncytial virus vaccines. Vaccines (Basel) 2020;8(4):672. doi: 10.3390/vaccines8040672.
    1. Mochizuki H, Kusuda S, Okada K, Yoshihara S, Furuya H, Simões EAF, Asanuma H, Yoshida H, Katayose M, Imamura T, Suzumura H, Honma Y, Medical J, Maruyama K, Ohki Y, Ozasa K, Nariai A, Uchiyama A, Uryu H, Hosono S, Kondo M, Kawase Y, Ikeda K, Ikeda K, Naito A, Minami Y, Nakamura T, Baba A, Nagayama Y, Kaneda H, Ohki S, Shiraii M, Henmi Y, Suzuki C, Ieda K, Tanaka T, Kono Y, Nisizawa K, Niwa F, Ito H, Tokunaga Y, Takada Y, Nishikawa Y, Nagata I, Kajino Y, Watabe S, Yoshio H, Takahashi N, Sasaki N, Hayashidani M, Tateishi H, Matsushita K, Nakamura M, Nakayama H, Yamamoto G, Kanemitsu N, Takayanagi T, Sato A, Ibara S. Palivizumab prophylaxis in preterm infants and subsequent recurrent wheezing. Six-year follow-up study. Am J Respir Crit Care Med. 2017;196(1):29–38. doi: 10.1164/rccm.201609-1812OC.
    1. Ministero della Salute . Piano Nazionale Prevenzione Vaccinale. 2017.
    1. Regione Lombardia, Sistema Socio Sanitario. Benvenuti al Nido. 2017. Accessed Feb 23 2021. .
    1. ATS Brianza. Il controllo della crescita, i bilanci di salute. . Accessed 23 Feb 2021.

Source: PubMed

Sponsors en medewerkers

Medische omstandigheden

Geneesmiddelinterventies

3
Abonneren