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Published in: BMC Medicine 1/2015

Open Access 01-12-2015 | Research Article

Evaluating vaccination strategies for reducing infant respiratory syncytial virus infection in low-income settings

Authors: Piero Poletti, Stefano Merler, Marco Ajelli, Piero Manfredi, Patrick K Munywoki, D James Nokes, Alessia Melegaro

Published in: BMC Medicine | Issue 1/2015

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Abstract

Background

Respiratory syncytial virus (RSV) is a leading cause of lower respiratory tract disease and related hospitalization of young children in least developed countries. Individuals are repeatedly infected, but it is the first exposure, often in early infancy, that results in the vast majority of severe RSV disease. Unfortunately, due to immunological immaturity, infants are a problematic RSV vaccine target. Several trials are ongoing to identify a suitable candidate vaccine and target group, but no immunization program is yet in place.

Methods

In this work, an individual-based model that explicitly accounts for the socio-demographic population structure is developed to investigate RSV transmission patterns in a rural setting of Kenya and to evaluate the potential effectiveness of alternative population targets in reducing RSV infant infection.

Results

We find that household transmission is responsible for 39% of infant infections and that school-age children are the main source of infection within the household, causing around 55% of cases. Moreover, assuming a vaccine-induced protection equivalent to that of natural infection, our results show that annual vaccination of students is the only alternative strategy to routine immunization of infants able to trigger a relevant and persistent reduction of infant infection (on average, of 35.6% versus 41.5% in 10 years of vaccination). Interestingly, if vaccination of pregnant women boosts maternal antibody protection in infants by an additional 4 months, RSV infant infection will be reduced by 31.5%.

Conclusions

These preliminary evaluations support the efforts to develop vaccines and related strategies that go beyond targeting vaccines to those at highest risk of severe disease.
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Literature
1.
go back to reference Waris M. Pattern of respiratory syncytial virus epidemics in Finland: two-year cycles with alternating prevalence of groups A and B. J Infect Dis. 1991; 163:464–9.CrossRefPubMed Waris M. Pattern of respiratory syncytial virus epidemics in Finland: two-year cycles with alternating prevalence of groups A and B. J Infect Dis. 1991; 163:464–9.CrossRefPubMed
2.
go back to reference Mlinaric-Galinovic G, Welliver RC, Vilibic-Cavlek T, Ljubin-Sternak S, Drazenovic V, Galinovic I, et al. The biennial cycle of respiratory syncytial virus outbreaks in Croatia. Virol J. 2008; 5:18.CrossRefPubMedPubMedCentral Mlinaric-Galinovic G, Welliver RC, Vilibic-Cavlek T, Ljubin-Sternak S, Drazenovic V, Galinovic I, et al. The biennial cycle of respiratory syncytial virus outbreaks in Croatia. Virol J. 2008; 5:18.CrossRefPubMedPubMedCentral
3.
go back to reference Nokes DJ, Okiro EA, Ngama M, Ochola R, White LJ, Scott PD, et al. Respiratory syncytial virus infection and disease in infants and young children observed from birth in Kilifi District, Kenya. Clin Infect Dis. 2008; 46:50–7.CrossRefPubMedPubMedCentral Nokes DJ, Okiro EA, Ngama M, Ochola R, White LJ, Scott PD, et al. Respiratory syncytial virus infection and disease in infants and young children observed from birth in Kilifi District, Kenya. Clin Infect Dis. 2008; 46:50–7.CrossRefPubMedPubMedCentral
4.
go back to reference Ohuma EO, Okiro EA, Ochola R, Sande CJ, Cane PA, Medley GF, et al. The natural history of respiratory syncytial virus in a birth cohort: the influence of age and previous infection on reinfection and disease. Am J Epidemiol. 2012; 176:794–802.CrossRefPubMedPubMedCentral Ohuma EO, Okiro EA, Ochola R, Sande CJ, Cane PA, Medley GF, et al. The natural history of respiratory syncytial virus in a birth cohort: the influence of age and previous infection on reinfection and disease. Am J Epidemiol. 2012; 176:794–802.CrossRefPubMedPubMedCentral
5.
go back to reference Nokes DJ, Ngama M, Bett A, Abwao J, Munywoki PK, English M, et al. Incidence and severity of respiratory syncytial virus pneumonia in rural Kenyan children identified through hospital surveillance. Clin Infect Dis. 2009; 49:1341–9.CrossRefPubMedPubMedCentral Nokes DJ, Ngama M, Bett A, Abwao J, Munywoki PK, English M, et al. Incidence and severity of respiratory syncytial virus pneumonia in rural Kenyan children identified through hospital surveillance. Clin Infect Dis. 2009; 49:1341–9.CrossRefPubMedPubMedCentral
6.
go back to reference Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010; 375:1545–55.CrossRefPubMedPubMedCentral Nair H, Nokes DJ, Gessner BD, Dherani M, Madhi SA, Singleton RJ, et al. Global burden of acute lower respiratory infections due to respiratory syncytial virus in young children: a systematic review and meta-analysis. Lancet. 2010; 375:1545–55.CrossRefPubMedPubMedCentral
7.
go back to reference Berkley JA, Munywoki P, Ngama M, Kazungu S, Abwao J, Bett A, et al. Viral etiology of severe pneumonia among Kenyan infants and children. J Am Med Assoc. 2010; 303:2051–7.CrossRef Berkley JA, Munywoki P, Ngama M, Kazungu S, Abwao J, Bett A, et al. Viral etiology of severe pneumonia among Kenyan infants and children. J Am Med Assoc. 2010; 303:2051–7.CrossRef
8.
go back to reference Glezen WP, Taber LH, Frank AL, Kasel JA. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child. 1986; 140:543–6.PubMed Glezen WP, Taber LH, Frank AL, Kasel JA. Risk of primary infection and reinfection with respiratory syncytial virus. Am J Dis Child. 1986; 140:543–6.PubMed
9.
go back to reference Hall CB, Geiman JM, Biggar R, Kotok DI, Hogan PM, Douglas RG. Respiratory syncytial virus infections within families. N Engl J Med. 1976; 294:414–41.CrossRefPubMed Hall CB, Geiman JM, Biggar R, Kotok DI, Hogan PM, Douglas RG. Respiratory syncytial virus infections within families. N Engl J Med. 1976; 294:414–41.CrossRefPubMed
10.
go back to reference Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med. 2009; 360:588–98.CrossRefPubMedPubMedCentral Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, Staat MA, et al. The burden of respiratory syncytial virus infection in young children. N Engl J Med. 2009; 360:588–98.CrossRefPubMedPubMedCentral
11.
go back to reference Okiro EA, White LJ, Ngama M, Cane PA, Medley GF, Nokes DJ. Duration of shedding of respiratory syncytial virus in a community study of Kenyan children. BMC Infect Dis. 2010; 10:15.CrossRefPubMedPubMedCentral Okiro EA, White LJ, Ngama M, Cane PA, Medley GF, Nokes DJ. Duration of shedding of respiratory syncytial virus in a community study of Kenyan children. BMC Infect Dis. 2010; 10:15.CrossRefPubMedPubMedCentral
12.
go back to reference Fletcher JN, Smyth RL, Thomas HM, Ashby D, Hart CA. Respiratory syncytial virus genotypes and disease severity among children in hospital. Arch Dis Child. 1997; 77:508–11.CrossRefPubMedPubMedCentral Fletcher JN, Smyth RL, Thomas HM, Ashby D, Hart CA. Respiratory syncytial virus genotypes and disease severity among children in hospital. Arch Dis Child. 1997; 77:508–11.CrossRefPubMedPubMedCentral
13.
go back to reference Polack FP, Karron RA. The future of respiratory syncytial virus vaccine development. Pediatr Infect Dis J. 2004; 23:65–73.CrossRef Polack FP, Karron RA. The future of respiratory syncytial virus vaccine development. Pediatr Infect Dis J. 2004; 23:65–73.CrossRef
14.
go back to reference Anderson LJ, Dormitzer PR, Nokes DJ, Rappuoli R, Roca A, Graham BS. Strategic priorities for respiratory syncytial virus (RSV) vaccine development. Vaccine. 2013; 31:209–15.CrossRef Anderson LJ, Dormitzer PR, Nokes DJ, Rappuoli R, Roca A, Graham BS. Strategic priorities for respiratory syncytial virus (RSV) vaccine development. Vaccine. 2013; 31:209–15.CrossRef
15.
go back to reference Munywoki PK, Koech DC, Agoti CN, Lewa C, Cane PA, Medley GF, et al.The source of respiratory syncytial virus infection in infants: a household cohort study in rural Kenya. J Infect Dis. 2013; 209(10):1685–1692.PubMedPubMedCentral Munywoki PK, Koech DC, Agoti CN, Lewa C, Cane PA, Medley GF, et al.The source of respiratory syncytial virus infection in infants: a household cohort study in rural Kenya. J Infect Dis. 2013; 209(10):1685–1692.PubMedPubMedCentral
16.
go back to reference Ferguson NM, Cummings DAT, Cauchemez S, Fraser C, Riley S, Meeyai A, et al. Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature. 2005; 437:209–14.CrossRefPubMed Ferguson NM, Cummings DAT, Cauchemez S, Fraser C, Riley S, Meeyai A, et al. Strategies for containing an emerging influenza pandemic in Southeast Asia. Nature. 2005; 437:209–14.CrossRefPubMed
17.
go back to reference Merler S, Ajelli M. The role of population heterogeneity and human mobility in the spread of pandemic influenza. Proc R Soc B. 2010; 277(1681):557–65.CrossRefPubMed Merler S, Ajelli M. The role of population heterogeneity and human mobility in the spread of pandemic influenza. Proc R Soc B. 2010; 277(1681):557–65.CrossRefPubMed
18.
go back to reference Merler S, Ajelli M, Pugliese A, Ferguson NM. Determinants of the spatiotemporal dynamics of the 2009 H1N1 pandemic in Europe: implications for real-time modelling. PLOS Comput Biol. 2011; 7:1002205.CrossRef Merler S, Ajelli M, Pugliese A, Ferguson NM. Determinants of the spatiotemporal dynamics of the 2009 H1N1 pandemic in Europe: implications for real-time modelling. PLOS Comput Biol. 2011; 7:1002205.CrossRef
19.
go back to reference Merler S, Ajelli M, Fumanelli L, Vespignani A. Containing the accidental laboratory escape of potential pandemic influenza viruses. BMC Med. 2013; 11(3):252.CrossRefPubMedPubMedCentral Merler S, Ajelli M, Fumanelli L, Vespignani A. Containing the accidental laboratory escape of potential pandemic influenza viruses. BMC Med. 2013; 11(3):252.CrossRefPubMedPubMedCentral
22.
go back to reference United Nations, Department of Economic and Social Affairs. World Population Prospects. http://www.un.org/en/development/desa/population/. United Nations, Department of Economic and Social Affairs. World Population Prospects. http://​www.​un.​org/​en/​development/​desa/​population/​.
23.
go back to reference Gomes MGM, White LJ, Medley GF. Infection, reinfection, and vaccination under suboptimal immune protection: epidemiological perspectives. J Theor Biol. 2004; 228:539–49.CrossRefPubMed Gomes MGM, White LJ, Medley GF. Infection, reinfection, and vaccination under suboptimal immune protection: epidemiological perspectives. J Theor Biol. 2004; 228:539–49.CrossRefPubMed
24.
go back to reference Weber A, Weber M, Milligan P. Modeling epidemics caused by respiratory syncytial virus (RSV). Math Biosci. 2001; 172:95–113.CrossRefPubMed Weber A, Weber M, Milligan P. Modeling epidemics caused by respiratory syncytial virus (RSV). Math Biosci. 2001; 172:95–113.CrossRefPubMed
25.
go back to reference White LJ, Mandl NJ, Gomes MGM, Bodely–Tickell AT, Cane PA, Perez–Brena P, et al. Understanding the transmission dynamics of respiratory syncytial virus using multiple time series and nested models. Math Biosci. 2007; 209:222–39.CrossRefPubMedPubMedCentral White LJ, Mandl NJ, Gomes MGM, Bodely–Tickell AT, Cane PA, Perez–Brena P, et al. Understanding the transmission dynamics of respiratory syncytial virus using multiple time series and nested models. Math Biosci. 2007; 209:222–39.CrossRefPubMedPubMedCentral
26.
go back to reference Ochola R, Sande C, Fegan G, Scott PD, Medley GF, Cane PA, et al. The level and duration of RSV-specific maternal IgG in infants in Kilifi Kenya. PLOS ONE. 2009; 4:8088.CrossRef Ochola R, Sande C, Fegan G, Scott PD, Medley GF, Cane PA, et al. The level and duration of RSV-specific maternal IgG in infants in Kilifi Kenya. PLOS ONE. 2009; 4:8088.CrossRef
28.
go back to reference UNESCO, International Bureau of Education. http://www.ibe.unesco.org/. UNESCO, International Bureau of Education. http://​www.​ibe.​unesco.​org/​.
29.
go back to reference Cauchemez S, Carrat F, Viboud C, Valleron AJ, Boëlle PY. A Bayesian MCMC approach to study transmission of influenza: application to household longitudinal data. Stat Med. 2004; 23:3469–87.CrossRefPubMed Cauchemez S, Carrat F, Viboud C, Valleron AJ, Boëlle PY. A Bayesian MCMC approach to study transmission of influenza: application to household longitudinal data. Stat Med. 2004; 23:3469–87.CrossRefPubMed
30.
go back to reference Merler S, Ajelli M. Deciphering the relative weights of demographic transition and vaccination in the descrease of measles incidence in Italy. Proc R Soc B. 2014; 281:20132676.CrossRefPubMedPubMedCentral Merler S, Ajelli M. Deciphering the relative weights of demographic transition and vaccination in the descrease of measles incidence in Italy. Proc R Soc B. 2014; 281:20132676.CrossRefPubMedPubMedCentral
31.
go back to reference Nokes DJ, Okiro EA, Ngama M, White LJ, Ochola R, Scott PD, et al. Respiratory syncytial virus epidemiology in a birth cohort from Kilifi District, Kenya: infection during the first year of life. J Infect Dis. 2004; 190:1828–32.CrossRefPubMed Nokes DJ, Okiro EA, Ngama M, White LJ, Ochola R, Scott PD, et al. Respiratory syncytial virus epidemiology in a birth cohort from Kilifi District, Kenya: infection during the first year of life. J Infect Dis. 2004; 190:1828–32.CrossRefPubMed
32.
go back to reference Baguelin M, Flasche S, Camacho A, Demiris N, Miller E, Edmunds WJ. Assessing optimal target populations for influenza vaccination programmes: an evidence synthesis and modelling study. PLOS Med. 2013; 10:1001527.CrossRef Baguelin M, Flasche S, Camacho A, Demiris N, Miller E, Edmunds WJ. Assessing optimal target populations for influenza vaccination programmes: an evidence synthesis and modelling study. PLOS Med. 2013; 10:1001527.CrossRef
34.
go back to reference Glezen WP, Paredes A, Allison JE, Taber LH, Frank AL. Risk of respiratory syncytial virus infection for infants from low-income families in relationship to age, sex, ethnic group, and maternal antibody level. J Pediatr. 1981; 98:708–15.CrossRefPubMed Glezen WP, Paredes A, Allison JE, Taber LH, Frank AL. Risk of respiratory syncytial virus infection for infants from low-income families in relationship to age, sex, ethnic group, and maternal antibody level. J Pediatr. 1981; 98:708–15.CrossRefPubMed
35.
go back to reference Ferguson NM, Cummings DAT, Fraser C, Cajka JC, Cooley PC, Burke DS. Strategies for mitigating an influenza pandemic. Nature. 2006; 442:448–52.CrossRefPubMed Ferguson NM, Cummings DAT, Fraser C, Cajka JC, Cooley PC, Burke DS. Strategies for mitigating an influenza pandemic. Nature. 2006; 442:448–52.CrossRefPubMed
36.
go back to reference Ajelli M, Merler S. The impact of the unstructured contacts component in influenza pandemic modeling. PLOS ONE. 2008; 3:1519.CrossRef Ajelli M, Merler S. The impact of the unstructured contacts component in influenza pandemic modeling. PLOS ONE. 2008; 3:1519.CrossRef
37.
38.
go back to reference d’Onofrio A, Manfredi P, Poletti P. The interplay of public intervention and private choices in determining the outcome of vaccination programmes. PLOS ONE. 2012; 7:45653.CrossRef d’Onofrio A, Manfredi P, Poletti P. The interplay of public intervention and private choices in determining the outcome of vaccination programmes. PLOS ONE. 2012; 7:45653.CrossRef
Metadata
Title
Evaluating vaccination strategies for reducing infant respiratory syncytial virus infection in low-income settings
Authors
Piero Poletti
Stefano Merler
Marco Ajelli
Piero Manfredi
Patrick K Munywoki
D James Nokes
Alessia Melegaro
Publication date
01-12-2015
Publisher
BioMed Central
Published in
BMC Medicine / Issue 1/2015
Electronic ISSN: 1741-7015
DOI
https://doi.org/10.1186/s12916-015-0283-x

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