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

BMC Medicine

Alessia Melegaro⁵  D James Nokes³  Patrick K Munywoki¹  Piero Manfredi²  Marco Ajelli⁴  Stefano Merler⁴  Piero Poletti⁴ 

[1] Kenyan Medical Research Institute (KEMRI) - Wellcome Trust Research Programme, Centre for Geographic Medicine Research (Coast), Hospital Road, Kilifi, Kenya;Department of Statistics and Mathematics Applied to Economics, University of Pisa, via Ridolfi 10, Pisa, Italy;School of Life Sciences and WIDER, University of Warwick, Coventry CV4 7AL, Warwick, UK;Center for Information Technology, Bruno Kessler Foundation, via Sommarive, 18, Trento, Italy;Dondena Centre for Research on Social Dynamics and Public Policy, Department of Policy Analysis and Public Management, Universitá Commerciale L. Bocconi, via Rontgen n. 1, Milan, Italy

关键词: Household transmission;    Vaccination;    RSV;    Infectious diseases;    Computational models;   

Others  :  1139961
DOI  :  10.1186/s12916-015-0283-x

 received in 2014-10-14, accepted in 2015-01-22,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Poletti et al.; licensee BioMed Central.

【 图 表 】

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【 参考文献 】

• [1]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.
• [2]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. BioMed Central Full Text
• [3]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.
• [4]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.
• [5]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.
• [6]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.
• [7]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.
• [8]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.
• [9]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.
• [10]Hall CB, Weinberg GA, Iwane MK, Blumkin AK, Edwards KM, et al.: The burden of respiratory syncytial virus infection in young children. N Engl J Med. 2009, 360:588-98.
• [11]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. BioMed Central Full Text
• [12]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.
• [13]Polack FP, Karron RA: The future of respiratory syncytial virus vaccine development. Pediatr Infect Dis J. 2004, 23:65-73.
• [14]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.
• [15]Munywoki PK, Koech DC, Agoti CN, Lewa C, Cane PA, 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.
• [16]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.
• [17]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.
• [18]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.
• [19]Merler S, Ajelli M, Fumanelli L, Vespignani A: Containing the accidental laboratory escape of potential pandemic influenza viruses. BMC Med. 2013, 11(3):252. BioMed Central Full Text
• [20]The DHS Program, Demographic and Health Surveys. http://dhsprogram.com/data/.
• [21]Kenya Open Data. https://opendata.go.ke/.
• [22]United Nations, Department of Economic and Social Affairs. World Population Prospects. http://www.un.org/en/development/desa/population/.
• [23]Gomes MGM, White LJ, Medley GF: Infection, reinfection, and vaccination under suboptimal immune protection: epidemiological perspectives. J Theor Biol. 2004, 228:539-49.
• [24]Weber A, Weber M, Milligan P: Modeling epidemics caused by respiratory syncytial virus (RSV). Math Biosci. 2001, 172:95-113.
• [25]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.
• [26]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.
• [27]Munywoki PK, Koech DC, Agoti CN, Kibirige N, Kipoech J, Cane PA, et al. Influence of age, severity of infection, and co-infection on the duration of respiratory syncytial virus (RSV) shedding. Epidemiol Infect. 2014. http://dx.doi.org/10.1017/S0950268814001393.
• [28]UNESCO, International Bureau of Education. http://www.ibe.unesco.org/.
• [29]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.
• [30]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.
• [31]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.
• [32]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.
• [33]PATH’s Work in Vaccine Development. http://sites.path.org/vaccinedevelopment/.
• [34]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.
• [35]Ferguson NM, Cummings DAT, Fraser C, Cajka JC, Cooley PC, Burke DS: Strategies for mitigating an influenza pandemic. Nature 2006, 442:448-52.
• [36]Ajelli M, Merler S: The impact of the unstructured contacts component in influenza pandemic modeling. PLOS ONE 2008, 3:1519.
• [37]Graham BS: Protecting the family to protect the child: vaccination strategy guided by RSV transmission dynamics. J Infect Dis. 2014, 209:1679-81.
• [38]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.