Pneumococcal Colonization in the Familial Context and Implications for Anti-Pneumococcal Immunization in Adults: Results from the BINOCOLO Project in Sicily

Fabio Tramuto, Emanuele Amodio, Giuseppe Calamusa, Vincenzo Restivo, Claudio Costantino, Francesco Vitale, The BINOCOLO Group, Fabio Tramuto, Emanuele Amodio, Giuseppe Calamusa, Vincenzo Restivo, Claudio Costantino, Francesco Vitale, The BINOCOLO Group

Abstract

The spread of Streptococcus pneumoniae within families has been scarcely investigated so far. This feasibility study aimed to estimate the prevalence of pneumococcal carriage in school-aged children and co-habiting relatives and to explore the potential link between the family environment and the sharing of pneumococcal serotypes covered by the vaccine. Oropharyngeal samples of 146 subjects belonging to 36 different family groups were molecularly tested for pneumococcal detection and serotyping. The overall prevalence of pneumococcal carriage was 65.8% (n = 96/146), whereas it was higher among schoolchildren (77.8%, n = 28/36); subjects of seven years of age had the highest odds of being colonized (odds ratio, OR = 5.176; p = 0.145). Pneumococcal serotypes included in the 13-valent conjugate vaccine formulation were largely detected in the study population and multiple serotypes colonization was considerable. Factors relating to a close proximity among people at the family level were statistically associated with pneumococcal carriage (OR = 2.121; p = 0.049), as well as active smoking habit with a clear dose-response effect (ORs = 1.017-3.326). About half of family clusters evidenced similar patterns of carried pneumococcal serotypes and the odds of sustaining a high level of intrafamilial sharing increased with household size (ORs = 1.083-5.000). This study highlighted the potential role played by the family environment in sustaining both the circulation and horizontal transmission of pneumococcus.

Keywords: Streptococcus pneumoniae; carriage; colonization; conjugate vaccine; family; horizontal transmission; real-time PCR; schoolchildren; serotypes.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Relative proportions of concurrent PCV13 serotypes identified in oropharyngeal swab specimens collected from healthy subjects positive for Streptococcus pneumoniae (co-colonization).
Figure 2
Figure 2
Distribution of PCV13 serotype (in ranking order) of colonizing pneumococcal strains collected from schoolchildren and household contacts. Bar graphs indicate the percentage of each serotype determined in relation to the total number of identified serotypes in the study period. Labels including the character “/” identify potential cross-reacting molecular targets.

References

    1. Simell B., Auranen K., Käyhty H., Goldblatt D., Dagan R., O’Brien K.L. The fundamental link between pneumococcal carriage and disease. Expert Rev. Vaccines. 2012;11:841–855. doi: 10.1586/erv.12.53.
    1. O’Brien K.L., Wolfson L.J., Watt J.P., Henkle E., Deloria-Knoll M., McCall N., Lee E., Mulholland K., Levine O.S., Cherian T., et al. Burden of disease caused by Streptococcus pneumoniae in children younger than 5 years: Global estimates. Lancet. 2009;374:893–902. doi: 10.1016/S0140-6736(09)61204-6.
    1. Drijkoningen J.J., Rohde G.G. Pneumococcal infection in adults: Burden of disease. Clin. Microbiol. Infect. 2014;20:45–51. doi: 10.1111/1469-0691.12461.
    1. Greenberg D., Givon-Lavi N., Newman N., Bar-Ziv J., Dagan R. Nasopharyngeal carriage of individual Streptococcus pneumoniae serotypes during pediatric pneumonia as a means to estimate serotype disease potential. Pediatr. Infect. Dis. J. 2011;30:227–233. doi: 10.1097/INF.0b013e3181f87802.
    1. Syrjänen R.K., Auranen K.J., Leino T.M., Kilpi T.M., Mäkelä P.H. Pneumococcal acute otitis media in relation to pneumococcal nasopharyngeal carriage. Pediatr. Infect. Dis. J. 2005;24:801–806. doi: 10.1097/01.inf.0000178072.83531.4f.
    1. Hill P.C., Cheung Y.B., Akisanya A., Sankareh K., Lahai G., Greenwood B.M., Adegbola R.A. Nasopharyngeal carriage of Streptococcus pneumoniae in Gambian infants: A longitudinal study. Clin. Infect. Dis. 2008;46:807–814. doi: 10.1086/528688.
    1. De Le Polain Waroux O., Flasche S., Prieto-Merino D., Edmunds W.J. Age-dependent prevalence of nasopharyngeal carriage of Streptococcus pneumoniae before conjugate vaccine introduction: A prediction model based on a meta-analysis. PLoS ONE. 2014;9:e86136. doi: 10.1371/journal.pone.0086136.
    1. Sicilian Region Official Gazette (GURS) 2003. [(accessed on 2 November 2016)]. Available online: .
    1. Sicilian Region Official Gazette (GURS) 2004. [(accessed on 2 November 2016)]. Available online: .
    1. Sicilian Region Official Gazette (GURS) 2010. [(accessed on 2 November 2016)]. Available online: .
    1. Isaacman D.J., McIntosh E.D., Reinert R.R. Burden of invasive pneumococcal disease and serotype distribution among Streptococcus pneumoniae isolates in young children in Europe: Impact of the 7-valent pneu-mococcal conjugate vaccine and considerations for future conjugate vaccines. Int. J. Infect. Dis. 2010;14:e197–e209. doi: 10.1016/j.ijid.2009.05.010.
    1. Rose M., Zielen S. Impact of infant immunization programs with pneumococcal conjugate vaccine in Europe. Expert Rev. Vaccines. 2009;8:1351–1364. doi: 10.1586/erv.09.78.
    1. Whitney C.G., Farley M.M., Hadler J., Harrison L.H., Bennett N.M., Lynfield R., Reingold A., Cieslak P.R., Pilishvili T., Jackson D., et al. Decline in invasive pneumococcal disease after the introduction of protein-polysaccharide conjugate vaccine. N. Engl. J. Med. 2003;348:1737–1746. doi: 10.1056/NEJMoa022823.
    1. Poehling K.A., Talbot T.R., Griffin M.R., Craig A.S., Whitney C.G., Zell E., Lexau C.A., Thomas A.R., Harrison L.H., Reingold A.L., et al. Invasive pneumococcal disease among infants before and after introduction of pneumococcal conjugate vaccine. JAMA. 2006;295:1668–1674. doi: 10.1001/jama.295.14.1668.
    1. Amodio E., Costantino C., Giuffrè M., Piccione M., Tramuto F., Vitale F. Invasive pneumococcal diseases in children aged 1–59 months in Sicily, Italy: Importance of active family paediatrician surveillance and vaccination coverage. Euromediterranean Biomed. J. 2014;9:19–23.
    1. Desai S., Policarpio M.E., Wong K., Gubbay J., Fediurek J., Deeks S. The epidemiology of invasive pneumococcal disease in older adults from 2007 to 2014 in Ontario, Canada: A population-based study. CMAJ Open. 2016;29:E545–E550. doi: 10.9778/cmajo.20160035.
    1. Chalmers J.D., Campling J., Dicker A., Woodhead M., Madhava H. A systematic review of the burden of vaccine preventable pneumococcal disease in UK adults. BMC Pulm. Med. 2016;11:77. doi: 10.1186/s12890-016-0242-0.
    1. Blasi F., Akova M., Bonanni P., Dartois N., Sauty E., Webber C., Torres A. Community-acquired pneumonia in adults: Highlighting missed opportunities for vaccination. Eur. J. Intern. Med. 2016 doi: 10.1016/j.ejim.2016.09.024. in press.
    1. Giese C., Mereckiene J., Danis K., O’Donnell J., O’Flanagan D., Cotter S. Low vaccination coverage for seasonal influenza and pneumococcal disease among adults at-risk and health care workers in Ireland, 2013: The key role of GPs in recommending vaccination. Vaccine. 2016;34:3657–3662. doi: 10.1016/j.vaccine.2016.05.028.
    1. Prato R., Fortunato F., Martinelli D. Pneumococcal pneumonia prevention among adults: Is the herd effect of pneumococcal conjugate vaccination in children as good a way as the active immunization of the elderly? Curr. Med. Res. Opin. 2016;32:543–545. doi: 10.1185/03007995.2015.1131150.
    1. Azzari C., Cortimiglia M., Nieddu F., Moriondo M., Indolfi G., Mattei R., Zuliani M., Adriani B., Degl’Innocenti R., Consales G., et al. Pneumococcal serotype distribution in adults with invasive disease and in carrier children in Italy: Should we expect herd protection of adults through infants’ vaccination? Hum. Vaccines Immunother. 2016;12:344–350. doi: 10.1080/21645515.2015.1102811.
    1. Moore M.R., Link-Gelles R., Schaffner W., Lynfield R., Lexau C., Bennett N.M., Petit S., Zansky S.M., Harrison L.H., Reingold A., et al. Effect of use of 13-valent pneumococcal conjugate vaccine in children on invasive pneumococcal disease in children and adults in the USA: Analysis of multisite, population-based surveillance. Lancet Infect. Dis. 2015;15:301–309. doi: 10.1016/S1473-3099(14)71081-3.
    1. Van Hoek A.J., Sheppard C.L., Andrews N.J., Waight P.A., Slack M.P., Harrison T.G., Ladhani S.N., Miller E. Pneumococcal carriage in children and adults two years after introduction of the thirteen valent pneumococcal conjugate vaccine in England. Vaccine. 2014;32:4349–4355. doi: 10.1016/j.vaccine.2014.03.017.
    1. Mosser J.F., Grant L.R., Millar E.V., Weatherholtz R.C., Jackson D.M., Beall B., Craig M.J., Reid R., Santosham M., O’Brien K.L. Nasopharyngeal carriage and transmission of Streptococcus pneumoniae in American Indian households after a decade of pneumococcal conjugate vaccine use. PLoS ONE. 2014;9:e79578. doi: 10.1371/journal.pone.0079578.
    1. Leino T., Auranen K., Jokinen J., Leinonen M., Tervonen P., Takala A.K. Pneumococcal carriage in children during their first two years: Important role of family exposure. Pediatr. Infect. Dis. J. 2001;20:1022–1027. doi: 10.1097/00006454-200111000-00004.
    1. Dhoubhadel B.G., Yasunami M., Nguyen H.A., Suzuki M., Vu T.H., Thuy Nguyen A.T., Dang D.A., Yoshida L.M., Ariyoshi K. Bacterial load of pneumococcal serotypes correlates with their prevalence and multiple serotypes is associated with acute respiratory infections among children less than 5 years of age. PLoS ONE. 2014;9:e110777. doi: 10.1371/journal.pone.0110777.
    1. Ansaldi F., de Florentiis D., Canepa P., Ceravolo A., Rappazzo E., Iudici R., Martini M., Botti G., Orsi A., Icardi G., et al. Carriage of Streptoccoccus pneumoniae in healthy adults aged 60 years or over in a population with very high and long-lasting pneumococcal conjugate vaccine coverage in children: Rationale and perspectives for PCV13 implementation. Hum. Vaccines Immunother. 2013;9:614–620. doi: 10.4161/hv.23253.
    1. Camilli R., Daprai L., Cavrini F., Lombardo D., D’Ambrosio F., del Grosso M., Vescio M.F., Landini M.P., Pascucci M.G., Torresani E., et al. Pneumococcal carriage in young children one year after introduction of the 13-valent conjugate vaccine in Italy. PLoS ONE. 2013;8:e76309. doi: 10.1371/journal.pone.0076309.
    1. Pasinato A., Indolfi G., Marchisio P., Valleriani C., Cortimiglia M., Spanevello V., Chiamenti G., Buzzetti R., Resti M., Azzari C., et al. Pneumococcal serotype distribution in 1315 nasopharyngeal swabs from a highly vaccinated cohort of Italian children as detected by RT-PCR. Vaccine. 2014;32:1375–1381. doi: 10.1016/j.vaccine.2014.01.023.
    1. Esposito S., Terranova L., Ruggiero L., Ascolese B., Montinaro V., Rios W.P., Galeone C., Principi N. Streptococcus pneumoniae and Staphylococcus aureus carriage in healthy school-age children and adolescents. J. Med. Microbiol. 2015;64:427–431. doi: 10.1099/jmm.0.000029.
    1. Principi N., Terranova L., Zampiero A., Montinaro V., Ierardi V., Peves Rios W., Pelucchi C., Esposito S. Pharyngeal colonization by Streptococcus pneumoniae in older children and adolescents in a geographical area characterized by relatively limited pneumococcal vaccination coverage. Pediatr. Infect. Dis. J. 2015;34:426–432. doi: 10.1097/INF.0000000000000637.
    1. Zuccotti G., Mameli C., Daprai L., Garlaschi M.L., Dilillo D., Bedogni G., Faccini M., Gramegna M., Torresani E., PneuMi Study Group (PMSG) Serotype distribution and antimicrobial susceptibilities of nasopharyngeal isolates of Streptococcus pneumoniae from healthy children in the 13-valent pneumococcal conjugate vaccine era. Vaccine. 2014;32:527–534. doi: 10.1016/j.vaccine.2013.12.003.
    1. Hsu K.K., Rifas-Shiman S.L., Shea K.M., Kleinman K.P., Lee G.M., Lakoma M., Pelton S.I., Finkelstein J.A., Huang S.S. Do community-level predictors of pneumococcal carriage continue to play a role in the conjugate vaccine era? Epidemiol. Infect. 2014;142:379–387. doi: 10.1017/S0950268813000794.
    1. Menezes A.P., Azevedo J., Leite M.C., Campos L.C., Cunha M., Carvalho Mda G., Reis M.G., Ko A.I., Weinberger D.M., Ribeiro G., et al. Nasopharyngeal carriage of Streptococcus pneumoniae among children in an urban setting in Brazil prior to PCV10 introduction. Vaccine. 2016;34:791–797. doi: 10.1016/j.vaccine.2015.12.042.
    1. Greenberg D., Givon-Lavi N., Broides A., Blancovich I., Peled N., Dagan R. The contribution of smoking and exposure to tobacco smoke to Streptococcus pneumoniae and Haemophilus influenzae carriage in children and their mothers. Clin. Infect. Dis. 2006;42:897–903. doi: 10.1086/500935.
    1. Shen P., Morissette M.C., Vanderstocken G., Gao Y., Hassan M., Roos A., Thayaparan D., Merlano M., Dorrington M.G., Nikota J.K., et al. Cigarette smoke attenuates the nasal host response to Streptococcus pneumoniae and predisposes to invasive pneumococcal disease in mice. Infect. Immun. 2016;84:1536–1547. doi: 10.1128/IAI.01504-15.
    1. Nuorti J.P., Butler J.C., Farley M.M., Harrison L.H., McGeer A., Kolczak M.S., Breiman R.F., Active Bacterial Core Surveillance Team Cigarette smoking and invasive pneumococcal disease. N. Engl. J. Med. 2000;342:681–689. doi: 10.1056/NEJM200003093421002.
    1. Le Rouzic O., Koné B., Kluza J., Marchetti P., Hennegrave F., Olivier C., Kervoaze G., Vilain E., Mordacq C., Just N., et al. Cigarette smoke alters the ability of human dendritic cells to promote anti-Streptococcus pneumoniae Th17 response. Respir. Res. 2016;17:94. doi: 10.1186/s12931-016-0408-6.
    1. Mameli C., Fabiano V., Daprai L., Bedogni G., Faccini M., Garlaschi M.L., Penagini F., Dilillo D., Torresani E., Gramegna M., et al. A longitudinal study of Streptococcus pneumoniae carriage in healthy children in the 13-valent pneumococcal conjugate vaccine era. Hum. Vaccines Immunother. 2015;11:811–817. doi: 10.1080/21645515.2015.1010945.
    1. Lakshman R., Murdoch C., Race G., Burkinshaw R., Shaw L., Finn A. Pneumococcal nasopharyngeal carriage in children following heptavalent pneumococcal conjugate vaccination in infancy. Arch. Dis. Child. 2003;88:211–214. doi: 10.1136/adc.88.3.211.
    1. Myint T.T., Madhava H., Balmer P., Christopoulou D., Attal S., Menegas D., Sprenger R., Bonnet E. The impact of 7-valent pneumococcal conjugate vaccine on invasive pneumococcal disease: A literature review. Adv. Ther. 2013;30:127–151. doi: 10.1007/s12325-013-0007-6.
    1. Steens A., Bergsaker M.A., Aaberge I.S., Rønning K., Vestrheim D.F. Prompt effect of replacing the 7-valent pneumococcal conjugate vaccine with the 13-valent vaccine on the epidemiology of invasive pneumococcal disease in Norway. Vaccine. 2013;31:6232–6238. doi: 10.1016/j.vaccine.2013.10.032.
    1. Tocheva A.S., Jefferies J.M., Rubery H., Bennett J., Afimeke G., Garland J., Christodoulides M., Faust S.N., Clarke S.C. Declining serotype coverage of new pneumococcal conjugate vaccines relating to the carriage of Streptococcus pneumoniae in young children. Vaccine. 2011;2:4400–4404. doi: 10.1016/j.vaccine.2011.04.004.
    1. Grivea I.N., Tsantouli A.G., Michoula A.N., Syrogiannopoulos G.A. Dynamics of Streptococcus pneumoniae nasopharyngeal carriage with high heptavalent pneumococcal conjugate vaccine coverage in Central Greece. Vaccine. 2011;29:8882–8887. doi: 10.1016/j.vaccine.2011.09.074.
    1. Kamng’ona A.W., Hinds J., Bar-Zeev N., Gould K.A., Chaguza C., Msefula C., Cornick J.E., Kulohoma B.W., Gray K., Bentley S.D., et al. High multiple carriage and emergence of Streptococcus pneumoniae vaccine serotype variants in Malawian children. BMC Infect. Dis. 2015;15:234. doi: 10.1186/s12879-015-0980-2.
    1. Kandasamy R., Gurung M., Thapa A., Ndimah S., Adhikari N., Murdoch D.R., Kelly D.F., Waldron D.E., Gould K.A., Thorson S., et al. Multi-serotype pneumococcal nasopharyngeal carriage prevalence in vaccine naïve Nepalese children, assessed using molecular serotyping. PLoS ONE. 2015;10:e0114286. doi: 10.1371/journal.pone.0114286.
    1. Azzari C., Moriondo M., Indolfi G., Cortimiglia M., Canessa C., Becciolini L., Lippi F., de Martino M., Resti M. Realtime PCR is more sensitive than multiplex PCR for diagnosis and serotyping in children with culture negative pneumococcal invasive disease. PLoS ONE. 2010;19:e9282. doi: 10.1371/journal.pone.0009282.
    1. Satzke C., Dunne E.M., Porter B.D., Klugman K.P., Mulholland E.K., PneuCarriage Project Group The PneuCarriage Project: A Multi-Centre comparative study to identify the best serotyping methods for examining pneumococcal carriage in vaccine evaluation studies. PLoS Med. 2015;12:e1001903. doi: 10.1371/journal.pmed.1001903.
    1. Darboe M.K., Fulford A.J., Secka O., Prentice A.M. The dynamics of nasopharyngeal Streptococcus pneumoniae carriage among rural Gambian mother-infant pairs. BMC Infect. Dis. 2010;5:195. doi: 10.1186/1471-2334-10-195.
    1. Brugger S.D., Frey P., Aebi S., Hinds J., Mühlemann K. Multiple colonization with S. pneumoniae before and after introduction of the seven-valent conjugated pneumococcal polysaccharide vaccine. PLoS ONE. 2010;16:e11638. doi: 10.1371/journal.pone.0011638.
    1. Turner P., Turner C., Jankhot A., Helen N., Lee S.J., Day N.P., White N.J., Nosten F., Goldblatt D. A longitudinal study of Streptococcus pneumoniae carriage in a cohort of infants and their mothers on the Thailand-Myanmar border. PLoS ONE. 2012;7:e38271. doi: 10.1371/journal.pone.0038271.
    1. Brimblecombe F.S., Cruickshank R., Masters P.L., Reid D.D., Stewart G.T. Family studies of respiratory infections. Br. Med. J. 1958;18:119–128. doi: 10.1136/bmj.1.5063.119.
    1. Masters P.L., Brumfitt W., Mendez R.L., Likar M. Bacterial flora of the upper respiratory tract in Paddington families, 1952–1954. Br. Med. J. 1958;1:1200–1205. doi: 10.1136/bmj.1.5081.1200.
    1. Dowling J.N., Sheehe P.R., Feldman H.A. Pharyngeal pneumococcal acquisitions in “normal” families: A longitudinal study. J. Infect. Dis. 1971;124:9–17. doi: 10.1093/infdis/124.1.9.
    1. Gwaltney J.M., Jr., Sande M.A., Austrian R., Hendley J.O. Spread of Streptococcus pneumoniae in families. II. Relation of transfer of S. pneumoniae to incidence of colds and serum antibody. J. Infect. Dis. 1975;132:62–68. doi: 10.1093/infdis/132.1.62.
    1. Satzke C., Turner P., Virolainen-Julkunen A., Adrian P.V., Antonio M., Hare K.M., Henao-Restrepo A.M., Leach A.J., Klugman K.P., Porter B.D., et al. Standard method for detecting upper respiratory carriage of Streptococcus pneumoniae: Updated recommendations from the World Health Organization Pneumococcal Carriage Working Group. Vaccine. 2013;32:165–179. doi: 10.1016/j.vaccine.2013.08.062.
    1. Da Gloria Carvalho M., Pimenta F.C., Jackson D., Roundtree A., Ahmad Y., Millar E.V., O’Brien K.L., Whitney C.G., Cohen A.L., Beall B.W. Revisiting pneumococcal carriage by use of broth enrichment and PCR techniques for enhanced detection of carriage and serotypes. J. Clin. Microbiol. 2010;48:1611–1618. doi: 10.1128/JCM.02243-09.

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