Indirect Effect of 7‐Valent Pneumococcal Conjugate Vaccine on Pneumococcal Colonization among Unvaccinated Household Members

Millar, Eugene V.; Watt, James; Bronsdon, Melinda A.; Dallas, Jean; Reid, Raymond; Santosham, Mathuram; O'Brien, Katherine L.

doi:10.1086/591966

Cited by 139 publications

(104 citation statements)

References 24 publications

(32 reference statements)

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“…[3][4][5][6] The rate of IPD has also declined among unvaccinated older children and adults. 3,7,8 However, data regarding the effects of PCV7 among infants who are too young to be fully immunized are limited. 9,10 Neonates and young infants are particularly vulnerable to serious bacterial infections, which may result from either vertical or horizontal transmission.…”

Section: Discussionmentioning

confidence: 99%

Invasive Pneumococcal Disease in Infants Younger Than 90 Days Before and After Introduction of PCV7

et al. 2013

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BACKGROUND: Introduction of the heptavalent pneumococcal conjugate vaccine (PCV7) changed the epidemiology of invasive pneumococcal disease (IPD). We evaluated the changes that occurred after PCV7 introduction among Utah infants aged 1 to 90 days, too young to be fully immunized. METHODS: We identified children <18 years with culture-confirmed IPD from 1997–2010. We analyzed demographic, clinical, and serotype data for infants aged 1–90 days. The pre– and post–vaccine introduction periods spanned 1997–2000 and 2001–2010, respectively. RESULTS: Of 513 children with IPD, 36 were 1 to 90 days and accounted for 7% of IPD cases in both the pre– and post–vaccine introduction period. The pre–vaccine IPD incidence rate was 5.0 per 100 000 live births, and was unchanged in the post–vaccine introduction period. IPD caused by PCV7 serotypes decreased by 74% (from 2.2 to 0.58 per 100 000), whereas non-vaccine serotype IPD increased by 57% (from 2.8 to 4.4 per 100 000). Sixteen infants (44%) required intensive care, and 3 (8%) died. Bacteremia without focus (56%) and meningitis (44%) were the predominant syndromes in the pre– and post–vaccine introduction periods, respectively. In the post–vaccine introduction period, serotype 7F was the most common serotype among infants and was responsible for 50% of meningitis. CONCLUSIONS: The incidence of IPD in Utah infants aged 1 to 90 days caused by PCV7 serotypes decreased after PCV7 introduction, but overall incidence was unchanged. In the post–vaccine introduction period, serotype 7F predominated in this age group and was associated with meningitis.

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Section: Discussionmentioning

confidence: 99%

Invasive Pneumococcal Disease in Infants Younger Than 90 Days Before and After Introduction of PCV7

et al. 2013

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“…Carriage of bacterial pathogens is clinically important because in some individuals carriage may be a prelude to invasive infection (4)(5)(6)(7)(8)(9)(10)(11). In contrast, some early studies suggest that GAS carrier strains have reduced ability to cause disease (12)(13)(14).…”

mentioning

confidence: 99%

Natural Variation in the Promoter of the Gene Encoding the Mga Regulator Alters Host-Pathogen Interactions in Group A Streptococcus Carrier Strains

et al. 2013

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cHumans commonly carry pathogenic bacteria asymptomatically, but the molecular factors underlying microbial asymptomatic carriage are poorly understood. We previously reported that two epidemiologically unassociated serotype M3 group A Streptococcus (GAS) carrier strains had an identical 12-bp deletion in the promoter of the gene encoding Mga, a global positive gene regulator. Herein, we report on studies designed to test the hypothesis that the identified 12-bp deletion in the mga promoter alters GAS virulence, thereby potentially contributing to the asymptomatic carrier phenotype. Using allelic exchange, we introduced the variant promoter into a serotype M3 invasive strain and the wild-type promoter into an asymptomatic carrier strain. Compared to strains with the wild-type mga promoter, we discovered that strains containing the promoter with the 12-bp deletion produced significantly fewer mga and Mga-regulated gene transcripts. Consistent with decreased mga transcripts, strains containing the variant mga promoter were also significantly less virulent in in vivo and ex vivo models of GAS disease. Further, we provide evidence that the pleiotropic regulator protein CodY binds to the mga promoter and that the 12-bp deletion in the mga promoter reduces CodY-mediated mga transcription. We conclude that the naturally occurring 12-bp deletion in the mga promoter significantly alters the pathogen-host interaction of these asymptomatic carrier strains. Our findings provide new insight into the molecular basis of the carrier state of an important human pathogen.

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“…Reports from other countries have indicated that the prevalence of VT pneumococci is individually reduced after PCV7 administration (6,7). Millar et al reported that VT pneumococcal carriage was lower among adults and unvaccinated children living with others who received the PCV7 vaccine (8). In the United States, the decreased nasopharyngeal carriage of VT strains among PCV7-immunized children led to decreased transmission to nonimmunized children and adults (i.e., herd immunity) (4).…”

Section: Discussionmentioning

confidence: 99%

Changes in Streptococcus pneumoniae Serotypes in the Nasopharynx of Japanese Children after Inoculation with a Heptavalent Pneumococcal Conjugate Vaccine

et al. 2014

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SUMMARY:In this study, we prospectively investigated changes in Streptococcus pneumoniae serotypes among Japanese children after heptavalent pneumococcal conjugate vaccine (PCV7) inoculation. We acquired nasopharyngeal swabs from the children at each routine PCV7 inoculation and again at least 2 months after the last PCV7 inoculation. We defined 2 periods with regard to each culture: the inoculation period as``the period of pre-or incomplete vaccination'' and post-inoculation as``the period of post-or completed vaccination.'' The prevalence of vaccine-type (VT) pneumococci was significantly reduced from 9.5z in the inoculation-period cultures to 2.9z in the post-inoculation cultures ( P º 0.01). There was no statistical difference in the prevalence of non-vaccine-type pneumococci between the inoculation-period and post-inoculation cultures (24.1z versus 23.4z). The protection of PCV7 against nasopharyngeal colonization was inferred from the decrease in VT carriage post-inoculation. The decrease in VT carriage may be conducive to reducing VT transmission within the study area.

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Indirect Effect of 7‐Valent Pneumococcal Conjugate Vaccine on Pneumococcal Colonization among Unvaccinated Household Members

Abstract: Vaccine-type pneumococcal carriage was lower among adults and unvaccinated children living with a PCV7 vaccinee. This is attributable to reduced exposure and reduced transmission when exposure occurs.

Cited by 139 publications

References 24 publications

Invasive Pneumococcal Disease in Infants Younger Than 90 Days Before and After Introduction of PCV7

Invasive Pneumococcal Disease in Infants Younger Than 90 Days Before and After Introduction of PCV7

Natural Variation in the Promoter of the Gene Encoding the Mga Regulator Alters Host-Pathogen Interactions in Group A Streptococcus Carrier Strains

Changes in Streptococcus pneumoniae Serotypes in the Nasopharynx of Japanese Children after Inoculation with a Heptavalent Pneumococcal Conjugate Vaccine

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