#Bacterial Factors Required for #Transmission of #Streptococcus pneumoniae in #Mammalian Hosts (Cell Host Microbe, abstract)

[Source: Cell, Host & Microbe, full page: (LINK). Abstract, edited.]

Bacterial Factors Required for Transmission of Streptococcus pneumoniae in Mammalian Hosts

Hannah M. Rowe, Erik Karlsson, Haley Echlin, Ti-Cheng Chang, Lei Wang, Tim van Opijnen, Stanley B. Pounds, Stacey Schultz-Cherry, Jason W. Rosch

Published: May 21, 2019 / DOI: https://doi.org/10.1016/j.chom.2019.04.012

 

Highlights

  • A pneumococcal Tn-seq library was screened in a ferret transmission model
  • The fitness landscape of S. pneumoniae genes during mammalian transmission established
  • Metabolic factors enhance pneumococcal environmental stability
  • Vaccinating dams with identified factors blocks pneumococcal transmission in offspring

 

Summary

The capacity of Streptococcus pneumoniae to successfully transmit and colonize new human hosts is a critical aspect of pneumococcal population biology and a prerequisite for invasive disease. However, the bacterial mechanisms underlying this process remain largely unknown. To identify bacterial factors required for transmission, we conducted a high-throughput genetic screen with a transposon sequencing (Tn-seq) library of a pneumococcal strain in a ferret transmission model. Key players in both metabolism and transcriptional regulation were identified as required for efficient bacterial transmission. Targeted deletion of the putative C3-degrading protease CppA, iron transporter PiaA, or competence regulatory histidine kinase ComD significantly decreased transmissibility in a mouse model, further validating the screen. Maternal vaccination with recombinant surface-exposed PiaA and CppA alone or in combination blocked transmission in offspring and were more effective than capsule-based vaccines. These data underscore the possibility of targeting pneumococcal transmission as a means of eliminating invasive disease in the population.

Keywords: Streptococcus pneumoniae – transmission – ferret – influenza

Keywords: Streptococcus pneumoniae; IPD; Animal models.

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#Risk modeling the #mortality impact of #antimicrobial #resistance in secondary #pneumococcal #pneumonia infections during the 2009 #influenza #pandemic (Int J Infect Dis., abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

Int J Infect Dis. 2019 May 13. pii: S1201-9712(19)30211-5. doi: 10.1016/j.ijid.2019.05.005. [Epub ahead of print]

Risk modeling the mortality impact of antimicrobial resistance in secondary pneumococcal pneumonia infections during the 2009 influenza pandemic.

Barnes CE1, MacIntyre CR2.

Author information: 1 School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia. Electronic address: barnes103@hotmail.com. 2 School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia; The Kirby Institute, Sydney, Australia. Electronic address: r.macintyre@unsw.edu.au.

 

Abstract

OBJECTIVES:

The aim of this study was to estimate the impact of antimicrobial resistance (AMR) in secondary pneumococcal pneumonia infections on global mortality during the 2009 influenza pandemic, to estimate future pandemic mortality risk and to inform pandemic preparedness.

METHODS:

Risk analysis modeling was conducted using a multivariate risk formula. Literature reviews were conducted to generate global central estimates for each of the parameters of the risk formula in relation to the 2009 influenza pandemic, secondary pneumococcal pneumonia, rates of AMR and pneumococcal vaccine efficacy as a component of pandemic preparedness.

RESULTS:

Global Streptococcus pneumoniae AMR was estimated at 21.8% to 27.6%, and contributed to 1.8% to 2.3% of deaths during the 2009 influenza pandemic. When directly applied to mortality due to multidrug resistance, pneumococcal vaccination could potentially prevent 1,277 to 3,754 deaths and could have reduced mortality from multidrug resistant S. pneumoniae to 1% to 1.2%.

CONCLUSION:

AMR in secondary pneumococcal infections contributed towards a small percentage of the global mortality during the 2009 influenza pandemic. Increased S. pnuemoniae AMR could result in a three- to four-fold rise in mortality due to secondary pneumococcal infections in future influenza pandemics. Pneumococcal vaccination has an important role in preventing pneumococcal co-infections and combating AMR in all populations, and should be considered a key component of influenza pandemic preparedness or early action plans.

Copyright © 2019. Published by Elsevier Ltd.

KEYWORDS: Streptococcus pneumoniae; antimicrobial resistance; pandemic influenza; secondary pneumococcal pneumonia

PMID: 31096052 DOI: 10.1016/j.ijid.2019.05.005

Keywords: Pandemic Influenza; Streptococcus pneumoniae; Vaccines; Antibiotics; Drugs Resistance.

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#Influenza “Trains” the Host for Enhanced Susceptibility to Secondary #Bacterial #Infection (mBio, abstract)

[Source: US National Library of Medicine, full page: (LINK). Abstract, edited.]

MBio. 2019 May 7;10(3). pii: e00810-19. doi: 10.1128/mBio.00810-19.

Influenza “Trains” the Host for Enhanced Susceptibility to Secondary Bacterial Infection.

Shirey KA1, Perkins DJ1, Lai W1, Zhang W2, Fernando LR2, Gusovsky F3, Blanco JCG2, Vogel SN4.

Author information: 1 Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA. 2 Sigmovir Biosystems, Inc., Rockville, Maryland, USA. 3 Eisai Inc., Andover, Massachusetts, USA. 4 Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland, USA svogel@som.umaryland.edu.

 

Abstract

We previously reported that the Toll-like receptor 4 (TLR4) antagonist Eritoran blocks acute lung injury (ALI) therapeutically in mouse and cotton rat models of influenza. However, secondary (2°) bacterial infection following influenza virus infection is associated with excess morbidity and mortality. Wild-type (WT) mice infected with mouse-adapted influenza A/Puerto Rico/8/34 virus (PR8) and, 7 days later, with Streptococcus pneumoniae serotype 3 (Sp3) exhibited significantly enhanced lung pathology and lethality that was reversed by Eritoran therapy after PR8 infection but before Sp3 infection. Cotton rats infected with nonadapted pH1N1 influenza virus and then superinfected with methicillin-resistant Staphylococcus aureus also exhibited increased lung pathology and serum high-mobility-group box 1 (HMGB1) levels, both of which were blunted by Eritoran therapy. In mice, PR8 infection suppressed Sp3-induced CXCL1 and CXCL2 mRNA, reducing neutrophil infiltration and increasing the bacterial burden, all of which were reversed by Eritoran treatment. While beta interferon (IFN-β)-deficient (IFN-β-/-) mice are highly susceptible to PR8, they exhibited delayed death upon Sp3 superinfection, indicating that while IFN-β was protective against influenza, it negatively impacted the host response to Sp3 IFN-β-treated WT macrophages selectively suppressed Sp3-induced CXCL1/CXCL2 transcriptionally, as evidenced by reduced recruitment of RNA polymerase II to the CXCL1 promoter. Thus, influenza establishes a “trained” state of immunosuppression toward 2° bacterial infection, in part through the potent induction of IFN-β and its downstream transcriptional regulation of chemokines, an effect reversed by Eritoran.

 

IMPORTANCE

Enhanced susceptibility to 2° bacterial infections following infection with influenza virus is a global health concern that accounts for many hospitalizations and deaths, particularly during pandemics. The complexity of the impaired host immune response during 2° bacterial infection has been widely studied. Both type I IFN and neutrophil dysfunction through decreased chemokine production have been implicated as mechanisms underlying enhanced susceptibility to 2° bacterial infections. Our findings support the conclusion that selective suppression of CXCL1/CXCL2 represents an IFN-β-mediated “training” of the macrophage transcriptional response to TLR2 agonists and that blocking of TLR4 therapeutically with Eritoran after influenza virus infection reverses this suppression by blunting influenza-induced IFN-β.

Copyright © 2019 Shirey et al.

KEYWORDS: IFN-β; MRSA; Streptococcus pneumoniae; TLR4; cotton rats; influenza; macrophage training; secondary bacterial infection

PMID: 31064834 DOI: 10.1128/mBio.00810-19

Keywords: Influenza A; Streptococcus pneumoniae; Immunopathology; Animal models.

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#Infant #pneumococcal carriage during #influenza, #RSV and #hMPV #respiratory illness within a #maternal influenza #immunization trial (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Infant pneumococcal carriage during influenza, RSV and hMPV respiratory illness within a maternal influenza immunization trial

Alastair F Murray, Janet A Englund, Jane Kuypers, James M Tielsch, Joanne Katz, Subarna K Khatry, Steven C Leclerq, Helen Y Chu

The Journal of Infectious Diseases, jiz212, https://doi.org/10.1093/infdis/jiz212

Published: 06 May 2019

 

Abstract

In this post-hoc analysis of nasopharyngeal pneumococcal carriage in a community-based, randomized prenatal influenza vaccination trial in Nepal with weekly infant respiratory illness surveillance, 457 of 605 (75.5%) infants with influenza, RSV or hMPV illness had pneumococcus detected. Pneumococcal carriage did not impact rates of lower respiratory tract disease for these three viruses. Influenza-positive infants born to mothers given influenza vaccine had lower pneumococcal carriage rates compared to infants born to placebo mothers (58.1% versus 71.6%, p=0.03). No difference was observed in RSV- or hMPV-infected infants (p=0.94, 0.11). Maternal influenza immunization may impact infant acquisition of pneumococcus during influenza infection.

pneumococcus, influenza, vaccine, RSV, hMPV, maternal immunization

Issue Section: Brief Report

This content is only available as a PDF.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

Keywords: Seasonal Influenza; Streptococcus pneumoniae; RSV; Metapneumovirus; Vaccines; Pregnancy.

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CAL02, a novel #antitoxin liposomal agent, in severe #pneumococcal #pneumonia: a first-in-human, double-blind, placebo-controlled, randomised trial (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

CAL02, a novel antitoxin liposomal agent, in severe pneumococcal pneumonia: a first-in-human, double-blind, placebo-controlled, randomised trial

Prof Pierre-François Laterre, MD, Gwenhael Colin, MD, Prof Pierre-François Dequin, MD, Thierry Dugernier, MD, Thierry Boulain, MD, Samareh Azeredo da Silveira, PhD, Frédéric Lajaunias, PhD, Antonio Perez, MD, Bruno François, MD

Published: May 02, 2019 / DOI: https://doi.org/10.1016/S1473-3099(18)30805-3

 

Summary

Background

Severe community-acquired pneumonia caused by Streptococcus pneumoniae is associated with high morbidity and mortality rates. CAL02, a novel antitoxin agent with an unprecedented mode of action, consists of liposomes that capture bacterial toxins known to dysregulate inflammation, cause organ damage, and impede immune defence. We aimed to assess the safety of CAL02 as an add-on therapy to antibiotics.

Methods

This randomised, double-blind, multicentre, placebo-controlled trial was done in ten intensive care units (ICUs) in France and Belgium (but only six units enrolled patients), in patients with severe community-acquired pneumococcal pneumonia who required ICU admission and had been identified as being infected with S pneumoniae. We randomly assigned participants in two stages—the first stage randomly assigned six patients (1:1) to either low-dose CAL02 or placebo, and the second stage randomly assigned 18 patients (14:4) to either high-dose CAL02 or placebo, and stratified in four blocks (4:1, 4:1, 3:1, and 3:1), in addition to standard of care. Block randomisation was done with a computer-generated random number list. Participants, investigators, other site study personnel, the sponsor, and the sponsor’s designees involved in study management and monitoring were masked to the randomisation list and treatment assignment. Patients were treated with low-dose (4 mg/kg) or high-dose (16 mg/kg) CAL02 or placebo (saline), in addition to standard antibiotic therapy. Two intravenous doses of study treatment were infused, with a 24 h interval, at a concentration of 10 mg/mL, stepwise, over a maximum of 2 h on days 1 and 2. The primary objective of the study was to assess the safety and tolerability of low-dose and high-dose CAL02 in patients with severe community-acquired pneumonia treated with standard antibiotic therapy, and the primary analysis was done on the safety population (all patients who received at least one dose of the study treatment). Efficacy was a secondary outcome. This trial is registered with ClinicalTrials.gov, number NCT02583373.

Findings

Between March 21, 2016, and Jan 13, 2018, we screened 280 patients with community-acquired pneumonia. 19 patients were enrolled and randomly assigned, resulting in 13 patients in the CAL02 groups (three assigned to low-dose CAL02 and ten assigned to high-dose CAL02) and six in the placebo group. One patient randomly assigned to placebo was allocated to the wrong treatment group and received high-dose CAL02 instead of placebo. Thus, 14 patients received CAL02 (three received low-dose CAL02 and 11 received high-dose CAL02) and five patients received placebo, constituting the safety population. At baseline, the mean APACHE II score for the total study population was 21·5 (SD 4·9; 95% CI 19·3–23·7) and 11 (58%) of 19 patients had septic shock. Adverse events occurred in 12 (86%) of 14 patients in the CAL02 treatment groups combined and all five (100%) patients in the placebo group. Serious adverse events occurred in four (29%) of 14 patients in the CAL02 treatment groups combined and two (40%) of five patients in the placebo group. One non-serious adverse event (mild increase in triglycerides) in a patient in the high-dose CAL02 group was reported as related to study drug. However, analysis of the changes in triglyceride levels in the CAL02 groups compared with the placebo group revealed no correlation with administration of CAL02. No adverse events were linked to local tolerability events. All patients, apart from one who died in the low CAL02 group (death not related to the study drug) achieved clinical cure at the test of cure visit between days 15 and 22. The sequential organ failure assessment score decreased by mean 65·0% (95% CI 50·7–79·4) in the combined CAL02 groups compared with 29·2% (12·8–45·5) in the placebo group between baseline and day 8.

Interpretation

The nature of adverse events was consistent with the profile of the study population and CAL02 showed a promising safety profile and tolerability. However, the difference between high-dose and low-dose CAL02 could not be assessed in this study. Efficacy was in line with the expected benefits of neutralising toxins. The results of this study support further clinical development of CAL02 and provide a solid basis for a larger clinical study.

Funding

Combioxin.

Keywords: Streptococcus pneumoniae; Pneumonia; Antitoxin.

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IL-17A plays a double-edged role in #Streptococcus pneumoniae #pathogenesis during an #influenza virus #coinfection (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

IL-17A plays a double-edged role in Streptococcus pneumoniae pathogenesis during an influenza virus co-infection

Ganesh Ambigapathy, Taylor Schmit, Ram Kumar Mathur, Suba Nookala, Saad Bahri, Liise-anne Pirofski, M Nadeem Khan

The Journal of Infectious Diseases, jiz193, https://doi.org/10.1093/infdis/jiz193

Published: 23 April 2019

 

Abstract

Background

We sought to determine the role of host IL-17A response against colonizing Streptococcus pneumoniae (Spn), and its transition to a pathogen during an influenza virus (PR8) co-infection.

Method

Wild-type C57BL/6 mice were intranasally inoculated with Spn serotype 6A to establish colonization, and later infected with the influenza strain, PR8, resulting in invasive Spn disease. The role of the IL-17A response in colonization and co-infection was investigated in WT, RoRγt-/- and RAG1-/- mice with antibody mediated depletion of IL-17A (WT) and CD90 cells (RAG1-/-).

Results

RAG1-/- mice did not clear colonization and IL-17A neutralization impaired 6A clearance in WT mice. RoRγt-/- mice also had reduced clearance. Spn-PR8 co-infection elicited a robust IL-17A response in the nasopharynx; IL-17A neutralization reduced Spn invasive disease. RoRγt-/- mice also had reduced Spndisease in a co-infection model. Depletion of CD90+ cells suppressed the IL-17A response and reduced Spn invasion in RAG1-/- mice.

Conclusion

Our data show that while IL-17A reduces Spn colonization, co-infection with influenza virus elicits a robust innate IL-17A response that promotes inflammation and Spn disease in the NP.

Spn, influenza, co-infection, IL17A, host response

Topic: influenza – rag1 gene – interleukin-17 – orthomyxoviridae – streptococcus pneumoniae – mice – coinfection – microbial colonization

Issue Section: Major Article

This content is only available as a PDF.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Streptococcus pneumoniae; Influenza A.

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Persistent circulation of #vaccine #serotypes and serotype #replacement after five years of #UK #infant #immunisation with #PCV13 (J Infect Dis., abstract)

[Source: Journal of Infectious Diseases, full page: (LINK). Abstract, edited.]

Persistent circulation of vaccine serotypes and serotype replacement after five years of UK infant immunisation with PCV13

Rama Kandasamy, DPhil FRACP, Merryn Voysey, MBiostat, Sarah Collins, MPH, Guy Berbers, PhD, Hannah Robinson, MSc, Irene Noel, MSc, Harri Hughes, MSc, Susan Ndimah, MSc, Katherine Gould, PhD, Norman Fry, PhD, Carmen Sheppard, PhD, Shamez Ladhani, PhD MRCPCH, Matthew D Snape, MD FRACP, Jason Hinds, PhD, Andrew J Pollard, PhD FRCPCH

The Journal of Infectious Diseases, jiz178, https://doi.org/10.1093/infdis/jiz178

Published: 20 April 2019

 

Abstract

Background

Following programmatic introduction of the 13-valent pneumococcal conjugate vaccine (PCV13), there is residual carriage and disease due to PCV13 covered serotypes.

Methods

988 PCV13-immunised children aged 13-48 months were enrolled between February 2014 and August 2015 (late-PCV13), and had nasopharyngeal pneumococcal carriage compared with 567 PCV7-immunised children enrolled into a study between November 2010 and September 2011 (early-PCV13). Nasopharyngeal pneumococci were molecular-serotyped by microarray. Invasive pneumococcal disease (IPD) cases were identified through enhanced national surveillance. Blood collected from the late-PCV13 cohort was assessed for levels of serotype-specific serum IgG by multiplex immunoassay.

Results

Compared with PCV7-immunised children, carriage among PCV13-immunised children was significantly lower for serotypes 19A (OR=0.08, 95% CI 0.02-0.25), 6C (OR=0.11, 95% CI 0.03-0.32) and 7F (8 vs 0 cases).

IPD incidence in children <5 years was significantly lower for serotypes 1 (IRR=0.03, 95% CI 0-0.19) and 7F (IRR=0.13, 95% CI 0.05-0.36) but not 19A (IRR=0.6, 95% CI 0.3-1.12) or serotype 3 (IRR=2.3, 95% CI 0.86-6.15) in the late-PCV13 period than in the early-PCV13 period. The most significant rises in IPD incidence were for serotypes 8, 12F, and 24F.

Children from the late-PCV13 period, who had serum analysed, and were not carrying a PCV13 serotype, had high levels of antibody presumed to be due to natural exposure, to serotypes 3 (24/204, 11.76%) and 19A (14/204, 6.86%).

Conclusions

PCV13 has reduced serotype 19A carriage among vaccinated children however, disease is not fully controlled. We also found, no impact of PCV13 on serotype 3 carriage or disease, and emergence of non-PCV13 serotype disease.

Pneumococcus, children, adults, carriage, sero-prevalence, invasive, disease

Issue Section: Major Article

This content is only available as a PDF.

© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

This article is published and distributed under the terms of the Oxford University Press, Standard Journals Publication Model (https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model)

Keywords: Streptococcus pneumoniae; Vaccines; UK.

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Effect of 10-valent #PCV on #IPD and #nasopharyngeal carriage in #Kenya: a longitudinal surveillance study (Lancet, abstract)

[Source: The Lancet, full page: (LINK). Abstract, edited.]

Effect of ten-valent pneumococcal conjugate vaccine on invasive pneumococcal disease and nasopharyngeal carriage in Kenya: a longitudinal surveillance study

Laura L Hammitt, MD, Anthony O Etyang, ChB, Susan C Morpeth, FRACP, John Ojal, PhD, Alex Mutuku, MSc, Neema Mturi, MRCPCH, Jennifer C Moisi, PhD, Ifedayo M Adetifa, PhD, Angela Karani, BSc, Donald O Akech, BSc, Mark Otiende, MSc, Tahreni Bwanaali, MBA, Jackline Wafula, BSN, Christine Mataza, KRCHN, Edward Mumbo, BSc, Collins Tabu, MPH, Maria Deloria Knoll, PhD, Evasius Bauni, PhD, Prof Kevin Marsh, FMedSci, Prof Thomas N Williams, FMedSci, Tatu Kamau, MPH, Shahnaaz K Sharif, MD, Prof Orin S Levine, PhD, Prof J Anthony G Scott, FRCP

Open Access / PublishedApril 15, 2019 / DOI: https://doi.org/10.1016/S0140-6736(18)33005-8

 

Summary

Background

Ten-valent pneumococcal conjugate vaccine (PCV10), delivered at 6, 10, and 14 weeks of age was introduced in Kenya in January, 2011, accompanied by a catch-up campaign in Kilifi County for children aged younger than 5 years. Coverage with at least two PCV10 doses in children aged 2–11 months was 80% in 2011 and 84% in 2016; coverage with at least one dose in children aged 12–59 months was 66% in 2011 and 87% in 2016. We aimed to assess PCV10 effect against nasopharyngeal carriage and invasive pneumococcal disease (IPD) in children and adults in Kilifi County.

Methods

This study was done at the KEMRI-Wellcome Trust Research Programme among residents of the Kilifi Health and Demographic Surveillance System, a rural community on the Kenyan coast covering an area of 891 km2. We linked clinical and microbiological surveillance for IPD among admissions of all ages at Kilifi County Hospital, Kenya, which serves the community, to the Kilifi Health and Demographic Surveillance System from 1999 to 2016. We calculated the incidence rate ratio (IRR) comparing the prevaccine (Jan 1, 1999–Dec 31, 2010) and postvaccine (Jan 1, 2012–Dec 31, 2016) eras, adjusted for confounding, and reported percentage reduction in IPD as 1 minus IRR. Annual cross-sectional surveys of nasopharyngeal carriage were done from 2009 to 2016.

Findings

Surveillance identified 667 cases of IPD in 3 211 403 person-years of observation. Yearly IPD incidence in children younger than 5 years reduced sharply in 2011 following vaccine introduction and remained low (PCV10-type IPD: 60·8 cases per 100 000 in the prevaccine era vs 3·2 per 100 000 in the postvaccine era [adjusted IRR 0·08, 95% CI 0·03–0·22]; IPD caused by any serotype: 81·6 per 100 000 vs 15·3 per 100 000 [0·32, 0·17–0·60]). PCV10-type IPD also declined in the post-vaccination era in unvaccinated age groups (<2 months [no cases in the postvaccine era], 5–14 years [adjusted IRR 0·26, 95% CI 0·11–0·59], and ≥15 years [0·19, 0·07–0·51]). Incidence of non-PCV10-type IPD did not differ between eras. In children younger than 5 years, PCV10-type carriage declined between eras (age-standardised adjusted prevalence ratio 0·26, 95% CI 0·19–0·35) and non-PCV10-type carriage increased (1·71, 1·47–1·99).

Interpretation

Introduction of PCV10 in Kenya, accompanied by a catch-up campaign, resulted in a substantial reduction in PCV10-type IPD in children and adults without significant replacement disease. Although the catch-up campaign is likely to have brought forward the benefits by several years, the study suggests that routine infant PCV10 immunisation programmes will provide substantial direct and indirect protection in low-income settings in tropical Africa.

Funding

Gavi, The Vaccine Alliance and The Wellcome Trust of Great Britain.

Keywords: Streptococcus pneumoniae; Vaccines; IPD; Kenya.

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#Immunogenicity and reactogenicity of 10-valent versus 13-valent #PCVs among #infants in Ho Chi Minh City, #Vietnam: a #RCT (Lancet Infect Dis., abstract)

[Source: The Lancet Infectious Diseases, full page: (LINK). Abstract, edited.]

Immunogenicity and reactogenicity of ten-valent versus 13-valent pneumococcal conjugate vaccines among infants in Ho Chi Minh City, Vietnam: a randomised controlled trial

Beth Temple, MSc,  Nguyen Trong Toan, MD, Vo Thi Trang Dai, MSc, Kathryn Bright, BN, Paul Vincent Licciardi, PhD, Rachel Ann Marimla, BBiomed, Cattram Duong Nguyen, PhD, Doan Y Uyen, MD, Anne Balloch, MSc, Tran Ngoc Huu, MD, Prof Edward Kim Mulholland, MD

Open Access / PublishedApril 08, 2019 / DOI: https://doi.org/10.1016/S1473-3099(18)30734-5

 

Summary

Background

Few data are available to support the choice between the two currently available pneumococcal conjugate vaccines (PCVs), ten-valent PCV (PCV10) and 13-valent PCV (PCV13). Here we report a head-to-head comparison of the immunogenicity and reactogenicity of PCV10 and PCV13.

Methods

In this parallel, open-label, randomised controlled trial, healthy infants from two districts in Ho Chi Minh City, Vietnam, were randomly allocated (in a 3:3:5:4:5:4 ratio), with use of a computer-generated list, to one of six infant PCV schedules: PCV10 in a 3 + 1 (group A), 3 + 0 (group B), 2 + 1 (group C), or two-dose schedule (group D); PCV13 in a 2 + 1 schedule (group E); or no infant PCV (control; group F). Blood samples were collected from infants between 2 months and 18 months of age at various timepoints before and after PCV doses and analysed (in a blinded manner) by ELISA and opsonophagocytic assay. The trial had two independent aims: to compare vaccination responses between PCV10 and PCV13, and to evaluate different schedules of PCV10. In this Article, we present results pertaining to the first aim. The primary outcome was the proportion of infants with an IgG concentration of at least 0·35 μg/mL for the ten serotypes common to the two vaccines at age 5 months, 4 weeks after the two-dose primary vaccination series (group C vs group E, per protocol population). An overall difference among the schedules was defined as at least seven of ten serotypes differing in the same direction at the 10% level. We also assessed whether the two-dose primary series of PCV13 (group E) was non-inferior at the 10% level to a three-dose primary series of PCV10 (groups A and B). This trial is registered with ClinicalTrials.gov, number NCT01953510.

Findings

Of 1424 infants screened between Sept 30, 2013, and Jan 9, 2015, 1201 were allocated to the six groups: 152 (13%) to group A, 149 (12%) to group B, 250 (21%) to group C, 202 (17%) to group D, 251 (21%) to group E, and 197 (16%) to group F. 237 (95%) participants in group C (PCV10) and 232 (92%) in group E (PCV13) completed the primary vaccination series and had blood draws within the specified window at age 5 months, at which time the proportion of infants with IgG concentrations of at least 0·35 μg/mL did not differ between groups at the 10% level for any serotype (PCV10–PCV13 risk difference −2·1% [95% CI −4·8 to −0·1] for serotype 1; −1·3% [–3·7 to 0·6] for serotype 4; −3·4% [–6·8 to −0·4] for serotype 5; 15·6 [7·2 to 23·7] for serotype 6B; −1·3% [–3·7 to 0·6] for serotype 7F; −1·6% [–5·1 to 1·7] for serotype 9V; 0·0% [–2·7 to 2·9] for serotype 14; −2·1% [–5·3 to 0·9] for serotype 18C; 0·0% [–2·2 to 2·3] for serotype 19F; and −11·6% [–18·2 to −4·9] for serotype 23F). At the same timepoint, two doses of PCV13 were non-inferior to three doses of PCV10 for nine of the ten shared serotypes (excluding 6B). Reactogenicity and serious adverse events were monitored according to good clinical practice guidelines, and the profiles were similar in the two groups.

Interpretation

PCV10 and PCV13 are similarly highly immunogenic when used in 2 + 1 schedule. The choice of vaccine might be influenced by factors such as the comparative magnitude of the antibody responses, price, and the relative importance of different serotypes in different settings.

Funding

National Health and Medical Research Council of Australia, and Bill & Melinda Gates Foundation.

Keywords: Streptococcus pneumoniae; Vaccines; Vietnam.

——

#WGS #analysis of #MDR #serotype 15A #Streptococcus pneumoniae in #Japan and the emergence of a highly resistant serotype 15A-ST9084 clone (Antimicrob Agents Chemother., abstract)

[Source: Antimicrobial Agents and Chemotherapy, full page: (LINK). Abstract, edited.]

Whole-genome sequencing analysis of multidrug-resistant serotype 15A Streptococcus pneumoniae in Japan and the emergence of a highly resistant serotype 15A-ST9084 clone

Satoshi Nakano, Takao Fujisawa, Yutaka Ito, Bin Chang, Yasufumi Matsumura, Masaki Yamamoto, Shigeru Suga, Makoto Ohnishi, Miki Nagao

DOI: 10.1128/AAC.02579-18

 

ABSTRACT

Since the introduction of pneumococcal conjugate vaccines, an increase in the incidence of disease attributable to serotype 15A-ST63 pneumococci has been observed in many regions worldwide. We conducted a nationwide pediatric pneumococcal infection surveillance study between 2012 and 2014 in Japan. In the surveillance study, we detected multidrug-resistant serotype 15A-CC63 strains (resistant to macrolides, penicillin, cefotaxime and meropenem); in this study, we analyzed these resistant isolates to determine the dynamics and mechanism of resistance using whole-genome sequencing. In most of the penicillin-, cefotaxime- and meropenem-resistant strains, recombination occurred in the pbp2x region resulting in the acquisition of additional cefotaxime resistance to penicillin and meropenem. In the multidrug-resistant serotype 15A-CC63 strains, we identified a specific clone with ST9084, and all of the isolates were recovered from Yamaguchi prefecture in Japan. All of the serotype 15A-ST9084 isolates had a novel pbp2x-43 that was inserted by recombination events. The conserved amino acid motif profiles of pbp1a, pbp2b and pbp2x of the strains were identical to those in serotype 19A-ST320. A Bayesian analysis-based date estimation suggested that this clone emerged in approximately 2002 before the introduction of PCV in Japan. This clone should be monitored because serotype 15A is not contained in the currently used PCV13 and it was resistance to beta-lactams, which are often use in a clinical setting.

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Keywords: Antibiotics; Drugs Resistance; Beta-lactams; Penicillin; Cefotaxime; Meropenem; S. pneumoniae; Japan.

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