Mapping diphtheria-pertussis-tetanus vaccine coverage in Africa, 2000–2016: a spatial and temporal modelling study

By Jonathan F Mosser, MD, William Gagne-Maynard, MS, Puja C Rao, MPH, Aaron Osgood-Zimmerman, MS, Nancy Fullman, MPH, Nicholas Graetz, MPH, et al.

The Lancet, May 2019

 

Estimated third-dose (DPT3) coverage increased in 72·3% (95% uncertainty interval [UI] 64·6–80·3) of second-level administrative units in Africa from 2000 to 2016, but substantial geographical inequalities in DPT coverage remained across and within African countries. In 2016, DPT3 coverage at the second administrative (ie, district) level varied by more than 25% in 29 of 52 countries, with only two (Morocco and Rwanda) of 52 countries meeting the Global Vaccine Action Plan target of 80% DPT3 coverage or higher in all second-level administrative units with high confidence (posterior probability ≥95%). Large areas of low DPT3 coverage (≤50%) were identified in the Sahel, Somalia, eastern Ethiopia, and in Angola. Low first-dose (DPT1) coverage (≤50%) and high relative dropout (≥30%) together drove low DPT3 coverage across the Sahel, Somalia, eastern Ethiopia, Guinea, and Angola.

 

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Influenza Vaccine Effectiveness in Preventing Influenza-associated Hospitalizations During Pregnancy: A Multi-country Retrospective Test Negative Design Study, 2010–2016

By Mark G Thompson, Jeffrey C Kwong, Annette K Regan, Mark A Katz, Steven J Drews, Eduardo Azziz-Baumgartner, Nicola P Klein, Hannah Chung, Paul V Effler, Becca S Feldman, Kimberley Simmonds, Brandy E Wyant, Fatimah S Dawood,  Michael L Jackson, Deshayne B Fell, Avram Levy, Noam Barda, Lawrence W Svenson, Rebecca V Fink, Sarah W Ball, Allison Naleway

Clinical Infectious Diseases, May 2019

 

The Pregnancy Influenza Vaccine Effectiveness Network (PREVENT) consisted of public health or healthcare systems with integrated laboratory, medical, and vaccination records in Australia, Canada (Alberta and Ontario), Israel, and the United States (California, Oregon, and Washington). Sites identified pregnant women aged 18 through 50 years whose pregnancies overlapped with local influenza seasons from 2010 through 2016. Administrative data were used to identify hospitalizations with acute respiratory or febrile illness (ARFI) and clinician-ordered real-time reverse transcription polymerase chain reaction (rRT-PCR) testing for influenza viruses. Overall IVE was estimated using the test-negative design and adjusting for site, season, season timing, and high-risk medical conditions

 

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Safety and Immunogenicity of Pneumococcal Conjugate Vaccines in a High-risk Population: A Randomized Controlled Trial of 10-Valent and 13-Valent Pneumococcal Conjugate Vaccine in Papua New Guinean Infants

By William S Pomat, Anita H J van den Biggelaar, Sandra Wana, Jacinta P Francis, Vela Solomon, Andrew R Greenhill, Rebecca Ford, Tilda Orami, Megan Passey, Peter Jacoby, Lea-Ann Kirkham, Deborah Lehmann, Peter C Richmond

Clinical Infectious Diseases, May 2019

 

PCV10 and PCV13 were studied head-to-head in a randomized controlled trial in Papua New Guinea in which 262 infants received 3 doses of PCV10 or PCV13 at 1, 2, and 3 months of age. Serotype-specific immunoglobulin G (IgG) concentrations, and pneumococcal and nontypeable Haemophilus influenzae (NTHi) carriage were assessed prevaccination and at 4 and 9 months of age. Infants were followed up for safety until 9 months of age.

 

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Persistence of Nasopharyngeal Pneumococcal Vaccine Serotypes and Increase of Nonvaccine Serotypes Among Vaccinated Infants and Their Mothers 5 Years After Introduction of Pneumococcal Conjugate Vaccine 13 in The Gambia

By Effua Usuf, Christian Bottomley, Ebrima Bojang, Isatou Cox, Abdoulie Bojang, Rebecca Gladstone, Beate Kampmann, Philip C Hill, Anna Roca

Clinical Infectious Diseases, May 2019

 

The widespread use of pneumococcal conjugate vaccine (PCV) has brought about a dramatic decrease in pneumococci of vaccine serotypes (VTs) but nonvaccine serotypes (NVTs) have emerged.

 

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Sustaining pneumococcal vaccination after transitioning from Gavi support: a modelling and cost-effectiveness study in Kenya

by John Ojal, PhD; Ulla Griffiths, PhD; Laura L Hammitt, MD; Ifedayo Adetifa, PhD; Donald Akech, BSc; Collins Tabu, PhD; et al.

To be published in The Lancet Global Health, May 2019. 

 

 

In 2009, Gavi, the World Bank, and donors launched the pneumococcal Advance Market Commitment, which helped countries access more affordable pneumococcal vaccines. As many low-income countries begin to reach the threshold at which countries transition from Gavi support to self-financing (3-year average gross national income per capita of US$1580), they will need to consider whether to continue pneumococcal conjugate vaccine (PCV) use at full cost or to discontinue PCV in their childhood immunisation programmes. Using Kenya as a case study, researchers assessed the incremental cost-effectiveness of continuing PCV use.

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

by Laura L Hammitt, MD; Anthony O Etyang, ChB; Susan C Morpeth, FRACP; John Ojal, PhD; Alex Mutuku, MSc; Neema Mturi, MRCPCH; et al.

Published in The Lancet, 15 April 2019.

 

 

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. Researchers aimed to assess PCV10 effect against nasopharyngeal carriage and invasive pneumococcal disease (IPD) in children and adults in Kilifi County.

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Molecular characterization and epidemiology of Streptococcus pneumoniae serotype 24F in Denmark

by Kavalari ID, Fuursted K, Krogfelt KA, Slotved HC

Published in Scientific Reports, 02 April 2019

 

Since 2012, Denmark has observed an increase of invasive pneumococcal infections (IPD) due to Streptococcus pneumoniae serotype 24F. Researchers present epidemiological data on 24F IPD cases, and characterization of 48 24F clinical isolates based on clonal relationship, antimicrobial resistance (AMR) determinants and virulence factors. IPD surveillance data from (1999-2016) were used to calculate the incidence and age-distribution of serotype 24F IPD and the effect of pneumococcal conjugated vaccines (PCV). Characterization of forty-eight 24F isolates (14.7% of all 24F isolates from the period) was based on whole-genome sequencing analysis (WGS). The IPD cases of serotype 24F showed a significant increase (p < 0.05) for all age groups after the PCV-13 introduction in 2010. The majority of tested 24F isolates consisted of two MLST types, i.e. the ST72 and the ST162. Serotype 24F IPD increased in Denmark after the PCV-13 introduction in parallel with an increase of the ST162 clone. The genotypic penicillin binding protein (PBP) profile agreed with the phenotypical penicillin susceptibility. The virulence genes lytA, ply, piaA, piaB, piaC, rspB and the cpsA/wzg were detected in all 24F isolates, while the pspA and zmpC genes were absent.

 

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Maternal pertussis vaccination and its effects on the immune response of infants aged up to 12 months in the Netherlands: an open-label, parallel, randomised controlled trial

by Daan Barug, MD; Inge Pronk, BSc; Marlies A van Houten, MD; Florens G A Versteegh, PhD; Mirjam J Knol, PhD; Jan van de Kassteele, PhD; et al.

Published in The Lancet Infectious Diseases, 01 April 2019.

 

Maternal tetanus, diphtheria, and acellular pertussis (Tdap) vaccination offers protection for neonates against clinical pertussis until primary vaccinations, but maternal antibodies also interfere with infants' immune responses to primary vaccinations. Researchers investigated the effect of maternal Tdap vaccination on the pertussis antibody responses of infants starting primary vaccinations at age 3 months. In an open-label, parallel, randomised, controlled trial, pregnant women aged 18–40 years with a low risk of pregnancy complications were recruited through independent midwives at 36 midwife clinics in the Netherlands and received Tdap vaccination either at 30–32 weeks of pregnancy (maternal Tdap group) or within 48 h after delivery (control group). All term-born infants were vaccinated with the diphtheria, tetanus, and pertussis-inactivated poliomyelitis- Haemophilus influenzae type B-hepatitis B six-in-one vaccine and a ten-valent pneumococcal vaccine at 3 months, 5 months, and 11 months. Randomisation was done using a number generator in a 1:1 ratio and with sealed envelopes. Participants and clinical trial staff were not masked, but laboratory technicians were unaware of study group assignments. The primary endpoint was serum IgG pertussis toxin antibody concentrations at age 3 months. Cord blood and infant blood samples were collected at age 2 months, 3 months, 6 months, 11 months, and 12 months. Analysis was done by modified intention to treat with all randomly assigned participants in case a laboratory result was available. This trial is registered with ClinicaltTrialsRegister.eu (EudraCT 2012-004006-9) and trialregister.nl (NTR number NTR4314). The trial is now closed to new participants. Between Jan 16, 2014, and March 4, 2016, 118 pregnant women were enrolled into our study, with 58 in the maternal Tdap group and 60 in the control group. The geometric mean concentration (GMC) of pertussis toxin antibodies were higher in infants in the maternal Tdap group than in the control group infants at age 3 months (GMC ratio 16.6, 95% CI 10.9–25.2) and also significantly higher compared with control infants at age 2 months. After primary vaccinations, antibody concentrations for pertussis toxin, filamentous haemagglutinin, and pertactin were significantly lower at all time points in infants of the maternal Tdap group than in infants in the control group. No safety issues after maternal Tdap vaccination were encountered. In view of the high pertussis toxin antibody concentrations at age 3 months, maternal vaccination supports a delay of the first pertussis vaccination in infants until at least age 3 months. Maternal antibody interference affects antibody concentrations after primary and booster vaccinations. The clinical consequences of this interference remain to be established.  Article access can be found here.    
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Maternal immunisation to improve the health of HIV-exposed infants

by Angela M Bengtson, PhD; Alan M Sanfilippo, PhD; Brenna L Hughes, MD; David A Savitz, PhD.

Published in The Lancet Infectious Diseases, 01 April 2019.

 

 

HIV-exposed but uninfected (HEU) infants are at an increased risk of many infectious diseases that can contribute to the high mortality seen among HEU children. Maternal immunisation could be a promising strategy to reduce infections in HEU infants. However, very little research has explored the effect of HIV on the immunogenicity and effectiveness of vaccines given during pregnancy. Researchers reviewed available evidence on maternal immunisation among women living with HIV (WLWH) for all vaccines recommended, considered, or being investigated for routine or risk-based use during pregnancy. Of the 11 vaccines included, only three have been investigated in WLWH. Available evidence suggests that maternal HIV infection limits the immunogenicity of several vaccines, leaving HEU infants more susceptible to infection during their first few months of life. Whether maternal immunisation reduces the infectious morbidity and mortality associated with infectious diseases in HEU children remains unknown. Researchers concluded the Review by identifying future research priorities.  Article access can be found here.   
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Prediction and validation of immunogenic domains of pneumococcal proteins recognized by human CD4+ T-cells

by van de Garde MDB, van Westen E, Poelen MCM, Rots NY, van Els CACM

Published in Infection and Immunity, 25 March 2019. 

 

 

CD4+ T-cell mechanisms are implied in protection against pneumococcal colonization; however, their target antigens and function are not well defined. In contrast to high-throughput protein arrays for serology, basic antigen tools for CD4+ T-cell studies are lacking. Here researchers evaluate the potential of a bioinformatics tool in silico prediction of immunogenicity as a method to reveal domains of pneumococcal proteins targeted by human CD4+ T-cells.

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Changes in Serotype of Streptococcus pneumoniae After the Introduction of the 13-Valent Pneumococcal Vaccine in a Homogenous Population on Jeju Island

by Yoo JR, Heo ST, Oh H, Oh S, Kim YR, Lee KH

Published in Infection & Chemotherapy, March 2019. 

 

Researchers compared the serotypes of Streptococcus pneumoniae between the pre-pneumococcal conjugate vaccine (PCV)13 era and post-PCV13 era among homogenous inhabitants of an isolated South Korean island. A total of 325 S. pneumoniae strains were isolated. In the pre-PCV13 era, 19A/F, 15A/F, 19B, and 23A serotypes were identified. In the post-PCV13 era, 15 serotypes were identified. The 19F and 23A serotypes showed the highest prevalence in the pre- and post-PCV13 era, respectively. After PCV13 introduction, the PCV 13 serotype coverage rate was decreased (80.0% and 30.5% in the pre- and post-PCV13 eras, respectively), while the proportion of non-PCV 13 serotypes increased.

 

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Safety and immunogenicity of pneumococcal conjugate vaccines in preterm infants

by López-Sanguos C, Rivero Calle I, Rodriguez Tenreiro C, Raguindin PF, Martinón-Torres F

Published in Expert Opinion on Drug Safety, 23 March 2019. 

 

 

The introduction of pneumococcal conjugate vaccines (PCVs) in the routine immunization program has resulted in a significant decline in invasive pneumococcal diseases (IPD) around the world. Preterm infants are a special group at a high risk of invasive infection by encapsulated bacteria. However, their slow growth accrual and prolonged hospital stays frequently lead to delays in immunization, which contributes to their risk of severe infections.

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Evaluation of a phased pneumococcal conjugate vaccine introduction in Mongolia using enhanced pneumonia surveillance and community carriage surveys: a study protocol for a prospective observational study and lessons learned

by La Vincente SF, von Mollendorf C, Ulziibayar M, Satzke C, Dashtseren L, Fox KK, Dunne EM, Nguyen CD, de Campo J, de Campo M, Thomson H, Surenkhand G, Demberelsuren S, Bujinlkham S, Do LAH, Narangerel D, Cherian T, Mungun T, Mulholland EK

Published in BMC Public Health, 21 March 2019. 

 

 

Streptococcus pneumoniae causes substantial morbidity and mortality among children. The introduction of pneumococcal conjugate vaccines (PCV) has the potential to dramatically reduce disease burden. As with any vaccine, it is important to evaluate PCV impact, to help guide decision-making and resource-allocation. Measuring PCV impact can be complex, particularly to measure impact on one of the most common and significant diseases caused by the pneumococcus, namely pneumonia. Here researchers outline the protocol developed to evaluate the impact of 13-valent PCV (PCV13) on childhood pneumonia in Mongolia, and a number of lessons learned in implementing the evaluation that may be helpful to other countries seeking to undertake pneumonia surveillance.

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Impact of 13-valent pneumococcal conjugate vaccination on invasive pneumococcal disease in children under 15 years old in Madrid, Spain, 2007 to 2016: The HERACLES clinical surveillance study

by Picazo JJ, Ruiz-Contreras J, Casado-Flores J, Negreira S, Baquero-Artigao F, Hernández-Sampelayo T, Otheo E, Amo MD, Méndez C; Heracles Study Group

Published in Vaccine, 19 March 2019.

 

 

Streptococcus pneumoniae is a major cause of morbidity and mortality worldwide. Using the data from the HERACLES clinical surveillance study (2007-2016), researchers describe the population impact of the 13-valent pneumococcal conjugate vaccine (PVC13) on invasive pneumococcal disease (IPD) in children <15 years of age in the Community of Madrid, Spain.

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Ongoing Exposure of U.K. Infants to Vaccine Serotype Pneumococci

by Mary Slack, FRCPATH; Andrew Vyse, PhD; Harish Madhava, MD; Ralf-Rene Reinert, MD; Gillian Ellsbury, MD; Carole Czudek, PhD; Bradford Gessner, MD

Published in The Pediatric Infectious Disease Journal, April 2019. doi: 10.1097/INF.0000000000002184  "To the editors: 

We read with interest the article by Makwana et al. The authors note that most childhood invasive pneumococcal disease (IPD) cases are now due to non-13 valent pneumococcal conjugate vaccine (PCV13) serotypes though PCV13 serotypes remain in circulation with serotypes 3 and 19A listed among the top 10 that caused IPD in children in 2015/16. Of the 25 cases with PCV13-type IPD in 2015/16, 11 (44%) were due to serotype 19A.

 

Key insight is given into the IPD burden in infants 3–11 months of age, which over the 6-year study period accounted for a substantial proportion (508/1255, 40%) of the total in children <5 years of age. Additionally, meningitis was most prevalent in infants (209/456 cases, 45.8%) and was associated with the highest case fatality (9.6%). The most recent data from 2015/16 showed 103/271 (38%) of IPD cases occurred in infants 3–11 months of age, with 5 (4.8%) attributed to PCV13 serotypes. This reflects an increase in infant IPD compared with 2014/15 and slightly exceeds the number of cases in this age group in 2010/11 when PCV13 was first introduced illustrating a continuing and substantial burden of infant IPD. ..."

 

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Integrated Safety Profile of a New Approved, Fully Liquid DTaP5-HB-IPV-Hib Vaccine

by Jin Xu, PhD; Jon E. Stek, MS; Eddy Ziani, MD; G. Frank Liu, PhD; Andrew W. Lee, MD

Published in The Pediatric Infectious Disease Journal, April 2019. doi: 10.1097/INF.0000000000002257

 

 

DTaP5-HB-IPV-Hib is a fully liquid, hexavalent vaccine containing a 5-antigen pertussis component, approved since 2016 in Europe [Vaxelis; DTaP5-HB-IPV-Hib vaccine: Diphtheria, tetanus, pertussis (5 acellular components: pertussis toxoid [PT], filamentous haemagglutinin [FHA], pertactin (PRN), and fimbriae Types 2 and 3 [FIM]), hepatitis B (recombinant DNA: rDNA), poliomyelitis (inactivated) and Haemophilus influenzae type b conjugate vaccine (adsorbed); MCM Vaccine B.V., The Netherlands] for primary and booster vaccination in infants and toddlers against diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis and invasive diseases caused by Haemophilus influenzae type b. The comparator vaccine (control) was INFANRIX hexa (GlaxoSmithKline Biologics S.A., Rixensart, Belgium) (DTaP3-IPV-HepB/Hib) in European studies and PENTACEL (DTaP5-IPV/Hib) (Sanofi Pasteur, Swiftwater, PA) in US studies.

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Invasive Pneumococcal Disease in Neonates Prior to Pneumococcal Conjugate Vaccine Use in South Africa 2003–2008

by Krishnee Moodley, MBChB, FCPath, MMed; Yacoob Mahomed Coovadia, MBChB, FCPathSA; Cheryl Cohen, MBChB, PhD; Susan Meiring, MBChB, DTM&H; Sarona Lengana, MBChB, DipHIVManSA; Linda De Gouveia, NDMed Tech; Claire von Mollendorf, MBChB, MSc, PhD; Penny Crowther-Gibson, MSc, MSc; Vanessa Quan, MBChB, MPH; Brian Eley, MBChB; Gary Reubenson, MBBCh, FCPaed; Trusha Nana, MBChB, FCPath, MMed; Anne von Gottberg, MBChB, PhD

Published in The Pediatric Infectious Disease Journal, April 2019. doi: 10.1097/INF.0000000000002096

 

 

Neonatal invasive pneumococcal disease (IPD) in developing countries is poorly described. Researchers provide a baseline description of neonatal IPD in South Africa, before implementation of the 7-valent pneumococcal conjugate vaccine (PCV7) in 2009.

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The True Cost of Measles Outbreaks During the Postelimination Era

by Maria E. Sundaram, MSPH, PHD; L. Beryl Guterman, MSPH; Saad B. Omer, MBBS, MPH, PhD

Published in JAMA, 07 March 2019. doi: 10.1001/jama.2019.1506

 

 

"A large measles outbreak in Washington State has prompted officials to declare a state of emergency. As of March 4, 2019, the Washington State Health Department reported 71 confirmed cases, with the majority of cases among individuals who were not vaccinated or who had an unverified vaccination status. The outbreak is centered in a geographic cluster of persistently high vaccine exemption rates among young children. This cluster has persisted despite the overall reduction in vaccine exemptions in the state of Washington, subsequent to the introduction of legally mandated health care practitioner counseling of parents seeking vaccine exemptions.

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Influenza Epidemiology, Vaccine Coverage and Vaccine Effectiveness in Children Admitted to Sentinel Australian Hospitals in 2017: Results from the PAEDS-FluCAN Collaboration

by Christopher C Blyth, Kristine K Macartney, Jocelynne McRae, Julia E Clark, Helen S Marshall, Jim Buttery, Joshua R Francis, Tom Kotsimbos, Paul M Kelly, and Allen C Cheng

Published in Clinical Infectious Diseases, 05 March 2019. https://doi.org/10.1093/cid/ciy597

 

 

In 2017, Australia experienced record influenza notifications. Two surveillance programs combined to summarize the epidemiology of hospitalized influenza in children and report on vaccine effectiveness (VE) in the context of a limited nationally funded vaccination program.

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Vaccine Prophylaxis of Pneumococcal Infections in Children under Conditions of Severe Flood in the Amur River Basin

by Chuchalin AG, Onishchenko GG, Kolosov VP, Kurganova OP, Zaitseva TA, Manakov LG, Kholodok GN, Perelman JM, Kozlov RS, Ivakhnishina NM, Trotsenko OE, Bondarenko AP

Published in Interdisciplinary perspectives on infectious diseases, 18 February 2019. 

 

 

Pneumococcal infection being one of the dominant causes of acute respiratory diseases and exacerbation of chronic ones is a serious problem for human health and society. The flood in the Amur river basin in the summer of 2013 created a special zone and risk conditions for the formation of respiratory pathology in the Far-Eastern region of Russia. Researchers aimed to give clinical and epidemiological assessment of the effectiveness of vaccination programs of respiratory viral and pneumococcal infections and generalization of regional experience in the organization of a set of measures aimed at their prevention in the postflood period in the Far-Eastern region.

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