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  1. Article ; Online: Clonal Expansion of a Streptococcus pneumoniae Serotype 3 Capsule Variant Sequence Type 700 With Enhanced Vaccine Escape Potential After 13-Valent Pneumococcal Conjugate Vaccine Introduction.

    Kalizang'oma, Akuzike / Swarthout, Todd D / Mwalukomo, Thandie S / Kamng'ona, Arox / Brown, Comfort / Msefula, Jacquline / Demetriou, Hayley / Chan, Jia Mun / Roalfe, Lucy / Obolski, Uri / Lourenço, Jose / Goldblatt, David / Chaguza, Chrispin / French, Neil / Heyderman, Robert S

    The Journal of infectious diseases

    2024  

    Abstract: Background: Streptococcus pneumoniae serotype 3 remains a problem globally. Malawi introduced 13-valent pneumococcal conjugate vaccine (PCV13) in 2011, but there has been no direct protection against serotype 3 carriage. We explored whether vaccine ... ...

    Abstract Background: Streptococcus pneumoniae serotype 3 remains a problem globally. Malawi introduced 13-valent pneumococcal conjugate vaccine (PCV13) in 2011, but there has been no direct protection against serotype 3 carriage. We explored whether vaccine escape by serotype 3 is due to clonal expansion of a lineage with a competitive advantage.
    Methods: The distribution of serotype 3 Global Pneumococcal Sequence Clusters (GPSCs) and sequence types (STs) globally was assessed using sequences from the Global Pneumococcal Sequencing Project. Whole-genome sequences of 135 serotype 3 carriage isolates from Blantyre, Malawi (2015-2019) were analyzed. Comparative analysis of the capsule locus, entire genomes, antimicrobial resistance, and phylogenetic reconstructions were undertaken. Opsonophagocytosis was evaluated using serum samples from vaccinated adults and children.
    Results: Serotype 3 GPSC10-ST700 isolates were most prominent in Malawi. Compared with the prototypical serotype 3 capsular polysaccharide locus sequence, 6 genes are absent, with retention of capsule polysaccharide biosynthesis. This lineage is characterized by increased antimicrobial resistance and lower susceptibility to opsonophagocytic killing.
    Conclusions: A serotype 3 variant in Malawi has genotypic and phenotypic characteristics that could enhance vaccine escape and clonal expansion after post-PCV13 introduction. Genomic surveillance among high-burden populations is essential to improve the effectiveness of next-generation pneumococcal vaccines.
    Language English
    Publishing date 2024-03-26
    Publishing country United States
    Document type Journal Article
    ZDB-ID 3019-3
    ISSN 1537-6613 ; 0022-1899
    ISSN (online) 1537-6613
    ISSN 0022-1899
    DOI 10.1093/infdis/jiae040
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Risk factors for pneumococcal carriage in adults living with HIV on antiretroviral therapy in the infant pneumococcal vaccine era in Malawi.

    Thindwa, Deus / Mwalukomo, Thandie S / Msefula, Jacquline / Jambo, Kondwani C / Brown, Comfort / Kamng'ona, Arox / Mwansambo, Charles / Ojal, John / Flasche, Stefan / French, Neil / Heyderman, Robert S / Swarthout, Todd D

    AIDS (London, England)

    2022  Volume 36, Issue 14, Page(s) 2045–2055

    Abstract: Objective: Adults living with HIV (ALWHIV) on antiretroviral therapy (ART) are at high risk of pneumococcal carriage and disease. To help evaluate carriage risk in African ALWHIV at least 4 years after infant pneumococcal conjugate vaccination ... ...

    Abstract Objective: Adults living with HIV (ALWHIV) on antiretroviral therapy (ART) are at high risk of pneumococcal carriage and disease. To help evaluate carriage risk in African ALWHIV at least 4 years after infant pneumococcal conjugate vaccination introduction in 2011, we assessed association between pneumococcal carriage and potential risk factors.
    Methods: Nasopharyngeal swabs were collected from adults aged 18-40 years attending an ART clinic during rolling, cross-sectional surveys in Blantyre, Malawi between 2015 and 2019. We fitted generalized additive models to estimate the risk of sex, social economic status (SES), living with a child less than 5 years, and ART duration on carriage.
    Results: Of 2067 adults, median age was 33 years (range 28-37), 1427 (69.0%) were women, 1087 (61.4%) were in low-middle socioeconomic-status (SES), 910 (44.0%) were living with a child less than 5 years, and median ART duration was 3 years (range 0.004-17). We estimated 38.2 and 60.6% reductions in overall and vaccine-serotype carriage prevalence. Overall carriage was associated with low SES, living with a child less than 5 years and shorter duration on ART. By contrast, vaccine-type carriage was associated with living without a child less than 5 years and male sex.
    Conclusion: Despite temporal reductions in overall and vaccine-serotype carriage, there is evidence of incomplete vaccine-serotype indirect protection. A targeted-vaccination campaign should be considered for ALWHIV, along with other public health measures to further reduce vaccine-serotype carriage and therefore disease.
    MeSH term(s) Adult ; Female ; Humans ; Infant ; Male ; Carrier State/epidemiology ; Cross-Sectional Studies ; HIV Infections/complications ; HIV Infections/drug therapy ; Malawi/epidemiology ; Nasopharynx ; Pneumococcal Infections/epidemiology ; Pneumococcal Infections/prevention & control ; Pneumococcal Vaccines ; Prevalence ; Risk Factors ; Streptococcus pneumoniae ; Infant, Newborn ; Child, Preschool
    Chemical Substances Pneumococcal Vaccines
    Language English
    Publishing date 2022-08-19
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 639076-6
    ISSN 1473-5571 ; 0269-9370 ; 1350-2840
    ISSN (online) 1473-5571
    ISSN 0269-9370 ; 1350-2840
    DOI 10.1097/QAD.0000000000003365
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 2228: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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  3. Article ; Online: The metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi.

    Obolski, Uri / Swarthout, Todd D / Kalizang'oma, Akuzike / Mwalukomo, Thandie S / Chan, Jia Mun / Weight, Caroline M / Brown, Comfort / Cave, Rory / Cornick, Jen / Kamng'ona, Arox Wadson / Msefula, Jacquline / Ercoli, Giuseppe / Brown, Jeremy S / Lourenço, José / Maiden, Martin C / French, Neil / Gupta, Sunetra / Heyderman, Robert S

    Nature communications

    2023  Volume 14, Issue 1, Page(s) 7477

    Abstract: Streptococcus pneumoniae causes substantial mortality among children under 5-years-old worldwide. Polysaccharide conjugate vaccines (PCVs) are highly effective at reducing vaccine serotype disease, but emergence of non-vaccine serotypes and persistent ... ...

    Abstract Streptococcus pneumoniae causes substantial mortality among children under 5-years-old worldwide. Polysaccharide conjugate vaccines (PCVs) are highly effective at reducing vaccine serotype disease, but emergence of non-vaccine serotypes and persistent nasopharyngeal carriage threaten this success. We investigated the hypothesis that following vaccine, adapted pneumococcal genotypes emerge with the potential for vaccine escape. We genome sequenced 2804 penumococcal isolates, collected 4-8 years after introduction of PCV13 in Blantyre, Malawi. We developed a pipeline to cluster the pneumococcal population based on metabolic core genes into "Metabolic genotypes" (MTs). We show that S. pneumoniae population genetics are characterised by emergence of MTs with distinct virulence and antimicrobial resistance (AMR) profiles. Preliminary in vitro and murine experiments revealed that representative isolates from emerging MTs differed in growth, haemolytic, epithelial infection, and murine colonisation characteristics. Our results suggest that in the context of PCV13 introduction, pneumococcal population dynamics had shifted, a phenomenon that could further undermine vaccine control and promote spread of AMR.
    MeSH term(s) Child ; Humans ; Animals ; Mice ; Infant ; Child, Preschool ; Streptococcus pneumoniae/genetics ; Pneumococcal Infections/epidemiology ; Pneumococcal Infections/prevention & control ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Malawi/epidemiology ; Virulence/genetics ; Drug Resistance, Bacterial/genetics ; Pneumococcal Vaccines ; Serogroup ; Nasopharynx ; Carrier State/epidemiology
    Chemical Substances Anti-Bacterial Agents ; Pneumococcal Vaccines
    Language English
    Publishing date 2023-11-17
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-023-43160-y
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: High residual carriage of vaccine-serotype Streptococcus pneumoniae after introduction of pneumococcal conjugate vaccine in Malawi.

    Swarthout, Todd D / Fronterre, Claudio / Lourenço, José / Obolski, Uri / Gori, Andrea / Bar-Zeev, Naor / Everett, Dean / Kamng'ona, Arox W / Mwalukomo, Thandie S / Mataya, Andrew A / Mwansambo, Charles / Banda, Marjory / Gupta, Sunetra / Diggle, Peter / French, Neil / Heyderman, Robert S

    Nature communications

    2020  Volume 11, Issue 1, Page(s) 2222

    Abstract: There are concerns that pneumococcal conjugate vaccines (PCVs) in sub-Saharan Africa sub-optimally interrupt Streptococcus pneumoniae vaccine-serotype (VT) carriage and transmission. Here we assess PCV carriage using rolling, prospective nasopharyngeal ... ...

    Abstract There are concerns that pneumococcal conjugate vaccines (PCVs) in sub-Saharan Africa sub-optimally interrupt Streptococcus pneumoniae vaccine-serotype (VT) carriage and transmission. Here we assess PCV carriage using rolling, prospective nasopharyngeal carriage surveys between 2015 and 2018, 3.6-7.1 years after Malawi's 2011 PCV13 introduction. Carriage decay rate is analysed using non-linear regression. Despite evidence of reduction in VT carriage over the study period, there is high persistent residual carriage. This includes among PCV-vaccinated children 3-5-year-old (16.1% relative reduction from 19.9% to 16.7%); PCV-unvaccinated children 6-8-year-old (40.5% reduction from 26.4% to 15.7%); HIV-infected adults 18-40-years-old on antiretroviral therapy (41.4% reduction from 15.2% to 8.9%). VT carriage prevalence half-life is similar among PCV-vaccinated and PCV-unvaccinated children (3.26 and 3.34 years, respectively). Compared with high-income settings, there is high residual VT carriage 3.6-7.1 years after PCV introduction. Rigorous evaluation of strategies to augment vaccine-induced control of carriage, including alternative schedules and catch-up campaigns, is required.
    MeSH term(s) Adolescent ; Adult ; Child ; Child, Preschool ; Cross-Sectional Studies ; Demography ; Female ; HIV Infections ; Humans ; Infant ; Malawi ; Male ; Nasopharynx/immunology ; Pneumococcal Vaccines/administration & dosage ; Prevalence ; Prospective Studies ; Serogroup ; Streptococcus pneumoniae/immunology ; Streptococcus pneumoniae/isolation & purification ; Time Factors ; Vaccination ; Vaccines, Conjugate/administration & dosage ; Vaccines, Conjugate/adverse effects
    Chemical Substances Pneumococcal Vaccines ; Vaccines, Conjugate
    Language English
    Publishing date 2020-05-06
    Publishing country England
    Document type Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-020-15786-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Evaluation of Pneumococcal Serotyping of Nasopharyngeal-Carriage Isolates by Latex Agglutination, Whole-Genome Sequencing (PneumoCaT), and DNA Microarray in a High-Pneumococcal-Carriage-Prevalence Population in Malawi.

    Swarthout, Todd D / Gori, Andrea / Bar-Zeev, Naor / Kamng'ona, Arox W / Mwalukomo, Thandie S / Bonomali, Farouck / Nyirenda, Roseline / Brown, Comfort / Msefula, Jacquline / Everett, Dean / Mwansambo, Charles / Gould, Katherine / Hinds, Jason / Heyderman, Robert S / French, Neil

    Journal of clinical microbiology

    2020  Volume 59, Issue 1

    Abstract: Accurate assessment of the serotype distribution associated with pneumococcal colonization and disease is essential for evaluating and formulating pneumococcal vaccines and for informing vaccine policy. For this reason, we evaluated the concordance ... ...

    Abstract Accurate assessment of the serotype distribution associated with pneumococcal colonization and disease is essential for evaluating and formulating pneumococcal vaccines and for informing vaccine policy. For this reason, we evaluated the concordance between pneumococcal serotyping results by latex agglutination, whole-genome sequencing (WGS) with PneumoCaT, and DNA microarray for samples from community carriage surveillance in Blantyre, Malawi. Nasopharyngeal swabs were collected according to WHO recommendations between 2015 and 2017 by using stratified random sampling among study populations. Participants included healthy children 3 to 6 years old (vaccinated with the 13-valent pneumococcal conjugate vaccine [PCV13] as part of the Expanded Program on Immunization [EPI]), healthy children 5 to 10 years old (age-ineligible for PCV13), and HIV-infected adults (18 to 40 years old) on antiretroviral therapy (ART). For phenotypic serotyping, we used a 13-valent latex kit (Statens Serum Institut [SSI], Denmark). For genomic serotyping, we applied the PneumoCaT pipeline to whole-genome sequence libraries. For molecular serotyping by microarray, we used the BUGS Bioscience Senti-SP microarray. A total of 1,347 samples were analyzed. Concordance was 90.7% (95% confidence interval [CI], 89.0 to 92.2%) between latex agglutination and PneumoCaT, 95.2% (95% CI, 93.9 to 96.3%) between latex agglutination and the microarray, and 96.6% (95% CI, 95.5 to 97.5%) between the microarray and PneumoCaT. By detecting additional vaccine serotype (VT) pneumococci carried at low relative abundances (median, 8%), the microarray increased VT detection by 31.5% over that by latex serotyping. To conclude, all three serotyping methods were highly concordant in identifying dominant serotypes. Latex serotyping is accurate in identifying vaccine serotypes and requires the least expertise and resources for field implementation and analysis. However, WGS, which adds population structure, and microarray, which adds multiple-serotype carriage, should be considered at regional reference laboratories for investigating the importance of vaccine serotypes at low relative abundances in transmission and disease.
    MeSH term(s) Adolescent ; Adult ; Carrier State/epidemiology ; Child ; Child, Preschool ; Cross-Sectional Studies ; Humans ; Infant ; Latex Fixation Tests ; Malawi/epidemiology ; Nasopharynx ; Oligonucleotide Array Sequence Analysis ; Pneumococcal Infections ; Pneumococcal Vaccines ; Prevalence ; Serotyping ; Young Adult
    Chemical Substances Pneumococcal Vaccines
    Language English
    Publishing date 2020-12-17
    Publishing country United States
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 390499-4
    ISSN 1098-660X ; 0095-1137
    ISSN (online) 1098-660X
    ISSN 0095-1137
    DOI 10.1128/JCM.02103-20
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1188: Show issues Location:
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    Jg. 1995 - 2021: Lesesall (1.OG)
    ab Jg. 2022: Lesesaal (EG)

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