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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
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Article ; Online: Invasiveness potential of pneumococcal serotypes in children after introduction of PCV13 in Blantyre, Malawi.

Kirolos, Amir / Swarthout, Todd D / Mataya, Andrew A / Bonomali, Farouck / Brown, Comfort / Msefula, Jacquline / Bar-Zeev, Naor / Iroh Tam, Pui-Ying / Alaerts, Maaike / Bilima, Sithembile / Heyderman, Robert S / French, Neil

BMC infectious diseases

2023 Volume 23, Issue 1, Page(s) 56

Abstract: Introduction: The introduction of PCV13 to the Malawi infant immunization schedule in 2011 has been associated with reduced disease from Streptococcus pneumoniae. Improved understanding of serotypes with high invasive potential can guide future ... ...

Abstract	Introduction: The introduction of PCV13 to the Malawi infant immunization schedule in 2011 has been associated with reduced disease from Streptococcus pneumoniae. Improved understanding of serotypes with high invasive potential can guide future vaccination interventions. We aimed to estimate pneumococcal serotypes associated with acute respiratory infection (ARI) and invasive pneumococcal disease (IPD) in hospitalized children in Blantyre, Malawi. Methods: We analysed data from healthy children under 5 years in the community in Blantyre and children admitted to Queen Elizabeth Central Hospital with ARI between 2015 and 2018. Nasopharyngeal swabs from children were tested for S. pneumoniae and serotyped by latex agglutination if positive. We analysed culture-positive blood and cerebrospinal fluid samples from admitted children between 2012 and 2018 to identify cases of IPD after the introduction of PCV13. We calculated the age-adjusted odds ratio (OR) of carriage for S. pneumoniae vaccine serotypes (VT) comparing those with ARI to healthy children. We also calculated age-adjusted ORs comparing serotypes causing IPD to carriage in the community with OR > 1 indicating high invasive potential. Results: Serotypes 5 (OR 24.73 [95% CI 7.90-78.56] p < 0.001), 1 (OR 23.38 [95% CI 9.75-56.06] p < 0.001), and 6B (OR 4.73 [95% CI 1.66-11.64] p = 0.001) had high invasive potential. Serotype 6B was no longer significant (OR 1.34 [95% CI 0.07-6.87] p = 0.777) in a sensitivity analysis accounting for year of recruitment. The prevalence of S. pneumoniae carriage in the community was 72.6% [95% CI 71.3-74.0] (3078/4238) and 23.4% (719/3078) of positive community samples were VT. The carriage prevalence in those hospitalised with ARI was 45.5% [95% CI 42.1-48.9] (389/855) and 43.8% of hospital attendees reported antibiotic use prior to admission. We did not identify significant associations with carriage of any serotypes in those with ARI. Conclusions: Pneumococcal serotypes 5 and 1 are associated with high invasive potential. Despite high community pneumococcal carriage, pre-hospital antibiotic usage likely reduces pneumococcal detection among children admitted in this setting and further research is needed to investigate serotypes associated with ARI. Data from this study can guide future preventative vaccination strategies in Malawi.
MeSH term(s)	Infant ; Child ; Humans ; Child, Preschool ; Serogroup ; Malawi/epidemiology ; Carrier State/epidemiology ; Nasopharynx ; Streptococcus pneumoniae ; Pneumococcal Infections/epidemiology ; Pneumococcal Infections/prevention & control ; Pneumococcal Vaccines ; Respiratory Tract Infections ; Anti-Bacterial Agents
Chemical Substances	Pneumococcal Vaccines ; Anti-Bacterial Agents
Language	English
Publishing date	2023-01-26
Publishing country	England
Document type	Journal Article
ZDB-ID	2041550-3
ISSN	1471-2334 ; 1471-2334
ISSN (online)	1471-2334
ISSN	1471-2334
DOI	10.1186/s12879-023-08022-4
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Article ; Online: Cross-sectional health centre and community-based evaluation of the impact of pneumococcal and malaria vaccination on antibiotic prescription and usage, febrile illness and antimicrobial resistance in young children in Malawi: the IVAR study protocol.

Singleton, David / Ibarz-Pavon, Ana / Swarthout, Todd D / Bonomali, Farouck / Cornick, Jennifer / Kalizang'oma, Akuzike / Ntiza, Noah / Brown, Comfort / Chipatala, Raphael / Nyangulu, Wongani / Chirombo, James / Kawalazira, Gift / Chibowa, Henry / Mwansambo, Charles / Maleta, Kenneth Mphatso / French, Neil / Heyderman, Robert S

BMJ open

2023 Volume 13, Issue 5, Page(s) e069560

Abstract: Introduction: Vaccination is a potentially critical component of efforts to arrest development and dissemination of antimicrobial resistance (AMR), though little is known about vaccination impact within low-income and middle-income countries. This study ...

Abstract	Introduction: Vaccination is a potentially critical component of efforts to arrest development and dissemination of antimicrobial resistance (AMR), though little is known about vaccination impact within low-income and middle-income countries. This study will evaluate the impact of vaccination on reducing carriage prevalence of resistant Methods and analysis: Six cross-sectional surveys will be implemented within primary healthcare centres (n=3000 users of outpatient facilities per survey) and their local communities (n=700 healthy children per survey): three surveys in Blantyre district (PCV13 component) and three surveys in Mangochi district (RTS,S/AS01 component). We will evaluate antibiotic prescription practices and AMR carriage in children ≤3 years. For the PCV13 component, surveys will be conducted 9, 18 and 33 months following a 3+0 to 2+1 schedule change. For the RTS,S/AS01 component, surveys will be conducted 32, 44 and 56 months post-RTS,S/AS01 introduction. Six health centres in each study component will be randomly selected for study inclusion. Between intervention arms, the primary outcome will be the difference in penicillin non-susceptibility prevalence among Ethics and dissemination: This study has been approved by the Kamuzu University of Health Sciences (Ref: P01-21-3249), University College London (Ref: 18331/002) and University of Liverpool (Ref: 9908) Research Ethics Committees. Parental/caregiver verbal or written informed consent will be obtained prior to inclusion or recruitment in the health centre-based and community-based activities, respectively. Results will be disseminated via the Malawi Ministry of Health, WHO, peer-reviewed publications and conference presentations.
MeSH term(s)	Humans ; Child ; Infant ; Child, Preschool ; Streptococcus pneumoniae ; Pneumococcal Infections/epidemiology ; Pneumococcal Infections/prevention & control ; Anti-Bacterial Agents/pharmacology ; Anti-Bacterial Agents/therapeutic use ; Cross-Sectional Studies ; Malaria Vaccines ; Malawi/epidemiology ; Drug Resistance, Bacterial ; Pneumococcal Vaccines ; Vaccination ; Penicillins ; Nasopharynx ; Malaria/epidemiology ; Malaria/prevention & control ; Carrier State/epidemiology
Chemical Substances	Anti-Bacterial Agents ; Malaria Vaccines ; Pneumococcal Vaccines ; Penicillins
Language	English
Publishing date	2023-05-12
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2022-069560
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Article ; Online: Changing Incidence of Invasive Pneumococcal Disease in Infants Less Than 90 Days of Age Before and After Introduction of the 13-Valent Pneumococcal Conjugate Vaccine in Blantyre, Malawi: A 14-Year Hospital Based Surveillance Study.

Koenraads, Marianne / Swarthout, Todd D / Bar-Zeev, Naor / Brown, Comfort / Msefula, Jacquline / Denis, Brigitte / Dube, Queen / Gordon, Stephen B / Heyderman, Robert S / Gladstone, Melissa J / French, Neil

The Pediatric infectious disease journal

2022 Volume 41, Issue 9, Page(s) 764–768

Abstract: Background: Invasive pneumococcal disease (IPD) in young infants is uncommon but associated with high morbidity and mortality. Accurate data on the burden of IPD in young infants in low-income countries are lacking. We examined the burden of IPD in ... ...

Abstract	Background: Invasive pneumococcal disease (IPD) in young infants is uncommon but associated with high morbidity and mortality. Accurate data on the burden of IPD in young infants in low-income countries are lacking. We examined the burden of IPD in infants <90 days old in Blantyre, Malawi over a 14-year period and evaluated the indirect impact of the 13-valent pneumococcal conjugate vaccine (PCV13) on vaccine-serotype IPD (VT-IPD) in this population. Methods: We conducted laboratory-based prospective IPD surveillance in infants <90 days of age admitted to Queen Elizabeth Central Hospital in Blantyre between 2005 and 2018, including 7 years pre-PCV13 and 7 years post-PCV13 introduction. IPD was defined as Streptococcus pneumoniae identified by culture from blood or cerebrospinal fluid. Serotypes were determined by multiplex polymerase chain reaction and latex agglutination testing. Results: We identified 130 cases of culture-confirmed IPD in infants <90 days old between 2005 and 2018. Total IPD incidence was declining before PCV13 introduction. The mean incidence of IPD was significantly lower in the post-PCV13 era. Serotypes 5 (27.8%) and 1 (15.6%) were most prevalent. Even after PCV13 introduction, VTs remained the primary cause of IPD, with serotype 5 accounting for 17.4% and serotype 1 for 13.0% of cases in young infants. Conclusion: Vaccine serotypes 1 and 5 were the main cause of IPD in neonates and young infants, both before and after PCV13 introduction. This suggests incomplete indirect protection with persisting VT carriage across the population despite vaccination in this setting. Alternative vaccine schedules and other vaccine introduction approaches need to be considered to protect this vulnerable population.
MeSH term(s)	Hospitals ; Humans ; Incidence ; Infant ; Infant, Newborn ; Malawi/epidemiology ; Pneumococcal Infections/epidemiology ; Pneumococcal Infections/prevention & control ; Pneumococcal Vaccines ; Prospective Studies ; Serogroup ; Vaccines, Conjugate
Chemical Substances	Pneumococcal Vaccines ; Vaccines, Conjugate
Language	English
Publishing date	2022-06-13
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	392481-6
ISSN	1532-0987 ; 0891-3668
ISSN (online)	1532-0987
ISSN	0891-3668
DOI	10.1097/INF.0000000000003606
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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
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Article ; Online: Complete Genome Sequence of Streptococcus pneumoniae Strain BVJ1JL, a Serotype 1 Carriage Isolate from Malawi.

Betts, Modupeh / Jarvis, Seth / Jeffries, Aaron / Gori, Andrea / Chaguza, Chrispin / Msefula, Jacquline / Weight, Caroline M / Kwambana-Adams, Brenda / French, Neil / Swarthout, Todd D / Brown, Jeremy S / Heyderman, Robert S

Microbiology resource announcements

2021 Volume 10, Issue 39, Page(s) e0071521

Abstract: Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and bacteremia. Serotype 1 is rarely carried but is commonly associated with invasive pneumococcal disease, and in the African "meningitis belt," it is prone to cause cyclical ... ...

Abstract	Streptococcus pneumoniae is a leading cause of pneumonia, meningitis, and bacteremia. Serotype 1 is rarely carried but is commonly associated with invasive pneumococcal disease, and in the African "meningitis belt," it is prone to cause cyclical epidemics. We report the complete genome sequence of S. pneumoniae serotype 1 strain BVJ1JL, isolated in Malawi.
Language	English
Publishing date	2021-09-30
Publishing country	United States
Document type	Journal Article
ISSN	2576-098X
ISSN (online)	2576-098X
DOI	10.1128/MRA.00715-21
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Article ; Online: Association between household air pollution and nasopharyngeal pneumococcal carriage in Malawian infants (MSCAPE): a nested, prospective, observational study.

Dherani, Mukesh K / Pope, Daniel / Tafatatha, Terence / Heinsbroek, Ellen / Chartier, Ryan / Mwalukomo, Thandie / Crampin, Amelia / Mitsi, Elena / German, Esther L / Nikolaou, Elissavet / Solórzano, Carla / Ferreira, Daniela M / Swarthout, Todd D / Hinds, Jason / Mortimer, Kevin / Gordon, Stephen B / French, Neil / Bruce, Nigel G

The Lancet. Global health

2022 Volume 10, Issue 2, Page(s) e246–e256

Abstract: Background: Household air pollution from solid fuels increases the risk of childhood pneumonia. Nasopharyngeal carriage of Streptococcus pneumoniae is a necessary step in the development of pneumococcal pneumonia. We aimed to assess the association ... ...

Abstract	Background: Household air pollution from solid fuels increases the risk of childhood pneumonia. Nasopharyngeal carriage of Streptococcus pneumoniae is a necessary step in the development of pneumococcal pneumonia. We aimed to assess the association between exposure to household air pollution and the prevalence and density of S pneumoniae carriage among children. Methods: The Malawi Streptococcus pneumoniae Carriage and Air Pollution Exposure study was a nested, prospective, observational study of children participating in the cluster randomised controlled Cooking and Pneumonia Study (CAPS) in the Karonga Health and Demographic Surveillance System (HDSS) area in northern Malawi. CAPS compared the effects of a cleaner burning biomass-fuelled cookstove (intervention group) with traditional open-fire cooking (control group) on the incidence of pneumonia in children. Eligible children aged 6 weeks or 6 months (those recruited a 6 weeks were also followed up at age 6 months) were identified by the Karonga HDSS centre. Nasopharyngeal swabs were taken to detect S pneumoniae, and infant exposure to particulate matter with a diameter of ≤2·5 μm (PM Findings: Between Nov 15, 2015, and Nov 2, 2017, 485 children were recruited (240 from the intervention group and 245 from the control group). Of all 450 children with available data at age 6 months, 387 (86% [95% CI 82-89]) were positive for S pneumoniae. Geometric mean PM Interpretation: Despite the absence of effect from the intervention cookstove, household air pollution exposure was significantly associated with the prevalence of nasopharyngeal S pneumoniae carriage. These results provide empirical evidence for the potential mechanistic association between exposure to household air pollution and childhood pneumonia. Funding: Bill & Melinda Gates Foundation.
MeSH term(s)	Air Pollution, Indoor/statistics & numerical data ; Carrier State/epidemiology ; Cooking/methods ; Female ; Humans ; Infant ; Malawi/epidemiology ; Male ; Nasopharynx/microbiology ; Pneumococcal Infections/epidemiology ; Prospective Studies ; Streptococcus pneumoniae/isolation & purification
Language	English
Publishing date	2022-01-17
Publishing country	England
Document type	Journal Article ; Observational Study ; Research Support, Non-U.S. Gov't
ZDB-ID	2723488-5
ISSN	2214-109X ; 2214-109X
ISSN (online)	2214-109X
ISSN	2214-109X
DOI	10.1016/S2214-109X(21)00405-8
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Article ; Online: Pneumococcal pneumonia and carriage in Africa before and after introduction of pneumococcal conjugate vaccines, 2000-2019: protocol for systematic review.

Kalata, Newton L / Nyazika, Tinashe K / Swarthout, Todd D / Everett, Dean / French, Neil / Heyderman, Robert S / Gordon, Stephen B / Jambo, Kondwani C

BMJ open

2019 Volume 9, Issue 11, Page(s) e030981

Abstract: Introduction: Africa harbours a high burden of pneumococcal disease, with associated high mortality rates. Despite 34 countries introducing the pneumococcal conjugate vaccine, which reduces the risk of pneumococcal carriage (a prerequisite for disease) ... ...

Abstract	Introduction: Africa harbours a high burden of pneumococcal disease, with associated high mortality rates. Despite 34 countries introducing the pneumococcal conjugate vaccine, which reduces the risk of pneumococcal carriage (a prerequisite for disease) of some of the most pathogenic pneumococcal serotypes, it remains uncertain whether they will achieve the sustained direct or indirect protection necessary to reduce pneumococcal carriage to levels sufficient to interrupt transmission and disease. We will therefore summarise the available data on the impact of the pneumococcal conjugate vaccine in reducing vaccine serotype carriage and pneumococcal pneumonia in Africa between 2000 and 2019. Methods and analysis: Using a predetermined search strategy, we will conduct a comprehensive search of PubMed, MEDLINE database, the Excerpta Medica Database, the ISI Web of Science (Science Citation Index), Scopus and the African Index Medicus to identify published studies reporting the prevalence of Ethics and dissemination: This systematic review will not require ethical approval as we will be using already published data. The final manuscript will be submitted for publication in a peer-reviewed journal and presented at conferences. Prospero registration number: CRD42019130976.
MeSH term(s)	Africa/epidemiology ; Carrier State/epidemiology ; Carrier State/immunology ; Heptavalent Pneumococcal Conjugate Vaccine/immunology ; Humans ; Pneumococcal Vaccines/immunology ; Pneumonia, Pneumococcal/epidemiology ; Pneumonia, Pneumococcal/immunology ; Pneumonia, Pneumococcal/prevention & control ; Pneumonia, Pneumococcal/transmission ; Prevalence ; Streptococcus pneumoniae/isolation & purification ; Systematic Reviews as Topic
Chemical Substances	10-valent pneumococcal conjugate vaccine ; 13-valent pneumococcal vaccine ; Heptavalent Pneumococcal Conjugate Vaccine ; Pneumococcal Vaccines
Language	English
Publishing date	2019-11-13
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2599832-8
ISSN	2044-6055 ; 2044-6055
ISSN (online)	2044-6055
ISSN	2044-6055
DOI	10.1136/bmjopen-2019-030981
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Article ; Online: Erratum for Betts et al., "Complete Genome Sequence of Streptococcus pneumoniae Strain BVJ1JL, a Serotype 1 Carriage Isolate from Malawi".

Microbiology resource announcements

2021 Volume 10, Issue 42, Page(s) e0098521

Language	English
Publishing date	2021-10-21
Publishing country	United States
Document type	Journal Article ; Published Erratum
ISSN	2576-098X
ISSN (online)	2576-098X
DOI	10.1128/MRA.00985-21
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Article ; Online: Waning of antibody levels induced by a 13-valent pneumococcal conjugate vaccine, using a 3 + 0 schedule, within the first year of life among children younger than 5 years in Blantyre, Malawi: an observational, population-level, serosurveillance study.

Swarthout, Todd D / Henrion, Marc Y R / Thindwa, Deus / Meiring, James E / Mbewe, Maurice / Kalizang'Oma, Akuzike / Brown, Comfort / Msefula, Jacquline / Moyo, Brewster / Mataya, Andrew A / Barnaba, Susanne / Pearce, Emma / Gordon, Melita / Goldblatt, David / French, Neil / Heyderman, Robert S

The Lancet. Infectious diseases

2022 Volume 22, Issue 12, Page(s) 1737–1747

Abstract: Background: Pneumococcal conjugate vaccines (PCVs) induce serotype-specific IgG antibodies, effectively reducing vaccine-serotype carriage and invasive pneumococcal disease (IPD). IgG production wanes approximately 1 month after vaccination in absence ... ...

Abstract	Background: Pneumococcal conjugate vaccines (PCVs) induce serotype-specific IgG antibodies, effectively reducing vaccine-serotype carriage and invasive pneumococcal disease (IPD). IgG production wanes approximately 1 month after vaccination in absence of serotype-specific exposure. With uncertainty surrrounding correlate of protection (CoP) estimates and with persistent vaccine-serotype carriage and vaccine-serotype IPD after PCV13 introduction, we aimed to profile population-level immunogenicity among children younger than 5 years in Blantyre, Malawi. Methods: For this serosurveillance study, we used a random subset of samples from a prospective population-based serosurvey in Blantyre, Malawi, done between Dec 16, 2016, and June 27, 2018. Sample selection was based on age category optimisation among children younger than 5 years, adequate sample volume, and available budget. We measured serotype-specific IgGs against the 13 vaccine serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F) and two non-vaccine serotypes (12F and 33F), as well as IgGs against three pneumococcal proteins (PsaA, NanA, and Ply), using ELISA and a direct-binding electrochemiluminescence-based multiplex assay. We estimated population-level, serotype-specific immunogenicity profiles using a linear spline regression model. Analyses included samples stratified to 20 3-month age strata (eg, age <3 months to 57-59 months). Findings: We evaluated 638 plasma samples: 556 primary samples and 82 unique secondary samples (each linked to one primary sample). Immunogenicity profiles revealed a consistent pattern among vaccine serotypes except serotype 3: a vaccine-induced IgG peak followed by waning to a nadir and subsequent increase in titre. For serotype 3, we observed no apparent vaccine-induced increase. Heterogeneity in parameters included age range at post-vaccination nadir (from 11·2 months [19A] to 27·3 months [7F]). The age at peak IgG titre ranged from 2·69 months (5) to 6·64 months (14). Titres dropped below CoPs against IPD among nine vaccine serotypes (1, 3, 4, 5, 6B, 7F, 9V, 18C, and 23F) and below CoPs against carriage for ten vaccine serotypes (1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F). Increasing antibody concentrations among older children and seroincident events were consistent with ongoing vaccine-serotype exposure. Interpretation: A 3 + 0 PCV13 schedule with high uptake has not led to sustained population-level antibody immunity beyond the first year of life. Indeed, post-vaccine antibody concentrations dropped below putative CoPs for several vaccine serotypes, potentially contributing to persistent vaccine-serotype carriage and residual vaccine-serotype IPD in Malawi and other similar settings. Policy decisions should consider alternative vaccine strategies, including a booster dose, to achieve sustained vaccine-induced antibody titres, and thus control. Funding: Bill & Melinda Gates Foundation, Wellcome UK, and National Institute for Health and Care Research.
MeSH term(s)	Child ; Humans ; Infant ; Adolescent ; Child, Preschool ; Vaccines, Conjugate ; Malawi/epidemiology ; Prospective Studies ; Antibodies, Bacterial ; Pneumococcal Vaccines ; Pneumococcal Infections/epidemiology ; Pneumococcal Infections/prevention & control ; Immunoglobulin G
Chemical Substances	Vaccines, Conjugate ; Antibodies, Bacterial ; Pneumococcal Vaccines ; Immunoglobulin G
Language	English
Publishing date	2022-08-24
Publishing country	United States
Document type	Observational Study ; Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2061641-7
ISSN	1474-4457 ; 1473-3099
ISSN (online)	1474-4457
ISSN	1473-3099
DOI	10.1016/S1473-3099(22)00438-8
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In stock of ZB MED Cologne/Königswinter

Order via subito