Complete Genome Sequence of Streptococcus pneumoniae Strain BVJ1JL, a Serotype 1 Carriage Isolate from Malawi.

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

Invasiveness potential of pneumococcal serotypes in children after introduction of PCV13 in Blantyre, Malawi.

IntroductionThe 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.MethodsWe 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.ResultsSerotypes 5 (OR 24.73 [95% CI 7.90-78.56] p ConclusionsPneumococcal 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

The metabolic, virulence and antimicrobial resistance profiles of colonising Streptococcus pneumoniae shift after PCV13 introduction in urban Malawi

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

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

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

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.

BackgroundInvasive 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 aged MethodsWe conducted laboratory-based prospective IPD surveillance in infants aged ResultsWe identified 130 cases of culture-confirmed IPD in infants ConclusionVaccine 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

Risk factors for pneumococcal carriage in adults living with HIV on antiretroviral therapy in the infant pneumococcal vaccine era in Malawi.

ObjectiveAdults 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.MethodsNasopharyngeal swabs were collected from adults aged 18-40 years attending an ART clinic during rolling, cross-sectional surveys in Blantyre, Malawi between 2015-2019. We fitted generalised additive models to estimate the risk of sex, social economic status (SES), living with a child ResultsOf 2,067 adults, median age was 33y (range 28-37), 1,427 (69.0%) were females, 1,087 (61.4%) were in low-middle socio-economic-status (SES), 910 (44.0%) were living with a child ConclusionDespite 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

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.

BackgroundPneumococcal 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.MethodsFor 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 FindingsWe 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.InterpretationA 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.FundingBill & Melinda Gates Foundation, Wellcome UK, and National Institute for Health and Care Research