المؤلفون: Eva Heinz, Oliver Pearse, Allan Zuza, Sithembile Bilima, Chisomo Msefula, Patrick Musicha, Patriciah Siyabu, Edith Tewesa, Fabrice E. Graf, Rebecca Lester, Samantha Lissauer, Jennifer Cornick, Joseph M. Lewis, Kondwani Kawaza, Nicholas R. Thomson, Nicholas A. Feasey

المصدر: Genome Medicine, Vol 16, Iss 1, Pp 1-17 (2024)

مصطلحات موضوعية: AMR, Malawi, Genome surveillance, Healthcare-associated, Nosocomial infections, Surface antigens, Medicine, Genetics, QH426-470

الوصف: Abstract Background Infections caused by multidrug-resistant gram-negative bacteria present a severe threat to global public health. The WHO defines drug-resistant Klebsiella pneumoniae as a priority pathogen for which alternative treatments are needed given the limited treatment options and the rapid acquisition of novel resistance mechanisms by this species. Longitudinal descriptions of genomic epidemiology of Klebsiella pneumoniae can inform management strategies but data from sub-Saharan Africa are lacking. Methods We present a longitudinal analysis of all invasive K. pneumoniae isolates from a single hospital in Blantyre, Malawi, southern Africa, from 1998 to 2020, combining clinical data with genome sequence analysis of the isolates. Results We show that after a dramatic increase in the number of infections from 2016 K. pneumoniae becomes hyperendemic, driven by an increase in neonatal infections. Genomic data show repeated waves of clonal expansion of different, often ward-restricted, lineages, suggestive of hospital-associated transmission. We describe temporal trends in resistance and surface antigens, of relevance for vaccine development. Conclusions Our data highlight a clear need for new interventions to prevent rather than treat K. pneumoniae infections in our setting. Whilst one option may be a vaccine, the majority of cases could be avoided by an increased focus on and investment in infection prevention and control measures, which would reduce all healthcare-associated infections and not just one.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1756-994XTest

الوصول الحر: https://doaj.org/article/389b70344adb4c468575cb18c6a2d66dTest

المؤلفون: Kayla G. Barnes, Joshua I. Levy, Jillian Gauld, Jonathan Rigby, Oscar Kanjerwa, Christopher B. Uzzell, Chisomo Chilupsya, Catherine Anscombe, Christopher Tomkins-Tinch, Omar Mbeti, Edward Cairns, Herbert Thole, Shannon McSweeney, Marah G. Chibwana, Philip M. Ashton, Khuzwayo C. Jere, John Scott Meschke, Peter Diggle, Jennifer Cornick, Benjamin Chilima, Kondwani Jambo, Kristian G. Andersen, Gift Kawalazira, Steve Paterson, Tonney S. Nyirenda, Nicholas Feasey

المصدر: Nature Communications, Vol 14, Iss 1, Pp 1-11 (2023)

مصطلحات موضوعية: Science

الوصف: Abstract The COVID-19 pandemic has profoundly impacted health systems globally and robust surveillance has been critical for pandemic control, however not all countries can currently sustain community pathogen surveillance programs. Wastewater surveillance has proven valuable in high-income settings, but less is known about the utility of water surveillance of pathogens in low-income countries. Here we show how wastewater surveillance of SAR-CoV-2 can be used to identify temporal changes and help determine circulating variants quickly. In Malawi, a country with limited community-based COVID-19 testing capacity, we explore the utility of rivers and wastewater for SARS-CoV-2 surveillance. From May 2020–May 2022, we collect water from up to 112 river or defunct wastewater treatment plant sites, detecting SARS-CoV-2 in 8.3% of samples. Peak SARS-CoV-2 detection in water samples predate peaks in clinical cases. Sequencing of water samples identified the Beta, Delta, and Omicron variants, with Delta and Omicron detected well in advance of detection in patients. Our work highlights how wastewater can be used to detect emerging waves, identify variants of concern, and provide an early warning system in settings with no formal sewage systems.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/d44d0de541934d628984d02c52f9cee8Test

المؤلفون: Catherine Anscombe, Samantha Lissauer, Herbert Thole, Jamie Rylance, Dingase Dula, Mavis Menyere, Belson Kutambe, Charlotte van der Veer, Tamara Phiri, Ndaziona P. Banda, Kwazizira S. Mndolo, Kelvin Mponda, Chimota Phiri, Jane Mallewa, Mulinda Nyirenda, Grace Katha, Henry Mwandumba, Stephen B. Gordon, Kondwani C. Jambo, Jennifer Cornick, Nicholas Feasey, Kayla G. Barnes, Ben Morton, Philip M. Ashton, Blantyre COVID-19 Consortium

المصدر: BMC Infectious Diseases, Vol 23, Iss 1, Pp 1-9 (2023)

مصطلحات موضوعية: COVID, SARS-CoV-2, ISARIC, Delta, Mortality, LMIC, Infectious and parasitic diseases, RC109-216

الوصف: Abstract Background Compared to the abundance of clinical and genomic information available on patients hospitalised with COVID-19 disease from high-income countries, there is a paucity of data from low-income countries. Our aim was to explore the relationship between viral lineage and patient outcome. Methods We enrolled a prospective observational cohort of adult patients hospitalised with PCR-confirmed COVID-19 disease between July 2020 and March 2022 from Blantyre, Malawi, covering four waves of SARS-CoV-2 infections. Clinical and diagnostic data were collected using an adapted ISARIC clinical characterization protocol for COVID-19. SARS-CoV-2 isolates were sequenced using the MinION™ in Blantyre. Results We enrolled 314 patients, good quality sequencing data was available for 55 patients. The sequencing data showed that 8 of 11 participants recruited in wave one had B.1 infections, 6/6 in wave two had Beta, 25/26 in wave three had Delta and 11/12 in wave four had Omicron. Patients infected during the Delta and Omicron waves reported fewer underlying chronic conditions and a shorter time to presentation. Significantly fewer patients required oxygen (22.7% [17/75] vs. 58.6% [140/239], p

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2334Test

الوصول الحر: https://doaj.org/article/4d8bcf03a04c4deb972cc0267183a58eTest

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

المصدر: BMJ Open, Vol 13, Iss 5 (2023)

مصطلحات موضوعية: Medicine

الوصف: 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 Streptococcus pneumoniae and extended spectrum beta-lactamase-producing Escherichia coli and Klebsiella species. We will leverage two large ongoing cluster-randomised vaccine evaluations in Malawi assessing; first, adding a booster dose to the 13-valent pneumococcal conjugate vaccine (PCV13) schedule, and second, introduction of the RTS,S/AS01 malaria vaccine.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 S. pneumoniae nasopharyngeal carriage isolates in healthy children. The study is powered to detect an absolute change of 13 percentage points (ie, 35% vs 22% penicillin non-susceptibility).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.

وصف الملف: electronic resource

العلاقة: https://bmjopen.bmj.com/content/13/5/e069560.fullTest; https://doaj.org/toc/2044-6055Test

الوصول الحر: https://doaj.org/article/9b6cb803eb674811b969d933d75a7944Test

المؤلفون: Ben Morton, Kayla G. Barnes, Catherine Anscombe, Khuzwayo Jere, Prisca Matambo, Jonathan Mandolo, Raphael Kamng’ona, Comfort Brown, James Nyirenda, Tamara Phiri, Ndaziona P. Banda, Charlotte Van Der Veer, Kwazizira S. Mndolo, Kelvin Mponda, Jamie Rylance, Chimota Phiri, Jane Mallewa, Mulinda Nyirenda, Grace Katha, Paul Kambiya, James Jafali, Henry C. Mwandumba, Stephen B. Gordon, Blantyre COVID-19 Consortium, Jennifer Cornick, Kondwani C. Jambo

المصدر: Nature Communications, Vol 12, Iss 1, Pp 1-12 (2021)

مصطلحات موضوعية: Science

الوصف: Clinical management of COVID-19 in resource-poor settings has distinct challenges and detailed patient characterisation is needed. Here, the authors describe the clinical and immunological profiles of patients at a hospital in Malawi with confirmed and suspected COVID-19.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/5ac0ac388c3f4d77be678f53c3d46ebeTest

المؤلفون: Néhémie Nzoyikorera, Idrissa Diawara, Pablo Fresia, Fakhreddine Maaloum, Khalid Katfy, Kaotar Nayme, Mossaab Maaloum, Jennifer Cornick, Chrispin Chaguza, Mohammed Timinouni, Houria Belabess, Khalid Zerouali, Naima Elmdaghri

المصدر: BMC Genomics, Vol 22, Iss 1, Pp 1-9 (2021)

مصطلحات موضوعية: Streptococcus pneumoniae, Serotype 1, Whole genome sequencing, Comparative genomic analysis, Biotechnology, TP248.13-248.65, Genetics, QH426-470

الوصف: Abstract Background Streptococcus pneumoniae serotype 1 remains a leading cause of invasive pneumococcal diseases, even in countries with PCV-10/PCV-13 vaccine implementation. The main objective of this study, which is part of the Pneumococcal African Genome project (PAGe), was to determine the phylogenetic relationships of serotype 1 isolates recovered from children patients in Casablanca (Morocco), compared to these from other African countries; and to investigate the contribution of accessory genes and recombination events to the genetic diversity of this serotype. Results The genome average size of the six-pneumococcus serotype 1 from Casablanca was 2,227,119 bp, and the average content of coding sequences was 2113, ranging from 2041 to 2161. Pangenome analysis of the 80 genomes used in this study revealed 1685 core genes and 1805 accessory genes. The phylogenetic tree based on core genes and the hierarchical bayesian clustering analysis revealed five sublineages with a phylogeographic structure by country. The Moroccan strains cluster in two different lineages, the five invasive strains clusters altogether in a divergent clade distantly related to the non-invasive strain, that cluster with all the serotype 1 genomes from Africa. Conclusions The whole genome sequencing provides increased resolution analysis of the highly virulent serotype 1 in Casablanca, Morocco. Our results are concordant with previous works, showing that the phylogeography of S. pneumoniae serotype 1 is structured by country, and despite the small size (six isolates) of the Moroccan sample, our analysis shows the genetic cohesion of the Moroccan invasive isolates.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1471-2164Test

الوصول الحر: https://doaj.org/article/6171737c45724d0bafd50a8b5421713fTest

المؤلفون: Amy K. Cain, Laura M. Nolan, Jennifer Cornick, Karl A. Hassan

المصدر: Frontiers in Microbiology, Vol 12 (2021)

مصطلحات موضوعية: antibiotic, antibiotic resistance, molecular mechanisms, bacterial pathogenesis, host microbe, microscopy, Microbiology, QR1-502

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fmicb.2021.737958/fullTest; https://doaj.org/toc/1664-302XTest

الوصول الحر: https://doaj.org/article/c35f24e068324f5d9c4cecac0c16bc12Test

المؤلفون: Mariem Hanachi, Anmol Kiran, Jennifer Cornick, Emna Harigua-Souiai, Dean Everett, Alia Benkahla, Oussama Souiai

المصدر: Bioinformatics and Biology Insights, Vol 14 (2020)

مصطلحات موضوعية: Biology (General), QH301-705.5

الوصف: Streptococcus pneumoniae serotype 1 is a common cause of global invasive pneumococcal disease. In New Caledonia, serotype 1 is the most prevalent serotype and led to two major outbreaks reported in the 2000s. The pneumococcal conjugate vaccine 13 (PCV13) was introduced into the vaccination routine, intending to prevent the expansion of serotype 1 in New Caledonia. Aiming to provide a baseline for monitoring the post-PCV13 changes, we performed a whole-genome sequence analysis on 67 serotype 1 isolates collected prior to the PCV13 introduction. To highlight the S. pneumoniae serotype 1 population structure, we performed a multilocus sequence typing (MLST) analysis revealing that NC serotype 1 consisted of 2 sequence types: ST3717 and the highly dominant ST306. Both sequence types harbored the same resistance genes to beta-lactams, macrolide, streptogramin B, fluoroquinolone, and lincosamide antibiotics. We have also identified 36 virulence genes that were ubiquitous to all the isolates. Among these virulence genes, the pneumolysin sequence presented an allelic profile associated with disease outbreaks and reduced hemolytic activity. Moreover, recombination hotspots were identified in 4 virulence genes and more notably in the cps locus ( cps2L ), potentially leading to capsular switching, a major mechanism of the emergence of nonvaccine types. In summary, this study represents the first overview of the genomic characteristics of S. pneumoniae serotype 1 in New Caledonia prior to the introduction of PCV13. This preliminary description represents a baseline to assess the impact of PCV13 on serotype 1 population structure and genomic diversity.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1177-9322Test

الوصول الحر: https://doaj.org/article/1718fbc8a69f4c5ba2f680108c76eb4eTest

المؤلفون: Taj Azarian, Patrick K Mitchell, Maria Georgieva, Claudette M Thompson, Amel Ghouila, Andrew J Pollard, Anne von Gottberg, Mignon du Plessis, Martin Antonio, Brenda A Kwambana-Adams, Stuart C Clarke, Dean Everett, Jennifer Cornick, Ewa Sadowy, Waleria Hryniewicz, Anna Skoczynska, Jennifer C Moïsi, Lesley McGee, Bernard Beall, Benjamin J Metcalf, Robert F Breiman, P L Ho, Raymond Reid, Katherine L O'Brien, Rebecca A Gladstone, Stephen D Bentley, William P Hanage

المصدر: PLoS Pathogens, Vol 14, Iss 11, p e1007438 (2018)

مصطلحات موضوعية: Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5

الوصف: Streptococcus pneumoniae serotype 3 remains a significant cause of morbidity and mortality worldwide, despite inclusion in the 13-valent pneumococcal conjugate vaccine (PCV13). Serotype 3 increased in carriage since the implementation of PCV13 in the USA, while invasive disease rates remain unchanged. We investigated the persistence of serotype 3 in carriage and disease, through genomic analyses of a global sample of 301 serotype 3 isolates of the Netherlands3-31 (PMEN31) clone CC180, combined with associated patient data and PCV utilization among countries of isolate collection. We assessed phenotypic variation between dominant clades in capsule charge (zeta potential), capsular polysaccharide shedding, and susceptibility to opsonophagocytic killing, which have previously been associated with carriage duration, invasiveness, and vaccine escape. We identified a recent shift in the CC180 population attributed to a lineage termed Clade II, which was estimated by Bayesian coalescent analysis to have first appeared in 1968 [95% HPD: 1939-1989] and increased in prevalence and effective population size thereafter. Clade II isolates are divergent from the pre-PCV13 serotype 3 population in non-capsular antigenic composition, competence, and antibiotic susceptibility, the last of which resulting from the acquisition of a Tn916-like conjugative transposon. Differences in recombination rates among clades correlated with variations in the ATP-binding subunit of Clp protease, as well as amino acid substitutions in the comCDE operon. Opsonophagocytic killing assays elucidated the low observed efficacy of PCV13 against serotype 3. Variation in PCV13 use among sampled countries was not independently correlated with the CC180 population shift; therefore, genotypic and phenotypic differences in protein antigens and, in particular, antibiotic resistance may have contributed to the increase of Clade II. Our analysis emphasizes the need for routine, representative sampling of isolates from disperse geographic regions, including historically under-sampled areas. We also highlight the value of genomics in resolving antigenic and epidemiological variations within a serotype, which may have implications for future vaccine development.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1553-7366Test; https://doaj.org/toc/1553-7374Test

الوصول الحر: https://doaj.org/article/9b56e239f6754399bf8895d3c27b4ec4Test

المؤلفون: Dean B Everett, Jennifer Cornick, Brigitte Denis, Claire Chewapreecha, Nicholas Croucher, Simon Harris, Julian Parkhill, Stephen Gordon, Enitan D Carrol, Neil French, Robert S Heyderman, Stephen D Bentley

المصدر: PLoS ONE, Vol 7, Iss 9, p e44250 (2012)

مصطلحات موضوعية: Medicine, Science

الوصف: Malawi commenced the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the routine infant immunisation schedule in November 2011. Here we have tested the utility of high throughput whole genome sequencing to provide a high-resolution view of pre-vaccine pneumococcal epidemiology and population evolutionary trends to predict potential future change in population structure post introduction.One hundred and twenty seven (127) archived pneumococcal isolates from randomly selected adults and children presenting to the Queen Elizabeth Central Hospital, Blantyre, Malawi underwent whole genome sequencing.The pneumococcal population was dominated by serotype 1 (20.5% of invasive isolates) prior to vaccine introduction. PCV13 is likely to protect against 62.9% of all circulating invasive pneumococci (78.3% in under-5-year-olds). Several Pneumococcal Molecular Epidemiology Network (PMEN) clones are now in circulation in Malawi which were previously undetected but the pandemic multidrug resistant PMEN1 lineage was not identified. Genome analysis identified a number of novel sequence types and serotype switching.High throughput genome sequencing is now feasible and has the capacity to simultaneously elucidate serotype, sequence type and as well as detailed genetic information. It enables population level characterization, providing a detailed picture of population structure and genome evolution relevant to disease control. Post-vaccine introduction surveillance supported by genome sequencing is essential to providing a comprehensive picture of the impact of PCV13 on pneumococcal population structure and informing future public health interventions.

وصف الملف: electronic resource

العلاقة: http://europepmc.org/articles/PMC3438182?pdf=renderTest; https://doaj.org/toc/1932-6203Test

الوصول الحر: https://doaj.org/article/0bac02d9820a4a85b34f5951018af4ecTest