Search

The SARS-CoV-2 genome occupies a unique place in infection biology - it is the most highly sequenced genome on earth (making up over 20% of public sequencing datasets) with fine scale information on sampling date and geography, and has been subject to unprecedented intense analysis. As a result, these phylogenetic data are an incredibly valuable resource for science and public health. However, the vast majority of the data was sequenced by tiling amplicons across the full genome, with amplicon schemes that changed over the pandemic as mutations in the viral genome interacted with primer binding sites. In combination with the disparate set of genome assembly workflows and lack of consistent quality control (QC) processes, the current genomes have many systematic errors that have evolved with the virus and amplicon schemes. These errors have significant impacts on the phylogeny, and therefore over the last few years, many thousands of hours of researchers time has been spent in "eyeballing" trees, looking for artefacts, and then patching the tree. Given the huge value of this dataset, we therefore set out to reprocess the complete set of public raw sequence data in a rigorous amplicon-aware manner, and build a cleaner phylogeny. Here we provide a global tree of 4,471,579 samples, built from a consistently assembled set of high quality consensus sequences from all available public data as of June 2024, viewable at https://viridian.taxonium.org . Each genome was constructed using a novel assembly tool called Viridian ( https://github.com/iqbal-lab-org/viridian ), developed specifically to process amplicon sequence data, eliminating artefactual errors and mask the genome at low quality positions. We provide simulation and empirical validation of the methodology, and quantify the improvement in the phylogeny. We hope the tree, consensus sequences and Viridian will be a valuable resource for researchers.

National action plans enumerate many interventions as potential strategies to reduce the burden of bacterial antimicrobial resistance (AMR). However, knowledge of the benefits achievable by specific approaches is needed to inform policy making, especially in low-income and middle-income countries (LMICs) with substantial AMR burden and low health-care system capacity. In a modelling analysis, we estimated that improving infection prevention and control programmes in LMIC health-care settings could prevent at least 337 000 (95% CI 250 200-465 200) AMR-associated deaths annually. Ensuring universal access to high-quality water, sanitation, and hygiene services would prevent 247 800 (160 000-337 800) AMR-associated deaths and paediatric vaccines 181 500 (153 400-206 800) AMR-associated deaths, from both direct prevention of resistant infections and reductions in antibiotic consumption. These estimates translate to prevention of 7·8% (5·6-11·0) of all AMR-associated mortality in LMICs by infection prevention and control, 5·7% (3·7-8·0) by water, sanitation, and hygiene, and 4·2% (3·4-5·1) by vaccination interventions. Despite the continuing need for research and innovation to overcome limitations of existing approaches, our findings indicate that reducing global AMR burden by 10% by the year 2030 is achievable with existing interventions. Our results should guide investments in public health interventions with the greatest potential to reduce AMR burden., Competing Interests: Declaration of interests A meeting held to coordinate this paper was supported by the Bill & Melinda Gates Foundation (INV-055356 to RL) and the Africa Centres for Disease Control and Prevention (to all authors). Neither funder had any role in the design, writing, or the decision to submit the paper for publication. RL has received grant funding from the National Science Foundation (CCF1918628). LYH reports an institutional research grant for research on antimicrobial resistance from the Singapore National Medical Research Council (MOH-001010–00). EC reports providing unrestricted antibiotic stewardship lectures to clinical conferences organised by Pfizer in Australia in 2023. All other authors declare no competing interests., (Copyright © 2024 Published by Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: The continued emergence of Salmonella enterica serovar Typhi, with ever increasing antimicrobial resistance, necessitates the use of vaccines in endemic countries. A typhoid fever outbreak in Harare, Zimbabwe, in 2018 from a multidrug resistant S Typhi with additional resistance to ciprofloxacin was the catalyst for the introduction of a typhoid conjugate vaccine programme. We aimed to investigate the emergence and evolution of antimicrobial resistance of endemic S Typhi in Zimbabwe and to determine the population structure, gene flux, and sequence polymorphisms of strains isolated before a typhoid conjugate vaccine programme to provide a baseline for future evaluation of the effect of the vaccination programme., Methods: In this genomic epidemiology study, we used short-read whole-genome sequencing of S Typhi isolated from clinical cases of typhoid fever in Harare, Zimbabwe, between Jan 1, 2012, and Feb 9, 2019, to determine the S Typhi population structure, gene flux, and sequence polymorphisms and reconstructed the evolution of antimicrobial resistance. Maximum likelihood time-scaled phylogenetic trees of Zimbabwe isolates in the context of global isolates obtained from the National Center for Biotechnology Information were constructed to infer spread and emergence of antimicrobial resistance., Findings: The population structure of S Typhi in Harare, Zimbabwe, from 2012 to 2019 was dominated by multidrug resistant genotype 4.3.1.1.EA1 (H58) that spread to Zimbabwe from neighbouring countries in around 2009 (95% credible interval 2008·5-2010·0). Acquisition of an IncN plasmid carrying antimicrobial resistance genes including a qnrS gene and a mutation in the quinolone resistance determining region of gyrA gene contributed to non-susceptibility and resistance to quinolone antibiotics. A minority population of antimicrobial susceptible S Typhi genotype 3.3.1 strains were present throughout., Interpretation: The currently dominant S Typhi population is genotype 4.3.1.1 that spread to Zimbabwe and acquired additional antimicrobial resistance though acquisition of a plasmid and mutation in the gyrA gene. This study provides a baseline population structure for future evaluation of the effect of the typhoid conjugate vaccine programme in Harare., Funding: Bill & Melinda Gates Foundation and the Biotechnology and Biological Sciences Research Council Institute Strategic Programme., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

In counteracting highly infectious and disruptive respiratory diseases such as COVID-19, vaccination remains the primary and safest way to prevent disease, reduce the severity of illness, and save lives. Unfortunately, vaccination is often not the first intervention deployed for a new pandemic, as it takes time to develop and test vaccines, and confirmation of safety requires a period of observation after vaccination to detect potential late-onset vaccine-associated adverse events. In the meantime, nonpharmacologic public health interventions such as mask-wearing and social distancing can provide some degree of protection. As climate change, with its environmental impacts on pathogen evolution and international mobility continue to rise, highly infectious respiratory diseases will likely emerge more frequently and their impact is expected to be substantial. How quickly a safe and efficacious vaccine can be deployed against rising infectious respiratory diseases may be the most important challenge that humanity will face in the near future. While some organizations are engaged in addressing the World Health Organization's "blueprint for priority diseases", the lack of worldwide preparedness, and the uncertainty around universal vaccine availability, remain major concerns. We therefore propose the establishment of an international candidate vaccine pool repository for potential respiratory diseases, supported by multiple stakeholders and countries that contribute facilities, technologies, and other medical and financial resources. The types and categories of candidate vaccines can be determined based on information from previous pandemics and epidemics. Each participant country or region can focus on developing one or a few vaccine types or categories, together covering most if not all possible potential infectious diseases. The safety of these vaccines can be tested using animal models. Information for effective candidates that can be potentially applied to humans will then be shared across all participants. When a new pandemic arises, these pre-selected and tested vaccines can be quickly tested in RCTs for human populations., Competing Interests: Peter Hotez is a co-inventor of a COVID-19 recombinant protein vaccine technology owned by Baylor College of Medicine (BCM) that was recently licensed by BCM non-exclusively and with no patent restrictions to several companies committed to advance vaccines for low- and middle-income countries. The co-inventors have no involvement in license negotiations conducted by BCM. Similar to other research universities, a long-standing BCM policy provides its faculty and staff, who make discoveries that result in a commercial license, a share of any royalty income, according to BCM policy. Jerome H. Kim services as the consultant for SK bioscience and Moderna. Other authors declare no competing financial interests.

Background: The Global Typhoid Genomics Consortium was established to bring together the typhoid research community to aggregate and analyse Salmonella enterica serovar Typhi (Typhi) genomic data to inform public health action. This analysis, which marks 22 years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000)., Methods: This is a meta-analysis of global genotype and antimicrobial resistance (AMR) determinants extracted from previously sequenced genome data and analysed using consistent methods implemented in open analysis platforms GenoTyphi and Pathogenwatch., Results: Compared with previous global snapshots, the data highlight that genotype 4.3.1 (H58) has not spread beyond Asia and Eastern/Southern Africa; in other regions, distinct genotypes dominate and have independently evolved AMR. Data gaps remain in many parts of the world, and we show the potential of travel-associated sequences to provide informal 'sentinel' surveillance for such locations. The data indicate that ciprofloxacin non-susceptibility (>1 resistance determinant) is widespread across geographies and genotypes, with high-level ciprofloxacin resistance (≥3 determinants) reaching 20% prevalence in South Asia. Extensively drug-resistant (XDR) typhoid has become dominant in Pakistan (70% in 2020) but has not yet become established elsewhere. Ceftriaxone resistance has emerged in eight non-XDR genotypes, including a ciprofloxacin-resistant lineage (4.3.1.2.1) in India. Azithromycin resistance mutations were detected at low prevalence in South Asia, including in two common ciprofloxacin-resistant genotypes., Conclusions: The consortium's aim is to encourage continued data sharing and collaboration to monitor the emergence and global spread of AMR Typhi, and to inform decision-making around the introduction of typhoid conjugate vaccines (TCVs) and other prevention and control strategies., Funding: No specific funding was awarded for this meta-analysis. Coordinators were supported by fellowships from the European Union (ZAD received funding from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 845681), the Wellcome Trust (SB, Wellcome Trust Senior Fellowship), and the National Health and Medical Research Council (DJI is supported by an NHMRC Investigator Grant [GNT1195210])., Competing Interests: MC, ZD, DI, AA, MA, MC, KC, JC, BH, KK, MM, CP, SV, HW, AA, AA, SA, JA, PA, BB, AB, JC, Kd, AD, Jd, PD, CD, SD, ME, LF, DG, GG, MG, AG, CG, MG, RH, RH, YH, JH, OI, JI, JJ, CJ, DJ, JJ, GK, AK, AK, AK, SK, RK, RK, AL, ML, RL, SL, GM, TM, CM, AM, GN, SN, SN, TN, SN, EN, IO, SP, AP, FQ, FQ, SR, SR, DR, PR, RR, TR, JR, SS, SS, KS, MS, JS, JS, VS, JS, RS, SS, MS, AS, AS, KT, DT, AT, MT, MT, RT, NT, ST, KV, MV, BV, FW, JW, GD, SA, JK, DA, SB, KH No competing interests declared, NF NAF chairs the Wellcome Surveillance and Epidemiology of Drug Resistant Infections (SEDRIC) group, which has a focus on antimicrobial resistance. This could be perceived as relevant although not a direct conflict, IB IB has consulted to BlueDot and the NHL Players' Association, AP AJP is chair of the UK Department of Health and Social Care's (DHSC) Joint Committee on Vaccination and Immunisation (JCVI) but does not take part in the JCVI COVID-19 committee. He was a member of WHO SAGE until 2022. AJPs employer, Oxford University has entered into a partnership with AstraZeneca for development of a COVID-19 vaccine. AJP has provided advice to Shionogi & Co., Ltd on development of a COVID19 vaccine, (© 2023, Carey et al.)

Competing Interests: MH-A is currently conducting research to assess the impact of vaccines in reducing antimicrobial resistance, which is funded by the Bill & Melinda Gates Foundation, and is funded by both the IDWeek (Boston, MA, USA) and World Vaccine Congress (Barcelona, Spain) for travel and accommodation to attend and present at both conferences on the role of vaccines in reducing antimicrobial resistance. TM and BVC have no competing interests to declare. The authors alone are responsible for the views expressed in this article and they do not necessarily represent the views, decisions, or policies of the institutions with which they are affiliated. AI-assisted technologies were used in the writing process to improve the readability and language of the work, application was done with human oversight and control and all authors carefully reviewed and edited the result.

Antibiotics help in preventing and treating infections and increasing life expectancy globally. Globally, many people's lives are being threatened by the emergence of antimicrobial resistance (AMR). The cost of treating and preventing infectious diseases has increased due to AMR. Bacteria can resist the effects of antibiotics by altering drug targets, inactivating drugs, and activating drug efflux pumps. According to estimates, five million individuals died in 2019 from AMR-related causes, wherein 1.3 million deaths were directly linked to bacterial AMR. Sub-Saharan Africa (SSA) experienced the greatest mortality rate from AMR in 2019. In this article, we discuss AMR's causes and challenges SSA faces in implementing AMR prevention measures and propose recommendations to address the challenges. Antibiotic misuse and overuse, widespread usage in agriculture, and the pharmaceutical industry's absence of new antibiotic development are the factors contributing to AMR. SSA's challenges in preventing AMR include poor AMR surveillance and lack of collaboration, irrational use of antibiotics, weak medicine regulatory systems, lack of infrastructural and institutional capacities, lack of human resources, and inefficient infection prevention and control (IPC) practices. The challenges faced by countries in SSA can be addressed by increasing the public's knowledge of antibiotics and AMR, promoting antibiotic stewardship, improving AMR surveillance, promoting collaboration within and beyond countries, antibiotics regulatory enforcement, and improving the practice of IPC measures at home, food handling establishments, and healthcare facilities., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: This study was conducted to explore the epidemiology and microbiological pattern of the cholera outbreaks that occurred in Zimbabwe from 2018 to 2019., Study Setting and Design: This descriptive study used secondary data of 9971 out of 10 730 suspected cases from the Zimbabwean National Diseases Surveillance system and microbiology data of 241 out of 371 patients from the National Microbiology Reference Laboratory in Harare, for the period 5 September 2018 and 3 January 2019. Descriptive analysis was performed to describe the characteristics of the outbreak in terms of person, place and time., Results: A cumulative total of 10 730 suspected, 371 laboratory-confirmed cholera cases and 68 deaths were reported in Zimbabwe through the situation analysis report (sitrep). The attack rate during the outbreak was 174.6 per 100 000 with a case fatality rate of 0.63%. Most cases seen were among adults from Harare province. Antimicrobial sensitivity testing results showed that a multidrug resistant strain of Vibrio cholerae O1, Ogawa serotype was responsible for the outbreak. The treatment of cases was changed from the standard recommended medicine ciprofloxacin to azithromycin as confirmed by the antimicrobial sensitivity test results. Strategies employed to contain the outbreak included mass oral cholera vaccination in the hotspot areas of Harare, provision of improved and appropriate sanitation measures, provision of safe and adequate water, chlorination of water and improved waste management practice., Conclusions: The recurrence of a cholera outbreak is a global concern, especially with the emergence of multi-drug resistant strains of the causal organism. Improving water, sanitation, hygiene infrastructure, health system strengthening measures and inter-sectoral collaboration in responding to the cholera outbreak was key to controlling the outbreak., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Public Health Genomics (PHG) is a relatively new field. The wide application of genomic technologies played a pivotal role in elucidating the full genomic sequence of the SARS-CoV-2 virus. This breakthrough proved to be the starting point in the manufacture of diagnostic kits and the subsequent making of vaccines. Beyond the COVID-19 pandemic, many African countries can take advantage of the various investments in genomic technologies to introduce and intensify the use of genomics for public health gain. Public Health Genomics effectively monitors, prevents, and manages non-communicable and infectious diseases. However, there are several challenges to implementing PHG in Africa. In this perspective article, we discuss the utilization of PHG during the COVID-19 pandemic, the lessons learned from using PHG to manage and contain the COVID-19 pandemic, as well as potential challenges Africa may face when putting PHG into practice compared to challenges of other regions. We also discuss our recommendations for overcoming these challenges., (© 2022 Wiley Periodicals LLC.)

Introduction: Extended spectrum beta-lactamase (ESBL) producing Escherichia coli have become widespread among food producing animals. These strains serve as a reservoir of antibiotic resistance genes (ARGs) and act as a possible source of infection to humans as transmission can occur by direct or indirect contact., Methods: This study investigated the faecal carriage of ESBL producing and colistin resistant E. coli in poultry over a 2-year period (2017-2019) from Zimbabwe. A total of 21 ESBL positive isolates from poultry cloacal specimens were selected for whole genome sequencing from animal E. coli isolates bio-banked at the National Microbiology Reference laboratory using phenotypic susceptibility testing results from the National Escherichia coli Surveillance Program to provide representation of different geographical regions and year of isolation. Cloacal swabs were collected from 3000 broiler live birds from farm 1 and from farm 2, 40 backyard chickens and 10 ducks were sampled. Antimicrobial susceptibility and ESBL testing were performed as per Clinical Laboratory Standards Institute guidelines. Whole genome sequencing of ESBL producing isolates was used to determine sequence types (STs), ARGs, and phylogroups., Results: Twenty-one of the included E. coli isolates were confirmed as ESBL producers. Three defined sequence type clonal complexes (CCs) were identified (ST10CC, ST155CC and ST23CC), with ST10CC associated with the most antibiotic resistant profile. The ESBL phenotype was linked to the presence of either cefotaximase-Munich-14 (CTX-M-14) or CTX-M-79. Plasmid mediated quinolone resistant determinants identified were qnrB19 and qnrS1 and one ST10CC isolate from farm 1 broiler chickens harbored a mobile colistin resistance gene ( mcr-1 ). Phylogenetic groups most identified were B1, A and unknown., Discussions: The avian ESBL producing E. coli belonged to a diverse group of strains. The detection of several ARGs highlights the importance of implementing enhanced control measures to limit the spread in animals, environment, and humans. This is the first report of mcr-1 in Zimbabwe, which further underscores the importance of the One Health approach to control the spread and development of AMR., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Takawira, Pitout, Thilliez, Mashe, Gutierrez, Kingsley, Peirano, Matheu, Midzi, Mwamakamba, Gally, Tarupiwa, Mukavhi, Ehlers, Mtapuri-Zinyowera and Kock.)

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century.

Zimbabwe continues to confront the COVID-19 pandemic; there is an urgent need for the rapid scale-up of genomic surveillance efforts. In this piece, we express concern on the limited capacity for SARS-CoV-2 genomic surveillance in Zimbabwe due to limited skillsets and laboratory infrastructural deficiencies. We call for an urgent need for funding from the government of Zimbabwe to set up a robust genomic surveillance program to detect SARS-CoV-2 variants of concern in Zimbabwe and guide public health responses accordingly., Competing Interests: None to declare, (© 2021 The Author(s).)

Background: Advances in SARS-CoV-2 sequencing have enabled identification of new variants, tracking of its evolution, and monitoring of its spread. We aimed to use whole genome sequencing to describe the molecular epidemiology of the SARS-CoV-2 outbreak and to inform the implementation of effective public health interventions for control in Zimbabwe., Methods: We performed a retrospective study of nasopharyngeal samples collected from nine laboratories in Zimbabwe between March 20 and Oct 16, 2020. Samples were taken as a result of quarantine procedures for international arrivals or to test for infection in people who were symptomatic or close contacts of positive cases. Samples that had a cycle threshold of less than 30 in the diagnostic PCR test were processed for sequencing. We began our analysis in July, 2020 (120 days since the first case), with a follow-up in October, 2020 (at 210 days since the first case). The phylogenetic relationship of the genome sequences within Zimbabwe and global samples was established using maximum likelihood and Bayesian methods., Findings: Of 92 299 nasopharyngeal samples collected during the study period, 8099 were PCR-positive and 328 were available for sequencing, with 156 passing sequence quality control. 83 (53%) of 156 were from female participants. At least 26 independent introductions of SARS-CoV-2 into Zimbabwe in the first 210 days were associated with 12 global lineages. 151 (97%) of 156 had the Asp614Gly mutation in the spike protein. Most cases, 93 (60%), were imported from outside Zimbabwe. Community transmission was reported 6 days after the onset of the outbreak., Interpretation: Initial public health interventions delayed onset of SARS-CoV-2 community transmission after the introduction of the virus from international and regional migration in Zimbabwe. Global whole genome sequence data are essential to reveal major routes of spread and guide intervention strategies., Funding: WHO, Africa CDC, Biotechnology and Biological Sciences Research Council, Medical Research Council, National Institute for Health Research, and Genome Research Limited., Competing Interests: Declaration of interests We declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

This study was designed to characterize extended-spectrum beta-lactamase (ESBL)-producing extra-intestinal pathogenic Escherichia coli (E.coli) (ExPEC) associated with urinary tract infections in nine different geographic regions of Zimbabwe over a 2-year period (2017-2019). A total of 48 ESBL-positive isolates from urine specimen were selected for whole-genome sequencing from 1246 Escherichia coli isolates biobanked at the National Microbiology Reference laboratory using phenotypic susceptibility testing results from the National Escherichia coli Surveillance Programme to provide representation of different geographical regions and year of isolation. The majority of ESBL E. coli isolates produced cefotaximase-Munich (CTX-M)-15, CTX-M-27, and CTX-M-14. In this study, sequence types (ST) 131 and ST410 were the most predominant antimicrobial-resistant clones and responsible for the increase in ESBL-producing E. coli strains since 2017. Novel ST131 complex strains were recorded during the period 2017 to 2018, thus showing the establishment and evolution of this antimicrobial-resistant ESBL clone in Zimbabwe posing an important public health threat. Incompatibility group F plasmids were predominant among ST131 and ST410 isolates with the following replicons recorded most frequently: F1:A2:B20 (9/19, 47%), F2:A1: B (5/19, 26%), and F1:A1:B49 (8/13, 62%). The results indicate the need for continuous tracking of different ESBL ExPEC clones on a global scale, while targeting specific STs (e.g. ST131 and ST410) through control programs will substantially decrease the spread of ESBLs among ExPEC., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants.

Background: Typhoid fever, caused by S. enterica ser. Typhi, continues to be a substantial health burden in developing countries. Little is known of the genotypic diversity of S. enterica ser. Typhi in Zimbabwe, but this is key for understanding the emergence and spread of this pathogen and devising interventions for its control., Objectives: To report the molecular epidemiology of S. enterica ser. Typhi outbreak strains circulating from 2012 to 2019 in Zimbabwe, using comparative genomics., Methods: A review of typhoid cases records from 2012 to 2019 in Zimbabwe was performed. The phylogenetic relationship of outbreak isolates from 2012 to 2019 and emergence of antibiotic resistance was investigated by whole-genome sequence analysis., Results: A total 22 479 suspected typhoid cases, 760 confirmed cases were reported from 2012 to 2019 and 29 isolates were sequenced. The majority of the sequenced isolates were predicted to confer resistance to aminoglycosides, β-lactams, phenicols, sulphonamides, tetracycline and fluoroquinolones (including qnrS detection). The qnrS1 gene was associated with an IncN (subtype PST3) plasmid in 79% of the isolates. Whole-genome SNP analysis, SNP-based haplotyping and resistance determinant analysis showed that 93% of the isolates belonged to a single clade represented by multidrug-resistant H58 lineage I (4.3.1.1), with a maximum pair-wise distance of 22 SNPs., Conclusions: This study has provided detailed genotypic characterization of the outbreak strain, identified as S. Typhi 4.3.1.1 (H58). The strain has reduced susceptibility to ciprofloxacin due to qnrS carried by an IncN (subtype PST3) plasmid resulting from ongoing evolution to full resistance., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

Background: Typhoid fever remains a major public health problem in Zimbabwe with recurrent outbreaks reported since 2009. To provide guidance on appropriate treatment choice in order to minimise the morbidity and mortality of typhoid fever and prevent large scale outbreaks, we investigated the antimicrobial susceptibility patterns, prevalence of Salmonella enterica serotype Typhi (S. Typhi) H58 haplotype and molecular subtypes of S. Typhi from outbreak strains isolated from 2009 to 2017 in Zimbabwe and compared these to isolates from neighbouring African countries., Methods: Antimicrobial susceptibility testing was performed on all isolates using the disk diffusion, and E-Test, and results were interpreted using Clinical and Laboratory Standards Institute (CLSI) guidelines (2017). S. Typhi H58 haplotype screening was performed on 161 (58.3%) isolates. Pulsed-field gel electrophoresis (PFGE) was performed on 91 selected isolates across timelines using antibiotic susceptibility results and geographical distribution (2009 to 2016)., Results: Between 2009 and 2017, 16,398 suspected cases and 550 confirmed cases of typhoid fever were notified in Zimbabwe. A total of 276 (44.6%) of the culture-confirmed S. Typhi isolates were analysed and 243 isolates (88.0%) were resistant to two or more first line drugs (ciprofloxacin, ampicillin and chloramphenicol) for typhoid. The most common resistance was to ampicillin-chloramphenicol (172 isolates; 62.3%). Increasing ciprofloxacin resistance was observed from 2012 to 2017 (4.2 to 22.0%). Out of 161 screened isolates, 150 (93.2%) were haplotype H58. Twelve PFGE patterns were observed among the 91 isolates analysed, suggesting some diversity exists among strains circulating in Zimbabwe. PFGE analysis of 2013, 2014 and 2016 isolates revealed a common strain with an indistinguishable PFGE pattern (100% similarity) and indistinguishable from PFGE patterns previously identified in strains isolated from South Africa, Zambia and Tanzania., Conclusions: Resistance to first line antimicrobials used for typhoid fever is emerging in Zimbabwe and the multidrug resistant S. Typhi H58 haplotype is widespread. A predominant PFGE clone circulating in Zimbabwe, South Africa, Zambia and Tanzania, argues for cross-border cooperation in the control of this disease.