The phylogeography and incidence of multi-drug resistant typhoid fever in sub-Saharan Africa

Park, Se Eun; Thanh, Duy Pham; Boinett, Christine J.; Wong, Vanessa; Pak, Gi Deok; Panzner, Ursula; Espinoza, Ligia María Cruz; Kalckreuth, Vera von; Im, Justin; Schütt-Gerowitt, Heidi; Crump, John A.; Breiman, Robert F.; Adu‐Sarkodie, Yaw; Owusu‐Dabo, Ellis; Rakotozandrindrainy, Raphäel; Soura, Abdramane; Aseffa, Abraham; Gasmelseed, Nagla; Keddy, Karen H.; May, Jürgen; Sow, Amy Gassama; Aaby, Péter; Biggs, Holly M.; Hertz, Julian T.; Montgomery, Joel M.; Cosmas, Leonard; Olack, Beatrice; Fields, Barry S.; Sarpong, Nimako; Razafindrabe, Tsiriniaina Jean Luco; Raminosoa, Tiana Mirana; Kabore, Leon Parfait; Sampo, Emmanuel; Teferi, Mekonnen; Yeshitela, Biruk; Tayeb, Muna Ahmed El; Sooka, Arvinda; Meyer, Christian G.; Krumkamp, Ralf; Dekker, Denise; Jaeger, Anna; Poppert, Sven; Tall, Adama; Niang, A; Bjerregaard-Andersen, Morten; Løfberg, Sandra Valborg; Seo, Hye Jin; Jeon, Hyon Jin; Deerin, Jessica Fung; Park, Jinkyung; Konings, Frank; Ali, Mohammad; Clemens, John D.; Hughes, Peter J.; Sendagala, Juliet Nsimire; Vudriko, Tobias; Downing, Robert; Ikumapayi, Usman N.; Mackenzie, Grant; Obaro, Stephen K.; Argimón, Silvia; Aanensen, David M.; Page, Andrew J.; Keane, Jacqueline A.; Duchêne, Sebastián; Dyson, Zoe A.; Holt, Kathryn E.; Dougan, Gordon; Marks, Florian; Baker, Stephen

doi:10.1038/s41467-018-07370-z

Cited by 102 publications

(110 citation statements)

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“…The prevention of typhoid fever through immunization and other measures has the potential to decrease antibiotic use and limit the emergence of resistant S. Typhi strains. The emergence of antimicrobial resistant (AMR) S. Typhi infections contributed to the WHO guidelines for the introduction of typhoid fever vaccination in populations at high risk of infection [ 5 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ].…”

Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity of Vi-DT conjugate vaccine among 6-23-month-old children: Phase II, randomized, dose-scheduling, observer-blind Study

et al. 2020

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Background Typhoid causes significant mortality among young children in resource-limited settings. Conjugate typhoid vaccines could significantly reduce typhoid-related child deaths, but only one WHO-prequalified typhoid conjugate vaccine exists for young children. To address this gap, we investigated the safety, immunogenicity and dose-scheduling of Vi-DT typhoid conjugate vaccine among children aged 6-23 months. Methods In this single center, observer blind, phase II trial, participants were randomly assigned (2:2:1) to receive one or two doses of Vi-DT or comparator vaccine. Anti-Vi IgG titer and geometric mean titers (GMT) were determined at 0, 4, 24 and 28 weeks. Data were analyzed using per-protocol and immunogenicity (a subset of intention-to-treat analysis) sets. The trial is registered with ClinicalTrials.gov (NCT03527355). Findings Between April and July 2018, 285 children were randomized; 114 received one or two doses of Vi-DT while 57 received comparator. 277 completed the study follow-up per protocol; 112 and 110 from single- and two-dose Vi-DT schedules, respectively and 55 from the placebo group were included in the per protocol analysis. Safety profile is satisfactory. Thirteen serious adverse events were reported during the 28-week follow-up, none of which were related to Vi-DT. The seroconversion rate four weeks after the first dose was 100% (95% CI 98·3-100) in Vi-DT recipients and 7·0% (95% CI 2·8-16·7) in comparator recipients (p<0·0001). Similarly, the seroconversion rate 4 weeks after the second dose was 98·2% (95% CI 93· 6-99·5) and 21·8% (95% CI 13·0-34·4) among Vi-DT and comparator groups, respectively (p<0·0001). Anti-Vi IgG GMT was significantly higher in Vi-DT than in control group at all post-vaccination visits (p<0·0001). Interpretation Both single and two doses of Vi-DT vaccine are safe, well tolerated, and immunogenic for infants and toddlers in a moderately endemic setting.

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Section: Introductionmentioning

confidence: 99%

Safety and immunogenicity of Vi-DT conjugate vaccine among 6-23-month-old children: Phase II, randomized, dose-scheduling, observer-blind Study

et al. 2020

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“…Typhi, genotype 3.3.2, which included a Bangladesh-specific monophyletic group with relatives in Nepal, that we further divided into 3.3.2.Bd1 and 3.3.2.Bd2 based on distinct QRDR mutations conferring reduced susceptibility to fluoroquinolones (Fig 4A). These novel Bangladesh-associated lineages (4.3.1.3, 3.3.2.Bd1, 3.3.2.Bd2) have been added to the GenoTyphi genotyping scheme, which will facilitate their detection and tracking in future surveillance efforts, and over time will reveal whether they remain localized to Bangladesh or being to disseminate through Asia and Africa as has been observed for H58 lineages I and II [6, 13, 27, 43].…”

Section: Discussionmentioning

confidence: 99%

“…Typhi was historically associated with self-transmissible IncHI1 plasmids that harbor composite transposons [9, 12]. The global burden of MDR typhoid is driven to a significant degree by the dissemination of the highly clonal, expanding haplotype H58 (genotype 4.3.1), which is now dominant in many endemic settings throughout Africa and Asia [7, 9, 13, 14]. H58 S. Typhi encoding nonsynonymous mutations in the quinolone resistance determining region (QRDR) of DNA gyrase genes gyrA and gyrB and DNA topoisomerase IV genes parC and parE have shown reduced susceptibility to fluoroquinolones [7, 15].…”

Section: Introductionmentioning

confidence: 99%

Population structure and antimicrobial resistance patterns of Salmonella Typhi isolates in Bangladesh from 2004 to 2016

Rahman

Dyson

Klemm

et al. 2019

Preprint

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BackgroundMulti-drug resistant typhoid fever remains an enormous public health threat in low and middle-income countries. However, we still lack a detailed understanding of the epidemiology and genomics of S. Typhi in many regions. Here we have undertaken a detailed genomic analysis of typhoid in Bangladesh to unravel the population structure and antimicrobial resistance patterns in S. Typhi isolated in between 2004-2016.Principal findingsWhole genome sequencing of 202 S. Typhi isolates obtained from three study locations in urban Dhaka revealed a diverse range of S. Typhi genotypes and AMR profiles. The bacterial population within Dhaka were relatively homogenous with little stratification between different healthcare facilities or age groups. We also observed evidence of transmission of Bangladeshi genotypes with neighboring South Asian countries (India, Pakistan and Nepal) suggesting these are circulating throughout the region. This analysis revealed a decline in H58 (genotype 4.3.1) isolates from 2011 onwards, coinciding with a rise in a diverse range of non-H58 genotypes and a simultaneous rise in isolates with reduced susceptibility to fluoroquinolones, potentially reflecting a change in treatment practices. We identified a novel S. Typhi genotype, subclade 3.3.2 (previously defined only to clade level, 3.3), which formed two localised clusters (3.3.2.Bd1 and 3.3.2.Bd2) associated with different mutations in the Quinolone Resistance Determining Region (QRDR) of gene gyrA.SignificanceOur analysis of S. Typhi isolates from Bangladesh isolated over a twelve year period identified a diverse range of AMR profiles and genotypes. The observed increase in non-H58 genotypes associated with reduced fluoroquinolone susceptibility may reflect a change in treatment practice in this region and highlights the importance of continued molecular surveillance to monitor the ongoing evolution of AMR in Bangladesh. We have defined new genotypes and lineages of Bangladeshi S. Typhi which will facilitate identification of these emerging AMR clones in future surveillance efforts.Author SummaryTyphoid fever, caused by Salmonella enterica serovar Typhi, is an acute and often life-threatening febrile illness in developing countries. Until recently, there have been limited studies focusing on the epidemiology and disease burden of typhoid in poor resource settings including Bangladesh. This study highlights the urgent need for sustained genomics based surveillance studies to monitor the population structure and ongoing evolution of AMR. Our data revealed a diverse range of S. Typhi genotypes and AMR patterns among 202 isolates collected from three urban areas in Dhaka. Moreover, we defined a new genotype, subclade 3.3.2 (previously typed only to clade level, 3.3) with two Bangladesh-localiased clades 3.3.2.Bd1 and 3.3.2.Bd2 showing reduced susceptibility to fluoroquinolones. Our data shows a significant increase in non-H58 genotypes carrying QRDR mutations from 2012 onwards, replacing MDR H58 genotypes. Our data suggest that a shift in treatment practice towards third generation cephalosporins to control typhoid might be beneficial, in addition to the introduction of vaccination programs and improvements in water sanitation and hygiene (WASH) in Bangladesh.

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“…This principle recognizes that processes such as birth, death and reproduction are inherently random events, and that low-abundance organisms are the most vulnerable to local extinction due to sampling effects [30]. Speciation refers to the evolutionary processes by which new species arise through genetic diversification [22], with classical driving forces including genomic recombination (e.g., with horizontal gene transfer [31][32][33][34], phage interactions [35,36] and highly mobile iterative and conjugative elements (ICEs) [37,38]), exposure of microorganisms to antibiotics [39,40], and physical isolation [41,42]. Finally, dispersal refers to the migration of organisms on both spatial and temporal scales.…”

Section: The Four Tenets Of Vellend's Modelmentioning

confidence: 99%

The Best of All Worlds: Streptococcus pneumoniae Conjunctivitis through the Lens of Community Ecology and Microbial Biogeography

et al. 2019

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The study of the forces which govern the geographical distributions of life is known as biogeography, a subject which has fascinated zoologists, botanists and ecologists for centuries. Advances in our understanding of community ecology and biogeography—supported by rapid improvements in next generation sequencing technology—have now made it possible to identify and explain where and why life exists as it does, including within the microbial world. In this review, we highlight how a unified model of microbial biogeography, one which incorporates the classic ecological principles of selection, diversification, dispersion and ecological drift, can be used to explain community dynamics in the settings of both health and disease. These concepts operate on a multiplicity of temporal and spatial scales, and together form a powerful lens through which to study microbial population structures even at the finest anatomical resolutions. When applied specifically to curious strains of conjunctivitis-causing, nonencapsulated Streptococcus pneumoniae, we show how this conceptual framework can be used to explain the possible evolutionary and disease-causing mechanisms which allowed these lineages to colonize and invade a separate biogeography. An intimate knowledge of this radical bifurcation in phylogeny, still the only known niche subspecialization for S. pneumoniae to date, is critical to understanding the pathogenesis of ocular surface infections, nature of host-pathogen interactions, and developing strategies to curb disease transmission.

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The phylogeography and incidence of multi-drug resistant typhoid fever in sub-Saharan Africa

Cited by 102 publications

References 45 publications

Safety and immunogenicity of Vi-DT conjugate vaccine among 6-23-month-old children: Phase II, randomized, dose-scheduling, observer-blind Study

Safety and immunogenicity of Vi-DT conjugate vaccine among 6-23-month-old children: Phase II, randomized, dose-scheduling, observer-blind Study

Population structure and antimicrobial resistance patterns of Salmonella Typhi isolates in Bangladesh from 2004 to 2016

The Best of All Worlds: Streptococcus pneumoniae Conjunctivitis through the Lens of Community Ecology and Microbial Biogeography

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