ORCID Profile
0000-0002-7797-9080
Current Organisations
London School of Hygiene and Tropical Medicine
,
Mashhad University of Medical Sciences Faculty of Medicine
,
University of Cambridge
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Publications
Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes
Publisher: eLife Sciences Publications, Ltd
Date: 12-09-2023
DOI: 10.7554/ELIFE.85867
The Surveillance for Enteric Fever in Asia Project (SEAP), Severe Typhoid Fever Surveillance in Africa (SETA), Surveillance of Enteric Fever in India (SEFI), and Strategic Typhoid Alliance Across Afri
Publisher: Oxford University Press (OUP)
Date: 29-07-2020
DOI: 10.1093/CID/CIAA367
Abstract: Building on previous multicountry surveillance studies of typhoid and others salmonelloses such as the Diseases of the Most Impoverished program and the Typhoid Surveillance in Africa Project, several ongoing blood culture surveillance studies are generating important data about incidence, severity, transmission, and clinical features of invasive Salmonella infections in sub-Saharan Africa and South Asia. These studies are also characterizing drug resistance patterns in their respective study sites. Each study answers a different set of research questions and employs slightly different methodologies, and the geographies under surveillance differ in size, population density, physician practices, access to healthcare facilities, and access to microbiologically safe water and improved sanitation. These differences in part reflect the heterogeneity of the epidemiology of invasive salmonellosis globally, and thus enable generation of data that are useful to policymakers in decision-making for the introduction of typhoid conjugate vaccines (TCVs). Moreover, each study is evaluating the large-scale deployment of TCVs, and may ultimately be used to assess post-introduction vaccine impact. The data generated by these studies will also be used to refine global disease burden estimates. It is important to ensure that lessons learned from these studies not only inform vaccination policy, but also are incorporated into sustainable, low-cost, integrated vaccine-preventable disease surveillance systems.
A Race against Time: Reduced Azithromycin Susceptibility in Salmonella enterica Serovar Typhi in Pakistan
Publisher: American Society for Microbiology
Date: 26-08-2020
Abstract: The emergence of XDR Salmonella Typhi in Pakistan has left azithromycin as the only viable oral treatment option. Here, we report the detection of an azithromycin resistance-associated mutation in one S. Typhi isolate. This finding is important because any possible spread of azithromycin resistance in S. Typhi isolates would make it nearly impossible to treat in outpatient settings due to the need of injectable antibiotics. Our findings also signify the importance of introduction of typhoid conjugate vaccine in regions of endemicity such as Pakistan.
Spontaneous Emergence of Azithromycin Resistance in Independent Lineages of Salmonella Typhi in Northern India
Publisher: Oxford University Press (OUP)
Date: 30-01-2021
DOI: 10.1093/CID/CIAA1773
Abstract: The emergence and spread of antimicrobial resistance (AMR) pose a major threat to the effective treatment and control of typhoid fever. The ongoing outbreak of extensively drug-resistant Salmonella Typhi (S. Typhi) in Pakistan has left azithromycin as the only remaining broadly efficacious oral antimicrobial for typhoid in South Asia. Ominously, azithromycin-resistant S. Typhi organisms have been subsequently reported in Bangladesh, Pakistan, and Nepal. Here, we aimed to understand the molecular basis of AMR in 66 S. Typhi organisms isolated in a cross-sectional study performed in a suburb of Chandigarh in Northern India using whole-genome sequencing and phylogenetic analysis. We identified 7 S. Typhi organisms with the R717Q mutation in the acrB gene that was recently found to confer resistance to azithromycin in Bangladesh. Six out of the seven azithromycin-resistant S. Typhi isolates also exhibited triple mutations in gyrA (S83F and D87N) and parC (S80I) genes and were resistant to ciprofloxacin. These contemporary ciprofloxacin/azithromycin-resistant isolates were phylogenetically distinct from each other and from those reported from Bangladesh, Pakistan, and Nepal. The independent emergence of azithromycin-resistant typhoid in Northern India reflects an emerging broader problem across South Asia and illustrates the urgent need for the introduction of typhoid conjugate vaccines in the region.
Reorganization of Substance Use Treatment and Harm Reduction Services During the COVID-19 Pandemic: A Global Survey
Publisher: Frontiers Media SA
Date: 29-04-2021
DOI: 10.3389/FPSYT.2021.639393
Abstract: Background: The coronavirus disease 2019 (COVID-19) pandemic has impacted people with substance use disorders (SUDs) worldwide, and healthcare systems have reorganized their services in response to the pandemic. Methods: One week after the announcement of the COVID-19 as a pandemic, in a global survey, 177 addiction medicine professionals described COVID-19-related health responses in their own 77 countries in terms of SUD treatment and harm reduction services. The health responses were categorized around ( 1 ) managerial measures and systems, ( 2 ) logistics, ( 3 ) service providers, and ( 4 ) vulnerable groups. Results: Respondents from over 88% of countries reported that core medical and psychiatric care for SUDs had continued however, only 56% of countries reported having had any business continuity plan, and 37.5% of countries reported shortages of methadone or buprenorphine supplies. Participants of 41% of countries reported partial discontinuation of harm-reduction services such as needle and syringe programs and condom distribution. Fifty-seven percent of overdose prevention interventions and 81% of outreach services were also negatively impacted. Conclusions: Participants reported that SUD treatment and harm-reduction services had been significantly impacted globally early during the COVID-19 pandemic. Based on our findings, we highlight several issues and complications resulting from the pandemic concerning people with SUDs that should be tackled more efficiently during the future waves or similar pandemics. The issues and potential strategies comprise the following: (1) helping policymakers to generate business continuity plans, (2) maintaining the use of evidence-based interventions for people with SUDs, (3) being prepared for adequate medication supplies, (4) integrating harm reduction programs with other treatment modalities, and (5) having specific considerations for vulnerable groups such as immigrants and refugees.
Global diversity and antimicrobial resistance of typhoid fever pathogens: insights from 13,000SalmonellaTyphi genomes
Publisher: Cold Spring Harbor Laboratory
Date: 30-12-2022
DOI: 10.1101/2022.12.28.22283969
Abstract: 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 twenty-one years since the publication of the first Typhi genome, represents the largest Typhi genome sequence collection to date (n=13,000), and provides a detailed overview of global genotype and antimicrobial resistance (AMR) distribution and temporal trends, generated using open analysis platforms (GenoTyphi and Pathogenwatch). 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 potential of travel-associated data to provide informal “sentinel” surveillance for such locations. The data indicate ciprofloxacin non-susceptibility ( resistance determinant) is widespread across geographies and genotypes, with high-level 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. 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.
Author response: Global diversity and antimicrobial resistance of typhoid fever pathogens: Insights from a meta-analysis of 13,000 Salmonella Typhi genomes
Publisher: eLife Sciences Publications, Ltd
Date: 03-07-2023
A global survey on changes in the supply, price and use of illicit drugs and alcohol, and related complications during the 2020 COVID-19 pandemic
Publisher: Cold Spring Harbor Laboratory
Date: 21-07-2020
DOI: 10.1101/2020.07.16.20155341
Abstract: COVID-19 has infected more than 13 million people worldwide and impacted the lives of many more, with a particularly devastating impact on vulnerable populations, including people with substance use disorders (SUDs). Quarantines, travel bans, regulatory changes, social distancing and ‘lockdown’ measures have affected drug and alcohol supply chains and subsequently their availability, price and use patterns, with possible downstream effects on presentations of SUDs and demand for treatment. Given the lack of multicentric epidemiologic studies, we conducted a rapid global survey within the International Society of Addiction Medicine (ISAM) network in order to understand the status of substance-use patterns during the current pandemic. Cross-sectional survey. Worldwide. Starting on April 4 th , 2020 during a 5-week period, the survey received 185 responses from 77 countries. To assess addiction medicine professionals’ perceived changes in drug and alcohol supply, price, use pattern and related complications during the COVID-19 pandemic. Participants reported (among who answered “decreased” or “increased”, percentage of those who were in majority is reported in the parenthesis) a decrease in drug supply (69.0%), and at the same time an increase in price (95.3%) globally. With respect to changes in use patterns, an increase in alcohol (71.7%), cannabis (63.0%), prescription opioids (70.9%), and sedative/hypnotics (84.6%) use was reported while the use of hetamines (59.7%), cocaine (67.5%), and opiates (58.2%) was reported to decrease overall. The global report on changes in the availability, use patterns and complications of alcohol and drugs during the COVID-19 pandemic should be considered in making new policies and in developing mitigating measures and guidelines during the current pandemic (and probable future ones) in order to minimize risks to SUDs. Authors claimed no competing interest
Evaluation of Typhoid Conjugate Vaccine Effectiveness in Ghana (TyVEGHA) Using a Cluster-Randomized Controlled Phase IV Trial: Trial Design and Population Baseline Characteristics
Publisher: MDPI AG
Date: 19-03-2021
Abstract: Typhoid fever remains a significant health problem in sub-Saharan Africa, with incidence rates of cases per 100,000 person-years of observation. Despite the prequalification of safe and effective typhoid conjugate vaccines (TCV), some uncertainties remain around future demand. Real-life effectiveness data, which inform public health programs on the impact of TCVs in reducing typhoid-related mortality and morbidity, from an African setting may help encourage the introduction of TCVs in high-burden settings. Here, we describe a cluster-randomized trial to investigate population-level protection of TYPBAR-TCV®, a Vi-polysaccharide conjugated to a tetanus-toxoid protein carrier (Vi-TT) against blood-culture-confirmed typhoid fever, and the synthesis of health economic evidence to inform policy decisions. A total of 80 geographically distinct clusters are delineated within the Agogo district of the Asante Akim region in Ghana. Clusters are randomized to the intervention arm receiving Vi-TT or a control arm receiving the meningococcal A conjugate vaccine. The primary study endpoint is the total protection of Vi-TT against blood-culture-confirmed typhoid fever. Total, direct, and indirect protection are measured as secondary outcomes. Blood-culture-based enhanced surveillance enables the estimation of incidence rates in the intervention and control clusters. Evaluation of the real-world impact of TCVs and evidence synthesis improve the uptake of prequalified/licensed safe and effective typhoid vaccines in public health programs of high burden settings. This trial is registered at the Pan African Clinical Trial Registry, accessible at Pan African Clinical Trials Registry (ID: PACTR202011804563392).
Spontaneous emergence of azithromycin resistance in independent lineages of Salmonella Typhi in Northern India
Publisher: Cold Spring Harbor Laboratory
Date: 23-10-2020
DOI: 10.1101/2020.10.23.351957
Abstract: The emergence and spread of antimicrobial resistance (AMR) pose a major threat to the effective treatment and control of typhoid fever. The ongoing outbreak of extensively drug resistant (XDR) Salmonella Typhi ( S . Typhi) in Pakistan has left azithromycin as the only remaining broadly efficacious oral antimicrobial for typhoid in South Asia. Ominously, azithromycin resistant S . Typhi organisms have been subsequently reported in Bangladesh, Pakistan, and Nepal. Here, we aimed to understand the molecular basis of AMR in 66 S . Typhi isolated in a cross-sectional study performed in a suburb of Chandigarh in Northern India using whole genome sequencing (WGS) and phylogenetic analysis. We identified seven S . Typhi organisms with the R717Q mutation in the acrB gene that was recently found to confer resistance to azithromycin in Bangladesh. Six out of the azithromycin-resistant S . Typhi isolates also exhibited triple mutations in gyrA (S83F and D87N) and parC (S80I) genes and were resistant to ciprofloxacin. These contemporary ciprofloxacin/azithromycin-resistant isolates were phylogenetically distinct from each other and from those reported from Bangladesh, Pakistan, and Nepal. The independent emergence of azithromycin resistant typhoid in Northern India reflects an emerging broader problem across South Asia and illustrates the urgent need for the introduction of typhoid conjugate vaccines (TCVs) in the region. We identified ciprofloxacin/azithromycin-resistant Salmonella Typhi ( S . Typhi) in Chandigarh in Northern India. The independent emergence of ciprofloxacin/azithromycin-resistant typhoid in Bangladesh, Pakistan, Nepal, and India and the continued spread of extensively-drug resistant (XDR) typhoid in Pakistan highlight the limitations of licensed oral treatments for typhoid fever in South Asia.
The genomic epidemiology of multi-drug resistant invasive non-typhoidal Salmonella in selected sub-Saharan African countries
Publisher: BMJ
Date: 08-2021
DOI: 10.1136/BMJGH-2021-005659
Abstract: Invasive non-typhoidal Salmonella (iNTS) is one of the leading causes of bacteraemia in sub-Saharan Africa. We aimed to provide a better understanding of the genetic characteristics and transmission patterns associated with multi-drug resistant (MDR) iNTS serovars across the continent. A total of 166 iNTS isolates collected from a multi-centre surveillance in 10 African countries (2010–2014) and a fever study in Ghana (2007–2009) were genome sequenced to investigate the geographical distribution, antimicrobial genetic determinants and population structure of iNTS serotypes–genotypes. Phylogenetic analyses were conducted in the context of the existing genomic frameworks for various iNTS serovars. Population-based incidence of MDR-iNTS disease was estimated in each study site. Salmonella Typhimurium sequence-type (ST) 313 and Salmonella Enteritidis ST11 were predominant, and both exhibited high frequencies of MDR Salmonella Dublin ST10 was identified in West Africa only. Mutations in the gyrA gene (fluoroquinolone resistance) were identified in S . Enteritidis and S . Typhimurium in Ghana an ST313 isolate carrying bla CTX-M-15 was found in Kenya. International transmission of MDR ST313 (lineage II) and MDR ST11 (West African clade) was observed between Ghana and neighbouring West African countries. The incidence of MDR-iNTS disease exceeded 100/100 000 person-years-of-observation in children aged years in several West African countries. We identified the circulation of multiple MDR iNTS serovar STs in the s led sub-Saharan African countries. Investment in the development and deployment of iNTS vaccines coupled with intensified antimicrobial resistance surveillance are essential to limit the impact of these pathogens in Africa.
Unlocking the Potential of Genomic Data to Inform Typhoid Fever Control Policy: Supportive Resources for Genomic Data Generation, Analysis, and Visualization
Publisher: Oxford University Press (OUP)
Date: 05-2023
DOI: 10.1093/OFID/OFAD044
Abstract: The global response to the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic demonstrated the value of timely and open sharing of genomic data with standardized metadata to facilitate monitoring of the emergence and spread of new variants. Here, we make the case for the value of Salmonella Typhi (S. Typhi) genomic data and demonstrate the utility of freely available platforms and services that support the generation, analysis, and visualization of S. Typhi genomic data on the African continent and more broadly by introducing the Africa Centres for Disease Control and Prevention's Pathogen Genomics Initiative, SEQAFRICA, Typhi Pathogenwatch, TyphiNET, and the Global Typhoid Genomics Consortium.
The international and intercontinental spread and expansion of antimicrobial-resistant Salmonella Typhi: a genomic epidemiology study
Publisher: Elsevier BV
Date: 08-2022
Related Organisations
London School Of Hygiene And Tropical Medicine
Location: United Kingdom of Great Britain and Northern Ireland
Mashhad University Of Medical Sciences Faculty Of Medicine
Location: Iran (Islamic Republic of)
University Of Cambridge
Location: United Kingdom of Great Britain and Northern Ireland
Related Funding Activities
No related grants have been discovered for Megan Carey.