Prof. dean everett

The ticking time-bomb: The hidden extent of the AMR landscape and the potential untreatable hospital ESKAPE infections across the UAE: A Phenotypic and Genotypic profiling and mapping study.

In 2020, the World Health Organization (WHO) announced its top global health challenges (https://www.who.int/news-room/photo-story/photo-story-detail/urgent-health-challenges-for-the-next-decade). Of the 13 threats to humankind identified up until 2030, 5 were infectious disease related and 1 specifically Antimicrobial Resistance (AMR) related. AMR is one of humankind’s biggest global challenges. 

This study will i) Retrospectively define AMR phenotypic and genotypic diversity over a 14-year period (2010-2024) across ALL major pathogens; ii) Characterize genomic-determinants of antimicrobial resistance of these isolates and undertake expanded sensitivity screening beyond currently available antimicrobials in order to inform local and national future treatment policy; iii) Prospectively define the prevalence of ESKAPE pathogens in adult and pediatric in-patients admitted to hospitals across the UAE and to trace cases back to the community; iv) Identify the source and/or spread of infection and/or hotspots; v) Employ whole genome sequencing to assess dissemination of AMR clones within the population and by demographics; vi) Assess antibiotic consumption and correlate this to antimicrobial resistance profiles to inform local policy of antibiotic use; vii) Assess temporal-spatial contexts for these key pathogens in the UAE through molecular epidemiological analyses to find out how they are contributing to local and global rising trends of antimicrobial resistance; and viii) Define clinical associations and outcome of AMR infection.

Abu Dhabi Pregnancy Risk Assessment Monitoring System (WAMDA)

WAMDA is a population-based surveillance system that provides information on women that have recently given birth and their newborn. WAMDA is a partnership between the Early Childhood Authority (ECA), The Abu Dhabi Public Health Center (ADPHC), and Khalifa University College of Medicine and Health Sciences. The goal of WAMDA is to provide information that will help improve the health of mothers and babies, and to reduce the incidence of Low Birth Weight in Abu Dhabi. The surveillance platform samples >10% of Abu Dhabi births and collects data on at least 3600 mothers and their new born child every calendar year. 

One Health AMR Molecular Biosecurity Programme

The development of antimicrobial resistance (AMR) is one the of the top 10 global threats to human health in the 21st Century. The One Health AMR Programme will combine cutting-edge metagenomic technologies applied at scale with innovative AI and big data epidemiology approaches to implement a world first molecular One Health epidemiological analysis of AMR at a national scale. This world leading project will pioneer the molecular epidemiological approach to One Health AMR. This will enhance national health biosecurity in the UAE and lead global thinking implementation of the One Health approach. Innovative data mining of metagenomic data will demonstrate proof of concept for metagenomic data to address wider human health and societal challenges. Project outputs will feed directly into the UAE AMR National Action Plan and provide international policy guidance.

National Pilot Study

Primary objective: To sequence all archived E. coli and Salmonella samples from participating laboratories between 2020-2025 to identify possible transmissions across Human, Animal and the Environment, specifically for AMR.

Secondary objectives:

1. To define the transmission and spread patterns of these infectious diseases
2. To provide baseline data on the genomic diversity and characteristics of these key pathogens across these One Health sectors.
3. To identify the specific genes responsible for antibiotic resistance and other important clinical traits (e.g. virulence), and to place these data within a global context
4. To carry out molecular epidemiological analysis to trace the spread and infer transmission patterns of AMR pathogens
5. To prospectively collect and store clinically relevant AMR pathogens at the Khalifa University and MBRU, which will serve as a repository for future AMR studies.  

Deciphering the impact of mask and other non-pharmacological interventions on epidemiology and seasonality of Influenza and RSV

Human Influenza and RSV viruses cause significant morbidity and mortality worldwide. They are the major cause of acute respiratory diseases in humans, causing several serious global pandemics because of their transmission dynamics and great antigenic variability. Pandemic influenza is usually caused by influenza A virus, due to its rapid antigenic variation, strong replication capacity, and transmission ability associated with genetic reassortment. Influenza B virus, often neglected, has been circulating and, in some seasons, has predominated over influenza A, particularly among children. Vaccines against influenza A/H1N1 and A/H3N2 have been used effectively for more than 20 years for controlling and preventing potential pandemics.

The overall aim of this study is to utilize the already in place outstanding influenza and RSV sentinel surveillance system in UAE to fully characterize that population both clinically and demographically and use this information to define the impact of Covid-19 prevention measures on Influenza. The study will i) Define the impact of Mask and other non-pharmacological interventions on epidemiology and seasonality of Influenza and RSV; ii) Characterize incoming and circulating influenza and RSV strains; iii) Define genomic and epidemiological associations with circulating viruses; and iv) Create and test epidemiological models of influenza and RSV for future public health surveillance and interventions.

One Health Associated Antimicrobial Resistance: A UAE Public Health crisis

OBJECTIVES

We propose to conduct a comprehensive analysis of antimicrobial resistance (AMR) pathogens collected from routine diagnostic work across UAE healthcare, agricultural, veterinary and environmental facilities. Leveraging advanced molecular techniques, we will perform high-resolution genomic characterization of these isolates and integrate detailed patient demographic and clinical data. This integrated approach will uncover the underlying mechanisms driving resistance, quantify the clinical burden, and inform targeted, evidence-based interventions. Our project will transform our understanding of AMR, enhance national public health security, and guide tailored strategies to mitigate this increasing public health crisis.

Primary objective: To comprehensively sequence, analyse, and evaluate E. coli and Salmonella isolates from participating centers between 2020 and 2025, to elucidate the clinical burden of antimicrobial resistance and quantify the contribution of environmental reservoirs to its dissemination—particularly through the horizontal transfer of AMR plasmids across human, animal, and environmental interfaces.

Secondary objectives:

1. Assess and document the genomic diversity of E. coli and Salmonella isolates (2020–2025) by cataloguing sequence types, plasmid profiles, and resistance determinants
2. Quantify the transmission dynamics across human, animal, and environmental sectors by applying phylodynamic models that reconstruct the evolutionary history of these pathogens
3. Assess the role of plasmids in driving antimicrobial resistance by evaluating high-risk plasmid variants across clinical isolates and environmental reservoirs.
4. Identify genetic traits that enable E. coli and Salmonella to adapt to diverse ecological niches by performing a genome-wide association study (GWAS) on the collected data
5. Compare local genomic data with international sequencing databases to evaluate the proportion of clinical infections arising from imported versus endemic strains, establishing quantitative benchmarks to guide targeted public health interventions.
6. Identify candidate markers for Phase 2 development of biosensors for use across all sectors (Human, Animal and Environment) to enable proactive interventions to stop the spread of AMR in the UAE

Computational Modeling-Based Approach Targeting Major Pathogens (COMBAT-PATHOGENS Study)

We are establishing a cutting-edge, AI-driven clinical discovery platform aimed at initially tackling two major disease threats in the UAE/MENA region: Klebsiella pneumoniae and Respiratory Syncytial Virus (RSV). Harnessing clinical-multi-omics, systems biology, and state-of-the-art machine learning, we will accelerate the identification of novel therapeutic targets. This will form the basis of a platform for bacteria and viral drug discovery capabilities at KU.

For K. pneumoniae, a major driver of antibiotic-resistant hospital infections, multi-omics will illuminate resistance pathways and vulnerabilities, guiding AI models to pinpoint high-value drug targets, catalyzing next-generation antimicrobial design.

For RSV, the leading cause of severe respiratory illness, particularly in infants, we will assess current treatment efficacy through local strain genomics. AI will then uncover conserved viral epitopes, laying the groundwork for precision-engineered antibodies and peptide-based therapeutics.

This project aligns with Khalifa University’s strategic vision to lead in biomedical innovation. By translating AI-enabled discovery into actionable therapies, we will directly support clinicians/public health authorities in combatting infectious diseases, bridging local priorities with global health imperative

Objectives 

1. To develop the first comprehensive clinical-multi-omics pathogen database for Kpn and RSV in the region
2. To develop an innovative machine learning computational platform that identifies targets and novel chemical antimicrobials
3. Adapt the machine learning computational platform to incorporate omics data and assess the risk that target sites will develop resistance
4. Develop computational translation of targets into actionable chemistry

Anemia in developing and developed countries, and its impact on healthspan and health economics.

Anemia remains the top endemic condition globally with 25% of the world’s population (1.92 billion) afflicted by this disease.  The World Health Organization (WHO) estimates anemia to affect half a billion women 15–49 years of age and 269 million children 6–59 months of age worldwide (2019 estimates.  Up to date, only limited large-scale screening programs of anemia have been implemented in low- and middle-income countries (LMIC).

To combat this endemic which is a true global health and public health urgency, we intend to conduct anemia screening via POC testing in developed country, and then mass screening program in LMICs in a stepwise approach. Although anemia screening programs have been undertaken already in LMICs, this study will investigate screening of children in both developed countries and LMICs, and in addition, look into potential causal factors of anemia in LMICs, and then evaluate the health economics of anemia on lifespan and healthspan of pediatric populations.

OBJECTIVES:

1. To determine the feasibility of using a point-of-care tool for the diagnosis of anemia in children in the UAE.
2. To determine the prevalence of anemia in pediatric populations in Africa (Nigeria, Ghana, Tanzania, and Ethiopia) using the point-of-care testing
3. To determine the prevalence of anemia in pediatric populations in Africa (Nigeria, Ghana, Tanzania, and Ethiopia) using the point-of-care testing
4. To identify the proportion of the children with anemia who are suffering from IDA.
5. To explore potential risk factors for anemia, including diet/malnutrition, infectious diseases, and hemoglobinopathies.
6. To determine the impact of anemia in children on anthropometric measures, QoL, YPLL and DALYs

Data-Driven Vaccine Strategy in the UAE: Integrating Malaffi and AMR Surveillance to Identify Circulating Vaccine-Preventable Pathogens and Inform Public Health Interventions

Vaccination is a cornerstone of our public health, offering a proactive solution to prevent infectious diseases, reduce morbidity and mortality, and mitigate the overuse of antimicrobials. Countries, including thee UAE, face increasingly complex healthcare challenges, including antimicrobial resistance (AMR), waning vaccine-induced immunity, and demographic shifts, as such precise and up-to-date vaccination data are vital to ensure effective and equitable disease prevention.

Objectives

1. Determine real-world vaccine coverage across four key age groups (under 5s, adolescents, adults, and older adults) using anonymized Malaffi health record data.
2. Identify which vaccine-preventable pathogens are still circulating in the community, using the national AMR pathogen surveillance database, and determine their prevalence by age group.
3. Evaluate associations between vaccine coverage gaps and the continued presence of specific vaccine preventable diseases, particularly those with multidrug resistance profiles.
4. Define geographic and demographic clusters of under-immunization and pathogen burden, enabling targeted public health responses.
5. Inform vaccine policy, including optimization of existing vaccination programs and prioritization of new vaccines as they become available (e.g., RSV, meningococcal B, newer pneumococcal conjugate vaccines).

Study of Antimicrobial Resistance (STARS) on the UAE National Burns Unit: A Phenotypic and Genotypic profiling study to improve infection prevention and management. 

The Burn Unit at SSMC is the UAE National Burn Unit and it also serves patients from neighboring countries. The Burn Unit provides a 24/7 unique service for critically ill burn patients of different age groups across all Emirates. The goal of the unit is to achieve excellence in the management of burn patients through evidence-based practices.

The importance of Antimicrobial Resistance (AMR) is recognised globally as a major threat to humankind. The spectrum of AMR challenges is broad, but is especially important for Gram-negative bacteria, such as extended spectrum beta-lactamase (ESBL) producing bacteria, including Escherichia coli and Klebsiella pneumoniae; MRSA (Methicillin Resistant Staphylococcus aureus) and other Hospital superbugs such as Candida auris. Although significant for all infections, the consequences of AMR in severe infections, such as patients with major burns are devastating. 

Burn patients remain at higher risk for all types of infections secondary to loss of the skin barrier as well as immunosuppression experienced because of a systemic inflammatory response triggered by the injured tissue. The burn wound surface provides a favorable niche for microbial colonization and proliferation and infections may originate from the patient’s skin and gastrointestinal and respiratory flora (endogenous), or may also be transferred via contact with contaminated external surfaces and soiled hands of healthcare workers (exogenous). 

Study Aim:

To define the phenotypic and genotypic clinical epidemiological population characteristics of historical and prospectively collected pathogens from SSMC’s burns unit, and to identify routes of transmission and spread in cases of healthcare-associated infection and/or outbreaks.

Study objectives:

1. To retrospectively define clinical infectious disease epidemiology of the Burns unit infections over the previous 3 years since its inception.
2. To determine the genetic epidemiology of archived Burns patient multi-drug resistant isolates
3. To prospectively collect and define ongoing in-patient burns unit infections over a 2-year period to assess the epidemiology of causative pathogens both genotypically and phenotypically.
4. To characterize genomic determinants of antimicrobial resistance of historical and current isolates and undertake expanded sensitivity screening beyond currently available antimicrobials in order to inform local and national future treatment policy moving forward.
5. To prospectively sample the Burns unit’s environment, to identify possible sources of transmission and/or spread of infection when a healthcare-associated outbreak occurs with a particular pathogen to inform infection control practices.
6. Employ whole genome sequencing to assess dissemination of AMR clones and outbreaks within the population and by demographics.
7. To assess antibiotic consumption and to correlate this to antimicrobial resistance profiles to inform local policy of antibiotic use.
8. To define clinical associations and outcomes of infection within the Burns unit.
9. To prospectively collect and preserve copies of pathogens at Khalifa University for research purposes.

Antimicrobial Susceptibility and Virulence Traits of Helicobacter Pylori in Children and adults of Abu Dhabi, United Arab Emirates

Helicobacter pylori is a bacteria referred to as the stomach bug that can cause chronic inflammation of the stomach and may lead to ulcers in the stomach and in the first part of the small intestine. In the long run, it may even result in stomach cancer. Stomach cancer is the second most common cancer among Emirati males. This bacteria is very common and infects more than half of the people worldwide. In United Arab Emirates (UAE), it is found in 41% of the whole population and in 55% of the Emirati people. A significant percentage of non-local Emirati residents originates from regions with very high prevalence of this infection. More individuals in UAE might be infected knowing that it infects about 75% of people in the surrounding countries. It can spread among families probably through oro-oral or feco-oral routes. 

Aims 

This study aims to determine the antimicrobial susceptibility trends of H. pylori from gastric biopsy specimens of local patients of Abu Dhabi Emirates to the following antibiotics: Amoxicillin, Clarithromycin, Metronidazole, Levofloxacin, Tetracycline, Rifampicin and rifabutin. It will, for the first time, properly inform local physicians as to the evidence based right choice of antibiotics to be used in managing H. pylori infection.

This study through WGS also aims to identify the key virulence factors of H. pylori from gastric biopsy specimens of local patients of Abu Dhabi, that can predict the severity of H. pylori infections and the extent of associated complications among local patients of Abu Dhabi.

Furthermore, considering the non-invasive relative ease of stool collection and along with emerging evidence of the feasibility of using stool specimens as an alternative source for genetic sequencing of H. pylori to determine its antibiotic resistance patterns and other attributes, this study will also look at collecting and storing stool samples from a small group of patients for future analysis and correlation with this project results. This will be the subject of future grant application as it will not be financially achievable within the funding constraints of the current application. 

Objectives 

Primary

1. Characterize the antimicrobial susceptibility pattern of H. pylori  to the seven antibiotics in question
2. Characterize the genetic epidemiology and antimicrobial resistance of H. pylori by whole genome sequencing
3. Correlate identified virulence factors of H. pylori to clincial data of symptoms and signs patients presented  with and to the endoscopic findings that are found in these patients.  

Secondary

Collect and store stool samples from a subgroup of patients for future research into molecular genetic stool testing for H. pylori.

The Genetic Epidemiology of the UAEs Dengue outbreak

Dengue fever is a mosquito-borne disease caused by dengue virus, prevalent in tropical and subtropical areas. It is frequently asymptomatic; if symptoms appear they typically begin 3 to 14 days after infection. These may include a high fever, headache, vomiting, muscle and joint pains, and a characteristic skin itching and skin rash. Recovery generally takes two to seven days. In a small proportion of cases, the disease develops into severe dengue (previously known as dengue hemorrhagic fever or dengue shock syndrome) with bleeding, low levels of blood platelets, blood plasma leakage, and dangerously low blood pressure.

OBJECTIVES

We know the UAE has had sporadic outbreaks of dengue which requires detailed investigation beyond mere serological analysis. Understanding the strains, their transmission links and outbreak clusters will better inform future preparedness and provide a roadmap for supporting the control efforts.

We will initiate a retrospective collection of dengue positive serum samples as part of routine diagnostic work across facilities and laboratories across the UAE that have these samples archived. We will use advanced molecular based methods to characterize the isolates as well as obtain data on patient demographic and clinical profiles. This data will be used to address the following study objectives.

Primary objective: To sequence the viral genomes of UAE Dengue Fever positive samples

Secondary objectives:

1. To define the transmission and spread patterns of this infectious disease during an outbreak
2. To assess the clinical risk factors and outcomes associated with infection
3. To provide baseline data on the genomic diversity and characteristics of this key pathogen across the UAE.
4. To collect and store clinically relevant samples, clinical and demographic metadata at the Khalifa University which will serve as a repository for future studies.  

An Integrative Omics, Machine Learning, and Clinical Epidemiology Approach to Defining Severe Respiratory Pathogen Risk Factors in the UAE: A Multifaceted Grant Proposal

The upper respiratory tract (URT) infections are linked to significant changes in the microbiome composition yet the mechanisms are not understood. The extent to which co-colonization with other pathogens impacts severity of disease and the role of antimicrobial resistance remain unclear. 

A recent study showed that gut microbes play an important role in severe SARS-CoV2 disease due to reduced microbial diversity. While groundbreaking, the study was limited (n=127 patients). Our study is powered by over 100,000 SARS-CoV2 patient nasopharyngeal swabs, with comprehensive case management and clinical outcome data, and viral genomes for each case. 

We hypothesize microbiome diversity will be significantly decreased in severe SARS-CoV2 cases. Furthermore, we propose that antibiotic treatment of patients increased the prevalence of antimicrobial resistance genes and resistance determinants. Understanding the risks associated with severe disease will lead to improved prevention protocols, treatment outcomes and interventions for respiratory pathogens. 

Objectives:

1. Define the risk factors associated with SARS-CoV2 susceptibility as a template for future pandemics
2. Identify genomic signatures for virulence in the pathogen genome that are associated with severe disease outcomes in the host.
3. Assess the role of the nasopharyngeal microbiome as a contributor to severe disease
4. Define the nasopharyngeal resistome to inform priority areas for community-acquired AMR reduction.
5. Develop a highly scalable and potentially real-time machine-learning pipeline to deliver instant predictions of the expected severity and treatment outcomes of newly infected SARS-CoV2 virus.