Longer description of your proposed project

Background

The global menace of Antimicrobial Resistance (AMR) poses a significant threat to human health, with an alarming toll on lives. In 2019 alone, an estimated 1.27 million deaths were directly linked to resistance, contributing to a staggering 4.95 million deaths worldwide [1]. This surpasses the annual mortality rates of tuberculosis (1.5 million), malaria (643,000), and HIV/AIDS (864,000). Without effective intervention, the projected scenario is bleak—global deaths attributed to AMR could soar to 10 million annually by 2050, with a striking 90% of these occurring in Africa and Asia [2].

Western sub-Saharan Africa bears the highest burden, witnessing 27.3 deaths per 100,000 (ranging from 20.9 to 35.3) directly attributable to AMR [1]. The broader association with AMR amplifies this impact, resulting in 114.8 deaths per 100,000 (ranging from 90.4 to 145.3). The gravity of the situation is further highlighted by an estimated Disability-Adjusted Life Years (DALYs) of 66,200 (ranging from 51,800 to 84,000) [1]. These statistics emphasize the urgent need for comprehensive strategies to combat AMR and mitigate its devastating impact, particularly in regions where the burden is most severe.

Phage therapy is a tractable solution to multidrug-resistant bacteria, that utilizes viruses with specific affinity for bacterial targets. With remarkable specificity, it minimizes collateral damage to commensal microbiota. Proven effective, studies in Australia achieved a 75% success rate in managing Staphylococcus and Pseudomonas infections. Its adaptability extends to complex scenarios like lung transplant patient care, highlighting its clinical efficacy. Positioned as a precise intervention, phage therapy offers promise in combating infections by multidrug-resistant bacterial pathogens [3,4].

Rationale

Amidst the pandemic's unequal drug distribution, particularly affecting Low- and Middle-Income Countries (LMICs), there is a crucial need for these nations to enhance their ability to respond locally.

Promoting phage-based solutions addresses immediate pandemic gaps and establishes a foundation for resilient strategies against global health crises and antimicrobial resistance. This approach rectifies historical neglect in Low- and Middle-Income Countries (LMICs), allowing these nations to shape responses on their terms. Considering regional factors is vital for justifying preclinical phage research. Tailoring research to local conditions, addressing biosafety concerns, and engaging with stakeholders enhance scientific rigor and applicability to diverse healthcare landscapes. This approach increases the likelihood of successful phage therapy integration, contributing to the global effort against antibiotic resistance.

The Idea

In 2020, we secured startup funds from Emergent Ventures to initiate the establishment of a laboratory dedicated to phage isolation. Successfully building the lab from the ground up and acquiring essential phage research equipment, we are currently in the process of registering it as a charity. The lab has been actively engaged in phage research and providing invaluable laboratory support to students across multiple universities in Nigeria. Our overarching goal is to evolve into an independent lab with end-to-end phage technology capabilities, serving as a pivotal hub for universities in Nigeria and fostering a comprehensive phage research network. This entails the capacity to isolate, characterize, store, and produce ready-to-use phages for clinical and animal applications.

We seek funding for:

1. Phage Bank: Addressing a major hurdle in phage research—consistent storage. Nigeria faces challenges with unreliable electrical supply, especially detrimental to -80°C freezers. Lack of solar support exacerbates this issue. Our priority is securing solar capacity to ensure a dependable phage repository within Nigeria. Inconsistent storage currently forces researchers to store phages outside the country, hindering local research. Closing this gap is crucial for fostering phage research by guaranteeing a stable electrical supply.

2. Pre-clinical and clinical trials study: At present, our focus lies in assessing the efficacy of phages for managing diabetic wounds in a mice model, with plans to advance to clinical trials in the coming year. Notably, this initiative marks the first clinical trial on phages in Africa. Our broader objective is to advance the utilization of phages and manufacture readily deployable phages for hospitals within Nigeria and beyond. Concurrently, our ongoing research involves the characterization of phages targeting Salmonella typhi, with intentions to progress to both pre-clinical and clinical trials in the near future.

Describe why you think you're qualified to work on this

My laboratory achieved a groundbreaking milestone by reporting the first phage genome from Nigeria4 marking a significant contribution to the global landscape of phage research. As a co-founder of the Africa Phage Forum, the largest collaborative network of its kind on the continent, I've played a pivotal role in fostering cooperation and knowledge exchange among phage researchers in Africa [5]. With a Ph.D. in medical microbiology and an extensive track record in phage research, including involvement in notable projects such as reporting two novel Escherichia coli lytic phages from Uganda [6] as well as the isolation of lytic phages against E. coli O157: H7 [7,8] , I bring a wealth of expertise to the table.

Currently, we have ongoing projects, including a PhD student-led initiative that involves evaluating the efficacy of phages in managing Salmonella typhi infections in a mice model. Two isolated phages have been characterized, with plans to progress to pre-clinical trials in the first quarter of the upcoming year.

Recognizing the importance of regulatory collaboration, I am actively engaged in discussions and co-publications with the AMR program coordinator at the Nigeria Centre for Disease Control. This collaborative effort aims to advance phage research in Nigeria by aligning our work with regulatory standards and ensuring a robust framework for future developments. My leadership extends beyond the laboratory, as evidenced by my keynote address at the 2022 World Antimicrobial Awareness Week. In this national platform, I had the honor of addressing the nation on the potential of phage therapy as a compelling alternative to combat drug resistance, further solidifying our dedication to bridging the gap between research and public awareness.

Other ways I can learn about you

X handle: @NnaemekaNnadi

Linkedin: https://www.linkedin.com/in/nnaemeka-emmanuel-nnadi-a39298b5/

Blog post https://phage.directory/capsid/resource-limited

https://phage.directory/capsid/ibadan-bacteriophage-research-team

How much money do you need?

We are requesting a range of 60,000 to 70,000 USD. 1. Solar system: We need a range of 7,000-10,000 USD to acquire and install a solar system for the phage bank. Ensuring sustainable energy sources to guarantee uninterrupted power supply is crucial for preserving phage viability and integrity. The use of Solar systems in the long run reduces the cost of energy making phage research more affordable and does not contribute to environmental pollution. 1. Pre-clinical phage study: The requested 20,000 USD for DNA extraction kits, nanopore flow cells, media and library kits serves as the backbone for our pre-clinical phage study. This investment not only supports cutting-edge sequencing technologies but also facilitates essential mice studies conducted in collaboration with the esteemed National Veterinary Research Institute, Vom. 2. Phage therapy ready product To enable end-to-end phage capacity, we need request the following equipment, sourced from the auction market as a strategic move to optimize costs without compromising quality a) Ultracentrifuge: 10,000 USD b) Peristaltic pump: 5,000 USD c) Transportation and logistics: 3,000 USD 3. Lab support staff and student’s support: a. My 30% FTE salary: 7,000 USD b. Master’s students’ salaries: 5,000 USD If we get extra money we would purchase an illumina sequencer. This will make sequencing cheaper

Links to any supporting documents or information

1 Murray, C. J. et al. Global burden of bacterial antimicrobial resistance in 2019: a systematic analysis. The Lancet (2022).

2 Walsh, T. R., Gales, A. C., Laxminarayan, R. & Dodd, P. C. Vol. 20 e1004264 (Public Library of Science San Francisco, CA USA, 2023).

3 Aslam, S. et al. Early clinical experience of bacteriophage therapy in 3 lung transplant recipients. American Journal of Transplantation 19, 2631-2639 (2019).

4 Ezemokwe, G. C. et al. Complete genome sequence of pseudomonas phage Zikora. Microbiology Resource Announcements 10, e00489-00421 (2021).

5 Michodigni, N. et al. The Africa Phage forum: A new collaborative network for bacteriophage Research in Africa. (2022).

6 Nale, J. Y. et al. Novel Escherichia coli-Infecting Bacteriophages Isolated from Uganda That Target Human Clinical Isolates. PHAGE 4, 141-149 (2023).

7 Ngene, A. C. et al. Bacteriophages as Bio-control agent against Food-Borne Pathogen E. coli O157: H7. IOSR Journal of Pharmacy and Biological Sciences 15, 23-36 (2020).

8 Ngene, A. C. et al. Identification of Escherichia coli O157: H7, Characterization, and Host Range Analysis of Bacteriophages Infecting Some Selected Pathogenic Bacteria from Jos, Nigeria. PHAGE (2023).

Estimate your probability of succeeding if you get the amount of money you asked for

Our vision of success is rooted in accessibility. By establishing a facility where anyone, regardless of geographic location, can initiate phage work and seamlessly navigate the journey from research to a final product, we are breaking down barriers in the field. This not only democratizes phage research but also fosters a global community of researchers and practitioners contributing to the fight against antibiotic resistance.

Success involves achieving a level of self-reliance that reduces dependence on external entities, such as those in Europe or the US. Our goal is to empower researchers and innovators within our region to independently take their phage work to fruition. This not only bolsters regional capabilities but also establishes us as a hub for phage research and development, contributing significantly to the global effort against antibiotic resistance.

Another facet of our success narrative is the establishment of a robust phage repository. There are currently 13 reported phage biobanks across the world with none in Africa. With constant electricity ensuring long-term storage capabilities, we become a reliable custodian for phages. This repository serves as a valuable resource for researchers, offering a secure and accessible storage solution. It also fosters collaboration by providing a shared space for the global scientific community to deposit and access phages, fostering an open-source approach to research.

I'd estimate a high probability of success— around 85% given the goal of increasing capacity for research globally based on expertise, previous successes, and the existence of collaborations. I would also give the probability 40% when success is defined in terms of an output of the lab that would result in a significant contribution to the field such as having a large stock of phages in the biorepository that can be sourced by laboratories or hospitals across the globe.

By achieving success on these fronts, we aren't just advancing phage research locally; we are contributing to a global paradigm shift. The establishment of a self-sufficient facility with comprehensive capabilities not only benefits our immediate community but also elevates the collective effort against antibiotic resistance on a worldwide scale.