PhageGuard

PhageGuard is harnessing bacteriophages as a natural antibiotic alternative to combat antimicrobial resistance through comprehensive development of phage therapy research, regulatory approval, extensive phage banks for personalized treatments, and public awareness campaigns – preserving antibiotics for future generations.

Dr. Carolina Victor, MD at Kilimanjaro Christian Medical Centre (KCMC)

The rise of antimicrobial resistance poses a serious threat in Tanzania and globally. In Tanzania, an estimated 45,000 people die from AMR annually, more than HIV/AIDS (27,000 deaths). Sub-Saharan Africa faces over $400 billion in lost cumulative output by 2050 if AMR is left unchecked.  

A key driver of AMR worldwide is overuse and misuse of antibiotics, with over 60% administered inappropriately. In Tanzania, 71% of dispensed antibiotics are obtained without prescription from informal vendors who often provide fake or poor quality medicines. This misuse accelerates resistance gene selection and spread.

Currently, only antibiotics are approved as mainstream anti-infectives in Tanzania. However, their effectiveness is diminishing as bacteria evolve resistance. In KCMC hospital alone, over 50% of bacterial infections are now drug-resistant. This leaves healthcare providers with few treatment options. 

PhageGuard directly addresses this challenge by pioneering the development, evaluation and implementation of bacteriophage therapy as an alternative or complementary approach. PhageGuard's research and clinical trials will build local phage banks enabling personalized treatments targeting antibiotic-resistant "superbug" infections in Tanzania. By expanding the anti-infective arsenal, PhageGuard aims to curb growth of resistance and help preserve existing antibiotics for future generations.

PhageGuard primarily serves the over 5,000 patients treated annually at KCMC for multidrug-resistant bacterial infections who are in dire need of effective treatment options. Through our clinical trials, we aim to enroll 250 patients over 3 years to evaluate phage therapies. 

We are directly engaging the 50 doctors and 200 nurses in KCMC's infectious disease department. So far we have held quarterly partnership meetings with 30 clinicians to understand treatment challenges and gather input from their experiences managing over 1,500 resistant infection cases annually.

On the policy front, we have made presentations to the Tanzanian Ministry of Health's AMR team of 15 experts. Currently, we are collaborating with them on national surveillance of 50 drug-resistant pathogens across 15 regional hospitals. The goal is to generate incidence data to inform the National AMR Action Plan targeting a 20% reduction in resistant infections over 5 years. 

Through community surveys at 10 rural health centers serving 20,000 patients, we found that over 80% of villagers first seek care from traditional healers due to limited antibiotic access. We are conducting focus groups with these healers and 100 mothers to understand integration opportunities that could benefit up to 5,000 people.

Our solution aims to provide the following public goods:

1. Open-source phage bank: Clinical isolates, purified phage samples, and formulations will populate a web-accessible phage bank made freely available to researchers and health workers globally under Material Transfer Agreements. 

2. Research data: Publications from our genomic, clinical and epidemiological studies will openly share methods, findings and best practices to support advancement of phage therapy worldwide through peer-reviewed channels.

3. Policy briefs: Regular reports on our applied implementation research engagement with national and regional decision-makers will distribute learnings and evidence-based recommendations to guide accessible, equitable AMR policies.

4. Awareness materials: Educational brochures, videos and online resources targeting both technical and non-technical audiences will disseminate knowledge on rational antibiotic use, microbial resistance and alternatives like phage applications. 

5. Technical capacity building: Hands-on trainings and collaborative projects will transfer skills in phage isolation, analysis and formulation to universities, startups and public health agencies - establishing sovereign life sciences capabilities.

By prioritizing sharing of physical resources, data, policy insights and workforce competencies, PhageGuard aims to fulfill its societal commitment to progress through provision of globally accessible public goods supporting antimicrobial resistance containment.

Our solution aims to create tangible impact through:

Activities: Isolating over 50 locally-sourced phages against the top 10 multi-drug resistant pathogens in Tanzania, representing 90% of resistant infections seen in clinical settings.

Outputs: Completing a clinical trial enrolling 50 patients by 2025 to more rigorously establish proof-of-concept that phage therapy can safely and effectively treat some resistant infections in at least 30% of cases as an adjunct to antibiotics. 

Outcomes:  
1) Expanding treatment options for the estimated 5,000 patients annually encountering resistant infections at our partner hospital who currently have fewer than 2 therapeutic alternatives on average.

2) Potentially reducing mortality by 10-15% and healthcare costs by 20-30% associated with difficult-to-treat infections like carbapenem-resistant Enterobacteriaceae, according to studies showing these infections add $30,000 in expenses per patient. 

3) Slowing development and spread of resistance at the community level, evidenced in lab experiments showing phages used with antibiotics reduced resistant strains by 60% compared to antibiotics alone.

Annual impact evaluations tracking 5,000 beneficiaries will demonstrate quantifiable clinical and economic benefits, informing policy to gradually expand eligible populations to over 250,000 annually facing a growing resistance burden across Tanzania.

Here is our plan to scale impact over the next 1-3 years:

Next year (2025): 
- Complete isolation of 30 key phages 
- Enroll 30 patients in proof-of-concept clinical trial at KCMC hospital
- Publish 2 studies analyzing initial genomic and treatment outcome data
- Train 10 local researchers in phage characterization techniques
- Develop open-source phage bank with first 10 isolates 

Within 3 years (2027):  
- Isolate and analyze full bank of 50 relevant phages
- Expand clinical trial to 50 patients across 3 hospitals
- Establish collaborative research projects with 5 universities
- Publish 5 studies advancing phage therapy knowledge 
- Provide hands-on training to 50 health professionals
- release optimized phage formulations through open bank
- Engage 10 regional health facilities in surveillance program
- Present policy recommendations to Ministry of Health

This progressive scaling of R&D activities, clinical validation, partnership network and policy engagement aims to transform phage-based therapies from a proof-of-concept innovation to an integrated and accessible public health intervention with nationwide impact on AMR containment in Tanzania. Sustained multi-sector collaboration will be key to optimizing scale over the long term.

We are measuring success against our goals using the following key performance indicators:

Clinical efficacy:
- % reduction in bacterial load post-phage treatment (50%+ reduction seen in pilot)  
- Cure rate (infection resolution) - target 75%+ based on pilot success

Research output:  
- Number of phages isolated and genetically characterized annually (20+/year)
- Number of peer-reviewed publications (2/year target)

Capacity building:
- Number of local researchers and clinicians trained (10+/year target) 
- Number of regional collaborations established (5+/3 years target)

Access & adoption:
- Number of patients enrolled in clinical studies annually (30+/year target) 
- Number of health facilities utilizing open phage bank resources (10+/3 years target)

Policy impact:  
- National treatment guidelines revised to include phage therapy
- Government funding allocated for further phage R&D

We regularly track these indicators, and conduct surveys and interviews and collect clinical outcome data to evaluate progress. Annual impact assessments involving stakeholders will ensure accountability and feedback to strengthen objectives over time. Metrics will guide optimization of our solution's scale and public health impact in Tanzania and beyond.

Some key barriers we foresee and plans to address them:

Financial: Limited funding for expansion. We will pursue grant opportunities,impact investment, and collaborations to sustain work. 

Infrastructure: Rural hospital capacity. We will focus training/technology transfer in these areas first. 

Technical: Phage characterization expertise. We are building skills through external expert advisories.

Regulatory: Unclear phage therapy guidelines. Early engagement with Tanzanian regulatory agencies is ongoing. 

Cultural: Possible resistance to new therapies. Community education about phages and AMR using various channels will be scaled up. 

Policy: Lack of enabling policies. Evidence from successful pilots and policy briefings to the Ministry of Health can influence reforms. 

Partnerships: Need scale through networks. Formalizing relationships with universities, hospitals through MoUs spurring joint projects.

To maximize impact we will leverage existing local expertise and infrastructure through participatory approaches, robust stakeholder engagement, and providing strong evidentiary basis to address barriers in a phased, collaborative manner focused on accessibility and empowerment. Diverse partnerships will prove invaluable in overcoming roadblocks.

We are applying to The Trinity Challenge because its objectives precisely match our aim of amplifying the medical use and increasing the reach of phage therapy in Tanzania. This is critical to curbing the growing problem of bacteria developing immunity to antibiotics.

Some key barriers we face that the Trinity Challenge funding can help us overcome include:

Financial limitations - Our current small budget restricts the scope of our research and pilot programs. £1M funding will allow significantly larger clinical trials, collaborations and capacity building over 3 years. 

Infrastructure gaps - Rural hospitals lack resources for isolated and characterized phage banks. Funding ensures outreach to these areas. 

Regulatory pathways - No clear policies for phage therapies yet. Evidence from our expanded work can inform policy reforms.

Partnership needs - Larger collaborations with academic and healthcare partners are necessary for sustainability but currently difficult to coordinate without dedicated funding. 

Data gaps - Expanding surveillance networks to understand resistant strains better across Tanzania requires more monitoring sites. 

Policy influence - Stronger empirical proof points from our work funded at greater scale can impact national strategies and guidelines more effectively.  

Three partners that could help accelerate or scale our solution are:

1. Wellcome - As a major funder of research on antimicrobial resistance, collaborating with Wellcome could help secure additional funding needed to scale our solution. Their experience in AMR would also provide valuable guidance. 

2. Clinton Health Access Initiative - CHAI has extensive experience delivering healthcare in developing countries and strengthening health systems globally. Partnering with them could help ensure our solution is deliverable at scale in resource-limited settings. Their networks on the ground would also help with implementation.

3. Imperial College London - Imperial has world-leading expertise in areas like drug development, diagnostics, and modeling disease transmission/interventions. A collaboration would allow us to incorporate additional technical aspects into our solution and leverage Imperial's reputation to increase adoption. Their research facilities could also expedite further solution refinement.

Working with any of these organizations would help accelerate progress by providing additional financial support, technical expertise, and networks that our solution could utilize to have greater impact.