The History and Future of the “Neglected Tropical Diseases” – Integrating Qualitative and Quantitative Research to Improve Public Health Outcomes

"Antimicrobial resistance is a serious public health problem causing millions of infections and thousands of deaths in children and adults annually. An increasing number of infections are due to multidrug-resistant organisms (MDRO) resistant to most or even all antibiotics. MDRO cause serious and life-threatening infections among high-risk children and adults including those with chronic lung diseases such as cystic fibrosis, immunocompromise, and stem cell or organ transplant. However, there are few new antibiotics in development, and the rapid evolutionary capacity of bacteria facilitates the emergence of resistance. An emerging approach is bacteriophage or phage therapy. Phage are naturally occurring viruses that infect and kill specific bacterial species, and in some cases, specific strains. Several recent reports describe cases of successful phage therapy against MDRO infections, including by Graham Hatfull in collaboration with UK physicians to treat a lung transplant recipient with severe mycobacterial infection. However, the field is nascent, much remains undiscovered, and more basic and clinical research are needed to discover the potential of phage therapy. We propose to form a multi-disciplinary team to develop a complete phage discovery-to-patient entity, the Pittsburgh Phage Project (P3). This team is designed to leverage scholarly excellence in phage biology, infectious diseases, viral immunity, epidemiology, ethics, and clinical trials to form a new multi-disciplinary collaboration. We will conduct phage discovery from environmental sources and human subjects, determine phage biology and immunogenicity, identify panels of phage for specific MDRO, establish an ethical framework, and conduct clinical trials. The long-term goal will be to develop phage therapy candidates for major MDRO. Hospitals affiliated with the University of Pittsburgh provide advanced tertiary care for high-risk patients with complex conditions; thus, the P3 program is highly relevant. The Pitt environment provides a unique opportunity to leverage our strengths to create a world-class program in phage therapy."