Integrated Surveillance and Vaccine Development to Combat Community-Acquired Klebsiella Pneumoniae Infections

Klebsiella pneumoniae (Kp) is a commensal bacterium commonly found in the human gut, nasopharynx and skins. However, it can also cause severe infections, particularly among those with comorbidities and immunocompromised conditions. The global health threat posed by Kp is recognized by the World Health Organization and international health agencies due to its escalating and challenging-to-control nature. In Vietnam and Southeast Asia, there has been a concerning rise in severe Kp infections, especially among the elderly. Two major pathotypes of Kp exist: classical Kp (cKp) and hypervirulent Kp (hvKp). cKp is known for its high antimicrobial resistance (AMR) and is a frequent cause of hospital-acquired infections among immunocompromised individuals. In contrast, hvKp is characterized by numerous virulence factors and its ability to cause severe invasive community-acquired infections, even in healthy individuals. Both pathotypes have been identified in Vietnam, posing a significant threat for the emergence of strains exhibiting both AMR and hypervirulence. While hospital-acquired Kp infections have received significant attention, leading to ongoing improvements in infection control and antimicrobial stewardship programs in Vietnam, the emergence of Kp, especially hvKp, in communities is less understood. Research into community-acquired Kp infections faces two main interlinked challenges. Firstly, the current hospital surveillance system is isolate-based and cannot effectively distinguish community-acquired infections, resulting in a poor understanding of at-risk populations, disease sources, and drivers of transmission within communities. Secondly, research capacity to develop effective preventive measures such as vaccines is limited, partly due to gaps in understanding disease and pathogen characteristics. In this proposal, we aim to integrate patient-oriented surveillance and vaccine development to combat community-acquired Kp infections in Vietnam. We will define the epidemiological and clinical features of community-acquired Kp infections, and quantify the transmission rates of Kp in the community. To achieve this, we will conduct a one-year patient-focused hospital study in three national and provincial hospitals in Ho Chi Minh City (HCMC) and Ha Noi. This study will identify all cases of community-acquired Kp infections and characterize their incidence, AMR and genotypic profiles, clinical features and outcomes. Furthermore, we will collaborate with HCM Center for Disease Control to enroll households of the hospitalized cases and independent community households in HCMC to quantify transmission rates of Kp (both cKp and hvKp) in the community. Additionally, metadata and gut microbiota characterization from patients and household members will help identify potential risk factors for Kp colonization and infection. These findings will be shared with local stakeholders and policy makers, facilitating the development of local treatment guidelines and targeted public health interventions. We will also assess the human immune responses to Kp antigens among patients with bloodstream infections and their correlation with treatment outcomes. By collaborating with University of Science in HCMC, we will measure antibody and T cell responses to candidate proteins among patients with bloodstream infections from the hospital study and healthy individuals, and correlate these data with disease outcomes (survival, severity score, length of hospital stays). This investigation will identify robust candidates associated with enhanced survival for further development of vaccines and monoclonal antibodies. Through this collaborative and strategic project, we will enhance research capacity in Vietnam to address public health challenges posed by Kp and other emerging pathogens. The project findings will contribute to global efforts in understanding community transmission dynamics of Kp and advance the development of targeted therapeutics and vaccines.