Climate change and infectious disease: A prologue on multidisciplinary cooperation and predictive analytics

Climate change impacts global ecosystems at the interface of infectious disease agents and hosts and vectors for animals, humans, and plants. The climate is changing, and the impacts are complex, with multifaceted effects. In addition to connecting climate change and infectious diseases, we aim to draw attention to the challenges of working across multiple disciplines. Doing this requires concentrated efforts in a variety of areas to advance the technological state of the art and at the same time implement ideas and explain to the everyday citizen what is happening. The world's experience with COVID-19 has revealed many gaps in our past approaches to anticipating emerging infectious diseases. Most approaches to predicting outbreaks and identifying emerging microbes of major consequence have been with those causing high morbidity and mortality in humans and animals. These lagging indicators offer limited ability to prevent disease spillover and amplifications in new hosts. Leading indicators and novel approaches are more valuable and now feasible, with multidisciplinary approaches also within our grasp to provide links to disease predictions through holistic monitoring of micro and macro ecological changes. In this commentary, we describe niches for climate change and infectious diseases as well as overarching themes for the important role of collaborative team science, predictive analytics, and biosecurity. With a multidisciplinary cooperative “all call,” we can enhance our ability to engage and resolve current and emerging problems

Building Scientific Capability and Reducing Biological Threats: The Effect of Three Cooperative Bio-Research Programs in Kazakhstan.

Cooperative research programs aimed at reducing biological threats have increased scientific capabilities and capacities in Kazakhstan. The German Federal Foreign Office's German Biosecurity Programme, the United Kingdom's International Biological Security Programme and the United States Defense Threat Reduction Agency's Biological Threat Reduction Program provide funding for partner countries, like Kazakhstan. The mutual goals of the programs are to reduce biological threats and enhance global health security. Our investigation examined these cooperative research programs, summarizing major impacts they have made, as well as common successes and challenges. By mapping various projects across the three programs, research networks are highlighted which demonstrate best communication practices to share results and reinforce conclusions. Our team performed a survey to collect results from Kazakhstani partner scientists on their experiences that help gain insights into enhancing day-to-day approaches to conducting cooperative scientific research. This analysis will serve as a basis for a capability maturity model as used in industry, and in addition builds synergy for future collaborations that will be essential for quality and sustainment

Global health security threats and related risks in Latin America

The costs of responding and mitigating the COVID-19 pandemic is a critical example of the need for continual investment for global health security (GHS) preparedness in today’s inter-connected world as exemplified earlier with Ebola, Zika, and H1N1. Microbial diversity including endemic and emerging infectious diseases unique to Latin America are well known. When combined with geopolitical, socioeconomic, and environmental factors, especially climate change and human migration, which are expanding the range of disease vectors and pathogens, the risk for infectious disease outbreaks greatly increases. Enhancing GHS requires a greater awareness and cooperation within the region as well as more effective infectious disease surveillance systems. Frameworks such as the International Health Regulations and Global Health Security Agenda underpin policies to strengthen health systems. Greater international cooperation aimed to effectively enhance infectious disease surveillance are pivotal to increasing trust among partner countries and strengthen health security systems and best practices to respond and mitigate infectious disease outbreaks. Here we discuss infectious disease threats and risks associated with the current socioeconomic and political climate that influence GHS in order to demonstrate the need for further investment

A Case History in Cooperative Biological Research: Compendium of Studies and Program Analyses in Kazakhstan

Kazakhstan and the United States have partnered since 2003 to counter the proliferation of weapons of mass destruction. The US Department of Defense (US DoD) has funded threat reduction programs to eliminate biological weapons, secure material in repositories that could be targeted for theft, and enhance surveillance systems to monitor infectious disease outbreaks that would affect national security. The cooperative biological research (CBR) program of the US DoD’s Biological Threat Reduction Program has provided financing, mentorship, infrastructure, and biologic research support to Kazakhstani scientists and research institutes since 2005. The objective of this paper is to provide a historical perspective for the CBR involvement in Kazakhstan, including project chronology, successes and challenges to allow lessons learned to be applied to future CBR endeavors. A project compendium from open source data and interviews with partner country Kazakhstani participants, project collaborators, and stakeholders was developed utilizing studies from 2004 to the present. An earlier project map was used as a basis to determine project linkages and continuations during the evolution of the CBR program. It was determined that consistent and effective networking increases the chances to collaborate especially for competitive funding opportunities. Overall, the CBR program has increased scientific capabilities in Kazakhstan while reducing their risk of biological threats. However, there is still need for increased scientific transparency and an overall strategy to develop a capability-based model to better enhance and sustain future research. Finally, we offer a living perspective that can be applied to further link related studies especially those related to One Health and zoonoses and the assessment of similar capability-building programs

Data-driven epidemiologic approach to conducting site feasibility for a global phase III tuberculosis vaccine clinical trial.

An efficacious tuberculosis (TB) vaccine is critical to reducing the global burden of TB. TB vaccine trials require the identification of multiple sites globally that have both a high incidence of TB and the capacity to conduct a clinical trial. To expand the diversity of potential phase III TB vaccine trial sites to be considered for inclusion, we describe a novel epidemiologic method that incorporates approaches from a variety of public health practices. Our approach incorporates analytic methodology to enable quantification and validation of qualitative information from disparate data sources, and epidemiologic analysis to systematically assess site-specific TB epidemiology. The integration of robust data-driven practices, and more quantitatively focused analysis, allowed for the objective evaluation of sites, which resulted in the identification of sites and catchment areas with high TB burden that may not have been previously considered. This suggests that an integrated epidemiologic methodology, not traditionally utilized for clinical trial site evaluations, could be integrated into site feasibility assessments as it results in more rapid site identification and reduces unintended bias

Phase 1/2a Trial of Plasmodium vivax Malaria Vaccine Candidate VMP001/AS01B in Malaria-Naive Adults: Safety, Immunogenicity, and Efficacy.

A vaccine to prevent infection and disease caused by Plasmodium vivax is needed both to reduce the morbidity caused by this parasite and as a key component in efforts to eradicate malaria worldwide. Vivax malaria protein 1 (VMP001), a novel chimeric protein that incorporates the amino- and carboxy- terminal regions of the circumsporozoite protein (CSP) and a truncated repeat region that contains repeat sequences from both the VK210 (type 1) and the VK247 (type 2) parasites, was developed as a vaccine candidate for global use.We conducted a first-in-human Phase 1 dose escalation vaccine study with controlled human malaria infection (CHMI) of VMP001 formulated in the GSK Adjuvant System AS01B. A total of 30 volunteers divided into 3 groups (10 per group) were given 3 intramuscular injections of 15 μg, 30 μg, or 60 μg respectively of VMP001, all formulated in 500 μL of AS01B at each immunization. All vaccinated volunteers participated in a P. vivax CHMI 14 days following the third immunization. Six non-vaccinated subjects served as infectivity controls.The vaccine was shown to be well tolerated and immunogenic. All volunteers generated robust humoral and cellular immune responses to the vaccine antigen. Vaccination did not induce sterile protection; however, a small but significant delay in time to parasitemia was seen in 59% of vaccinated subjects compared to the control group. An association was identified between levels of anti-type 1 repeat antibodies and prepatent period.This trial was the first to assess the efficacy of a P. vivax CSP vaccine candidate by CHMI. The association of type 1 repeat-specific antibody responses with delay in the prepatency period suggests that augmenting the immune responses to this domain may improve strain-specific vaccine efficacy. The availability of a P. vivax CHMI model will accelerate the process of P. vivax vaccine development, allowing better selection of candidate vaccines for advancement to field trials

All volunteers immunized with VMP001/AS01_B generated antibodies to VMP001.

<p>Anti-VMP001 antibodies were detected in 80% of vaccinated individuals starting at two weeks post-1^st immunization. Titers were boosted to peak levels post-2^nd immunization, with 100% of subjects developing antibodies. A decrease in antibody titers was observed on the day of third immunization (8, 6 and 4 weeks post 2^nd immunization for cohorts 1, 2 and 3, respectively) followed by a slight increase post 3^rd immunization. Antibody titers, defined as a serum dilution that gives an OD₄₁₄ of 1.0, showed a continual decline post challenge (Po Ch). Box plot represents the 25–75 percentiles and Whiskers indicate the minimum and maximum values. GMTs of anti-VMP001 antibody were significantly higher in group 1 compared to group 2 at 2 time points (2weeks post 2nd, p = 0.01, and on the day of 3rd, vaccination, p = 0.002). GMTs of anti-VMP001 antibody were significantly higher in group 2 compared to group 3 at 2 time points (4weeks post DOC, p = 0.03, and 6 months post-DOC, P = 0.04). GMTs of anti-VMP001 antibody were significantly higher in group 1 compared to group 3 at 5 time points (2 weeks post 1st vaccination, p = 0.02, on the day of 2nd vaccination, p = 0.01, 2 weeks post 2nd vaccination, p = 0.04, on the day of 3rd vaccination p = 0.002, and 6 months post DOC, p = 0.034).</p