Emerging and reemerging infectious diseases: global trends and new strategies for their prevention and control

Abstract

To adequately prepare for potential hazards caused by emerging and reemerging infectious diseases, the WHO has issued a list of high-priority pathogens that are likely to cause future outbreaks and for which research and development (R&D) efforts are dedicated, known as paramount R&D blueprints. Within R&D efforts, the goal is to obtain effective prophylactic and therapeutic approaches, which depends on a comprehensive knowledge of the etiology, epidemiology, and pathogenesis of these diseases. In this process, the accessibility of animal models is a priority bottleneck because it plays a key role in bridging the gap between in-depth understanding and control efforts for infectious diseases. Here, we reviewed preclinical animal models for high priority disease in terms of their ability to simulate human infections, including both natural susceptibility models, artificially engineered models, and surrogate models. In addition, we have thoroughly reviewed the current landscape of vaccines, antibodies, and small molecule drugs, particularly hopeful candidates in the advanced stages of these infectious diseases. More importantly, focusing on global trends and novel technologies, several aspects of the prevention and control of infectious disease were discussed in detail, including but not limited to gaps in currently available animal models and medical responses, better immune correlates of protection established in animal models and humans, further understanding of disease mechanisms, and the role of artificial intelligence in guiding or supplementing the development of animal models, vaccines, and drugs. Overall, this review described pioneering approaches and sophisticated techniques involved in the study of the epidemiology, pathogenesis, prevention, and clinical theatment of WHO high-priority pathogens and proposed potential directions. Technological advances in these aspects would consolidate the line of defense, thus ensuring a timely response to WHO high priority pathogens.

Fig. 1

Transmission routes of high-priority pathogens to humans. a The source of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has not been identified. Bats and pangolins are presumed to be natural hosts, while transmission to humans may be mediated by intermediate hosts and cold chains. Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) originate from bats and are transmitted to humans by Paguma larvata and Camelus dromedarius, respectively. b Filoviruses originate from bats and are transmitted to humans, such as nonhuman primates, by wildlife. c Rift Valley fever virus (RVFV) originates from Aedes mosquitoes and is transmitted to humans by ruminants. Crimean Congo hemorrhagic fever virus (CCHFV) originates from Hyaloma asiaticum and is transmitted to humans by ruminants and domestic animals. d Lassa fever virus (LASV) originates from Mastomys natalensis and is transmitted to humans by corresponding contaminants. Zika virus (ZIKV) is transmitted to humans via the bite of Ades mosquitoes. Nipah virus (NiV) originates from bats and is transmitted to humans via pigs. (Created in BioRender)

Fig. 2

Choice of animal model. Animal models for filoviruses are taken as examples, and the susceptibility, cost, accessibility, and feasibility of nonhuman primates (NHPs), ferrets, guinea pigs, hamsters, and mice are presented. (Created in BioRender)

Fig. 3

The determination of immune correlates in animal models and immune correlates in COVID-19 patients are taken as examples. a In animal models and coronavirus disease 2019 (COVID-19) patients, a positive correlation between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was confirmed. b, c In COVID-19 convalescent animals, passive transfer of serum IgG protects naïve animals in a dose-dependent manner, while CD8⁺ T-cell depletion abolishes this protective effect to some extent. d SARS-CoV-2 rechallenge in convalescent animals increased neutralizing antibody (NAb), virus-specific binding antibody and IFN-γ responses. e In large-scale human clinical trials, a negative correlation between NAb titers and viral loads was noted. Taken together, these findings suggest that NAbs and virus-specific IgG are responsible for improved protection against COVID-19, while cellular immunity partially contributes to this protection. (Created in BioRender)

Fig. 4

Validation of potential vaccine-associated adverse effects (VADEs) and antibody-dependent enhancement (ADE) in animal models. a Antibodies at subconcentrations facilitate virus entry through Fc-FcR recognition. b Fcγ receptor blockade reduced virus entry and endocytosis. c Deposition of the complement cascade (C1q) facilitates virus entry and endocytosis. (Created in BioRender)