The SARS-CoV-2 pandemic underscores the alarming frequency of novel pathogen emergence in an era of global change [1], yet our ability to model the factors and interactions influencing the transmission of emerging pathogens remains limited [2]. Ecological and evolutionary theory can be used to identify gaps or biases in current data streams, and pinpoint features of host-pathogen biology most likely to be associated with emergence [2].
I applied a comparative approach to known features of coronavirus ecology and evolution to identify characteristics that lead some viruses to become pandemic while their relatives do not. Similarities and differences between MERS, which has repeatedly spilled over into human populations from a camel reservoir without extensive onward spread, and other coronaviruses point to a number of concrete directions for further research. These include a multi-host species atlas of host cell receptor distribution across the respiratory tract, as this shapes the transmission and virulence of viruses using such receptors [3]. Given the evidence for multiple coronavirus spillover events per decade preceding SARS-CoV-2, I also asked why there were only four (and now five) circulating coronaviruses, arguing that interactions between endemic and emergent pathogens via cross-reactive immunity might play a critical role [4].
Once transmission of an emergent pathogen is underway, accounting for geographic heterogeneities in the immune landscapes of populations and the surveillance data available are major challenges to inferring transmission patterns [1,2,5]. This has been a major focus of my work in the wake of the 2020 SARS-CoV-2 outbreak, where I led efforts to coordinate an interdisciplinary team across governmental and research institutions in Madagascar and other countries in Africa. First, we described variation in pathogen emergence risk, surveillance, and response capacity across 40+ sub-Saharan African countries [5]. Second, to explore the surveillance tools most effective at detecting the burden of pathogen emergence in settings where testing rates were low, we coordinated digitization of death records in Antananarivo, Madagascar to determine the excess mortality signal observable from such data. We used the 2018-2019 measles epidemic in the city as a test case, contributing to efforts to minimize reliance on traditional surveillance methods that are inequitably distributed [6]. We then characterized the association between existing human mobility metrics, including big data sources such as mobile phone data, and models of spatial patterns in infection in early phases of an epidemic [7] to identify gaps in surveillance informative for future disease control action. We integrated the output of these diverse lines of investigation to model the distribution of vaccination against an emergent pathogen in contexts where doses are limited (as was evidenced in SARS-CoV-2 vaccine rollout in low-income countries) [8].
These foundations open the way to developing a comparative research program on pathogen emergence, comparing pathogen lineages across host species and comparing transmission patterns across geographic contexts with varying host immune landscapes. Analysis is underway on patterns of immunity among endemic and emergent coronaviruses in Abidjan, Cote d’Ivoire . Future efforts will focus on settings that are currently understudied, in particular growing urban areas in the African region. I will leverage my expertise on eco-immunological drivers of pathogen transmission to probe the role cross-reactive immunity plays in enabling or preventing pathogen emergence for coronaviruses and other pathogen taxa with co-circulation of emergent and endemic lineages.
References
1. Baker RE, Mahmud AS, Miller IF, Rajeev M, Rasambainarivo F, Rice BL, et al. Infectious disease in an era of global change. Nature Reviews Microbiology. 2022;20: 193–205.
2. Glennon EE, Bruijning M, Lessler J, Miller IF, Rice BL, Thompson RN, et al. Challenges in modeling the emergence of novel pathogens. Epidemics. 2021;37: 100516.
3. Rice BL, Lessler J, McKee C, Metcalf CJE. Why do some coronaviruses become pandemic threats when others do not? PLoS Biology. 2022;20: e3001652.
4. Rice BL, Douek DC, McDermott AB, Grenfell BT, Metcalf CJE. Why are there so few (or so many) circulating coronaviruses? Trends Immunology. 2021;42: 751–763.
5. Rice BL, Annapragada A, Baker RE, Bruijning M, Dotse-Gborgbortsi W, Mensah K, et al. Variation in SARS-CoV-2 outbreaks across sub-Saharan Africa. Nature Medicine. 2021. doi:10.1038/s41591-021-01234-8
6. Rasambainarivo F, Rasoanomenjanahary A, Rabarison JH, Ramiadantsoa T, Ratovoson R, Randremanana R, Randrianarisoa S, Rajeev M, Masquelier B, Heraud JM, Metcalf CJE, Rice BL. Monitoring for outbreak-associated excess mortality in an African city: Detection limits in Antananarivo, Madagascar. International Journal of Infectious Diseases. 2020;103: 338–342.
7. Ramiadantsoa T, Metcalf CJE, Raherinandrasana AH, Randrianarisoa S, Rice BL, et al. Existing human mobility data sources poorly predicted the spatial spread of SARS-CoV-2 in Madagascar. Epidemics. 2022;38: 100534.
8. Rasambainarivo F, Ramiadantsoa T, Raherinandrasana A, Randrianarisoa S, Rice BL, Evans MV, et al. Prioritizing COVID-19 vaccination efforts and dose allocation within Madagascar. BMC Public Health. 2022;22: 724.
I applied a comparative approach to known features of coronavirus ecology and evolution to identify characteristics that lead some viruses to become pandemic while their relatives do not. Similarities and differences between MERS, which has repeatedly spilled over into human populations from a camel reservoir without extensive onward spread, and other coronaviruses point to a number of concrete directions for further research. These include a multi-host species atlas of host cell receptor distribution across the respiratory tract, as this shapes the transmission and virulence of viruses using such receptors [3]. Given the evidence for multiple coronavirus spillover events per decade preceding SARS-CoV-2, I also asked why there were only four (and now five) circulating coronaviruses, arguing that interactions between endemic and emergent pathogens via cross-reactive immunity might play a critical role [4].
Once transmission of an emergent pathogen is underway, accounting for geographic heterogeneities in the immune landscapes of populations and the surveillance data available are major challenges to inferring transmission patterns [1,2,5]. This has been a major focus of my work in the wake of the 2020 SARS-CoV-2 outbreak, where I led efforts to coordinate an interdisciplinary team across governmental and research institutions in Madagascar and other countries in Africa. First, we described variation in pathogen emergence risk, surveillance, and response capacity across 40+ sub-Saharan African countries [5]. Second, to explore the surveillance tools most effective at detecting the burden of pathogen emergence in settings where testing rates were low, we coordinated digitization of death records in Antananarivo, Madagascar to determine the excess mortality signal observable from such data. We used the 2018-2019 measles epidemic in the city as a test case, contributing to efforts to minimize reliance on traditional surveillance methods that are inequitably distributed [6]. We then characterized the association between existing human mobility metrics, including big data sources such as mobile phone data, and models of spatial patterns in infection in early phases of an epidemic [7] to identify gaps in surveillance informative for future disease control action. We integrated the output of these diverse lines of investigation to model the distribution of vaccination against an emergent pathogen in contexts where doses are limited (as was evidenced in SARS-CoV-2 vaccine rollout in low-income countries) [8].
These foundations open the way to developing a comparative research program on pathogen emergence, comparing pathogen lineages across host species and comparing transmission patterns across geographic contexts with varying host immune landscapes. Analysis is underway on patterns of immunity among endemic and emergent coronaviruses in Abidjan, Cote d’Ivoire . Future efforts will focus on settings that are currently understudied, in particular growing urban areas in the African region. I will leverage my expertise on eco-immunological drivers of pathogen transmission to probe the role cross-reactive immunity plays in enabling or preventing pathogen emergence for coronaviruses and other pathogen taxa with co-circulation of emergent and endemic lineages.
References
1. Baker RE, Mahmud AS, Miller IF, Rajeev M, Rasambainarivo F, Rice BL, et al. Infectious disease in an era of global change. Nature Reviews Microbiology. 2022;20: 193–205.
2. Glennon EE, Bruijning M, Lessler J, Miller IF, Rice BL, Thompson RN, et al. Challenges in modeling the emergence of novel pathogens. Epidemics. 2021;37: 100516.
3. Rice BL, Lessler J, McKee C, Metcalf CJE. Why do some coronaviruses become pandemic threats when others do not? PLoS Biology. 2022;20: e3001652.
4. Rice BL, Douek DC, McDermott AB, Grenfell BT, Metcalf CJE. Why are there so few (or so many) circulating coronaviruses? Trends Immunology. 2021;42: 751–763.
5. Rice BL, Annapragada A, Baker RE, Bruijning M, Dotse-Gborgbortsi W, Mensah K, et al. Variation in SARS-CoV-2 outbreaks across sub-Saharan Africa. Nature Medicine. 2021. doi:10.1038/s41591-021-01234-8
6. Rasambainarivo F, Rasoanomenjanahary A, Rabarison JH, Ramiadantsoa T, Ratovoson R, Randremanana R, Randrianarisoa S, Rajeev M, Masquelier B, Heraud JM, Metcalf CJE, Rice BL. Monitoring for outbreak-associated excess mortality in an African city: Detection limits in Antananarivo, Madagascar. International Journal of Infectious Diseases. 2020;103: 338–342.
7. Ramiadantsoa T, Metcalf CJE, Raherinandrasana AH, Randrianarisoa S, Rice BL, et al. Existing human mobility data sources poorly predicted the spatial spread of SARS-CoV-2 in Madagascar. Epidemics. 2022;38: 100534.
8. Rasambainarivo F, Ramiadantsoa T, Raherinandrasana A, Randrianarisoa S, Rice BL, Evans MV, et al. Prioritizing COVID-19 vaccination efforts and dose allocation within Madagascar. BMC Public Health. 2022;22: 724.
