Available online at www.sciencedirect.com ScienceDirect Influence of herd immunity in the cyclical nature of arboviruses 1,2 3 4 Guilherme S Ribeiro , Gabriel L Hamer , Mawlouth Diallo , 5 6 7 Uriel Kitron , Albert I Ko and Scott C Weaver We review and contrast the evidence for an effect of amplifying Introduction to arboviruses and their host herd immunity on circulation and human exposure to transmission arboviruses. Herd immunity of short-lived West Nile virus avian Arthropod-borne viruses (arboviruses) are transmitted amplifying hosts appears to play a limited role in levels of biologically, involving replication in arthropod vectors enzootic circulation and spillover infections of humans, which and vertebrate amplifying hosts [1]. The development are not amplifiers. In contrast, herd immunity of nonhuman of adaptive immunity, if it prevents secondary infection primate hosts for enzootic Zika, dengue, and chikungunya and viremia, removes hosts from the pool of susceptible viruses is much stronger and appears to regulate to a large amplifiers. Herd immunity can therefore have major extent the periodicity of sylvatic amplification in Africa. impacts on arbovirus circulation and disease, and Following the recent Zika and chikungunya pandemics, human the temporality and cycling of epidemic and endemic herd immunity in the Americas quickly rose to 50% in many transmission [2]. regions, although seroprevalence remains patchy. Modeling from decades of chikungunya circulation in Asia suggests that All arboviruses originated as zoonotic agents that rely on this level of herd immunity will suppress for many years major nonhuman animals as amplifying hosts by generating chikungunya and Zika epidemics in the Americas, followed by viremia needed for oral infection of the vector (Figure 1). smaller outbreaks as herd immunity cycles with a periodicity of Zika, yellow fever, dengue (DENV), and chikungunya up to several decades. (CHIKV) are four arboviruses with a history of sustained human-mosquito-human transmission in an urban cycle Addresses [3]. Here, we refer to these viruses as human-amplified 1 Instituto Gonc¸ alo Moniz, Fundac¸ a˜ o Oswaldo Cruz, Rua Waldemar urban arboviruses, although they also occur in more Falca˜ o, 121, Candeal, 40296-710, Salvador, BA, Brazil rural areas populated by Aedes (Stegomyia) aegypti and 2 Universidade Federal da Bahia, Salvador, Brazil sometimes A. (Stegomyia) albopictus mosquitoes. However, 3 Department of Entomology, Texas A&M University, College Station, TX, all originated in sylvatic, enzootic cycles involving USA 4 nonhuman primates (NHP) and arboreal mosquito Institut Pasteur de Dakar, Dakar, Senegal 5 vectors in Africa (YFV, CHIKV, ZIKV) or Asia (DENV). Population Biology, Ecology, and Evolution Graduate Program, Graduate Division of Biological and Biomedical Sciences, Department of The vast majority of human arboviral pathogens remain in Environmental Sciences, Emory University, Atlanta, GA, USA enzootic cycles with only dead-end, spillover infections of 6 Department of Epidemiology of Microbial Diseases, Yale School of humans that do not extend the transmission chain; an Public Health, New Haven, CT, USA 7 example we discuss here is West Nile virus (WNV). World Reference Center for Emerging Viruses and Arboviruses, Institute for Human Infections and Immunity, and Department of Microbiology and Immunology, University of Texas Medical Branch, The five viruses discussed below are members of the Galveston, 77555-0610 TX, USA genera Flavivirus (YFV, DENV, ZIKV and WNV) and Alphavirus (CHIKV). All except CHIKV produce pre- Corresponding author: Weaver, Scott C ([email protected]) dominately asymptomatic infections, with most apparent disease presenting initially as a flu-like illness with non- Current Opinion in Virology 2020, 40:1–10 specific signs and symptoms [3–6]. However, all of the flaviviruses have the potential to produce life-threatening This review comes from a themed issue on Viruses in a changing world disease or severe sequelae: hemorrhagic for YFV and DENV (principally in secondary infections for the latter); Edited by Kellie Ann Jurado and Sara Cherry congenital birth defects, neurodevelopmental delays and For a complete overview see the Issue and the Editorial neurological complications as Guillain-Barre´ syndrome, Available online 17th March 2020 for ZIKV [5,7]; and neuroinvasive disease, mainly in older https://doi.org/10.1016/j.coviro.2020.02.004 age groups, for WNV [6]. In contrast, CHIKV is usually 1879-6257/ã 2020 Elsevier B.V. All rights reserved. symptomatic with characteristic severe, debilitating, and often chronic arthralgia, but it can be fatal for neonates after peri-natal exposure and for the elderly, mainly those affected by underlying comorbidities [3]. www.sciencedirect.com Current Opinion in Virology 2020, 40:1–10 2 Viruses in a changing world Figure 1 Add itional factors • Weather • Viral fitness • Dynamics of vector abundance •Di spersal Mosqui toes Sho rt-Lived Human s Enzoo tic Hosts Con tribution of Herd Immunity Passerine Bird Hosts •CH IKV: Large Con tribution of Herd Immunity • DENV: • WNV: Small Large for serotype-specific immunity Add itional factors Limited duration of cross-serotype immunity • Dynamics of host abundance Likely li mited duration of cross-species immunity to ZIKV • Viral fitness • ZIKV: • Migration Large for species-specific immunity Likely small for cross-species immunity to DENV • WNV: Small, outside of large outbreaks in humans Add itional factors • Viral fitness • Movement and travel Con tribution of Herd Immunity • YFV: Large •CH IKV: Unknown • DENV: Unknown • ZIKV: Unknown Add itional factors Long-Lived • Dynamics of host abundance • Viral fitness Enzoo tic Hosts • Movement Non- Human Primate Hosts Current Opinion in Virology Influence of herd immunity and other factors on the cyclical transmission of arboviruses in humans. Arrows depict transmission pathways where (a) blue arrows illustrate maintenance of human-mosquito transmission observed for DENV, CHIKV and ZIKV; (b) red arrows depict enzootic transmission cycles seen for YFV, WNV, DENV, ZIKV and CHIKV, and (c) the red dashed arrow shows spillover transmission to humans from enzootic circulation of YFV and WNV and less frequently CHIKV, DENV and ZIKV. Here, we discuss herd immunity for these five animals (e.g. WNV), and contrast regions of recent arboviruses, with an emphasis on their spread throughout introductions (e.g. CHIKV in the Americas) with others the Americas since 1999. We also compare the human with long-term endemic circulation (e.g. CHIKV in Asia, amplified viruses with those amplified only by wild DENV throughout the tropics and subtropics). Current Opinion in Virology 2020, 40:1–10 www.sciencedirect.com Herd immunity and effects on arbovirus circulation and human exposure Ribeiro et al. 3 Enzootic arbovirus cycles and the effects of their herd immunity limits amplification frequency, but herd immunity on circulation and spillover that the viruses remain circulating at low levels between Enzootic cycles of ZIKV, CHIKV, DENV and YFV epizootics rather than becoming extinct [10 ]. The more The enzootic, sylvatic cycles of urban, human-amplified frequent amplification of ZIKV compared to the other arboviruses have received little attention relative to trans- three viruses also suggests that a shorter-lived vertebrate mission in urban settings. A long-term dataset comes from with faster population turnover may be involved in eastern Senegal, where three NHP species (Guinea addition to NHPs. baboon, Papio papio; patas monkeys, Erythrocebus patas; African green monkeys, Cercopithecus aethiopicus sabaeus) West Nile virus and short-lived enzootic hosts serve as amplifying hosts for these viruses, and several An inherent challenge with determining the effects of mosquito species transmit. Mosquito surveillance involv- avian (passerine birds are the main amplifying hosts) ing hundreds-of-thousands collected annually since the immunity on long-term patterns of WNV transmission 1970s by the Institut Pasteur and collaborators, as well as is the paucity of long-term data on amplification and spill- NHP sampling, has detected only periodic epizootic over to humans. Data on West Nile neuroinvasive disease amplifications. ZIKV had the highest annual amplification (WNND), the metric of human disease less vulnerable to frequency, with detection in mosquitoes during 25 differ- reporting bias than the more easily misdiagnosed West ent years from 1972 to 2015, including one period of Nile fever (WNF; [11]), do not necessarily reflect levels of 8 consecutive years (Figure 2). In contrast, YFV, DENV enzootic transmission by Culex mosquitoes [12,13]. and CHIKV were detected only during 19, 8 and 13 years, Although humans are not amplifying hosts, the probabil- respectively, during the same period [8]. Synchrony is not ity of spill-over disease is complicated by human herd always detected in these amplification patterns. Thus, immunity from prior exposure. Humans are long-lived, although weather patterns that influence mosquito popu- but the proportion of the population exposed to zoonotic lations have some effect on circulation [9], other factors mosquito-borne viruses like WNV is typically a small are also responsible for their periodicity. Age-stratified fraction [14]. However following large outbreaks, locally seroprevalence of NHP amplification hosts suggests that high levels of human herd immunity may occur Figure 2 CHIKV DENV-2 YFV ZIKAV 200 150 100 Number of strains 50 0 5 7 79 4 5 6 2 93