Arthropod-Borne Viruses The Outbreak Edition Printed Edition of the Special Issue Published in Tropical Medicine and Infectious Disease www.mdpi.com/journal/tropicalmed Rebekah C. Kading, Aaron C Brault and J. David Beckham Edited by Arthropod-Borne Viruses Arthropod-Borne Viruses: The Outbreak Edition Editors Rebekah C. Kading Aaron C Brault J. David Beckham MDPI • Basel • Beijing • Wuhan • Barcelona • Belgrade • Manchester • Tokyo • Cluj • Tianjin Editors Rebekah C. Kading Colorado State University USA Aaron C Brault Centers for Disease Control and Prevention USA J. David Beckham University of Colorado School of Medicine USA Editorial Office MDPI St. Alban-Anlage 66 4052 Basel, Switzerland This is a reprint of articles from the Special Issue published online in the open access journal Tropical Medicine and Infectious Disease (ISSN 2414-6366) (available at: https://www.mdpi.com/ journal/tropicalmed/special issues/Arthropod Borne Viruses). For citation purposes, cite each article independently as indicated on the article page online and as indicated below: LastName, A.A.; LastName, B.B.; LastName, C.C. Article Title. Journal Name Year , Article Number , Page Range. ISBN 978-3-03943-348-3 ( H bk) ISBN 978-3-03943-349-0 (PDF) c © 2020 by the authors. Articles in this book are Open Access and distributed under the Creative Commons Attribution (CC BY) license, which allows users to download, copy and build upon published articles, as long as the author and publisher are properly credited, which ensures maximum dissemination and a wider impact of our publications. The book as a whole is distributed by MDPI under the terms and conditions of the Creative Commons license CC BY-NC-ND. Contents About the Editors . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . vii Preface to ”Arthropod-Borne Viruses: The Outbreak Edition” . . . . . . . . . . . . . . . . . . . ix Rebekah C. Kading, Aaron C. Brault and J. David Beckham Global Perspectives on Arbovirus Outbreaks: A 2020 Snapshot Reprinted from: Trop. Med. Infect. Dis. 2020 , 5 , , doi:10.3390/tropicalmed5030142 . . . . . . . . . 1 The Endless Challenges of Arboviral Diseases in Brazil Reprinted from: Trop. Med. Infect. Dis. 2020 , 5 , 75, doi:10.3390/tropicalmed5020075 . . . . . . . . 7 Steven Hinojosa, Alexander Alquiza, Clarissa Guerrero, Diana Vanegas, Niko Tapangan, Narda Cano and Eduardo Olivarez Detection of a Locally-Acquired Zika Virus Outbreak in Hidalgo County, Texas through Increased Antenatal Testing in a High-Risk Area Reprinted from: Trop. Med. Infect. Dis. 2020 , 5 , 128, doi:10.3390/tropicalmed5030128 . . . . . . . 13 Matteo Ricc ` o, Giovanni Gualerzi, Silvia Ranzieri, Pietro Ferraro and Nicola Luigi Bragazzi Knowledge, Attitudes, Practices (KAP) of Italian Occupational Physicians towards Tick Borne Encephalitis Reprinted from: Trop. Med. Infect. Dis. 2020 , 5 , 117, doi:10.3390/tropicalmed5030117 . . . . . . . 19 Nurulhusna Ab Hamid, Siti Nurfadhlina Mohd Noor, Nur Rasyidah Isa, Rohaiyu Md Rodzay, Ainaa Mardia Bachtiar Effendi, Afiq Ahnaf Hafisool, Fatin Atirah Azman, Siti Farah Abdullah, Muhammad Khairi Kamarul Zaman, Mohd Iqbal Mohd Norsham, Noor Hasmiza Amanzuri, Nurliyana Abd Khalil, Izzah Farhah Zambari, Aimannur Najihah Mat Rani, Farah Diana Ariffin, Topek Omar, Nazni Wasi Ahmad and Han Lim Lee Vertical Infestation Profile of Aedes in Selected Urban High-Rise Residences in Malaysia Reprinted from: Trop. Med. Infect. Dis. 2020 , 5 , 114, doi:10.3390/tropicalmed5030114 . . . . . . . 33 Carla Julia da Silva Pessoa Vieira, David Jose ́ Ferreira da Silva, Jana ́ ına Rigotti Kubiszeski, La ́ ıs Ceschini Machado, Lindomar Jose ́ Pena, Roberta Vieira de Morais Bronzoni and Gabriel da Luz Wallau The Emergence of Chikungunya ECSA Lineage in a Mayaro Endemic Region on the Southern Border of the Amazon Forest Reprinted from: Trop. Med. Infect. Dis. 2020 , 5 , 105, doi:10.3390/tropicalmed5020105 . . . . . . . 45 Katherine I. Young, Joseph T. Medwid, Sasha R. Azar, Robert M. Huff, Hannah Drumm, Lark L. Coffey, R. Jason Pitts, Michaela Buenemann, Nikos Vasilakis, David Perera and Kathryn A. Hanley Identification of Mosquito Bloodmeals Collected in Diverse Habitats in Malaysian Borneo Using COI Barcoding Reprinted from: Trop. Med. Infect. Dis. 2020 , 5 , 51, doi:10.3390/tropicalmed5020051 . . . . . . . . 61 Teresa E. Sorvillo, Sergio E. Rodriguez, Peter Hudson, Megan Carey, Luis L. Rodriguez, Christina F. Spiropoulou, Brian H. Bird, Jessica R. Spengler and Dennis A. Bente Towards a Sustainable One Health Approach to Crimean–Congo Hemorrhagic Fever Prevention: Focus Areas and Gaps in Knowledge Reprinted from: Trop. Med. Infect. Dis. 2020 , 5 , 113, doi:10.3390/tropicalmed5030113 . . . . . . . 81 v Elysse N. Grossi-Soyster and A. Desiree LaBeaud Rift Valley Fever: Important Considerations for Risk Mitigation and Future Outbreaks Reprinted from: Trop. Med. Infect. Dis. 2020 , 5 , 89, doi:10.3390/tropicalmed5020089 . . . . . . . . 109 Nadia Castaldo, Elena Graziano, Maddalena Peghin, Tolinda Gallo, Pierlanfranco D’Agaro, Assunta Sartor, Tiziana Bove, Roberto Cocconi, Giovanni Merlino and Matteo Bassetti Neuroinvasive West Nile Infection with an Unusual Clinical Presentation: A Single-Center Case Series Reprinted from: Trop. Med. Infect. Dis. 2020 , 5 , 138, doi:10.3390/tropicalmed5030138 . . . . . . . 123 Robert G. McLean Letter to the Editor: Venezuelan Equine Encephalitis virus 1B Invasion and Epidemic Control—South Texas, 1971 Reprinted from: Trop. Med. Infect. Dis. 2020 , 5 , 104, doi:10.3390/tropicalmed5020104 . . . . . . . 129 Rebekah C. Kading, Lee W. Cohnstaedt, Ken Fall and Gabriel L. Hamer Emergence of Arboviruses in the United States: The Boom and Bust of Funding, Innovation, and Capacity Reprinted from: Trop. Med. Infect. Dis. 2020 , 5 , 96, doi:10.3390/tropicalmed5020096 . . . . . . . . 133 vi About the Editors Rebekah C. Kading , Ph.D.: Dr. Kading obtained her BS in Entomology/Wildlife Conservation from the University of Delaware, MS in Entomology from the University of Arkansas, and Ph.D. in Molecular Microbiology and Immunology from the Johns Hopkins Bloomberg School of Public Health. Between 2007 and 2014, Dr. Kading led studies on the ecology of arthropod-borne viruses in Colorado, Uganda, and Guatemala, and the transmission of Rift Valley fever virus (RVFV) by mosquitoes at the CDC Division of Vector-borne Diseases. Her research program is currently focused on RVFV transmission, as well as the ecology of virus circulation among bats. Aaron C Brault obtained his BS in Zoology from Texas A&M University and Ph.D. from the University of Texas Medical Branch. He then completed post-doctoral training as an American Society of Microbiology fellow at the Division of Vector-Borne Diseases (DVBD), Centers for Disease Control and Prevention in Fort Collins, Colorado, from 2001–2003. Following his ASM fellowship, he accepted a position as an associate professor at the Center for Vector-Borne Diseases and Department of Pathology, Microbiology and Immunology within the School of Veterinary Medicine at the University of California, Davis. After being promoted to associate professor, Dr. Brault returned to DVBD in 2009 as a staff scientist. His laboratory focused on arboviral pathogenesis and molecular genetics, and in 2019, was appointed as the lead for the arboviral diagnostics group within the branch. J. David Beckham obtained his MD from Baylor College of Medicine, followed by Internal Medicine Residency training at Baylor College of Medicine and Infectious Disease Fellowship Clinical Training at University of Colorado School of Medicine. He then completed post-doctoral training in virology at University of Colorado School of Medicine from 2005 to 2010. Since 2010, Dr. Beckham’s laboratory has studied the pathogenesis of flavivirus infections and mechanisms of neuroinflammatory responses to acute viral infections in the central nervous system. vii Tropical Medicine and Infectious Disease Editorial Global Perspectives on Arbovirus Outbreaks: A 2020 Snapshot Rebekah C. Kading 1, *, Aaron C. Brault 2 and J. David Beckham 3 1 Department of Microbiology, Immunology, and Pathology, Colorado State University, Campus Delivery 1690, Fort Collins, CO 80523, USA 2 Division of Vector-borne Diseases, Arboviral Diseases Branch, Centers for Disease Control and Prevention, Fort Collins, CO 80521, USA; zlu5@cdc.gov 3 Departments of Medicine, Neurology, and Immunology & Microbiology, Division of Infectious Diseases, University of Colorado School of Medicine, Rocky Mountain Regional VAMC, 12,700 E. 19th Avenue, B168, Denver, CO 80045, USA; david.beckham@cuanschutz.edu * Correspondence: rebekah.kading@colostate.edu; Tel.: + 1-970-491-7833 Received: 2 September 2020; Accepted: 4 September 2020; Published: 7 September 2020 Keywords: mosquito; tick; emerging infectious diseases; one health; vector-borne diseases When this special issue was first conceived in early 2019, we never anticipated that the publication of this collection of articles would be happening during a pandemic. While this outbreak collection is focused on viruses transmitted by arthropods, its release concurrent with the SARS-CoV-2 pandemic and international health emergency provides an appropriate context in which to draw attention to research focused on other high-consequence, epidemic-causing viruses that may be next to emerge on the global stage. Arthropod-borne pathogens account more than 17% of infectious diseases, affect millions of people around the world each year, and comprise a significant proportion of emerging human pathogens [ 1 – 4 ]. Dengue, as the most widespread arboviral disease, causes more than 90 million cases and approximately 40,000 deaths per year [ 3 ]. The emergence and explosive spread of Zika virus (ZIKV) has recently challenged the global health infrastructure to diagnose and differentiate ZIKV infections from infections with closely related arboviruses and to minimize the catastrophic effects of congenital infection. Additional arboviruses including Rift valley fever, Mayaro, West Nile, chikungunya, and tick-borne encephalitis viruses have captured the attention of the scientific community as emerging public health threats [ 3 , 5 ]. As the world responds to outbreak after outbreak, research on: surveillance and preparedness, virus transmission dynamics, ecology and epidemiology, diagnosis and treatment, public attitudes and practices and existing barriers and challenges to outbreak prevention and control of these and other emerging viruses will be needed to contribute to more effective mitigation strategies and for protecting public health. This Special Issue comprises a highly diverse group of articles from around the world, which highlight various aspects of arbovirus outbreaks in endemic regions and in areas of introduction. This issue showcases the important work that is being done to mitigate epidemic activity and protect human and animal health from emerging arboviral threats, as well as provides a unique insight into past epidemics. Articles in this issue include coverage of viruses transmitted by ticks as well as mosquitoes, discussions of clinical, epidemiological, and entomological perspectives, and includes emerging arboviruses from every hemisphere. Below is a brief tour of the articles in this collection (Figure 1). Trop. Med. Infect. Dis. 2020 , 5 , 142 1 www.mdpi.com / journal / tropicalmed Trop. Med. Infect. Dis. 2020 , 5 , 142 Figure 1. International scope of arbovirus outbreak-related articles included in the “Arthropod-borne Viruses: The Outbreak Edition” special collection. Venezuelan equine encephalitis virus (VEEV), Zika virus (ZIKV), West Nile virus (WNV), tick-borne encephalitis virus (TBEV), Japanese encephalitis virus (JEV), dengue virus (DENV), Rift Valley fever virus (RVFV), Crimean-Congo hemorrhagic fever virus (CCHV), Mayaro virus (MAYV), chikungunya virus (CHIKV), and yellow fever virus (YFV). Numbers indicate the associated reference. Southeast Asia : The two studies included in this collection from Southeast Asia provide corresponding perspectives on the transfer or “spillover” of zoonotic pathogens from natural transmission cycles into the human population. Young et al. [ 6 ] described the blood feeding patterns of mosquitoes in Malaysian Borneo, in an area undergoing significant changes in land cover and land use. They provided novel insights into how the host utilization patterns of some major mosquito vectors in di ff erent land use types could influence the spread and spillover of arboviruses, including Japanese encephalitis virus, between natural and epidemic cycles. As a complement to this work, Ab Hamid et al. [ 7 ] studied the vertical stratification of Aedes mosquitoes responsible for the transmission of dengue virus (DENV) in high-rise buildings in Malaysian cities. They reported mosquito infestations up to 21 stories high, demonstrating a unique risk of arbovirus transmission in urban settings [7]. South America : While screening sera from human patients in Sinop city, Brazil, de Silva Pessosa Vierra et al. [ 8 ] documented concurrent circulation of both Mayaro (MAYV) and chikungunya (CHIKV) viruses. While the MAYV genomes detected matched other strains known to be present, the CHIKV genome detected from one patient was of the East / Central / South African (ECSA) genotype. This genotype was distinct from strains already circulating in this area and represented an important discovery, that there was a separate introduction event of CHIKV into Brazil [ 8 ]. The simultaneous circulation of Aedes mosquito-borne viruses including DENV, CHIKV, ZIKV, and MAYV, and the stress this poses to the human population and health infrastructure in Brazil is discussed in detail by Magalhaes et al. [9]. Africa : This collection covers two hemorrhagic fever viruses endemic to Africa, Rift Valley fever virus (RVFV) and Crimean Congo hemorrhagic fever virus (CCHFV), both of which are listed as 2 Trop. Med. Infect. Dis. 2020 , 5 , 142 “select agents” [ 10 ] due to the severity of disease they could cause, as well as potential use as agents of bioterrorism. Rift Valley fever virus is endemic to Africa where it causes large epizootics typically associated with climate patterns and rainfall, and causes significant morbidity and mortality in both humans and animals [ 11 ]. This virus has spread to Saudi Arabia, Madagascar, and other island nations in the Indian Ocean (i.e., Mayotte, Comoros), but has not yet emerged in a transoceanic location. Mitigation of a RVFV outbreak carries with it many unique considerations, and would involve mobilization of diverse agencies focused on public health, animals and agriculture, and biosecurity. To this end, Grossi-Soyster and LaBeaud [ 12 ] reviewed major considerations for such risk mitigation pertaining to future outbreaks of RVFV, with a special emphasis on vaccines, travelers and tourism. Crimean Congo hemorrhagic fever virus, transmitted by ticks, was originally described from both central Africa as well as the Crimean region of Russia. This virus has alarmingly sustained continual epizootic activity from Africa north through Western Asia in recent years. Sorvillo et al. [13] comprehensively reviewed and discussed a One Health approach to CCHFV prevention and included a special focus on knowledge gaps that are critically important to address. North America : The United States has experienced invasions of West Nile and Zika viruses in recent decades, with continual threats of endemic re-emerging mosquito-borne viruses such as St. Louis, LaCrosse, Powassan, and Eastern equine encephalitis viruses. In 1971, a transboundary outbreak of Venezuelan equine encephalitis (VEE) virus epidemic strain 1b invaded South Texas. In a letter to the editor, McLean [ 14 ] provided a valuable first-hand account of the interagency response to this outbreak, and how this outbreak response remains the sole example of the successful prevention of VEE establishment in the United States. To build on this historical perspective, Kading et al. [ 15 ] provided a 30-year analysis on the reactionary response of funding agencies to the emergence and invasion of mosquito-borne viruses in the Americas and how these events have also stimulated the innovative development of traps and augmented surveillance capacity. As the most recent arbovirus introduction to the United States, ZIKV infections have been mostly associated with travelers, however local transmission was documented in areas of Florida and Texas [ 16 , 17 ]. To this end, Hinojosa et al. [ 16 ] reported locally-acquired cases of ZIKV in South Texas, particularly as surveillance e ff orts were increased out of specific concerns of virus infections in pregnant women. Europe . Tick-borne encephalitis (TBE) is a severe infection of the central nervous system, caused by tick-borne encephalitis virus (TBEV) in the family Flaviviridae . Incidence of TBE has increased in recent years throughout Europe, spread to new endemic foci, and became a notifiable disease in the European Union in 2012 [ 18 , 19 ]. The TBE vaccine licensed in Europe is recommended for all age groups in endemic areas with incidence rates exceeding 5 per 100,000 [ 19 , 20 ], however vaccination rates are very low [ 19 ]. Ricc ò et al. [ 18 ] conducted a knowledge, attitudes and practices survey of tick-borne encephalitis among occupational physicians in Italy, and found a lack of knowledge of TBE and low vaccine literacy among this stakeholder group. Improving knowledge of TBE, behavioral practices that prevent tick-bites, and vaccination would help prevent the spread of tick-borne infections such as TBE in Italy and elsewhere [ 18 ]. West Nile virus (WNV) has been circulating throughout Europe since the 1990s. A dramatic increase in WNV infections in multiple countries in Southern Europe was observed during 2018 in both humans and horses [ 21 ]. Castaldo et al. [ 22 ] provided a case report on two human patients from Italy. Clinical disease was characterized by atypical neurological presentation in these patients diagnosed with WNV neuroinvasive disease, involving the brainstem. The authors encouraged providers to remain alert to unusual disease presentations involving the central nervous system [22]. Author Contributions: Writing—original draft preparation, R.C.K.; writing—review and editing, A.C.B., J.D.B. All authors have read and agreed to the published version of the manuscript. Funding: This research received no external funding. Acknowledgments: Figure 1 was created using BioRender.com. Conflicts of Interest: The authors declare no conflict of interest. 3 Trop. Med. Infect. Dis. 2020 , 5 , 142 References 1. Jones, K.E.; Patel, N.G.; Levy, M.A.; Storeygard, A.; Balk, D.; Gittleman, J.L.; Daszak, P. Global trends in emerging infectious diseases. Nature 2008 , 451 , 990–993. [CrossRef] [PubMed] 2. 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This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http: // creativecommons.org / licenses / by / 4.0 / ). 5 Tropical Medicine and Infectious Disease Editorial The Endless Challenges of Arboviral Diseases in Brazil Tereza Magalhaes 1, *, Karlos Diogo M. Chalegre 2 , Cynthia Braga 3 and Brian D. Foy 1 1 Arthropod-Borne and Infectious Diseases Laboratory (AIDL), Department of Microbiology, Immunology and Pathology (MIP), Colorado State University, Fort Collins, CO 80523-1692, USA; Brian.Foy@colostate.edu 2 Oswaldo Cruz Institute (IOC), Oswaldo Cruz Foundation (FIOCRUZ), Vice Presidency of Production and Innovation in Health (VPPIS), Rio de Janeiro, RJ 21040-900, Brazil; diogochalegre@gmail.com 3 Aggeu Magalhaes Institute (IAM), Oswaldo Cruz Foundation (FIOCRUZ), Department of Parasitology, Recife, PE 50670-420, Brazil; braga@cpqam.fiocruz.br * Correspondence: Tereza.Magalhaes@colostate.edu Received: 30 April 2020; Accepted: 7 May 2020; Published: 9 May 2020 Abstract: In this Editorial, we list and discuss some of the main challenges faced by the population and public health authorities in Brazil concerning arbovirus infections, including the occurrence of concurrent epidemics like the ongoing SARS-CoV-2 / COVID-19 pandemic. Keywords: dengue; zika; chikungunya; coronavirus; co-endemic Optimal ecological and environmental conditions support year-long breeding of mosquito vectors of arboviruses in several Brazilian States. This, combined with socioeconomical factors that facilitate mosquito breeding (e.g., intermittent water supply that leads to short-term water storage in open-air artificial containers) and human exposure to mosquito bites, fosters cyclic and intense transmission of arboviruses in Brazil. In urban and peri-urban areas, the four dengue virus serotypes (DENV1-4), Zika virus (ZIKV), and chikungunya virus (CHIKV) are the most widespread and impactful mosquito-borne pathogens, all transmitted by the highly urbanized and anthropophagic Aedes aegypti Arboviral diseases impose a great health burden to the population in Brazil and represent a constant challenge to health authorities. Diagnosis (and therefore clinical management) and notification of arboviral infections in co-endemic places (where more than one arbovirus co-circulate) are extremely complex. Point-of-care virus-specific testing is non-existent in the public and private health care sectors, and the most important diagnosis is clinical-epidemiological, upon which a case is notified to health authorities as suspected or confirmed based on the Ministry of Health case definitions (which uses clinical symptoms and blood test results, such as platelet counts). However, diseases caused by DENV, ZIKV and CHIKV can lead to similar acute symptoms that may di ff er only in time of onset, duration and severity [ 1 ]—thus, only well-trained, experienced physicians are more apt to correctly diagnose a patient, but even these professionals can misdiagnose without available virus-specific tests. Arboviral diseases are nationally notifiable diseases in Brazil, but in the public sector, which exclusively serves more than 70% of the Brazilian population, only a small proportion of cases notified by health care units undergo confirmatory tests in public reference laboratories through virus-specific molecular or serological assays, or virus culture. For instance, among the notified dengue cases in 2020 (until April), only approximately 23% were tested in reference laboratories [ 2 ]. In addition, for DENV and ZIKV, cross-reactivity of serological assays represents a serious issue as it can lead to erroneous results [ 3 ]. O ffi cial government notifications may thus be biased by inaccurate clinical diagnosis and cross-reactive serological results, and clinical management of infections may not be appropriate if the wrong diagnosis is made. The di ff erent socioeconomic realities of Brazilian States also contribute to inconsistencies of arboviral disease notifications. Trop. Med. Infect. Dis. 2020 , 5 , 75 7 www.mdpi.com / journal / tropicalmed Trop. Med. Infect. Dis. 2020 , 5 , 75 The cross-reactivity between DENV and ZIKV serological assays are due to similar antigenic regions of viral proteins of these genetically related flaviviruses that can be recognized by the same antibodies. Besides being an issue in serological tests, cross-reactive DENV and ZIKV immunity can have important epidemiological implications in places where these viruses co-circulate. For instance, in vitro , in vivo and epidemiological studies have shown that pre-existing DENV immunity can either protect or enhance ZIKV infection, and consequently impact disease development [ 4 – 6 ]. Other studies suggest that the atypically low dengue incidence observed after the Zika epidemics in Brazil and other Latin American countries was due, in part, to short-term DENV protection from ZIKV infections [ 7 , 8 ]. Importantly, this lower dengue incidence was followed by a significant increase in dengue cases [ 2 , 7 ]. The impact of pre-existing DENV and ZIKV immunity in further heterologous infections and, importantly, in clinical diseases, needs to be continuously assessed in endemic areas. It is also possible that ZIKV or other arboviruses may establish sylvatic transmission cycles in Brazil, as discussed by other authors [ 9 ]. If one looks at the map of Paulista, for example, a municipality within the Recife Metropolitan Region (RMR) in Pernambuco State that was heavily a ff ected by ZIKV and CHIKV, forested areas surround all the urban areas where the viruses co-circulated and human cases were concentrated in 2015-16 (Figure 1 and [ 10 ]). These forested areas may harbor several sylvatic mosquitoes like Aedes albopictus , Haemagogus janthinomys , and Sabethes tarsopus that feed on non-human primates (NHPs) and may serve as vectors of arboviruses [ 11 ]. In addition, NHPs like the common marmoset Callithrix jacchus are abundant in the area [ 12 ] and found near humans. Importantly, ZIKV RNA and antibodies against several arboviruses have been found in NHPs in di ff erent regions of Brazil, including marmosets [ 13 – 16 ]. The seriousness of an established sylvatic arbovirus transmission cycle in NHPs and sylvatic mosquitoes in Brazil is well represented by yellow fever virus (YFV), which causes sporadic spillover human outbreaks leading to hundreds of deaths. Although a few studies have found little evidence of sylvatic ZIKV transmission in Brazil [ 16 , 17 ], the possibility of a sylvatic cycle being established in distinct Brazilian regions and at di ff erent times cannot be excluded. Further governmental or research-related arbovirus surveillance activities should intensify monitoring of sylvatic mosquitoes, NHPs and other small mammals, as the establishment of sylvatic cycles will require changes in the design of control programs. The ZIKV outbreaks that occurred in Brazil in 2014-16 probably ceased due to herd immunity—however, instead of disappearing, the virus is still circulating in areas that were intensely affected, like the RMR, even if at low rates. In addition, virus transmission during the outbreaks was focal across metropolitan regions, where some areas were more intensely hit than others within the same municipality [ 4 ], corroborating the notion of clustered household / community transmission of arboviruses transmitted by Ae. aegypti . The low but constant circulation of ZIKV, the presence of prior virus foci with surrounding patchy areas containing higher numbers of naïve people, and the possibility of a sylvatic cycle being established in some regions increase the chances of unexpected re-emergence of the virus. It will also be important to assess the importance of sexual transmission among the sustained, low ZIKV circulation in endemic regions, as the epidemiological relevance of ZIKV sexual transmission may be higher than previously thought ([18] and Magalhaes et al., unpublished). Escalating the problem of arboviral disease surveillance and management, concurrent outbreaks / epidemics of arboviruses and non-arthropod-borne pathogens can further complicate clinical diagnosis and completely overwhelm / saturate the health care system, as we may be seeing now with the pandemic of coronavirus disease (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The number of notified dengue, Zika and chikungunya cases in Brazil in 2020 have reached over 660,000 by April [ 2 ], reflecting a di ffi cult year for arboviral diseases in the country (Figure 2A). Although the true incidences of SARS-CoV-2 infections and COVID-19 cases are unknown in Brazil due to the very limited testing (currently, the Brazilian government recommends that only severe cases are tested in health clinics and hospitals), the notified numbers of infections and deaths are starting to increase, indicating a worsening epidemic scenario as of April 2020 (Figure 2B) [ 2 ]. At the moment, health care units like the local rapid-access units (Unidades de Pronto 8 Trop. Med. Infect. Dis. 2020 , 5 , 75 Atendimento-UPAs), which serve communities like the Paulista population (~330,000 habitants), are working with a reduced number of sta ff as some individuals have fallen ill and many elderly professionals or those with comorbidities are on leave due to fear of becoming infected with the virus. In a recent serosurvey of SARS-CoV-2 antibodies among health professionals in Pernambuco State, 60% have tested positive, confirming these professionals are under very high risk of infection [ 19 ]. Although the highest numbers of notified arboviral diseases seemed to have occurred in March 2020, it is very likely that case notification has dropped as a result of fewer people infected with arboviruses seeking health facilities due to the SARS-CoV-2 pandemic. In fact, it would be important to see if household mosquito transmission of arboviruses increases because of social isolation during the COVID-19 pandemic, considering the endophilic behavior of Ae. aegypti (although social isolation is necessary, it is also important to assess its e ff ects on other health factors). The blunt reality is that health care units have been dealing with a peak in arbovirus infections and COVID-19 cases concomitantly. Besides the many troubles inherent to an overwhelmed health care system, concurrent epidemics also can complicate clinical-epidemiological diagnoses. Some studies show that dengue cases can be misdiagnosed as respiratory infections and vice-versa [ 20 , 21 ]. Coinfections during concurrent epidemics must also be considered as they may worsen clinical diseases. Coinfections of influenza virus and DENV have been identified in several occasions during concurrent epidemics [ 22 – 24 ]. Future control e ff orts and programs must consider concurrent epidemics as they will most likely continue to happen in the future (e.g., epidemics of DENV and new strains of influenza virus). Figure 1. Mapped cases of Zika virus (ZIKV) and chikungunya virus (CHIKV) infections in Paulista, Pernambuco State, Brazil, in 2015-16. Note the green / forested areas surrounding the urban areas where cases were concentrated: an optimal interface for the establishment of sylvatic cycles of arbovirus transmission (this map was published in [10]). 9 Trop. Med. Infect. Dis. 2020 , 5 , 75 * + * + Figure 2. Cumulative notified cases of dengue, Zika and chikungunya ( a ) and COVID-19 ( b ) in Brazil as of April 2020. Conclusions E ff ective management of arboviral diseases in Brazil requires confronting major challenges. The co-endemicity of multiple and related arboviruses complicates clinical-epidemiological diagnoses, clinical management and case notification, in addition to impacting the epidemiology of arboviral diseases in unclear ways. The possible establishment of sylvatic transmission cycles will represent a significant additional challenge to the development of control programs and should be constantly monitored. 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