Which Plagues are Coming Next?

*Ricardo Izurieta, Adriana Campos, Jeegan Parikh and Tatiana Gardellini*

## **Abstract**

Plagues and pandemics are no longer distant thoughts of the past. Previously referred as moments in history, infectious diseases have re-emerged as potential existential threats to mankind. International Health Security researchers have repeatedly warned society about impending pandemics and in 2020, the world experienced its first major pandemic in over a century. The SARS-CoV-2/COVID-19 pandemic came fast and hit hard, impacting the entire world within months of discovery. Although SARS-CoV-2 was a completely novel virus, there are an assortment of novel and timeworn pathogens fostering the potential to become the next pandemic. This chapter focuses on pathogens ranging from yeast to virus, capable of transmission through food, water, air, or animal, that could emerge as the next International Health Security threat.

**Keywords:** pandemic, vector-borne diseases, airborne diseases, waterborne diseases, foodborne diseases, public health, infectious diseases, International Health Security

#### **1. Introduction**

The current COVID-19 pandemic has given the world a new lesson that the war against human pathogens is not over. The next plagues are coming, that is for sure, we just do not know when and where they will emerge. The transcontinental global movement of human populations, animals, products, and food in unprecedented numbers and at immeasurable speeds has determined the emergence of new plagues. The International Health Security panorama is changing with the incorporation of vast geographical areas to the agroindustry; the displacement of large population groups either due to problems of floods, drought, wars, or people that search for better living conditions. In addition, the disposal of biological waste and the weaponization of pathogenic microorganisms are phenomena with serious consequences. International multinational cooperation is needed to improve the development and availability of drugs and vaccines at a global level, as well as, improving preventive health services, keeping safe all repositories of infectious agents, and the establishment of an International Health Security System focused on Infectious Disease Surveillance and Control.

#### **2. Methods**

An organized, systematic, four-step methodology for collecting key information was carried out to write this chapter. In a first step a search in websites such

as the World Health Organization (WHO), the Centers for Disease Control and Prevention (CDC), and the National Institutes of Health (NIH) was conducted to identify emerging infectious diseases pathogens. In a second step, the main emerging infectious diseases pathogens were classified in viruses, bacteria, parasites and fungi as well as by their mechanism of transmission. In a third step, all updated manuscripts related with each one the selected pathogens were extracted from scientific databases including Pubmed, MEDLINE, Google Scholar, and SCOPUS. Finally, all pathogens were classified using the WHO Pandemic Phase Descriptions and Main Actions by Phase [1].

### **3. Pathogens to study**

#### **3.1 Vector-borne**

Vector-borne diseases are transmitted, either biologically or mechanically, via insect vectors or animal vectors. Vector-borne diseases were the cause of great plagues in the previous centuries and continue to take human lives every year. Although the invention of pesticides, better hygiene and sanitation, and improved physical barriers have contributed to the decreased incidence of these type of infections, globalization, deforestation, and global warming are causing Vectorborne diseases to experience a comeback [2]. With enough conditions in their favor, Vector-borne diseases are capable to expand from being endemic in some areas to becoming a pandemic. Vectors range from insects to mammals and are present in all parts of the world. The pathogens described in this section are transmitted by mosquitoes, ticks, rodents, lice, and fleas.

An important factor regarding Vector-borne diseases and their respective vectors compared to other mechanisms of infectious disease transmission (e.g., airborne, foodborne) is the emerging data indicating vectors are capable of hosting more than one pathogen at a time [3–7]. Co-transmission and co-infection are not well understood yet are raising questions regarding clinical manifestation, virulence, and possible future implications. Although the mechanisms of co-infections are not well comprehended, there are documented case reports with individuals presenting more than one Vector-borne disease at the same time [8–10]. Specifically, there is rising concern about mosquitoes and their capability to co-infect humans, with recent studies showing *Aedes aegypti* [4, 7] and *Ae. albopictus* [3] capable of transmitting Zika, Chikungunya, and Dengue viruses within one bite.

#### *3.1.1 Viruses*

#### *3.1.1.1 Yellow fever virus*

Yellow fever (YF), one of the deadliest infectious diseases less than a century ago [11], was historically a neglected infectious disease unit the 1902 creation of the Pan American Health Organization (PAHO) and International Sanitary Bureau of the American Republics [12]. Yellow fever is caused by the etiological agent yellow fever virus (YFV), belongs to the flavivirus genus and, is a part of the arboviruses group (i.e., a commonly used, yet unofficial, name for viruses transmitted by arthropods). [11]. YFV circulates between humans, non-human primates, and several species of mosquito vectors (*Aedes, Haemagogus, Saberges)*. Currently, YFV has not adapted as well to humans as Dengue virus, leaving YFV as a zoonotic disease but with a future capability to extend to an anthroponotic. In the past decade there is an increase in

#### *Which Plagues are Coming Next? DOI: http://dx.doi.org/10.5772/intechopen.96820*

concern of non-primate transmission which could go unnoticed and spillover to large human populations [13]. Due to the nature of the virus requiring epizootic transmission, unfortunately, YFV cannot be eradicated from the planet. *Aedes aegypti* and *Aedes albopictus* which are present in over 150 countries suggest nearly half of the global population is at risk of YFV transmission [14]. Traditionally, YF affects the Americas and the African continent with its warm temperatures and suitable habitat for the mosquito vectors of the virus. There are seven major genotypes of YFV, differentiating the American and African cases – with 5 circulating within Africa and 2 in the Americas. Depending on the location of cases and the type of mosquito species native to the area there are three main types of YF transmission – urban, sylvatic, and intermediate (only Africa). Urban transmission is caused mainly by *Aedes aegypti* or a similar urban mosquito as the transmitter in humans [11, 15]. Sylvatic transmission appears between non-human primates and sylvatic mosquitoes, typically apart of the *Haemagogus* or *Sabethes* genera. In Africa alone, YF is estimated to kill over 70 thousand individuals a year [16]. The case fatality rate (CFR) depends on the location of infection, with South America having a higher CFR (40–60%) compared to Africa (closer to 20%) [17]. However, most cases are mild and resolve with supportive care. Moreover, in areas with co-transmission of both Dengue and YF viruses, it is possible that previous Dengue infections may protect against severe YF infections [18]. Similarly, to how YFV is thought to have traveled from the African continent to the West Indies centuries ago on shipping routes, it is capable to continue expanding in the current age with increased globalization and construction within the vector habitat. As mentioned above, YF is endemic in mostly South American and Africa, with outbreaks consistently seen each year. Although not often heard about in North America and Asian countries, Yellow Fever was endemic hundreds of years ago in cities like New York, Philadelphia, Memphis, and New Orleans [19] and has the possibility to emerge in Asian countries [20, 21]. Although *Aedes* mosquitoes are also native in parts of Asia, the absence of YF cases has long been a scientific enigma [21, 22]. Common theories to the lack of YF cases in Asia are: the east African mountain range provides a natural barrier for Asia [21], competition with Dengue virus limits YF transmission [23], and vector competency [20] among others. However, in the recent years an increased number of imported YF cases into Asian countries have raised alarms to the potential introduction of YFV to the local environment [20]. The most important factor describing whether or not YFV will be transmitted in a specific area is the vector. Fortunately, YFV can only be transmitted via the bite of an infected mosquito, making mosquito control programs essential in YFV transmission reduction. However, the world currently is experiencing a re-emergence of YF due to increased globalization, deforestation, and climate change, with recent outbreaks occurring in Brazil [24, 25]. With globalization, both humans and mosquitos may hitch rides to different parts of the world where YF transmission is uncommon and becoming an International Health Security issue. Furthermore, the present deforestation occurring throughout the world, especially in the South American and African forests, is closing the distance between humans, infected non-human primates, and mosquitos. Lastly, the increasing temperatures seen due to climate change may have implications on YFV vectors and their global distribution [16] – increasing the risk for contracting YF. In a recent study, an increase in temperature is estimated to increase the chance of the annual amount of YF death by over 90% [16]. Currently, countries with endemic YFV transmission have mosquito control programs capable of decreasing/controlling mosquito populations. Furthermore, the use of Geographic Information Systems (GIS) in conjunction with mathematical models [11] assist in predicting future YF outbreaks and viral transmission [16].

Lastly, one of the most important tools available to fight infectious diseases exists against the Yellow Fever virus – a vaccine. The earliest version of a YF live-attenuated vaccine was created in 1936 and the same vaccine strain (17D) is still presently effective and used in areas with endemic transmission [11].

#### *3.1.1.2 Dengue virus*

Dengue virus (DENV) occurs in over 100 countries causing nearly 100 million acute infections and half a million deaths each year [26, 27]. The disease itself is characterized by an acute fever which is transmitted from mosquitos (*Ae. aegypti* and *Ae. albopictus*) to humans, however, most cases are asymptomatic. Anywhere from 5–20% of cases progress to severe dengue which includes bleeding, shock, organ failure, and death. Severe forms of Dengue are known as dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Dengue is described as early as 1600 and continues to be endemic to many parts of the world [27]. Similarly, to the Yellow Fever efforts initiated by PAHO, a major *Aedes aegypti* eradication program between 1947 and 1970 aimed to eliminate this mosquito species and therefore, eliminate Dengue. However, *Ae. aegypti* reinfestation occurred shortly after and has even increased in dispersion in the recent decades [27]. Like other infectious diseases, Dengue is thought as an exotic disease – perhaps many individuals have not even heard of Dengue before. It may surprise many individuals in developed countries that Dengue's main vector *Ae. aegypti* is capable of living in almost all continents except Antarctica [28]. Dengue was common in port cities in the Caribbean and all throughout the Americas and continues to cause outbreaks in developed areas such as the Florida (2020) and Hawaii (2015) [29]. A significant barrier in the diagnosis and reporting of Dengue is the commonality the disease shares with other Flaviviruses such as Yellow Fever virus and Zika and its cross-reactivity in serological testing. The aforementioned diseases share similar flu-like symptoms and serological misdiagnoses are believed to fuel the underreporting of DENV and other Flavivirus infections. As Dengue cases continue to increase it is essential to understand the current epidemiology and public health programs in place to reduce the outbreak risk and reinforce International Health Security. Dengue virus shares many similar characteristics with YFV - it is a part of the Flaviviridae family, and its main vectors are *Aedes aegypti* and *Ae. albopictus* mosquitoes. Typically, DENV is found in tropical and subtropical regions and unlike other viruses, individuals may be re-infected by different serotypes. This is especially important in public health prevention programs and epidemic mitigations. Unfortunately, individuals infected with one serotype only produce antibodies capable of neutralizing that specific serotype, leaving the individual unprotected against the other 3 serotypes. Moreover, through antibody-dependent enhancement, re-infection by a different serotype increases the risk of severe dengue disease [26]. In 2019 a vaccine against DENV was approved for individuals aged 9–45 years and who had experienced a prior DENV infection. However, providing this vaccine to individuals without prior DENV infection also increases the risk for the antibody-dependent enhancement and therefore greatly limiting who may be immunized [30]. In a pandemic scenario this limitation would be disastrous.

#### *3.1.1.3 Zika virus*

One of the most famous infectious diseases of recent decades, Zika came into the international spotlight during its 2015 epidemic. Although Zika virus (ZIKV) was discovered in a Ugandan forest over 50 years ago, in 2015 it emerged as a global epidemic affecting multiple countries and causing widespread panic [31]. In 2016,

#### *Which Plagues are Coming Next? DOI: http://dx.doi.org/10.5772/intechopen.96820*

the World Health Organization (WHO) declared the outbreak as a Public Health Emergency of International Concern, with ZIKV affecting throughout the Americas and Caribbean. One of the main reasons for the declaration and widespread worry is the increase in microcephaly cases and other neurological disorders that ZIKV brought with it. Interestingly, prior to the outbreaks in the recent decade, ZIKV infections were considered benign [32]. It was the increase in neurological disorders such as Guillain-Barré syndrome in older children and adults and microcephaly and other birth defects in newborns in the 2015 Brazil outbreak that forewarned the local and international community of the potential adverse effects from a ZIKV infection [32]. Although the incidence of Zika cases has decreased since the 2015– 2016 epidemic, a substantial amount of Zika research continues to provide new data and information on this infectious disease. Current research suggest Zika will be around until the foreseeable future with research indicating ZIKV actually circulates in areas previously unknown. Moreover, in 2019 Europe's first autochthonous case [31] was identified and further confirmed the importance of vector control and public health programs. Like the flaviviruses mentioned above, ZIKV's main vectors are *Ae. aegypti* and *Ae. albopictus* placing a large proportion of the global population at risk of infection; therefore, threatening International Health Security [31, 33]. Although *Aedes* mosquitos are the confirmed vector for ZIKV*, Culex* genera mosquitoes, mostly *Culex quinquefasciatus*, are theorized to be capable to transmit Zika, further expanding its geographic reach [34]. However, recent studies did not support the ability for Culex mosquitoes to transmit ZIKV [35, 36]. In conjunction with its vectors wide global reach, a high proportion of Zika cases are asymptomatic and those who are symptomatic mirror symptoms to dengue and the flu (e.g., fever, rash, muscle and joint pain) compounding the barriers to diagnosis, treatment, and epidemic mitigation efforts.
