*3.2.1.8 MERS-CoV*

In 2012, a novel beta-coronavirus was identified to be the causative agent for acute respiratory disease in humans in Saudi Arabia and was named Middle East Respiratory Syndrome-related coronavirus (MERS-CoV) [104, 112]. Bats are the main mammalian reservoir for MERS-CoV with dromedary camels as the source of human infection [104, 112]. This enveloped +ssRNA virus is transmitted from animals to human through close contact with infected dromedary camels and/or person-to-person through respiratory droplets [104, 112]. The majority of cases of MERS-CoV are limited to Middle East with the lack of rapid global spread due to poor efficiency of person-to-person transmission [104]. MERS-CoV infection results in symptoms similar to other beta-coronaviruses and range from mild influenza like illness to severe disease with respiratory distress, septic shock, and multi-organ failure [112]. The initial case in 2012 was followed by an outbreak in Middle East in 2014 impacting 27 countries in Europe, Asia, Middle East, and North America with cases related to Middle East travel history [104]. The associated Korean outbreak in 2015 was precipitated due to a super spreader event with the individual having travel history to Middle Eastern countries [104, 112]. Till December 2019, a total of 2499 confirmed cases and 858 deaths have been reported due to MERS-CoV [68]. Research studies have shown the natural susceptibility among Alpacas and Llamas camelids to MERS-CoV [113, 114]. This raises the potential of widening of the geographic distribution of MERS-CoV to the South American region with high new world camelids population (Peru, Argentina, Chile, Bolivia) if the virus is introduced to these regions, becoming a threat for International Health Security in the Americas. Currently, the virus in stage-3 of pathogenic evolution and phase-3 of pandemic alert level. The lack of vaccine or treatment along with the potential for viral mutation that could increase zoonotic and/or person-to-person transmission may increase the epidemic potential of MERS-CoV and cause an International Health Security threat.

#### *3.2.1.9 Hantavirus*

Different than any previously mentioned pathogens, Hantaviruses are an entire genus capable of causing human diseases. In 1981, this group of -ssRNA viruses were introduced into the Bunyaviridae family [115]. Before 1993, Hantaviruses were thought to be solely responsible to cause hemorrhagic fever with renal syndrome (HRFS) in old world [115]. The main reservoirs for this type of viruses are rodents such as Cricetidae and Muridae. In 1993, the first new world Hantavirus was found in the Southwestern region of the US. This virus would later be named Sin Nombre virus (SNV) and be known to cause hantavirus cardiopulmonary syndrome (HPS) [115]. Since the discovery of SNV, the hantavirus genus includes more than 20 species and 30 genotypes [115]. Scientists have identified the deer mouse as the major host of SNV with cases confirmed in at least 30 US states [116]. The transmission of virus in humans is predominantly through inhalation of aerosolized rodent urine or salivary droppings. The pulmonary syndrome presents flu-like symptom lasting 3 to 5 days and after 7 days the cardiopulmonary phase may begin [115, 116]. Unfortunately, diagnosis of HPS has proved difficult and leads to misdiagnosis and underreporting [116]. Currently, the SNV has a high case fatality rate of 35% with no licensed antivirals or vaccine. Since close contact with or among rodents account for majority of exposures, rodent prevention and population surveillance is essential for transmission control. In 1996, a study found evidence of person-toperson transmission of another hantavirus in Argentine, raising concern of larger outbreaks in future [117]. Luckily person-to-person transmission is rare, if nonexistent suggesting pathogen is in stage-2 of pathogenic evolution and thus, phase-2 of pandemic alert level. Yet, recent outbreaks of other Hantaviruses (e.g., Andes virus) are an alarm for International Health Security surveillance systems who worry about future local outbreaks or global pandemics due to potential for personto-person transmission.

#### *3.2.2 Bacteria*

#### *3.2.2.1 Burkholderia pseudomallei*

This gram-negative bacillus is commonly found in environment and is the etiologic agent of a serious disease "Melioidosis" in humans and animals [118]. The agent was first identified in 1911 in Burma but was named *Burkholderia pseudomallei* in 1992 [119]. Melioidosis, also known as "Whitmore disease" mimics various other diseases such as community-acquired pneumonia, tuberculosis and sepsis and has a case fatality rate of 10–40% in humans [120–122]. Infection with *B. psuedomallei* is seen in numerous wild and domestic animal species with most cases seen in pigs, sheep, and goats [123]. The disease was first identified in Australia in 1950 and is currently endemic in Northern Australia and South East Asia [119, 120, 122]. In addition to the endemic areas, sporadic cases of *B. pseudomallei* occur in non-endemic areas of Central America, South America, and Africa and result in an estimated 165,000 cases per year worldwide with 89,000 of these cases having fatal outcomes [119, 122]. The predominant method of transmission is percutaneous inoculation, inhalation of aerosols, or ingestion of contaminated water with rare incidence of placental transmission [118–120]. *B. pseudomallei* infects both humans and animals but very rarely there is person-to-person, animal-to-animal or zoonotic transmission [120, 123]. The infectious form of *B. pseudomallei* can persist for prolonged periods in the environmental with soil or water acting as reservoir [123]. Improvement in diagnostic facilities and risk factors such as increased diabetes prevalence, anthropogenic changes, and globalization of humans and animals

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

may result in increase in infections by *B. pseudomallei* [123]. The lack of animal to humans or person-to-person transmission suggest the gram-negative bacteria is in stage-1 of pathogenic evolution. In the US, melioidosis is not a nationally notifiable disease but *B. pseudomallei* is a tier-1 select agent with a potential for use as a bioweapon due to its ability to infect humans and animals [123]. *B. pseudomallei* is resistant to penicillin, ampicillin, 1st and 2nd generation cephalosporins, and aminoglycosides like gentamycin, tobramycin and streptomycin. The therapeutic management consists of an 10–15 days intensive therapy with ceftazidime or carbapenems (meropenem/imipenem) followed by eradication therapy with trimethoprim-sulfamethoxazole [124]. The increase in areas with endemicity and susceptibility to infections in large number of species suggests a future risk in increase in reported cases and thus warrants increased awareness and attention from International Health Security experts. The lack of vaccine and long-term pharmaceutical therapy would further complicate the response in case of an outbreak.

#### *3.2.2.2 Coxiella burnetti*

*Coxiella burnetti*, the causative agent of Q fever in humans is an intracellular gram-negative coccobacilli that occurs in all geographic regions of the world except New Zealand [125–127]. The main reservoir of *C. burnetti* are cattle, sheep, and goats with marine mammals, birds, and arthropods reported to harbor the bacterium [127, 128]. Ticks are the main source of transmission of the bacterium in domestic animals but are not the source of transmission in humans [125]. Human Q fever is a worldwide zoonosis transmitted due to the inhalation of aerosolized bacteria from the environment. The bacterium is mostly spread in the environment due to shedding of bacteria in mammalian birth products, milk, feces, and urine with the bacterium surviving in the environment for long period [125, 128]. There have been only anecdotal reports of person-to-person transmission [127, 128] suggesting the pathogen is currently in stage 2 of evolution. The epidemiological profile of *C. burnetti* differs by countries and ranges from sporadic cases such as in US marines in Iraq, an epidemic in Cayenne, French Guiana, a major outbreak in Netherlands from 2007–2010, and a hyperendemic situation in Africa [127–129]. The widespread geographical distribution of *C. burnetti*, the recent outbreaks and description of disease in South-East Asia, India, and Brazil suggest the disease is very common cause of fever in the inter-tropical areas [127, 128]. The strains of *C. burnetti* resistant to doxycycline and erythromycin has been reported in many endemic areas of the world however most isolates still remain susceptible to doxycycline, fluoroquinolones, and trimethoprim-sulfamethoxazole [128]. The CDC has recently classified *C. burnetti* as select agent with potential to be used as in bioweapon [128]. Currently, *C. burnetti* causes zoonotic diseases but has not resulted in human-to-human transmission and thus is at the phase-3 of WHO pandemic alert level. The ability of *C. burnetti* to infect wide range of vertebrate and invertebrate hosts, persist in environment for long time, and cause massive outbreaks such as in Netherlands suggest that *C. burnetti* could become a major International Health Security threat in future with potential to cause pandemics.

#### *3.2.2.3 Bacillus anthracis*

This gram-positive spore forming bacilli is the causative agent of anthrax, a zoonotic disease which is rare in humans and common in animals. Human anthrax is a highly contagious disease and can be transmitted from animals to human through contact with infected animal or animal products or ingestion of animal meat. However, this highly virulent disease has no documented person-to-person

transmission [68, 130]. Herbivores animals are the primary reservoir of anthrax with all warm blood animals susceptible to *B. anthracis* infection [130]. Depending on the method of entry of the pathogenic endospores (inhalation, ingestion, skin), the disease can have respiratory (5%), cutaneous (94%), and gastrointestinal (1%) forms [130].

Worldwide approximately 20,000–100,000 cases of anthrax are reported annually, with the disease a major threat in arid regions of Central Asia, Africa, Middle East, Haiti, and South America [68, 131]. In the US, a total of 18 cases of inhalational anthrax and no case of gastrointestinal anthrax has been reported in the 20th century [132]. The largest outbreak of human anthrax was reported in Soviet Union in 1979, due to ingestion or contact with contaminated meat. The spores of the bacilli are resistant to environmental conditions such as drying, heating, ultraviolet (UV) rays, and gamma radiation and can survive for decades [68, 130]. This makes *B. anthracis* a major biological risk with a potential to be used in bioterrorist attack. In October–November 2001, intentional release of anthrax resulted in 22 cases of inhalational or cutaneous anthrax in US [133]. The drug of choice for treatment is oral or intravenous doxycycline or ciprofloxacin with the vaccine having no efficacy in post-exposure prophylaxis [130]. The causative agent is sensitive to most antibiotics with the exception of 3rd generation cephalosporins and trimethoprimsulfamethoxazole but requires long duration of treatment due to endospores [130]. Currently, the disease in in stage-2 of evolution of pathogenic microbe resulting in limited animal to human outbreaks and phase-2 pandemic security level. This combination of factors such as high virulence, persistence in environment, and the fact that it has already been weaponized makes *B. anthracis* a major concern for International Health Security.

#### *3.2.2.4 Mycobacterium tuberculosis*

Tuberculosis (TB) is a chronic inflammatory disease caused by an acid-fast bacilli *Mycobacterium tuberculosis*. In addition to *M. tuberculosis*, *M. bovis* a member of the *Mycobacteriaceae* genus also can cause TB infection [134]. With the advent of antibiotics, public health experts believed they had achieved control over TB however, the emergence of HIV pandemic in 1980s resulted in the re-emergence of TB [135]. In 2019, TB was the infectious disease responsible for the largest number of deaths due to communicable diseases worldwide [136]. The *M. tuberculosis* bacilli is transmitted from person-to-person through small droplet nuclei while *M. bovis* is a zoonotic disease transmitted from cow to humans through ingestion of unpasteurized milk [134, 137]. *M. tuberculosis* has also shown to have bidirectional transmission between elephants and humans i.e. reverse zoonosis and zoonosis [138, 139]. The zoonosis- reverse zoonosis transmission is mainly possible due to close contact between humans and elephants during training of elephants, living in close proximity, and cleaning of barn [138, 139]. The inappropriate usage of antimycobacterial agents and antibiotics associated selective pressure led to the emergence of drug resistance strains of *M. tuberculosis*. Multi-drug resistant TB (MDR-TB) is defined as resistance to isoniazid and rifampicin, two of the first line antimycobacterial agents. Additionally, selective strains of bacteria have emerged with resistance to even second line antimycobacterial agents causing extensively drug-resistant tuberculosis (XDR-TB) and some with total lack of susceptibility to antimycobacterial agents causing total drug-resistant tuberculosis (TB) [140]. MDR-TB chemotherapy consists of drugs with severe toxicity to be given for 18–24 months and thus MDR-TB is associated with significant morbidity and mortality.

TB affects all regions of the world with nearly a quarter of the world's population infected with *M. tuberculosis* [136]. In 2017, worldwide TB incidence was 10 million

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

with 1.57 million fatal outcomes [136]. Approximately 5.6% of the total TB cases and 3.6% of the incident cases were MDR-TB [136]. Nearly 70% of the global burden of TB was found in South-East Asia and Africa with India, China, and Russia having more than 50% of the global burden of MDR-TB [140]. Only 57% of all MDR-TB cases receives and completes treatment [140]. Tuberculosis is primarily a disease transmitted airborne from person-to-person and thus is in stage-5 of pathogenic evolution. MDR-TB continues to be a threat to public health and international security due to the concerns related to long duration of chemotherapy, lack of safe and effective antimycobacterial agents, morbidity, mortality, socioeconomic impact, airborne transmission and recent zoonotic-reverse zoonosis transmission. Many International Health Security experts believe MDR-TB could be the plague of century 21st.

#### *3.2.3 Fungi*
