Introductory Chapter: Recent Trends in Emerging and Reemerging Viral Contagions – The Day after Today

*Shailendra K. Saxena, Supriya Shukla, Swatantra Kumar, Vimal K. Maurya and Saniya Ansari*

#### **1. Introduction**

The increased interactions between people and animals and the easier spread of zoonotic pathogens have resulted from increased trade between communities. Following that, the emergence and spread of infectious diseases were facilitated by the growth of cities, the expansion of trade routes, increased travel, and the effects of an expanding human population on ecosystems, which increased the likelihood of outbreaks, epidemics, and even pandemics [1]. The terms "outbreak," "epidemic," and "pandemic" refer to a condition's occurrence in comparison to its expected rate as well as its geographic spread. An outbreak is defined as an unexpected rise in the population with a particular health condition or the occurrence of cases in a new location. An outbreak that spreads to a wider geographic area is called an epidemic. An epidemic that spreads globally is called a pandemic [2].

According to estimates, two-thirds of emerging human infections and about 60% of infectious diseases have zoonotic origins, with origins in wildlife. Humans are at high risk of infection as they are more likely to come into contact with animal and arthropod vectors of viral infections due to habitat destruction brought on by rapid urbanization. In the absence of specific immunity in these populations, such interactions have been one of the major factors increasing human susceptibility to infections by novel outbreaks [3]. Viral infections are majorly divided into three categories that are respiratory viral infections, arboviral infections, and bat-borne viral infections [4].

Over four million people die from acute respiratory diseases each year, and millions more are hospitalized in developing nations [5]. Human respiratory infections are brought on by more than 200 viral pathogens from the families *Orthomyxoviridae, Paramyxoviridae, Picornaviridae, Coronaviridae, Adenoviridae,* and *Herpesviridae*. Adenoviruses, Respiratory syncytial virus (RSV), influenza, and parainfluenza are still significant respiratory pathogens [6]. A recurring pattern in the world's landscape of infectious diseases has been the periods of dormancy that several pathogens experience after being first discovered, which are then preceded by their recurrence, frequently in more virulent forms. Arboviral diseases are transmitted by mosquitoes and are tedious to be diagnosed. The viral infections that are of major global concern are caused by arboviruses like West Nile virus (WNV), Japanese encephalitis virus (JEV), Dengue

#### **Figure 1.**

*Visualizing the history of pandemics. Data sources: CDC, WHO, BBC, Wikipedia, Historical records, Encyclopaedia Britannica, Johns Hopkins University; Source: Visual Capitalist. https://www.visualcapitalist. com/history-of-pandemics-deadliest/.*

virus (DENV), Chikungunya virus (CHIKV), Zika virus (ZIKV), Yellow fever virus (YFV), and others. *Aedes aegypti* mosquito populations are abundant throughout most of the nation, serving as effective carriers of DENV, CHIKV and ZIKV, which are still major threats worldwide (**Figure 1**, **Table 1**) [7].

#### **2. Global outbreaks/pandemics in 21st century**

#### **2.1 Avian influenza**

Humans can develop a variety of symptoms from asymptomatic or mild upper respiratory infections (fever and cough) to severe pneumonia, acute respiratory distress syndrome, shock, and even death from zoonotic influenza infections. The majority of human cases of avian influenza are brought on by direct or indirect contact with infected live or dead poultry or contaminated environments [8]. A total of 868 human cases of influenza A (H5N1) infection and 456 fatalities have been reported

*Introductory Chapter: Recent Trends in Emerging and Reemerging Viral Contagions – The Day... DOI: http://dx.doi.org/10.5772/intechopen.109162*

#### **Table 1.**

*Global outbreaks/pandemics in and before 21st century.*

globally from 21 countries between 2003 and October 21, 2022. Three human cases of influenza A (H5N1) infection have been reported in Europe thus far, including one case from the United Kingdom in 2021 and two cases from Spain in 2022 [9].

The average incubation time for the Influenza A (H5N1) virus is 2–5 days, but it can last up to 17 days. Humans who are infected typically experience fever, malaise, coughing, sore throats, and muscle aches. A pneumonia complication may cause severe illness and even death. In comparison to seasonal influenza infection, the case fatality rate for avian influenza in humans is significantly higher [10].

#### **2.2 Ebola virus disease**

The Sudan Ebolavirus (SUDV)-caused Ebola outbreak in the Republic of Uganda was declared on September 20, 2022, following the confirmation of a case in a village in Madudu Sub-County, Mubende District, central Uganda, on September 19 [11, 12]. Humans occasionally contract the severe, frequently fatal disease known as the Ebola virus disease (EVD), formerly known as Ebola hemorrhagic fever. The virus spreads among humans through human-to-human contact and also via animals. Around 50% of EVD cases end in death on average. In previous outbreaks, case fatality rates ranged from 25 to 90% [13].

Ebola vaccines have been designed and used to prevent the spread of outbreaks of the disease in Guinea and the Democratic Republic of the Congo (DRC). Infected individuals may be treated with early supportive care combined with early symptomatic treatment and re-hydration increases their survival. Inmazeb and Ebanga, two monoclonal antibodies, were authorized by the US Food and Drug Administration in late 2020 for the treatment of Zaire Ebola virus (Ebola virus) infection in adults and children [14].

#### **2.3 Marburg virus disease**

Marburg virus disease (MVD), formerly known as Marburg hemorrhagic fever, is a serious, often fatal illness that affects humans. It is a member of the same pathogen family as the Ebola virus. Due to two significant outbreaks that occurred concurrently in Marburg, Frankfurt, Belgrade, Serbia, as well as in Germany, the disease was first discovered in 1967 [15]. After nearly 18 years, two cases of Marburg virus disease were identified in Ghana's Ashanti region in July 2022. The risk of this 2022 outbreak spreading is high at the national level but low at the global level, according to WHO. The average fatality rate is around 50% in MVD cases. In previous outbreaks, case fatality rates ranged from 24 to 88%, depending on virus strain and case management [16].

The Fruit bats of the *Pteropodidae* family, *Rousettus aegyptiacus*, are thought to be natural hosts of the Marburg virus. The Marburg virus is transmitted to humans by fruit bats and spreads via human-to-human transmission [17]. Marburg virus infection is characterized by the sudden onset illness with excruciating headaches, high fever, and excruciating malaise. Within a week, many patients experience severe hemorrhagic symptoms, and in fatal cases, bleeding is typically present, frequently in multiple locations [15]. Early supportive care, including rehydration and symptom relief, improves survival. There is currently no licensed treatment that has been proven to neutralize the virus, but a variety of blood products, immune therapies, and drug therapies are being developed [18].

#### **2.4 Yellow fever**

A family of positive, single-stranded, enveloped RNA viruses known as the *Flaviviridae*. They can occasionally infect humans and are found in arthropods, primarily in ticks and mosquitoes [19]. The members of this family are major global causes of morbidity and mortality. YFV, DENV, JEV, WNV and ZIKV are a few of the viruses spread by mosquitoes [20].

Yellow fever is a viral hemorrhagic fever disease, transmitted by Aedes mosquitoes. Tropical regions of Africa, Central and South America are affected by this disease [21]. YF exhibits acute-onset jaundice along with constitutional symptoms like fatigue, headache, nausea, nausea, myalgia, fever, and nausea. Cases with severe symptoms may experience liver and multiple organ failure, and the CFR in these situations may reach 50% [22].

*Introductory Chapter: Recent Trends in Emerging and Reemerging Viral Contagions – The Day... DOI: http://dx.doi.org/10.5772/intechopen.109162*

The IgM ELISA assay and qRT-PCR are the two main methods used in laboratory diagnosis. Due to the cross-reactivity with other flaviviruses, a plaque reduction neutralization test (PRNT) may be required. There is a YF vaccine that is incredibly effective. Within 10 days of vaccination (80–100% effective), and within 30 days (99% effective), a single dose of the YF vaccine is sufficient to confer life-long immunity [23]. An unprecedented initiative, the eliminate yellow fever epidemics (EYE) strategy was introduced in 2017. The EYE partnership with more than 50 partners assists 40 at-risk nations in Africa and the Americas in preventing, detecting, and responding to suspected cases and outbreaks of yellow fever. The collaboration aims to safeguard vulnerable populations, stop the global spread, and swiftly contain outbreaks. More than a billion people are anticipated to be immune to the illness by 2026 [24].

Zika virus was first discovered in Uganda in 1947 in monkeys. Later, in 1952, it was discovered in people in the United Republic of Tanzania and Uganda. The Island of Yap (Federated States of Micronesia) reported the first known outbreak of the zika virus disease in 2007. This was followed by a significant zika virus infection outbreak in 2013 in French Polynesia and other Pacific region nations and territories [25]. Other important mosquito-borne flaviviruses are Japanese encephalitis virus (JEV), is responsible for causing 68,000 clinical cases per year, which is the primary cause of viral encephalitis in many Asian nations. JEV transmission is endemic in 24 countries in the WHO South-East Asia and Western Pacific regions, putting the health of more than three billion people at risk [26].

#### **2.5 Severe acute respiratory syndrome-associated coronavirus (SARS-CoV)**

The SARS-associated coronavirus (SARS-CoV)causes respiratory disease known as a severe acute respiratory syndrome (SARS). It was discovered at the end of February 2003 as part of an outbreak that began in China and spread to four other countries [27]. SARS is an airborne virus that, like the common cold and influenza, can spread through small droplets of saliva. It was the first severe and easily transmissible new disease to emerge in the twenty-first century, with a clear capacity to spread along international air travel routes [28]. The majority of SARS patients were previously healthy adults aged 25–70 years. A few suspected SARS cases among children under the age of 15 have been reported. The case fatality rate among people is around 3% [29].

#### **2.6 Nipah virus**

In 1998, a case outbreak of acute febrile encephalitis among pig handlers in Kampung Sungai Nipah, Malaysia, led to the discovery of NiV for the first time. Nipah virus (NiV) is a pathogenic Paramyxovirus that, along with the Hendra virus, is a member of the Paramyxoviridae, genus Henipavirus. It causes acute-onset encephalitis, which can be fatal to humans [30]. Pteropus Bats are thought to be the reservoir for the NiV, and contact with positive NiV cases or an intermediate animal host, such as pigs, usually results in transmission to humans. The virus can also spread from person to person, according to reports [31]. There have been NiV outbreaks in pigs reported from Malaysia and Singapore. Human disease has since been reported in Bangladesh, India, Malaysia, and Singapore. The latest outbreak was seen in May 2018 in Kerala, India [32].

The average incubation period for NiV disease in humans is 4–14 days, while the maximum incubation period is 21 days. Acute febrile encephalitis is the condition that the virus causes and symptoms include fever, headache, drowsiness, dizziness, and coma. NiV infection in humans and animals is confirmed by anti-Nipah IgM and IgG antibody detection, virus isolation, and RNA analysis [33].

#### **3. Global outbreaks that lead to Pandemic**

#### **3.1 Monkeypox**

A viral zoonotic disease called monkeypox is most common in tropical rain-forest regions of Central and West Africa, with sporadic exportations to other areas. As of November 8, 2022, a total of 78,599 cases were reported in newer areas; where monkeypox has never been previously reported; while 949 cases were reported from the endemic area [34]. The Monkeypox virus, a species of the *Orthopoxvirus* genus in the family *Poxviridae*, is the culprit behind monkeypox. Typically, monkeypox is a self-limiting illness with symptoms that last between 2 and 4 weeks. There may be severe cases. The case fatality rate has recently been in the range of 3–6%. Humans can contract monkeypox by coming into close contact with an animal or person who has the disease, as well as by coming into contact with contaminated objects. By coming into close contact with lesions, bodily fluids, respiratory droplets, and contaminated objects like bedding, the monkeypox virus can spread from one person to another [35]. Clinical symptoms of monkeypox typically include fever, rash, and swollen lymph nodes, and it can result in a variety of health issues. The monkeypox vaccines used in the smallpox eradication program also offered protection from that disease. There are more recent vaccines available, one of which is authorized for the prevention of monkeypox [36].

#### **3.2 SARS-CoV-2**

Hospitals in Wuhan, Hubei province, China, reported on a cluster of pneumonia cases with no known cause on December 31, 2019, grabbing the attention of people all over the world. A new coronavirus was identified and named as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) which was identified 2 weeks later in a bronchioalveolar lavage of the patients. The SARS-CoV-2 causes respiratory infections along with multi-organ involvement disease known as Coronavirus disease (COVID-19) [37].

Over 627 million cases, including over 6.5 million fatalities, had been reported globally as of October 30, 2022 [38]. Both symptomatic and asymptomatic individuals can spread the virus to others by coming into close contact (within six feet) and exchanging respiratory droplets. Transmission may also happen through aerosols and possibly through contact with infected surfaces [39].

Due to the rapid emergence of some variants in populations and the evidence of transmission or clinical implications, these variants are regarded as variants of concern. Omicron (B.1.1.529) variants found in changing sub-lineages have dominated the world's circulating variants since 2022. At the same time, the Alpha (B.1.1.7), Beta (B.1.351), Gamma (P.1), and Delta (B.1.617.2) were prior variants of concern that are less circulating [40].

*Introductory Chapter: Recent Trends in Emerging and Reemerging Viral Contagions – The Day... DOI: http://dx.doi.org/10.5772/intechopen.109162*

#### **3.3 Influenza**

The *Orthomyxoviridae* family of influenza viruses is frequently held responsible for epidemics and pandemics that affect humans. Prior to the 2009 pandemic, influenza pandemics occurred in 1918 (swine flu), 1957 (Asian flu), 1968 (Hong Kong flu), and 1977 (Russian flu) (pandemic influenza A H1N1) [41]. The influenza A, B, and C viruses are responsible for the acute respiratory illness influenza, which can appear locally or as a seasonal epidemic. Seasonal epidemics are brought on by the influenza A and B viruses, whereas influenza C viruses typically only cause minor illness. The antigenic characteristics of the two surface glycoproteins on influenza A viruses—hemagglutinin and neuraminidase—are used to further categorize them into subtypes. The influenza A virus has 16 hemagglutinin and 9 neuraminidase subtypes that have been isolated from birds (H1 to H16 and N1 to N9), and the RNA of an additional 2 haemagglutinin and neuraminidase subtypes that have been identified in bats (H17 and H18 and N10 and N11) [42].

The majority of human cases of avian influenza are brought on by direct or indirect contact with infected live or dead poultry or contaminated environments. A total of 868 human cases of influenza A (H5N1) infection, including these 2 cases, and 456 fatalities have been reported globally from 21 countries between 2003 and October 21, 2022. Three human cases of influenza A (H5N1) infection have been reported in Europe thus far, including one case from the United Kingdom in 2021 and two cases from Spain in 2022 [43].

Humans can develop a variety of symptoms from asymptomatic or mild upper respiratory infections (fever and cough) to severe pneumonia, acute respiratory distress syndrome, shock, and even death from zoonotic influenza infections. Animal influenza viruses can infect humans directly, and the resulting clinical illness can range from mild to severe, just like human influenza viruses [44]. A history of exposure to sick birds or travel to countries where avian influenza cases are being reported may raise suspicion of a novel influenza virus infection, but a definitive diagnosis requires laboratory tests that are typically only available through public health laboratories [9]. Identification of such infections is critical for determining the source of the virus, establishing evidence of person-to-person transmission, and assessing pandemic potential [41].

#### **3.4 MERS-CoV**

The zoonotic virus MERS-CoV, which causes respiratory infections, was first discovered in Saudi Arabia in 2012 and has since spread to 26 other nations. MERS-CoV infection has been linked to over 2207 lab-confirmed cases and 787 fatalities worldwide since 2012. The MERS-CoV clinical spectrum of illness includes asymptomatic infections all the way up to acute respiratory distress syndrome, which can lead to multiple organ failure and death. At 3–4 per 10 cases shows severe symptoms, the case-fatality rates (CFRs) have remained high [45].

The dynamics of this virus' transmission are currently poorly understood, and there is still no effective cure or preventative vaccine. Even in the absence of mutations conferring hyper-virulence, there is evidence for secondary, tertiary, and quaternary cases of MERS resulting from a single infected patient [46]. The natural reservoirs of this virus are bats, and patients have been reported who developed an infection from camels. The virus was transmitted in several countries' healthcare

facilities, including transmission from patients to healthcare providers and transmission between patients before MERS-CoV was identified. Because symptoms and other clinical features may be nonspecific, it is not always possible to identify patients with MERS-CoV early or without testing [47].

#### **4. Conclusions**

The diversity in geo-climate of the world faces constant threat of viral outbreaks. It is impossible to predict when the next viral outbreak will start or what virus it will be. Therefore, non-pharmaceutical interventions should be used first to control the viral transmission from person to person, according to pandemic preparedness plans. For outbreaks to be successfully controlled, community involvement is essential. A combination of interventions, including case management, infection prevention and control procedures, surveillance and contact tracing, a top-notch laboratory service, safe and respectable burials, and social mobilization, are necessary for effective outbreak control.

#### **5. Future perspectives**

Disturbingly, future outbreaks and a pandemic are still a possibility because there are no vaccines for the various viral infectious strains, no effective treatments, and a high mortality rate. Therefore, it is crucial to ponder quickly about the disease and ways to stop a virus-related pandemic. There is a need for the creation of antivirals that are particular to the virus as well as vaccines against viral strains. All governments should make sure that their citizens have access to viral disease treatments. Additionally, for the prevention of viral transmission to the globe, it must be limited at the initial stage. To stop a future outbreak and potential pandemic, it is crucial to spread awareness early among people around the world.

#### **Acknowledgements**

The authors are grateful to the Vice Chancellor, King George's Medical University (KGMU) Lucknow, for the encouragement and support for this work. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

#### **Funding**

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

#### **Conflict of interest**

None.

*Introductory Chapter: Recent Trends in Emerging and Reemerging Viral Contagions – The Day... DOI: http://dx.doi.org/10.5772/intechopen.109162*

### **Author details**

Shailendra K. Saxena\*, Supriya Shukla, Swatantra Kumar, Vimal K. Maurya and Saniya Ansari Centre for Advanced Research (CFAR), Faculty of Medicine, King George's Medical University (KGMU), Lucknow, India

\*Address all correspondence to<EMAIL_ADDRESS>
© 2022 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Section 2


3.3.2. Deep-Reinforcement Learning

In recent years, much attention has been given to deep-reinforcement learning (DRL) in task offloading. Reinforcement learning, RL, is a branch of artificial intelligence in which an agent interacts with the environment and learns using two functions: reward and punishment. Punishment is a negative reward. In RL, the learning cycle is not based on a training dataset; instead, the agent interacts with the environments with no prior knowledge and obtains immediate feedback based on its performance. The environment is modeled as a Markovian Decision Process (MDP). In RL an experience is defined as the triple (*st* , *at* ,*rt*), where *st* , *at* , and *rt* are, respectively the state, action and reward at the time

*t*. The agent determines the action based on a policy, *π*(*s*). Q-learning algorithm is an offline policy that estimates *π*(*s*) with guaranteed convergence. The mapping between the policy and the state at a given time *t* is given by (3) [45]

$$Q(s\_{l\prime}, a\_l) = Q(s\_{l\prime}, a\_l) + \mathfrak{a}(r\_l + \gamma \max\_a Q(s\_{l+1\prime}, a\_l) - Q(s\_l, a\_l)),\tag{3}$$

where *α* is the learning rate, and *γ* is the discount rate. In RL, the agent tends to maximize the rewards. This concept is illustrated in Figure 5.

**Figure 5.** Principles of DRL.

Offloading algorithms-based Q-Learning has been devised in many published reports such [11,43,44,46–48].

In [46], the authors devised a dynamic computation-offloading strategy for an MEC system using Markov decision process theory. The authors considered IoT devices with energy-harvesting techniques. The optimal offloading is achieved using a low-complex after-state learning method.

The problem of task offloading in the context of MEC has been formulated in [47] as a constrained Markov decision process (CMDP). The authors applied Lagrangian primaldual optimization and devised a deep-reinforcement learning algorithm to solve the relaxed CMDP.

Dynamic computational offloading for MEC systems with EH-enabled IoT devices considering multiple offloading servers has been studied and solved in [48]. The authors elaborated an offloading algorithm using deep Q-learning techniques.

Hardware implementation of the Q-learning algorithm received scant attention. Most of the reported implementation focuses on designing an accelerator using FPGA technology. The lowest power consumption has been reported to be 37 mW for a Q-matrix of dimensions eight states and four policies [49].

The work of [41] considered task offloading with energy harvesting for an IoT MEC system. The offloading problem has been formulated as a decentralized partially observable Markov decision process. They further reduced the computational complexity by searching for an approximated solution using an RL decentralized offloading algorithm. The results, obtained using Matlab simulations, showed that the proposed reduces both average delay and average energy consumption.

To this end, it is crucial to identify the power consumption during different activities of the end devices, in particular data processing, data transmission and communication. In the following section, specific design considerations for task offloading are presented, which may influence the power consumption and the latency of the software and hardware components of the IoMT systems. The main focus is attributed to the choice of the communication protocols for IoT devices with consideration of the energy consumption.