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Blog 1:  Zoonosis and Spillover: All Connected
(Dec 2022)
Ahmed, a 25 years old PhD student in Chemistry, lives in a city named Jeddah, located at the Kingdom of Saudi Arabia, with his family. It was a vacation in his university and he came to see his loved ones and friends in Jeddah. In his leisure hours he always prefers to visit Mahmud’s house and specially to spend times in a Dromedary camel barn that Mahmud's father owns. Ahmed loves camels. He also loves to consume their raw milk, which Mahmud offers him each time he visits that barn. Everything was going well until in a fine morning Ahmed felt a shortness of breath with symptoms of fever and cough. His parents took him to a nearby healthcare facility. After testing, he was diagnosed with a novel coronaviral disease. The year was 2012.
Those who are from biological science background, might have already realized the name of that causal agent of Ahmed’s disease, after checking out the year I have mentioned. Yes, you are right! Middle East Respiratory Syndrome Coronavirus or MERS-CoV, is the virus I am talking about. Now, you can blame me why I mentioned camel, why Jeddah and why this MERS-CoV? Do I have any special crush on these words? NO! I will discuss later in this blog what might have happened to Ahmed. But first we need to make ourselves familiar with few terminologies in biological science.
Zoonosis and Routes of transmission : In biology, especially in infectious disease biology, there is a common but valuable term, Zoonosis. Now, what do we mean by it? Why this even matters to us? According to the definition by World Health Organization (WHO), “A zoonosis is an infectious disease that has jumped from a non-human animal to humans.” From a recent data provided by WHO, 61% of all current human diseases are zoonotic in origin, in addition with 75% of emerging human diseases that are zoonotic. Although these zoonotic pathogens can be bacteria, viruses or even a parasite along with some unconventional agents, we will mainly focus on the viruses. Let us first understand how the animals spread harmful germs like viruses and causes mild to serious illness or even death to a person, although they are beneficial to human in agricultural aspect or some makes us happy by being a cute pet! Scientific body says, usually, the close connection between animals and people promotes zoonosis event. Not only from the domesticated and agricultural animals, the continuous interaction with wildlife is also one of the reasons behind this situation, which is of public health concern. How these interactions usually occur? CDC mentions five common ways through which viruses can transmit from animals to people. A. Direct Contact (Coming into contact with body fluids like saliva, blood, mucous, feces, urine) of a virally infected animal. Contact occurs by petting or touching animals and from their bites or scratches), B. Indirect Contact (In contact with such places where virally infected animals live or roam. These could be barns, chicken coop or pet habitats), C. Vector borne (Infected animals get bitten by insects followed by carrying those viruses with them and when those infected insects, so called vectors, bite a healthy person, the infection get transmitted), D. Foodborne (Eating or drinking unsafe and contaminated food, such as raw milk, undercooked meat or eggs, or raw fruits and vegetables. These contaminations occur from infected animals) and E. Waterborne (Drinking water that is contaminated with the feces or other body fluids from infected animals). As you all are aware of common routes of zoonosis occurrence, let us talk about ‘Zoonosis’ in detail. If you go through the history of zoonotic endemics, epidemics or pandemics, (No wait, do not pressurize yourself by thinking to read a bunch. Look into the occurrence of recent SARS-CoV2 pandemic) like how it started, how it follows the index infection and then spreads throughout the society as well as the whole world), you will surely find another terminology- ‘Spillover’.

Spillover: the ‘Core’ of zoonosis: While talking about ‘Zoonotic Spillover’, first I will bring up three types of hosts that deal with spill over phenomena, A. Reservoir host, B. Intermediate host (Bridge host) and C. Spill over host. The ‘zoonotic spill over’ or ‘host jump’ or ‘pathogen spill over’ defines a kind of cross-species transmission of any microbe into a host population that was not previously infected.” Let us take an example of recent COVID-19 infection. According to an article in Science, SARS-CoV-2 spillover likely occurred from bats and/or pangolins (ancestral virus) through unidentified intermediate host animals. Here bats and/or pangolins are the reservoir host for this virus. Reservoir host for any virus is a place where that microbe lives, grows and multiples without infecting the host. These strains infect susceptible domestic animals (such as mink), the intermediate host and likely adapt to these species through mutation. The virus then transmitted from mink or the respective intermediate host to farm workers who were in close contacts and also be transmitted to humans through contact with contaminated uncooked meat or food packaging. Here, you may say human beings are the spill over host. Now, you may wonder where the spill over took place? You can see at first the virus was in bats/pangolin from which they jumped to human being through an intermediate host in between. This jumping is actually known as a ‘Zoonotic spill over’. But I must say, the intermediate host may or may not be present in the spillover event. Because in few zoonotic cases the spill over hosts (Human being) got the infection from the reservoir host itself. Generally, these bridge hosts make a connection in between reservoir and spill over (recipient) host. I mentioned a term ‘Cross-species transmission’ and why so? I hope you know bats/pangolins and the human being are not under same species and transmission is occurring among them. In summarised form we thus must say if ‘zoonosis’ is the whole body then ‘spill over’ will be its’ heart or the core.

Spillover models: You might be thinking how viruses can jump the species barrier! How these tiny little fellows can overcome these. Ellwanger et al have discussed about four different models (known as spill over models) in a review paper and I will try to summarise it here-.
  1. Viruses can be transmitted directly from the source host to the recipient host or spill over host. Let us assume you got a bat bite last night and as you know bat is a wonderful reservoir for viruses, you got infected with one of them after 3/4 days of the bite.
  2. Viruses can also be transmitted from the source host to the recipient host through an intermediate vertebrate host, as I have already discussed previously.
  3. Virus can be transmitted from the source host to the recipient host through an intermediate invertebrate host. Consider, you have a pig farm. I hope you know pigs are the reservoir host of Japanese encephalitis virus (JEV). While you were working in that farm, you got bitten by some sweet Culex mosquitoes (I know they are not very sweet) and after few days you got sick. Congratulations you are now infected by JEV. So here Culex is that invertebrate intermediate host.
  4. Lastly, viruses can be transmitted from the source host to the recipient host through environment. Pigs release an enterovirus (Porcine enterovirus) into environment through feces. As you have the pig farm, suppose you came into contact with those feces and got that enteroviral infection. Or suppose in a summer time, you ate mangoes directly from trees without washing and without knowing that few minutes earlier a fruit bat licked that mango. Bat saliva contain viruses and that mango you just ate is containing that saliva. You are talented enough to realise what happens next.
So, as you can see, the ‘contact’, let it be with agricultural/domesticated animals or with wildlife, is a promising vehicle through which the viruses can move and jump.
Who is the villain? I will not emphasize more about this Zoonosis and spill over events because this is an infinite loop. Lots of researches are going on through the world by the scientific community and lots of new data and extraordinary concepts are becoming prominent. Thus, I can never finish this broad area in a small section of my blog. But for now, you might have a question, who is the villain then? The animal or the virus? First, this need to be mentioned that each organism is doing their own job. Virus is infecting and replicating different hosts for their own survival whereas animals need to live their life too. Then who is that devil behind all these phenomena? Yes. It is us. Yes, we are that devil who is continuously destroying the ecological balance by deforestation, continuous urbanization and thus, fostering the zoonotic spill over events. How? Suppose you are cutting down the trees randomly in a certain region of a forest because you want to build a multi storey building. It is good that you are creating habitats for others and for your own, but did you think that your own ‘habitat-making’ is the cause for ‘habitat loss’ of a bunch of wild animals and not only that, you are destroying their food source too. Habitat loss means a particular species has lesser of the natural spaces and resources available that they have depended upon in past to survive and thrive. You are just trespassing in their area, man. Just think about it, all these ‘contacts’, all these ‘interactions’ with wild life is happening because some greedy people want more and more. They are not even thinking the consequences of entering into wild life (encroachment of human population into wildlife habitat) where a lot of reservoir hosts for deadly viruses live. Bats, the only mammal that can fly and also hosts three (Filovirus, Henipavirus, Coronavirus) of the ten virus groups of pandemic concern, lives in roost. Bats need various roosting conditions at different times of the year and they often move around to find a favourable roost that means such roost that meets their needs. Few bats prefer hollow trees, few of them like caves and some use both at different times. Currently, destruction, degradation and fragmentation in the ecosystem that is solely caused by human beings are the causes behind ‘habitat loss’ in bat community. Being hopeless, they are entering into human civilization followed by direct or indirect interactions with us and Bam!! Lots of opportunities of emerging and re-emerging diseases to occur in that part. Scientists are saying all these anthropogenic changes along with the climate change are acting as  catalysts in zoonosis and spillover. Then why shouldn’t we call us the villain!
A successful spill over: Even if we are saying spill over is the core of zoonosis, it is not that easy to happen successfully. Spillover is a complex and multifactorial phenomenon, involving aspects associated with the hosts, microorganisms and the environment. The risks of a spillover event occurring will be primarily influenced by the prevalence and intensity of infection in reservoir hosts, from wild environments or farms. The distribution and density of infected hosts in a given environment is also a determining factor for the spillover risk. The prevalence and intensity of infection in reservoir hosts are also relevant because it determines the pathogen load in such species and the patterns of pathogen shedding. Next comes the immunological conditions of hosts, inter-species interactions (e.g., prey-predator interactions, habitat sharing) and several environmental aspects. The viral load observed in reservoir hosts again influences the excretion or shedding of viruses in the environment (through feces) or in the meat and body fluids of these animals. Viral characteristics (the virus is viable or not and if they are capable enough to transmit) influences the spill over risk too. Last but not the least, the frequency of human contact with animals as well as the dose and route of exposure to the viruses modulate the risk of spillover. Biological (genetics, immune status) and social aspects ( cultural practices, eating habits) have the capability to affect the mode, intensity and frequency of interactions with different host species or vectors. So, as you can see all these factors are the main barriers that need to be cleared for maintaining a successful spill over. If any of these barrier is unable to pass there will be no spill over. Feeling confused right? Don’t be because life is never easy. Here I am listing important factors which are essential enough to be maintained for a successful zoonotic spill over.
  • Reservoir host distribution
  • Reservoir host density
  • Pathogen prevalence
  • Pathogen intensity
  • Pathogen release from reservoir host
  • Pathogen survival and spread
  • Human exposure
  • Structural barriers
  • Innate immune response and molecular compatibility
  • Replication and dissemination cycles completed
  • Spillover
Let us pack up this blog now. I know, I have written a little part of this vast area. A huge amount of knowlege is still waiting in pubmed with some extra-ordinary research papers and review articles by great scientific bodies. My actual goal for writing this blog is to enlighten few snaps about this wonderful topic of public health.  So, what happened to Ahmed then? I hope you haven’t forgotten him yet. Can you relate the whole scenario that occurred to Ahmed, now? Let me tell you. Dromedary camel is the reservoir host of MERS-CoV. When Ahmed repeatedly visited that barn and drank raw camel milk, he, unknowingly made a contact with those camels which were already infected by the MERS-CoV. And then? The virus transmitted from those camels to Ahmed and after a certain incubation time he showed the symptoms. (Note: MERS-CoV outbreak occured in 2012 and Jeddah is a city in Saudi Arabia where this novel coronavirus was first identified)
Lastly you may ask me how we can prevent this zoonosis. A lot of counter measures and approaches have been taken for it but the most interesting one is the ‘One Health’ approach. Do you want to know about it, I will come up with this as my next topic in my blog.

Stay tuned.

(Written by Arkadeb)

Reference:
  1. Ellwanger JH, Chies JAB. Zoonotic spillover: Understanding basic aspects for better prevention. Genet Mol Biol. 2021 Jun 4;44(1 Suppl 1):e20200355. doi: 10.1590/1678-4685-GMB-2020-0355. PMID: 34096963; PMCID: PMC8182890.
  2. https://www.emro.who.int/fr/about-who/rc61/zoonotic-diseases.html
  3. Zhou P, Shi ZL. SARS-CoV-2 spillover events. Science. 2021 Jan 8;371(6525):120-122. doi: 10.1126/science.abf6097. PMID: 33414206.
  4. https://www.cdc.gov/onehealth/basics/zoonotic-diseases.














 
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