Introduction:

Microbial world have dominated the earth for billions of years and gradually evolved to all forms of life as we know it, including plants, animals and us, humans. If the microbial longevity on earth is a book of 1000 pages, the human’s life history on earth is less than a line of it! Microbes of all types, from bacteria, to fungus, to parasites and viruses have survived through infestation of their hosts, including humans for billions of years, and we just came to know them not long ago, less than a couple of hundreds years ago. By learning about the hygiene, use of detergents, alcohol, other disinfectants, then anti-microbial agents such as antibiotics, and vaccines, we were able to fight some of these infections befalling on us. So until a little while ago, we thought that infections and infestations have faded out, at least from the developed lands and only remains to be a struggle in the developing nations due to poor hygiene and poverty. But the last few decades have opened our eyes very well that the “survival of the fittest” is still the rule and we are all at the mercy of the rulers of the earth, the microbes and we might be at the verge of extinction soon. Unfortunately our life history on earth could be a lot shorter than what we thought, not because of the greed of our war machines, or the anger of the sun or another extraterrestrial attack on our being, but by microbial invasions! While we thought of “evolution” as an upward phenomenon to create us, humans so to rule the world and destroy it, we well observed and understood that “evolution” is in every direction, and the “wisest” is not the “winner”, but the “strongest”.

 Epidemics that have been a relatively rare incidents and exceptions in the past, have become the rule over the past couple of decades and have evolved to “Pandemics”! by our globalization, in fact we have helped the microbial world to get closer to all of us and we are not just sharing our gossips, greed, and ideas, but our germs. Through our infiltration to the nature and the wild, urbanization and destroying the environment, we have delineated the boundary between the civil and the wild life. As we will read in more detail in the following, more than %65 of our humans’ infections and the recent epidemics and pandemics are “Zoonotic” or originating from other animals, specially the wild life, into our very beings. It seems that the microbial invasions are all in full force and we are in full surrender, and we will fade out by acute attacks of epidemics and pandemics from outside, and at the same time, like Trojans invaded from within by the autoimmune disorders, cancers, degenerative, physical and mental disorders all caused by microbial invasions. If at the end anyone survives on earth, their genes have been mutated by the microbial attacks and we may not be humans after all as we know it today! Although these lines could be quite frightening and nightmarish, it is truly scientific and is known to microbiologists for a while. We may not have the solution to the survival yet, as the attacks are very serious and much sophisticated. But the first step is the knowledge of what is happening so to search for a collective solution and resistance altogether across the globe, that could never happen! In the following, after a brief review of the microbial invasions on humans throughout our short history, I will summarize an example of a few recent microbial invasions in the forms of epidemics and pandemics across the globe, while the list and detail of all could not be recorded here or perhaps anywhere else.


 Historical epidemics and pandemics:

Before the 20^th century, the major infection epidemic and pandemic in history has been “plague” or “black death” recorded as early as 429 BC befell in Athens, Greece and killed almost 100,000 people. (1) Different types of plague reportedly killed as much as 30% of the population of Europe, Western Asia and Northern Africa, between 165-180 AD; up to %40 of the population of Europe in only one year of 541-2; and up to %70 of the population of Europe again within four years of 1346-1350. (2) The first non-plague epidemics was viral hemorrhagic fever or Dengue fever that hit Mexico in 1545-8 with the death tolls of 5-15 million or up to %80 of the population, then again in 1576 that killed 2-2.5 million, up to half of the population of Mexico. (3) In a few centuries, other epidemics such as smallpox, measles, cholera, typhus and influenza attacked different part of the world and took their tolls. But these epidemics were sporadic and hit different countries or at the most regions, until in 19^th century when for the first time, cholera attacked the whole world in three pandemics, then influenza pandemic first in mid-19^th century, with the second pandemic in late 19^th century killing more than one million people world wide, until world war I, between 1918-20 when the biggest influenza pandemic sent more than 75,000,000 people of the earth to the graves, more than the casualties of the man made first world war, estimated 16 million at the most!(4)

 After the world war I and the biggest infection pandemic ever, for about 20 years there was a relative mercy by the microbes on the people of earth, humans continued sporadically causing wars and revolutions in different lands, until the world war II, 1939-45, when humans in competition with the influenza pandemic of early century could only kill about 60 millions of each others and lost to the microbial attack only by one minute virus! This perhaps woken up the microbes who soon in the cold war era, attacked the humans first in 1957-8 by Asian Flu world wide and killed over 2,000,000, then Hong Kong Flu in 1968-9 with the death toll of over 1,000,000; until a new modern sexual pandemic, called HIV, from 1960-present killed more than 30,000,000 of the world people! While in the past, there were at least a decade to a century time gap between different epidemics, since the start of the 21^st century, the world has witnessed year by year microbial invasions of all types, from dengue fever, to cholera, SARS, Ebola, malaria, influenza, etc. (5)

  H1N1:

Influenza A virus that was the cause of highest mortality of humans ever in the beginning of the last century, over time evolved and has been repeatedly appeared in different form, most recently as Influenza A (H1N1) virus, the most common cause of a partial pandemic worldwide in 2009 with more than 14,000 casualties. This type of influenza virus is consisted of two main subtypes, H1N1, H1N2, for containing glycoproteins Haemagglutinin (H) and Neuroaminidase (N). Haemagglutinin or the H component causes red blood cells to clump together and binds the virus to the infected cell. Neuraminidase or the N component is a type of glycoside hydrolase enzyme which help to move the virus particles through the infected cell and assist in budding from the host cells. Most recently, 2015-present, a new strain of H1N1 or swine influenza (since primarily infects pigs) has spread worldwide and claimed over 17,000 deaths by 2010 and is still ongoing in India with over 2,000 victims. In united states, northern sea otters off the coast of Washington state have also been reported to be infective source and a cause of pandemic of 2011 in Americas. In May 2013, seventeen people have been killed by this virus in Venezuela and as of early January 2014, Texas health officials have confirmed at least thirty-three H1N1 deaths and widespread outbreak during the 2013/2014 flu season, while twenty-one more deaths have been reported across the US. Meanwhile an outbreak hit several Canadian cities and Mexico. (6-7)

 HIV:

After plague and influenza, HIV by directly attacking humans’ immune system and causing AIDS (Acquired Immune Deficiency Syndrome) has been the most virulent and acute killer of all microbial invasions. This virus that has thus far claimed over 30,000,000 deaths worldwide was first clinically observed in 1981 in the United States. The initial cases were a cluster of injection drug users and gay men with no known cause of impaired immunity who showed symptoms of pneumocystis carinii pneumonia, a rare opportunistic infection that was known to occur in people with very compromised immune systems. Soon thereafter, additional gay men developed a previously rare skin cancer called Kaposi’s sarcoma. (8) AIDS in the beginning was labeled GRID (Gay-Related Immune Deficiency) as it was thought to be solely a homosexual related infectious disease, and later on “the 4H disease,” to single out homosexuals, heroin users, hemophiliacs and Haitians. However, later on it was discovered while the main route of transmission is through sexual contact, particularly among male homosexuals, it is not limited to this group, but the virus could be transmitted by blood, semen, genital secretions and even saliva and could affect a larger population than gay community alone. (9-10)

 HIV infects vital cells in the human immune system such as helper T cells (specifically CD4⁺ T cells), macrophages, and dendritic cells. HIV differs from many viruses in that it has very high genetic variability. This diversity is a result of its fast replication cycle, with the generation of about 10¹⁰ virions every day, coupled with a high mutation rate of approximately 3 x 10⁻⁵ per nucleotide base per cycle of replication. This complex scenario leads to the generation of many variants of HIV in a single infected patient in the course of one day. This variability is compounded when a single cell is simultaneously infected by two or more different strains of HIV. HIV is divided to the main groups, HIV-1(more virulent) & HIV-2 (less virulent). Three groups of HIV-1 have been identified on the basis of differences in the envelope region: M, N, and O. Group M is the most prevalent and is subdivided into eight subtypes, based on the whole genome, which are geographically distinct. The most prevalent are subtypes B (found mainly in North America and Europe), A and D (found mainly in Africa), and C (found mainly in Africa and Asia); these subtypes form branches in the phylogenetic tree representing the lineage of the M group of HIV-1. (11-3)


 SARS & MERS:

Severe acute respiratory syndrome (SARS) is a viral respiratory disease of caused by the coronavirus. Between November 2002 and July 2003, an outbreak of SARS in southern China caused an eventual 8,096 cases and 774 deaths reported in multiple countries with the majority of cases in Hong Kong. Within weeks, SARS spread from Hong Kong to infect individuals in 37 countries in early 2003, with no cases of SARS have been reported worldwide since 2004. (14-5)

 MERS (Middle East respiratory syndrome) also known as camel flu, is a viral respiratory infection caused by the another type of coronavirus, so far limited to the middle east deserts or Arabian peninsula. Just over 1000 cases of the disease have been reported as of May 2015, with a high mortality rate of about 40%. The first identified case occurred in 2012 in Saudi Arabia and most cases have occurred in the Arabian Peninsula, with an exceptional large outbreak recently in the Republic of Korea in 2015. (16-8)

Ebola & Zica Viruses:

Ebola virus is one of five known viruses within the genus of Ebolavirus. Four of the five known ebolaviruses, including EBOV, cause a severe and often fatal hemorrhagic fever in humans and other mammals, known as Ebola virus disease. Ebola virus has been the cause of the 2013–2015 an epidemic in west Africa with more than 11,000 deaths. Ebola virus is a single-stranded RNA virus with a high mortality rate of 83-90%. (19-25)

 Zika virus is a member of the Flaviviridae virus family. It is spread by daytime-active Aedes mosquitoes, and gets its name from the Zika forest in Uganda, where the virus was first isolated in 1947. Zika virus is related to dengue, yellow fever, Japanese encephalitis and West Nile viruses. The infection, known as Zika fever, often causes no or only mild symptoms, similar to a mild form of dengue fever. Since the 1950s, it has been known to occur within a narrow equatorial belt from Africa to Asia. In 2013-2014, the virus spread eastward across the Pacific Ocean in Oceania to to French Polynesia, New Caledonia, the Cook Islands, and Easter Island, and in 2015 to Mexico, Central America, the Caribbean, and South America, where the Zika outbreak has reached pandemic levels. Zika fever in pregnant women is associated with microcephaly, and in adults with the neurologic condition Guillain-Barre syndrome. (26-7)

 Norovirus:

As detailed in the last article of the site, Norovirus or the vomit bug or is a genus of Norwalk virus, named after Norwalk, Ohio in US, where an acute outbreak of gateroenteritis occurred among children in 1968. This virus is the most common cause of viral gastero-enteritis in humans, transmitted by fecally contaminated food or water, by person-to-person contact and via aerosolization of vomited virus and subsequent contamination of surfaces. Norovirus is a very tiny, un-enveloped RNA virus possessing the highest mutation rate even among other RNA viruses. Human and mammals serve as the natural host of Noroviurs, the leading cause of foodborne gasetroenteritis worldwide, affecting over 125 million people with over 200,000 deaths each year mostly in less developed countries and in the very young, elderly and immune-suppressed. Norovirus infection is characterized by nausea, vomiting, watery diarrhea, abdominal pain, lethargy, weakness, muscle aches, headaches, and low-grade fever. The disease is usually self-limiting in a few days, and severe illness is rare, but immunity is usually incomplete, temporary and not beyond a few years. (28-31)

 The common factors among these epidemic and pandemic viruses:

All these viruses mentioned here and many more, causing misery, morbidity and mortality for the human race through ages in the form of epidemics and pandemics are very simple, single stranded (- or + sense) viruses. By nature, these viruses can survive through entering the bodies of hosts, such as humans. A common feature among these viruses is their ability to dramatically modify cellular membranes to serve as platforms for genome replication and assembly of new virions, so to multiply in the hosts. These viral replication complexes (VRCs) serve two main functions: to increase replication efficiency by concentrating critical factors and to protect the viral genome from host anti-viral systems. Despite morphological differences in the replication complexes formed by members of each viral family, these viruses have evolved to use common cellular pathways to complete biogenesis. (32) Despite their simplicity and similarity, each has several different subtypes, their own characters and specialties, in genome production and mutation and causing different diseases across the host (animals and humans) organs. These viruses are not limited to the ones described here, but many more such as Hepatitis viruses, West Nile virus, Dengue virus, St. Louis Encephalitis Virus, Yellow Fever virus, Japanese Encephalitis virus, Poliovirus, Coxsackie virus, human rhinoviruses, Enteroviruses, Rubella virus, Alphaviruses, New World viruses including Venezuelan, Western and Eastern equine encephalites, Marburg virus, Borna Virus, Rabies, all influenza viruses, and many more that listing them here will be quite exhausting.

 Another sharing factor among many of these viruses including the ones mentioned here that are attacking humans worldwide, is that they are “zoonotics”, meaning they pass from an animal host to human. These zoonotic viruses through evolution and law of survival of the fittest, have been able to cross among species! Although viruses are not the only one among microbes to evolve as such but bacteria, fungi and parasites as well, viruses specially the single stranded ones are the champions. Zoonoses are the causes of over 1,400 or 61% of pathogens known to infect humans. Outbreaks of zoonoses have been traced to human interaction with and exposure to animals at fairs, petting zoos, wild life, etc., and also through foodborne diseases by eating animal meats. (33-7) Many outbreaks of zoonotic infections, e.g. Ecoli’s, Cryptosporidiosis, and Schistosomiosis outbreak infections have occurred in subjects visiting farm and farm fairs specially young children with low immunity defense. (38-43) The list of zoonotic diseases are exhaustive and a short list could include Brucellosis, Campylobacteriosis, ringworms, fleas, ticks, hookworms, round worms, rabies, salmonellosis, cat scratch disease, cryptococcosis, plague, sporotrichosis, Lyme disease, toxoplasmosis, influenzas, tuberculosis, tularemia,  chlamydiosis, lymphocytic choreomeningitis, pasteurellosis, rabit bite fever, monkeypox, ectoparasites, Newcastle disease, mycobacteriosis, Meliodosis, yersinosis, SARS, MERS, , Ebola, Zika virus, etc. that are passed on to humans via animals such as dogs, cats, ferrets, rabbits, rodents such as gerbils, guinea pigs, hamsters, hedgehogs, mice, rats; ticks, prairie dogs, birds, reptiles, amphibians, aquarium fish, bats, pigs and other farm animals, camels, palm Civets and other wild cats, different mosquitos, etc. This short list is not limited to foodborne infections such as salmonella, campylobacter, Shigella, clostridium botulinum, cryptosporidium, cyclospora, listeria monocytogenes, vibrio vulnificus, Yersinia entercolitis, e.coli, cholera, norovirus, etc. passed on to humans through contaminated water, milk, eggs, poultry, different meats, seafood and shellfish, and even fruits and vegetables. (44-5)

 These zoonotic diseases in the form of epidemics and pandemic are more and more threatening the human lives globally since modernization and industrialization, causing drastic changes in the environment (climate, dam constructions, deforestation, disruption of ecosystems, etc.), in agriculture and food production (from intensive systems of husbandry and farming monoculture to changing of traditional patterns of livestock movements), and in the demography and connectivity of the modern ‘global’ village (population growth, urbanization, international trading, world tourism and rapid transportation) (33) Anthropogenic changes, particularly those involving movements of infected people and animals or that change habitats in a manner likely to provide new opportunities for host‐parasite mixing, can further drive the introduction of both known and novel parasite genotypes to previously unaffected host individuals or species. In recent years, the emergence or re‐emergence of animal and human infectious diseases has been increasingly documented around the world (34), with an average of three new human infectious diseases being reported approximately every two years, and a new infecting organism described every week (35). Ancient diseases, such as schistosomiasis (42), are also presenting in novel environments and causing new or changing patterns of disease as human populations and their environments grow and change. Attempts to control infectious agents through large‐scale drug distribution or vaccination also add to the ever‐changing environment in which parasites and pathogens must either evolve, adapt or succumb (46).


 At least 60% of human diseases and 60–75% of new emerging diseases are multi-host zoonoses (47). Zoonotic reservoirs can maintain infections in times of change, thwart attempts to control or eliminate disease in human populations, as well as influence parasite evolution by providing opportunities for host switching or genetic exchange giving rise to novel genetic combinations. The World Bank has estimated that zoonoses have cost global economies more than $20BN in direct, and $200BN in indirect, costs between 2000 and 2010. Zoonotic disease risks are predicted to further increase as environmental change continues. The global human population is expected to increase from approximately 7.2 billion in 2014 to approximately 9.2 billion by 2050, with around one billion of this increase occurring in Africa alone (48). Standing populations of livestock in 2007 were estimated at 1.43 billion cattle, 1.87 billion sheep and goats, 0.98 billion pigs and 19.6 billion chickens, with average yearly increases of 5.1% and 3.6% in developing country meat and dairy sectors, respectively, since 1970 (49).

 The ‘megacities’ of the world constitute obvious melting pots for the mixing of human and animal parasites and their potential rapid spread, both locally and internationally. For instance, transmission of SIV (Simian immunodeficiency virus) from primates such as chimpanzees evolved to HIV to infect humans. (50) Such spill‐overs seem to have only occurred through urbanization and increased global proximity with almost no boundaries that gave rise to the HIV pandemic in the 20th century and costing 30,000,000 human lives. (51). Urbanization and large‐scale human population movements, often associated with conflict, have similarly been implicated in more recent outbreaks of potentially zoonotic origin diseases from leishmaniasis to Ebola. However, rural landscapes also pose ever increasing risks for the mixing of human and animal parasites, especially those exposed to recent anthropogenic changes such as new dam construction, flooding and changes in animal husbandry. The Food and Agriculture Organization estimates that livestock contributes to the livelihoods of 70% of the world’s rural poor. Not only are poor people and their livestock more at risk of contracting a range of zoonoses, once infected, it is the poor that are least likely to have access to health services and hence get appropriate medical or veterinary care. (49)

 Host switches, the process by which a parasite successfully jumps from one host species to another, are thought to have been a major process in the evolution of many zoonotic disease systems. In general, however, very little is known about the ecology and even less the evolution of infectious agents of wildlife, livestock and even companion animals relative to that of humans (35), and there are several examples where enzootic viruses of animals (e.g. SARS coronavirus, hantaviruses, Ebola and Marburg viruses, Nipah virus, Hendra virus and human immunodeficiency viruses) were completely unknown until they switched hosts and caused disease in humans (52).

Multiparasite systems are evolutionarily as well as ecologically dynamic. Hence, effective control of zoonotic infectious diseases must consider not only how best to deal with reservoir hosts and host switching, but also the possibility of novel parasites evolving and establishing. Polyparasitism, that is co‐infection with more than one parasite species, is the norm in animal populations, including humans, and particularly in the developing world. For instance, across much of sub‐Saharan Africa, humans can be co‐infected with S. mansoni and Schistosoma haematobium, their domestic livestock co‐infected with S. bovis, S. curassoni and/or S. mattheei and rodent wildlife co‐infected with S. mansoni and S. rodhaini. Through synergistic or antagonistic (including competitive exclusion) interactions among parasites, co‐infection may influence parasite establishment, growth, maturation, reproductive success and drug efficacy (53). Additionally, co‐infection by species belonging to the same genus can allow heterospecific (between species) pairings, resulting in either parthenogenesis (asexual reproduction where eggs occur without fertilization) or introgression (the introduction of genes from one species into that of another) and the production of hybrid offspring. Introgression, also known as introgressive hybridization, in genetics is the movement of a gene (gene flow) from one species into the gene pool of another by the repeated backcrossing of an interspecific hybrid with one of its parent species. Introgression is an important source of genetic variation in natural populations and may contribute to adaptation and even adaptive radiation (54).

 Conclusion:

Microbial invasions did not either start with “plague” as our ancient history record reveals, nor will end with the last of their attacks on us, Ebola or Zika virus! They have plagued (tormented, the dictionary meaning of the verb, due to historical torments of humans across ages) the earth, perhaps even before us to be around to recognize it, as they were once the only living organisms of the planet. In a positive outlook, the microbes are not around to torment or massacre, but to survive as they were the beginning of the life, and for sure without them, we will not survive. The microbes are not all around us, but within us, and they are not all vicious, but some friendly and help our system alive and functioning, like so many natural micorbiata in our saliva and guts. These friendly microbiata are not only in humans, but everywhere else on the planet, in plants, trees, and other animals, auxiliary to their growth and normal functioning, such as fermentation and hybridization.

 The fact that most of humans’ infectious diseases are “zoonotic” and passed on to us by other animals, could be an indication of our maltreatment of the environment, urbanization, globalization and breaching the boundary between us, the nature and the wild life. At the same time, “zoonosis” is the way of evolution and survival of the microbial world, by passing or jumping from species to species. While domestic animals and pets could pass on microbial infections to us, such as salmonella, but these types of infections have lower mortality and are of less epidemic or pandemic than infections through contact with the wild life. Zoonotic infections through the wild life such as SARS , through Palm civets, a type of wild cat native to southeast Asia, or raccoon dogs, ferrer badgers, and Chinese bats; or MERS through camels; or Ebola through fruit, or Zika virus through rhesus macaque monkey and a type of African mosquito, as detailed earlier have a very high mortality of up to %90, and tend to be rapidly spreading to epidemics and pandemics.

The mass murders of large population of humans across the globe by the epidemics and pandemics, does not seem to lessen but grow year after year, and spreading from one species to the other and form one land to the other and all. These eradications of humans by microbial epidemics and pandemics that have created panic among all of us, are only the casualties of their acute attacks. As outlined in many posts of this site, the latent invasions of the microbes, are the major causes of our morbidities and gradual mortalities through causation of cancers, auto-immune disorders, other physical and mental disorders. While the evolution thus far and in this token, seems to be on the side of microbial world as the “fittest”, the evolution has evolved us as humans, as the “intelligent matter” to ponder about all of these! Without the evolution of man, the matter and nature could not ever know of its ultimate capacity. No matter how strong the nature, the matter, or the microbial world, or even the universe, they could never reflect upon themselves and be amazed of their powers. Perhaps the evolution needed the man to do this importance task once and for all! So if the evolution has two edges, “the fittest”, i.e. the microbial world or the nature; and “the smartest”, i.e. humans, these could perhaps live together in a symbiotic nor antagonistic manner, side by side. We need to find that solution to survive longer on this planet, though we cannot live for ever or even as much as one page of the microbial life book of 1,000 pages!        

Dr.Mostafa Showraki, MD, FRCPC                                                                  Lecturer, School of Medicine, University of Toronto,Author: “ADHD:Revisited” Book/ “adhdrevisited.com”/”medicinerevisited.com”

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