BSc. (Hons) Semester-I Natural Science Introduction to infectious diseases Infectious diseases Infectious diseases are disorders that are caused by organisms, usually microscopic in size, such as bacteria, viruses, fungi, or parasites and rarely prions that are passed, directly or indirectly, from one person to another. Humans can also become infected following exposure to an infected animal that harbors a pathogenic organism that is capable of infecting humans. You can get infectious diseases from other people, bug bites and contaminated food, water, or soil. Some infectious diseases are minor, but some are very serious and even can cause death. Infectious diseases are a leading cause of death worldwide, particularly in low-income countries, especially in young children. Difference between infectious and Non-Infectious diseases Infectious diseases are caused by harmful organisms that get into your body from the outside, like viruses and bacteria. Non-infectious diseases aren’t caused by outside organisms, but by genetics, anatomical differences, getting older (aging) and the environment you live in. Noninfectious diseases cannot be obtained from other people, by getting a bug bite or from food. The flu, measles, HIV, strep throat, COVID-19 and salmonella are all examples of infectious diseases. Cancer, diabetes, congestive heart failure and Alzheimer’s disease are all examples of noninfectious diseases. Types of infectious diseases Infectious diseases can be viral, bacterial, parasitic, or fungal infections. There’s also a rare group of infectious diseases known as transmissible spongiform encephalopathies (TSEs). • Viral Infections: Viruses are a piece of information (DNA or RNA) inside of a protective shell (capsid). Viruses are much smaller than your cells and have no way to reproduce on their own. They get inside your cells and use your cells’ machinery to make copies of themselves. For Example: Common cold, Influenza, COVID-19, Hepatitis, Stomach flu (gastroenteritis). • Bacterial Infections: Bacteria are single-celled organisms with their instructions written on a small piece of DNA. Bacteria are all around us, including inside of our body and on our skin. Many bacteria are harmless or even helpful, but certain bacteria release toxins that can make you sick. For Example: Strep throat, Tuberculosis, Whooping cough, Urinary tract infection (UTI), Chlamydia, Gonorrhea, and other sexually transmitted infections (STIs). • Fungal infections: Like bacteria, there are many different fungi. They live on and in your body. When your fungi get overgrown or when harmful fungi get into your body through your mouth, your nose or a cut in your skin, you can get sick. For Example: Athlete’s foot (ringworm), Fungal nail infection, Thrush, Vaginal candidiasis (yeast infection). • Parasitic Infections: Parasites use the bodies of other organisms to live and reproduce. Parasites include worms (helminths) and some single-celled organisms (protozoa). For Example: Toxoplasmosis. Hookworms, Giardiasis, Pinworms. • Transmissible Spongiform Encephalopathies (TSEs/ Prion diseases): TSEs are caused by prions — faulty proteins that cause other proteins in your body, usually in your brain, to become faulty as well. Your body is unable to use these proteins or get rid of them, so they build up and make you sick. Prions are an extremely rare cause of infectious diseases. For Example: Creutzfeldt-Jakob disease (CJD) is a fatal neurodegenerative disorder. History of Germs, Vaccines and Diseases The term "germs" refers to the microscopic bacteria, viruses, fungi, and protozoa that can cause disease. Germ (microorganism), an informal word for a pathogen. Germ cell, cell that gives rise to the gametes of an organism that reproduces sexually. Germ is a deceptively simple word that came to us from Latin germen, meaning a sprout, bud, or offshoot. Germ Theory of Disease Germ theory states that specific microscopic organisms are the cause of specific diseases. The theory was developed, proved, and popularized in Europe and North America between about 1850 and 1920. Because its implications were so different from the centuries–old humoral theory, germ theory revolutionized the theory and practice of medicine and the understanding of disease. Until germ theory was accepted, the Miasma theory was prevalent which stated that the disease was caused by the decomposition of organic matter which released poisonous air carrying disease-causing agents. During the 1600s, the concept of spontaneous generation of diseases was proved wrong by the experiments performed by Francesco Redi. Anton Van Leeuwenhoek, the first microbiologist to observe the microorganisms under a microscope, also supported the germ theory of disease. Richard Bradley later postulated that diseases were caused by microorganisms which were later supported by Marcus Antonius Von Plenzic. Basic forms of germ theory were proposed by Girolamo Fracastoro in 1546, and expanded upon by Marcus von Plenciz in 1762. The French chemist and microbiologist Louis Pasteur, and the German physician Robert Koch are given much of the credit for development and acceptance of the theory. In the mid-19th century Pasteur showed that fermentation and putrefaction are caused by organisms in the air. He concluded that the microbes present in the air spoiled the fermentation broths. He performed various other fermentation processes for compounds like lactic acid, butyric acid, etc. Thus, he postulated the germ theory of fermentation which states that every fermentation process is acted upon by certain microbes. He further extended the theory to animal and human diseases. He observed that the diseases are also caused by the germs present in or around the body. In 1880s Koch identified the organisms that cause tuberculosis and cholera. Koch conclusively established that a particular germ could cause a specific disease. He did this by experimentation with anthrax. Using a microscope, he examined the blood of cows that had died of anthrax. He observed rod-shaped bacteria and suspected they caused anthrax. When he infected mice with blood from anthrax-stricken cows, the mice also developed anthrax. This led him to list four criteria to determine that a certain germ causes a particular disease. These criteria are known as Koch's Postulates and are still used today. • The microorganism must be identified only in the diseased individual and not in the healthy individual. • The microorganism should be isolated from the diseased individual and cultured. • The cultured microorganism should cause disease when introduced to a healthy individual. • The microbe should be isolated again from the experimental host and should be identical to the original organism. The final proof of the germ theory of disease came when Louis Pasteur grew anthrax bacillus in culture. He extracted blood from a sheep suffering from anthrax and placed it in sterile culture and allowed the bacilli to grow. He repeated the process until all the original cultures were eliminated from the final dish. The final culture when injected into the sheep produced anthrax. This proved that the bacillus was responsible for the disease. Vaccines/Vaccination Vaccine is a suspension of weakened, killed, or fragmented microorganisms or toxins or other biological preparation, such as those consisting of antibodies, lymphocytes, or messenger RNA (mRNA), that is administered primarily to prevent disease. A vaccine can confer active immunity against a specific harmful agent by stimulating the immune system to attack the agent. Once stimulated by a vaccine, the antibody-producing cells, called B cells (or B lymphocytes), remain sensitized and ready to respond to the agent should it ever gain entry to the body. A vaccine may also confer passive immunity by providing antibodies or lymphocytes already made by an animal or human donor. Vaccines are usually administered by injection (parenteral administration), but some are given orally or even nasally (in the case of flu vaccine). The First Vaccine The first vaccine was introduced by British physician Edward Jenner, who in 1796 used the cowpox virus (vaccinia) to confer protection against smallpox, a related virus, in humans. Edward Jenner expands on this discovery and inoculates 8-year-old James Phipps with matter collected from a cowpox sore on the hand of a milkmaid. Despite suffering a local reaction and feeling unwell for several days, Phipps made a full recovery. Two months later, in July 1796, Jenner inoculates Phipps with matter from a human smallpox sore in order to test Phipps’ resistance. Phipps remains in perfect health and becomes the first human to be vaccinated against smallpox. The term ‘vaccine’ is later coined, taken from the Latin word for cow, “vacca”. In 1881 French microbiologist Louis Pasteur demonstrated immunization against anthrax by injecting sheep with a preparation containing attenuated forms of the bacillus that causes the disease. Four years later he developed a protective suspension against rabies. The term “Vaccination” formulated by him. In 1894, Dr Anna Wessels Williams isolates a strain of the diphtheria bacteria that is crucial in the development of an antitoxin for the disease. In 1937 Max Theiler, Hugh Smith and Eugen Haagen develop the 17D vaccine against yellow fever. The vaccine is approved in 1938 and over a million people have receive it that year. Theiler goes on to be awarded the Nobel Prize. In 1939, bacteriologists Pearl Kendrick and Grace Eldering demonstrate the efficacy of the pertussis (whooping cough) vaccine. The scientists show that vaccination reduces the rates at which children get sick from 15.1 per 100 children to 2.3 per 100. By 1945, the first influenza vaccine is approved for military use, followed in 1946 by an approval for civilian use. The research is led by doctors Thomas Francis Jr and Jonas Salk, who both go on to be closely associated with the polio vaccine. From 1952– 1955, the first effective polio vaccine is developed by Jonas Salk and trials begin. Salk tests the vaccine on himself and his family the following year, and mass trials involving over 1.3 million children take place in 1954. In later years, vaccine for rotavirus, measles, Ebola virus and monkey pox were prepared. Trials are in process for vaccines to be used for Malaria and AIDS. In 2021, Effective COVID-19 vaccines are developed, produced, and distributed with unprecedented speed, using new mRNA technology. Evolution by Natural and Artificial Selection Evolution In biology, evolution is the change in the characteristics of a species over several generations and relies on the process of natural selection. It mostly relies on natural selection but can also be obtained through artificial selection. Almost all diseases result from a complex interaction between an individual’s genetic make-up and environmental agents. Subtle differences in genetic factors cause people to respond differently to the same environmental exposure. This explains why some individuals have a fairly low risk of developing a disease as a result of an environmental insult, while others are much more vulnerable. From an evolutionary perspective, infectious diseases have probably been the primary agent of natural selection over the past 5000 years, eliminating human hosts who were more susceptible to disease and sparing those who were more resistant. Natural Selection Natural selection is a mechanism of evolution. Organisms that are more adapted to their environment are more likely to survive and pass on the genes that aided their success. This process causes species to change and diverge over time. An adaptation is a physical or behavioural characteristic that helps an organism to survive in its environment. But not all characteristics of an animal are adaptations. Charles Darwin (1809-1882) and Alfred Russel Wallace (1823-1913) are jointly credited with coming up with the Theory of Evolution by Natural Selection, having co-published on it in 1858. Darwin has published his work as On the Origin of Species in 1859. Darwin defined evolution as "descent with modification", the idea that species change over time, give rise to new species, and share a common ancestor. In natural selection, genetic mutations that are beneficial to an individual's survival are passed on through reproduction. This results in a new generation of organisms that are more likely to survive to reproduce. For example, evolving long necks has enabled giraffes to feed on leaves that others can't reach, giving them a competitive advantage. Those with longer necks were able to survive to reproduce and so pass on the characteristic to the succeeding generation. Those with shorter necks and access to less food would be less likely to survive to pass on their genes to next generation. Artificial Selection Artificial Selection is selective breeding that is imposed by an external entity, usually humans, to enhance the frequency of desirable features. For example, by choosing which individuals to save seeds from or breed from one generation to the next. People have been artificially selecting plants and animals for thousands of years. These activities have amounted to large, long-term, practical experiments that clearly demonstrate that species can evolve dramatically through selective breeding. Cauliflower, broccoli, cabbage, kale, and kohlrabi bear little superficial resemblance to their wild mustard relatives. And yet, through many generations of artificial selection, these five distinct crops were intentionally evolved from a wild, weedy ancestor. Artificial selection Virus species specificity Viruses can be seen as obligate intracellular parasites. The virus must attach to a living cell, be taken inside, manufacture its proteins and copy its genome, and find a way to escape the cell so the virus can infect other cells and ultimately other individuals. Viruses can infect only certain species of hosts and only certain cells within that host. The molecular basis for this specificity is that a particular surface molecule, known as the viral receptor, must be found on the host cell surface for the virus to attach. It is described in figure below. In influenza virus infection, glycoproteins attach to a host epithelial cell. As a result, the virus is engulfed. RNA and proteins are made and assembled into new virions. Why Virus cross species barrier Many infectious diseases cross the species barrier. In most cases, humans come into contact with the animal itself during its handling and care, animal excreta, or animal parts (e.g., feathers, meat), or insect is the vector of transmission (dengue) of the infective microorganism. Sometimes infected animals are eaten by humans and cause disease by virus in their body. Most of these infectious agents are zoonotic, meaning that their usual host is a nonhuman vertebrate. Most viral diseases of humans are zoonotic in origin, having been historically transmitted to human populations from various animal species. Examples include SARS, Ebola, swine flu, rabies, and avian influenza. The exact mechanisms which facilitate cross-species transmission vary by pathogen, and even for common diseases are often poorly understood. It is believed that viruses with high mutation rates are able to rapidly adapt to new hosts and thereby overcome host- specific immunological defenses, allowing their continued transmission. A host shifting event occurs when a strain that was previously zoonotic begins to circulate exclusively among the new host species. Examples of viruses that transferred between hosts to gain new host ranges so that they cause outbreaks in those new hosts are in Table below. Virus(es) Original host New host Mechanism and/or time Measles virus Possibly cattle Humans Host switching and adaptation? Time not known; after the establishment of populations sufficient to allow transmission Smallpox virus Other primates or camels(?) Humans Host switching and adaptation? Time >10,000 yr ago? Influenza virus Water birds Humans, pigs, horses Host switching and adaptation, possible role of intermediate host; many examples. In humans viruses emerged in the period ∼1910-1916 and in ∼1957 and ∼1968. Reassortment involved in 1957 and 1968 emergences. Earlier epidemic viruses not characterized. Changes in several genes required for success in new host CPV Cats or similar carnivores Dogs Host switching and adaptation; several mutations in the capsid control binding to the canine transferrin receptor. Arose in early 1970s, spread worldwide in 1978 HIV-1 Old World primates, chimpanzees Humans Host switching and adaptation; virus entered human population approximately in 1930s and spread widely in 1970s; multiple introductions likely to give the HIV-1 M, N, and O Interactions between the virus and the cellular receptor often determine the host range of the virus and therefore constitute a species barrier. Minor mutations in the viral capsid or surface glycoproteins may already result in profound changes in cell tropism or host range of a virus. Many viruses have the capability to use various receptors. This implies that concepts such as host‐range barrier and host‐cell specificity may be rather flexible than rigid. The outbreak of SARS coronavirus (SARS-CoV) infections in humans represents something partway between a small step to man and the feared giant leap to mankind. There is strong evidence that this coronavirus was present in a population of animals in China, including the Himalayan palm civet (Paguma larvata). Through molecular changes, most likely in its spike glycoprotein, SARS-CoV broadened its host range in such a way that it became capable of attaching to human cells and infecting humans who were directly exposed to these animals. These transfers involve either increased exposure or the acquisition of variations that allow them to overcome barriers to infection of the new hosts. In these cases, devastating outbreaks can result. Steps involved in transfers of viruses to new hosts include contact between the virus and the host, infection of an initial individual leading to amplification and an outbreak, and the generation within the original or new host of viral variants that have the ability to spread efficiently between individuals in populations of the new host. Antibiotic Resistance Antibiotics are medicines used to prevent and treat bacterial infections. Antibiotic resistance occurs when bacteria change in response to the use of these medicines. This is also called Antimicrobial resistance. Antibiotic resistance leads to higher medical costs, prolonged hospital stays, and increased mortality. Cause of Antibiotic resistance It occurs naturally over time, usually through genetic changes. Antimicrobial resistant organisms are found in people, animals, food, plants and the environment (in water, soil and air). They can spread from person to person or between people and animals, including from food of animal origin. The main drivers of antimicrobial resistance include the misuse and overuse of antimicrobials; lack of access to clean water, sanitation and hygiene for both humans and animals; poor infection and disease prevention and control in health-care facilities and farms; poor access to quality, affordable medicines, vaccines and diagnostics; lack of awareness and knowledge; and lack of enforcement of legislation. The most serious concern with antibiotic resistance is that some bacteria have become resistant to almost all of the easily available antibiotics. These bacteria are able to cause serious disease, and this is a major public health problem. Important examples are: • methicillin-resistant Staphylococcus aureus (MRSA) • vancomycin-resistant Enterococcus (VRE) • multi-drug-resistant Mycobacterium tuberculosis (MDR-TB) • carbapenem-resistant Enterobacteriaceae (CRE) gut bacteria Through mutation and selection, bacteria can develop defense mechanisms against antibiotics. The three fundamental mechanisms of antimicrobial resistance are: (1) enzymatic degradation of antibacterial drugs (2) alteration of bacterial proteins that are antimicrobial targets (3) changes in membrane permeability to antibiotics. Human Physiological Limits to Fight Infectious Diseases Infection occurs when a pathogen invades body cells and reproduces. Infection usually leads to an immune response. If the response is quick and effective, the infection will be eliminated or contained so quickly that the disease will not occur. Sometimes infection leads to disease. Disease can occur when immunity is low or impaired, when virulence of the pathogen (its ability to damage host cells) is high, and when the number of pathogens in the body is great. Depending on the infectious disease, symptoms can vary greatly. Fever is a common response to infection: a higher body temperature can heighten the immune response and provide a hostile environment for pathogens. Inflammation, or swelling caused by an increase in fluid in the infected area, is a sign that white blood cells are on the attack and release substances involved in the immune response. Limitations • Person’s immune system does not work properly (immunosuppressed). This can result from immune deficiencies (immunodeficiency disorder) present at birth; medications that suppress the immune system, like steroids; unnecessary or overzealous immune responses, such as allergies; or immune responses to one’s self, called autoimmunity. • Weak Immune system due to smoking, alcohol and poor nutrition. • Someone is already sick or may be having other disease like AIDS, HIV. • Deficiency of required vitamins in the body. • Causative agents having Antibiotic resistance or resistance against medicine. • Infection spreads in other organs of the body or may be organ failure. Changing interactions and Emergence of New Diseases The World Health Organization warned in its 2007 report that infectious diseases are emerging at a rate that has not been seen before. Since the 1970s, about 40 infectious diseases have been discovered, including SARS, MERS, Ebola, chikungunya, avian flu, swine flu, Zika and most recently COVID-19, caused by a new coronavirus, SARS-CoV-2. With people traveling much more frequently and far greater distances than in the past, living in more densely populated areas, and coming into closer contact with wild animals, the potential for emerging infectious diseases to spread rapidly and cause global epidemics. Additionally, there is the potential for diseases to emerge as a result of deliberate introduction into human, animal, or plant populations for the purpose of war and terrorism. Such agents known as Bioterrorism Agents. These diseases include anthrax, smallpox, and tularemia. Factors in the Emergence or Re-emergence of Infectious Diseases For an emerging disease to become established at least two events have to occur – (1) the infectious agent has to be introduced into a vulnerable population (2) the agent has to have the ability to spread readily from person-to-person and cause disease. The infection also has to be able to sustain itself within the population, that is more and more people continue to become infected. There are many factors involved in the emergence of new infectious diseases or the reemergence of “old” infectious diseases. • Natural processes such as the evolution of Pathogens over time • Human behavior and practices (How the interaction between the human population and our environment has changed, especially in the last century). Infectious agents in animals are passed to humans (referred to as zoonoses). As the human population expands in number and into new geographical regions, the possibility that humans will come into close contact with animal species that are potential hosts of an infectious agent. • Population growth, migration from rural areas to cities, international air travel, poverty, wars, and destructive ecological changes due to economic development and land use. • Climate change allows the Earth's climate to be warms and habitats are altered, diseases can spread into new geographic areas. For example, warming temperatures allow mosquitoes - and the diseases they transmit - to expand their range into regions where they previously have not been found. • Re-emergence of diseases caused by antimicrobial resistance - the acquired resistance of pathogens to antimicrobial medications such as antibiotics. Bacteria, viruses, and other microorganisms can change over time and develop a resistance to the drugs used to treat diseases caused by the pathogens. Therefore, drugs that were effective in the past are no longer useful in controlling disease. • Another factor that can cause a disease to re-emerge is a decline in vaccine coverage. When a safe and effective vaccine exists, a growing number of people choose not to become vaccinated. This has been a particular problem with the measles vaccine. Number of people opting to take nonmedical vaccine exemptions for reasons of personal and philosophical belief. As a result of the decline in vaccine coverage, measles cases are highest by far this decade with more than 1,000 cases of measles reported in the U.S. in the first half of 2019.
