The spread and severity of infectious disease is influenced by many predisposing factors.
Recognize factors that are classified as predisposing to infectious disease
- Some predisposing factors of contracting infectious diseases can be anatomical, genetic, general and disease specific.
- Climate and weather, and other environmental factors that are affected by them, can also predispose people to infectious agents.
- Other factors such as overall health, age and diet are important considerations in the prevention of spreading infectious diseases.
- cystic fibrosis: Cystic fibrosis (also known as CF or mucoviscidosis) is an autosomal recessive genetic disorder that affects most critically the lungs, and also the pancreas, liver and intestine. It is characterized by abnormal transport of chloride and sodium across an epithelium, leading to thick, viscous secretions.
- Chronic granulomatous disease: Also known as CGD, is a diverse group of genetic diseases in which certain cells of the immune system have difficulty forming the reactive oxygen compounds (most importantly, the superoxide radical) used to kill certain ingested pathogens. This leads to the formation of granulomata (a special type of inflammation) in many organs.
The spread and severity of infectious disease is influenced by many predisposing factors. Some of these are more general and apply to many infectious agents, while others are disease specific. Others can be anatomical. For example, women suffer more frequently from urinary tract infections which can be attributed to their shorter urethra.
Genetics is another contributing factor. Cystic fibrosis is a genetic disease that causes alteration of the mucus in the lungs. This predisposes patients to chronic infections with bacteria which form biofilms in the lungs. The most common infectious agent is Pseudomonas aeruginosa. Another example is chronic granulomatous disease which directly affects the ability of the host immune system to fight invaders.
Climate and weather, and other environmental factors that are affected by them, can also predispose people to infectious agents. A long-standing puzzle has been why flu outbreaks occur seasonally. One possible explanation is that, because people are indoors more often during the winter, they are in close contact more often, and this promotes transmission from person to person. Another factor is that cold temperatures lead to drier air, which may dehydrate mucus, preventing the body from effectively expelling virus particles. The virus also survives longer on surfaces at colder temperatures and aerosol transmission of the virus is highest in cold environments (less than 5°C) with low relative humidity. Indeed, the lower air humidity in winter seems to be the main cause of seasonal influenza transmission in temperate regions. Some scientists speculate that the seasonal fluctuations of vitamin D levels can be a factor in the spread of influenza too.
Overall health is a very important factor in preventing disease. Some portions of the immune system itself have immuno-suppressive effects on other parts of the immune system, and immunosuppression may occur as an adverse reaction to treatment of other conditions. In general, deliberately-induced immunosuppression is performed to prevent the body from rejecting an organ transplant, treating graft-versus-host disease after a bone marrow transplant, or for the treatment of autoimmune diseases such as rheumatoid arthritis and Crohn’s disease. Of course, the immune system can be weak due to other reasons such as chemotherapy and HIV.
Age is another critical factor. Newborns and infants are more susceptible to infections as are the elderly.
Inadequate diet can raise the risks too. For example, globally, the severe malnutrition common in parts of the developing world causes a large increase in the risk of developing active tuberculosis and other opportunistic infections, due to its damaging effects on the immune system. Along with overcrowding, poor nutrition may contribute to the strong link observed between tuberculosis and poverty.
After an pathogen invades a host, it undergoes a series of phases that eventually lead to multiplication of the pathogen.
Outline the stages of disease: incubation, prodromal, acute and convalescence periods
- The first phase is characterized by complete lack or very few symptoms.
- As the pathogen starts to reproduce actively, the symptoms intensify. Bacterial and viral infections can both cause the same kinds of symptoms but there are some differences too.
- The last phases are characterized by decline in symptoms severity until their disappearance. However, even if the patients recover and return to normal, they may continue to be a source of infection.
- subclinical: Of a disease or injury, without signs and symptoms that are detectable by physical examination or laboratory test; not clinically manifest.
- clinical latency: The period for which an infection is subclinical.
- viral latency: A form of viral dormancy in which the virus does not replicate at all.
Stages of Disease
After an infectious agent invades a host (patient), it undergoes a series of phases (stages) that will eventually lead to its multiplication and release from the host.
STAGE 1: INCUBATION PERIOD
This refers to the time elapsed between exposure to a pathogenic organism, and from when symptoms and signs are first apparent. It may be as short as minutes to as long as thirty years in the case of variant Creutzfeldt–Jakob disease. While the term latency period is used as synonymous, a distinction is sometimes made between incubation period, the period between infection and clinical onset of the disease, and latent period, the time from infection to infectiousness. Whichever is shorter depends on the disease.
A person may be a carrier of a disease, such as Streptococcus in the throat, without exhibiting any symptoms. Depending on the disease, the person may or may not be contagious during the incubation period. During clinical latency, an infection is subclinical. With respect to viral infections, in clinical latency the virus is actively replicating. This is in contrast to viral latency, a form of dormancy in which the virus does not replicate.
STAGE 2: PRODROMAL PERIOD
In this phase, the numbers of the infectious agents start increasing and the immune system starts reacting to them. It is characterized by early symptoms that might indicate the start of a disease before specific symptoms occur. Prodromes may be non-specific symptoms or, in a few instances, may clearly indicate a particular disease. For example fever, malaise, headache and lack of appetite frequently occur in the prodrome of many infective disorders. It also refers to the initial in vivo round of viral replication.
STAGE 3: ACUTE PERIOD
This stage is characterized by active replication or multiplication of the pathogen and its numbers peak exponentially, quite often in a very short period of time. Symptoms are very pronounced, both specific to the organ affected as well as in general due to the strong reaction of the immune system.
Viral infections present with systemic symptoms. This means they involve many different parts of the body or more than one body system at the same time; i.e. a runny nose, sinus congestion, cough, body aches, etc. They can be local at times as in viral conjunctivitis or “pink eye” and herpes. Only a few viral infections are painful, like herpes. The pain of viral infections is often described as itchy or burning.
The classic symptoms of a bacterial infection are localized redness, heat, swelling and pain. One of the hallmarks of a bacterial infection is local pain, pain that is in a specific part of the body. For example, if a cut occurs and is infected with bacteria, pain occurs at the site of the infection. Bacterial throat pain is often characterized by more pain on one side of the throat. An ear infection is more likely to be diagnosed as bacterial if the pain occurs in only one ear.
After the pathogen reaches its peak in newly-produced cells or particles (for viruses), the numbers begin to fall sharply. Symptoms are still present but they are not as strong as in the acute illness phase.
STAGE 4: CONVALESCENCE PERIOD
The patient recovers gradually and returns to normal, but may continue to be a source of infection even if feeling better. In this sense, “recovery” can be considered a synonymous term.
Disease Reservoirs and Epidemics
Once discovered, natural reservoirs elucidate the complete life cycle of infectious diseases, providing effective prevention and control.
Give examples of disease reservoirs and distinguish between common source and propagated outbreaks
- Often the natural reservoirs for a human infectious disease are animals such as bats for SARS and rats for plague. Some diseases have no non-human reservoirs: poliomyelitis and smallpox are prominent examples. The natural reservoir of some diseases remains unknown.
- In epidemiology, an epidemic occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected based on recent experience.
- An epidemic may be restricted to one location; however, if it spreads to other countries or continents and affects a substantial number of people, it may be termed a pandemic.
- There are two types of epidemic outbreak: (1) In a common source outbreak, the affected individuals had exposure to a common agent. (2) In a propagated outbreak, the disease spreads person-to-person.
- pandemic: A disease that hits a wide geographical area and affects a large proportion of the population.
- common source outbreak: a type of epidemic outbreak where the affected individuals had an exposure to a common agent.
- propagated outbreak: a type of epidemic outbreak where the disease spreads person-to-person. Affected individuals may become independent reservoirs leading to further exposures.
A natural reservoir refers to the long-term host of the pathogen of an infectious disease. It is often the case that hosts do not get the disease carried by the pathogen or it is carried as a subclinical infection and so remains asymptomatic and non-lethal.
Once discovered, natural reservoirs elucidate the complete life cycle of infectious diseases, providing effective prevention and control. Some examples of natural reservoirs of infectious diseases include:
- Bubonic plague: marmots, black rats, prairie dogs, chipmunks, and squirrels for bubonic plague
- Chagas disease: armadillos and opossums and several species of New World Leishmania
- Babeiosis and Rocky Mountain spotted fever: ticks
- Colorado tick fever: ground squirrels, porcupines, and chipmunks
- Rabies: raccoons, skunks, foxes, and bats
- Cholera: shellfish
- Severe acute respiratory syndrome (SARS): bats
- Ebola: fruit bats, subhuman primates, and antelope called duikers
Some diseases have no non-human reservoir: poliomyelitis and smallpox are prominent examples. The natural reservoirs of some diseases still remain unknown.
In epidemiology, an epidemic occurs when new cases of a certain disease, in a given human population, and during a given period, substantially exceed what is expected, based on recent experience. Epidemiologists often consider the term outbreak to be synonymous to epidemic, but the general public typically perceives outbreaks to be more local and less serious than epidemics.
Epidemics of infectious disease are generally caused by:
- a change in the ecology of the host population (e.g. increased stress or increase in the density of a vector species)
- a genetic change in the parasite population
- the introduction of a new parasite to a host population (by movement of parasites or hosts)
Generally, an epidemic occurs when host immunity to a parasite population is suddenly reduced below that found in the endemic equilibrium and the transmission threshold is exceeded.
An epidemic may be restricted to one location; however, if it spreads to other countries or continents and affects a substantial number of people, it may be termed a pandemic. The declaration of an epidemic usually requires a good understanding of a baseline rate of incidence. Epidemics for certain diseases, such as influenza, are defined as reaching some defined increase in incidence above this baseline.
A few cases of a very rare disease may be classified as an epidemic, while many cases of a common disease (such as the common cold) would not. An epidemic disease is not required to be contagious, and the term has been applied to West Nile fever.
There are two types of epidemic outbreaks: (1) In a common source outbreak, the affected individuals had an exposure to a common agent. If the exposure is singular and all of the affected individuals develop the disease over a single exposure and incubation course, it can be termed a point-source outbreak. If the exposure was continuous or variable, it can be termed a continuous outbreak or intermittent outbreak, respectively.
(2) In a propagated outbreak, the disease spreads person-to-person. Affected individuals may become independent reservoirs leading to further exposures. Many epidemics will have characteristics of both common source and propagated outbreaks. For example, secondary person-to-person spread may occur after a common source exposure or environmental vectors may spread a zoonotic disease agent.
The conditions which govern the outbreak of epidemics include infected food supplies, such as drinking water contaminated by waste from people with cholera or typhoid fever or ‘fast food’ products contaminated with salmonella. The migrations of certain animals, such as rats, are in some cases responsible for the spread of plague, from which these animals die in great numbers.
Certain epidemics occur at certain seasons: for example, whooping-cough occurs in spring, whereas measles produces two epidemics – as a rule, one in winter and one in March. Influenza, the common cold, and other infections of the upper respiratory tract, such as sore throat, occur predominantly in the winter.
There is another variation, both as regards the number of persons affected and the number who die in successive epidemics: the severity of successive epidemics rises and falls over periods of five or ten years.
Infectious Disease Transmission
Defining the means of transmission of a pathogen is important in understanding its biology and in addressing the disease it causes.
Give examples of various modes of transmission, including direct and indirect transmission
- Infectious organisms may be transmitted either by direct or indirect contact.
- Transmission may occur through several different mechanisms. Transmission of infectious diseases may also involve a vector. Vectors may be mechanical or biological.
- Pathogens can also be transmitted horizontally or vertically.
- fomite: An inanimate object capable of carrying infectious agents (such as bacteria, viruses and parasites), and thus passively enabling their transmission between hosts.
- aerosolized: Dispersed as an aerosol; particulate.
- vector: A carrier of a disease-causing agent.
For infecting organisms to survive and repeat the infection cycle in other hosts, they (or their progeny) must leave an existing reservoir and cause infection elsewhere. Defining the means of transmission plays an important part in understanding the biology of an infectious agent and in addressing the disease it causes.
Infectious organisms may be transmitted either by direct or indirect contact. Direct contact occurs when an individual comes into contact with the reservoir. Indirect contact occurs when the organism is able to withstand the harsh environment outside the host for long periods of time and still remains infective when specific opportunity arises.
Transmission may occur through several different mechanisms. Respiratory diseases and meningitis are commonly acquired by contact with aerosolized droplets, spread by sneezing, coughing, talking, kissing, or even singing. Gastrointestinal diseases are often acquired by ingesting contaminated food and water. Washing hands is an effective measure to prevent contaminating food and water. A common method of transmission in under-developed countries is fecal-oral transmission. In such cases, sewage water is used to wash food or is consumed. Sexually transmitted diseases are acquired through contact with bodily fluids, generally as a result of sexual activity. Some infectious agents may be spread as a result of contact with a contaminated, inanimate object (known as a fomite), such as a coin passed from one person to another, while other diseases penetrate the skin directly.
Transmission of infectious diseases may also involve a vector. Vectors may be mechanical or biological. A mechanical vector picks up an infectious agent on the outside of its body and transmits it in a passive manner. An example of a mechanical vector is a housefly, which lands on cow dung, contaminating its appendages with bacteria from the feces and then lands on food. The pathogen never enters the body of the fly.
In contrast, biological vectors harbor pathogens within their bodies and deliver pathogens to new hosts in an active manner, usually a bite. Biological vectors are often responsible for serious blood-borne diseases, such as malaria, viral encephalitis, Chagas disease, Lyme disease, and African sleeping sickness. Biological vectors are usually, though not exclusively, arthropods, such as mosquitoes, ticks, fleas, and lice. Vectors are often required in the life cycle of a pathogen. A common strategy used to control vector borne infectious diseases is to interrupt the life cycle of a pathogen by killing the vector.
All of the above modes are examples of horizontal transmission because the infecting organism is transmitted from person to person in the same generation. There are also a variety of infections transmitted vertically, that is from mother to child during the birthing process or fetal development. Common disorders transmitted this way include AIDs, hepatitis, herpes, and cytomegalovirus.
Ecology, Epidemiology, and Evolution of Pathogens
Pathogens have evolved to adapt to their environment and their host in order to survive.
Discuss the contributing factors to pathogen evolution
- Ecological competence is the ability of an organism, often a pathogen, to survive and compete in new habitats.
- Epidemiology is another important tool used to study disease in a population.
- In most cases, microorganisms live in harmony with their hosts via mutual or commensal interactions.
- Diseases can emerge when existing parasites become pathogenic or when new pathogenic parasites enter a new host.
- zoonose: Infectious diseases transmitted between different species of animals, usually from a vertebrate animal to a human
- ecological competence: The ability of an organism, often a pathogen, to survive and compete in new habitats.
- virulence: The degree of pathogenicity within a group or species of parasites as indicated by case fatality rates and/or the ability of the organism to invade the tissues of the host and it is determined by virulence factors.
Ecological competence is the ability of an organism, often a pathogen, to survive and compete in new habitats. If a pathogen does not have this, it will likely become extinct. In the case of plant pathogens, it is also their ability to survive between growing seasons. For example, peanut clump virus can survive in the spores of its fungal vector until a new growing season begins and it can proceed to infect its primary host again.
Epidemiology is another important tool used to study disease in a population. For infectious diseases, it helps to determine if a disease outbreak is sporadic (occasional occurrence), endemic (regular cases often occurring in a region), epidemic (an unusually high number of cases in a region), or pandemic (a global epidemic). The Black Death (plague) of the 14th century reduced the world population from an estimated 450 million to 350 – 375 million.
In most cases, microorganisms live in harmony with their hosts via mutual or commensal interactions. Diseases can emerge when existing parasites become pathogenic or when new pathogenic parasites enter a new host. Coevolution between parasite and host can lead to hosts becoming resistant to the parasites or the parasites may evolve greater virulence, leading to immunopathological disease.
In addition, human activity is involved with many emerging infectious diseases, such as environmental change enabling a parasite to occupy new niches. When that happens, a pathogen that had been confined to a remote habitat has a wider distribution and possibly, a new host organism. Diseases transferred from nonhuman to human hosts are known as zoonoses.
Under disease invasion, when a parasite invades a new host species, it may become pathogenic in the new host. Several human activities have led to the emergence and spread of new diseases, such as encroachment on wildlife habitats, changes in agriculture, the destruction of rain forests, uncontrolled urbanization, modern transport.
According to evolutionary medicine, virulence increases with horizontal transmission (between non-relatives) and decreases with vertical transmission (from parent to child). Optimal virulence is a concept relating to the ecology of hosts and parasites. One definition of this is the host’s parasite-induced loss of fitness. The parasite’s fitness is determined by its success in transmitting its offspring to other hosts.
At one stage, the consensus was that over time, virulence moderated and parasitic relationships evolved toward symbiosis. This view has been challenged. A pathogen that is too restrained will lose out in competition to a more aggressive strain that diverts more host resources to its own reproduction. However, the host, being the parasite’s resource and habitat in a way, suffers from this higher virulence. This might induce faster host death, and act against the parasite’s fitness by reducing probability to encounter another host (killing the host too fast to allow for transmission).
Thus, there is a natural force providing pressure on the parasite to “self-limit” its virulence. The idea is then, that there exists an equilibrium point of virulence, where parasite’s fitness is highest. Any movement on the virulence axis, towards higher or lower virulence, will result in lower fitness for the parasite, and this will be selected against.
Safety in the Microbiology Laboratory
Working with microorganisms, especially pathogens, requires special equipment and safety practices.
Distinguish between the different biohazard levels 1, 2, 3 and 4
- The CDC categorizes various diseases in levels of biohazard: Level 1 being minimum risk and Level 4 being extreme risk.
- BSL-1 lab is used to perform research mostly on noninfectious microbes using standard equipment and routine lab safety procedures.
- BSL-2 work is performed with bacteria and viruses that cause only mild disease to humans, or are difficult to contract via aerosol in a lab setting. Safety regulations are stricter.
- In a BSL-3 setting, the work is with bacteria and viruses that can cause severe to fatal disease in humans, but for which vaccines or other treatments exist. The laboratory has special engineering and design features.
- BSL-4 level is mandatory for research on viruses and bacteria that cause severe to fatal disease in humans, and for which no vaccines or treatments are available. The use of a positive-pressure personnel suit is mandatory as well as many additional safety measures of the labs.
- biohazards: Biological substances that pose a threat to the health of living organisms, especially humans.
Keeping Safe in the Laboratory
Working with microorganisms, especially pathogens, requires special equipment and safety practices. Biological hazards, also known as biohazards, refer to biological substances that pose a threat to the health of living organisms, especially humans. The biohazard symbol is used in the labeling of biological materials that carry a significant health risk, including viral samples and used hypodermic needles.
The United States’ Centers for Disease Control and Prevention (CDC) categorize various diseases in levels of biohazard: Level 1 being minimum risk and Level 4 being extreme risk. Laboratories and other facilities are categorized as BSL (Biosafety Level) 1-4 or as P1 through P4 for short (Pathogen or Protection Level).
BIOHAZARD LEVEL 1:
Bacteria and viruses including Bacillus subtilis, Escherichia coli , canine hepatitis, varicella (chicken pox), as well as some cell cultures and non- infectious bacteria. Work is generally conducted on open bench tops using standard microbiological practices. At this level, precautions against the biohazardous materials in question are minimal, most likely involving gloves and some sort of facial protection. Decontamination procedures are similar in most respects to modern precautions against everyday microorganisms (i.e., washing one’s hands with anti-bacterial soap, washing all exposed surfaces of the lab with disinfectants, etc.). In a lab environment all materials used for cell and/or bacteria cultures are decontaminated via autoclave. Laboratory personnel have specific training in the procedures conducted in the laboratory and are supervised by a scientist with general training in microbiology or a related science.
BIOHAZARD LEVEL 2:
Bacteria and viruses that cause only mild disease to humans, or are difficult to contract via aerosol in a lab setting, such as hepatitis A, B, and C, influenza A, Lyme disease, salmonella, mumps, measles, scrapie, dengue fever, and HIV. BSL-2 differs from BSL-1 in that:
- laboratory personnel have specific training in handling pathogenic agents and are directed by scientists with advanced training;
- access to the laboratory is limited when work is being conducted;
- extreme precautions are taken with contaminated sharp items;
- certain procedures in which infectious aerosols or splashes may be created are conducted in biological safety cabinets or other physical containment equipment.
BIOHAZARD LEVEL 3:
Bacteria and viruses that can cause severe to fatal disease in humans, but for which vaccines or other treatments exist, such as anthrax, West Nile virus, Venezuelan equine encephalitis, SARS virus, tuberculosis, typhus, Rift Valley fever, Rocky Mountain spotted fever, yellow fever, and malaria. Among parasites Plasmodium falciparum, which causes malaria, and Trypanosoma cruzi, which causes trypanosomiasis (sleeping sickness), also come under this level.
Laboratory personnel have specific training in handling pathogenic and potentially lethal agents, and are supervised by competent scientists experienced in working with these agents. All procedures involving the manipulation of infectious materials are conducted within biological safety cabinets, specially designed hoods, or other physical containment devices, or by personnel wearing appropriate protective clothing and equipment. The laboratory has special engineering and design features.
BIOHAZARD LEVEL 4:
Viruses and bacteria that cause severe to fatal disease in humans, and for which vaccines or other treatments are not available, such as Bolivian and Argentine hemorrhagic fevers, Dengue hemorrhagic fever, Marburg virus, Ebola virus, hantaviruses, Lassa fever virus, Crimean-Congo hemorrhagic fever, and other hemorrhagic diseases. Variola virus (smallpox) is an agent that is worked with at BSL-4 despite the existence of a vaccine.
When dealing with biological hazards at this level the use of a positive-pressure personnel suit, with a segregated air supply, is mandatory. The entrance and exit of a Level Four biolab will contain multiple showers, a vacuum room, an ultraviolet-light room, autonomous detection system, and other safety precautions designed to destroy all traces of the biohazard. All air and water services going to and coming from a Biosafety Level 4 (P4) lab will undergo similar decontamination procedures to eliminate the possibility of an accidental release.
Finding Patient Zero and Tracking Diseases
The index case is identified in epidemiology studies by tracking down the infected patients to try to determine how the disease originated.
Describe the concept of patient zero or the index case
- The index or primary case is the initial patient in the population of an epidemiological investigation. It may indicate the source of the disease, the possible spread, and which reservoir holds the disease in-between outbreaks.
- In the early years of the AIDS epidemic, there was controversy about a so-called Patient Zero, who was the basis of a complex transmission scenario.
- Other prominent “Patient Zeroes” include Typhoid Mary.
- “Patient Zero”: A term used to refer to the index case in the spread of HIV in North America.
- epidemiology: The branch of a science dealing with the spread and control of diseases, computer viruses, concepts, etc., throughout populations or systems.
The index or primary case is the initial patient in the population of an epidemiological investigation. The index case may indicate the source of the disease, the possible spread, and which reservoir holds the disease in-between outbreaks. The index case is the first patient that indicates the existence of an outbreak. Earlier cases may be found and are labeled primary, secondary, tertiary, etc.
“Patient Zero” was used to refer to the index case in the spread of HIV in North America. The index case is identified in epidemiology studies by tracking down the infected patients to try to determine how the disease originated.
For example, in the early years of the AIDS epidemic there was controversy about a so-called Patient Zero, who was the basis of a complex transmission scenario. This epidemiological study showed how Patient Zero had infected multiple partners with HIV, and they in turn transmitted it to others and rapidly spread the virus to locations all over the world.
The CDC identified Gaëtan Dugas as the first person to bring HIV from Africa to the United States and to introduce it to gay bathhouses. Dugas was a flight attendant who was sexually promiscuous in several North American cities. He was vilified for several years as a “mass spreader” of HIV, and seen as the original source of the HIV epidemic among homosexual men. Later, the study’s methodology and conclusions representation were repudiated.
A 2007 study published in the Proceedings of the National Academy of Sciences claimed that, based on the results of genetic analysis, current North American strains of HIV probably moved from Africa to Haiti and then entered the United States around 1969, probably through a single immigrant. However, the immigrant died in St. Louis, Missouri of complications from AIDS in 1969, and most likely became infected in the 1950s, so there were prior carriers of HIV strains in North America.
In the eboloa outbreak of 2014, the Patient Zero was identified as a two year-old boy in Guinea who died on Dec. 2, 2013 of Ebolavirus during the fruitbat migration. His sister and mother and grandmother then died. Visitors from other villages came to pay their respects and tragically carried the virus back with them. As of November 2014, about 5,500 people had died of Ebolavirus.
Other prominent “Patient Zeroes” include Typhoid Mary. She was the first person in the United States identified as an asymptomatic carrier of the pathogen associated with typhoid fever. She was presumed to have infected some 51 people, three of whom died, over the course of her career as a cook. She was forcibly isolated twice by public health authorities and died after a total of nearly three decades in isolation.