Definition of Pathogen and research into the main features of bacteria, protozoa, fungi and viruses. Pathogens, or infectious agents, are microorganisms that cause disease or illness to their host. There are divided into four groups; bacteria, protozoa, fungi and viruses. The term pathogen most often describes an organism that disrupts the normal physiology of a plant or animal. In identifying a pathogen it is important to determine the properties that ‘contribute to its infectious capacity—a characteristic known as virulence.
The more virulent a pathogen, the fewer the number needed to establish an infection. ’1 Non-infectious causes of disease such as chemicals can also be referred to as pathogens. Bacteria are microscopic single celled organisms that are the most numerous and diverse living creatures on earth. They are not categorized as either plant or animal but as prokaryotes, a single cell that lacks a membrane bound nucleus and other internal structures. Bacteria can use almost any organic compound as a food source allowing them to thrive in almost any environment.
They absorb molecules through their membrane; the molecules are then broken down by the enzyme rich cytoplasm. Bacteria reproduce in one of three main ways, binary fission, budding and fragmentation. Binary fission (diagram 1) is the division of the bacteria into two identical bacteria, known as daughter cells. Budding (diagram 2) is when specialised areas of the cell expand outwards on stalks creating new cells at the ends. Fragmentation (diagram 3) is where new bacteria grow from fragments of the parental cell.
Bacteria can be grouped in many ways, one of which is shape. These groups are rod-shaped, bacillus; round, coccus; spiral, spirillum and incomplete spirals, vibrios. There are three types of symbiotic relationship between the host and bacteria; commensalism, this is when the relationship is of benefit to the bacteria but has no positive or negative impact on the host organism. Most bacteria in humans are commesalisitc. Mutualism is when both the host organism and the bacteria benefit. There are many types of bacteria that live within the body; in the ntestines, the mouth, nose and throat. They are provided with a constant food source and an environment in which they thrive and the host is provided protection from other microbes. A parasitic relationship is when the bacteria benefit to the detriment of the host. Pathogenic parasites are able to resist the body’s immune system and then thrive at the expense of the host. These bacteria produce exotoxins and endotoxins that can cause the symptoms of illness. Many bacteria have whip like limbs that are used for motion, these are called flagella.
Other bacteria types move their whole structure to gain propulsion whilst some are unable to move under their own power. Some bacteria have tiny projections on their surface called pili and fimbriae; these are used as tethers with which to attach themselves to other surfaces. The bacteria within the body are more beneficial than they are detrimental and allow for a continuous chemical exchange between host and the environment. The term ‘indigenous microbiota’ is used to describe bacteria that are regularly found in one anatomical area.
The variation in shape, reproduction method, lifespan and location of bacteria within the human body is huge, so much so that ‘there are no absolute rules about bacterial composition or structure, and there are many exceptions to any general statement. ’2 Diagram 1. Binary fission. Diagram 2. Budding. Diagram 3. Fragmentation. Protozoa are single celled eukaryotes, that is they have a nucleus and intracellular organelles. They are not classified as animals and are categorised on the basis of locomotion. Sarcodinians use pseudopodia, meaning false feet.
They are a temporary extension of the cytoplasm and are used to engulf food. They also use pseudopodia as a method of propulsion. Zooflagellates are able to move in a similar way to bacteria by using whip like limbs, which they also use for capturing food. Ciliophorans or ciliates use tiny hair like projections called cilia that are moved in a wave like motion to provide movement. Sporozoans have no method of self-propulsion so are considered immotile. Like bacteria many protozoa possess flagella and cilia that they use for movement and the capture of food. Some protozoa, ike bacteria, are heterotrophic, this means that they cannot synthesize their own food and must capture and absorb nutrients. Protozoa will consume bacteria, fungi and other protozoa either by engulfing them and breaking them down in food vacuoles or by absorbing them through their cell walls. Protozoa reproduce in a number of ways depending on the species. Like bacteria they reproduce using binary fission, however, they can split longitudinally or transversely. Some species use multiple fission; this is similar to binary fission but involves equal division into three or more identical parts.
Protozoa known as ciliates are able to reproduce sexually. Protozoa are widely known for being parasitic organisms, they are responsible for infections of; malaria, amoebic dysentery, leishmaniasis and many more. ‘Evidence suggests that many healthy persons harbour low numbers of pneumocystis carinii in their lungs. However, this parasite produces a frequently fatal pneumonia in immunosuppressed patients such as those with AIDS. ’3 The term protozoan covers a huge and complicated range of individual species and few share a common evolutionary history. Modern ultrastructural, biochemical, and genetic evidence has rendered the term protozoan highly problematic. Protozoans are no longer recognized as a formal group in current biological classification systems. ’4 Diagram 4. Reproduction of Ciliates. Diagram 5. Methods of locomotion of protozoa Fungi are eukaryotes and are classified eumycota, or true fungi. This is a classification that divides them from plants, animals and bacteria. The cell walls of fungi are comprised of the carbohydrate chitin and they are more closely linked to animals than plants.
Yeasts and moulds are some of the most commonly recognised fungi. Fungi have a specialised tissue called haustoria that is used to penetrate the tissue of a host organism; many species are parasitic and can have a serious impact on humans. The haustoria grow out from and area of the fungi called the hyphae, this is the main area of growth and is branching, filamentous structure. In some milder forms a parasitic fungal infection can take the form of ringworm, thrush or athlete’s foot. More serious cases include allergic bronchopulmonary aspergillosis which is caused by the mould aspergillus.
This can be a potentially fatal condition in immunosuppressed patients. ‘Intact skin and mucosal surfaces and a functional immune system serve as the primary barriers to colonization’5 Fungi, unlike bacteria, protozoa or viruses, do not need the tissue of a living host to survive. The vast majority of fungi free living. The reproduction of fungi can either be through binary fission, budding or sexual reproduction through the use of spores, this is a feature that differentiates them from viruses, bacteria and protozoa. In sexual reproduction the fungi produce male and female cells that fuse to form a spore.
These are tiny cells that are often produced in their millions which increases the chance of a spore coming to rest in a suitable location for it to thrive. Many of the diseases associated with fungi are of the skin or the respiratory tract. Fungal infections thrive where spore can take hold on skin, usually in an area of the body that is overlooked when washing i. e. folds in the skin and between the toes. Spores are easily inhaled and can lodge in the nose, mouth or throat where they can take hold and reproduce. Diagram6. Hyphae attachment. Diagram 7. Reproduction through spores.
A virus is a microscopic infectious agent at its most simple. Unlike bacteria, protozoa and fungi they are unable to reproduce or survive unless they are inside of the cells of the host organism, whether that is animal, plant or bacteria. The virus cannot store or generate its own energy or synthesise its own proteins. It must take the components that it requires for these actions from the cell that it invades. A virus is comprised of nucleic acid surrounded by a protein shell, the capsid. Some viruses also contain an envelope of fat cells between the inner and outer protein walls.
The outermost shell, or viron, has areas on its surface that recognises and attach to the host cell; when this happens specialised proteins are used to penetrate the cell wall of the host. Viruses are parasitic and are, more often than not, associated with the spread of disease; but this is often not the case. The function of a virus is to invade the host cell and reprogram the cell to create more viruses. It does this by using the proteins within the cell and small amounts of its nucleic acid. Anti-viral drugs are not always effective because the infected cells only contain a trace of the viral proteins.
A virus is able to transfer its genetic material to the host’s cells with speed and efficiency; it is because of this that recombinant DNA biotechnology may hold the key to halting genetic deficiency. A virus containing the functional copy of a defective gene could be injected into the patient; the virus would invade the faulty cells and reprogram them with the correct genetic make-up. It is suggested that viruses ‘should not even be considered organisms, in the strictest sense, because they are not free-living; i. e. , they cannot reproduce and carry on metabolic processes without a host cell. ’6 Diagram 8.
Structure of a Virus. TAQ2 The body is like a castle under siege, discuss. The body can be likened to a castle in that it is a structure comprised of an outer wall that protects the more important and sensitive structures on the inside. This wall must always be kept intact to prevent the ingress of harmful invaders. The body, like a castle, has occupants that require protection and nourishment, without whom the functions within would cease. They also require the levels of waste to be managed carefully. Typically a castle has one entrance through which only substances that will benefit the castle should pass.
There are many lines of defence to a castle; systems are in place to repel attackers and to fight them off should they gain access with back-up fighters in place should the front line be over-whelmed. Once a sieged castle is breached, invaders move swiftly through the building via narrow corridors and passageways; overrunning rooms and chambers, using them as places to regroup and build up numbers in preparation to move forward and continue the attack. It is important to understand what substances attack the body, how they gain entry, how they attack and how we defend.
The first line of defence against foreign organisms that are attempting to gain access to the body is referred to as the non-specific, or innate, defence system. These are systems that deal with any attacking microorganisms or particles, regardless of their type; whether its bacteria, fungi, dust or chemical irritant. These defences are what stop any unwanted invader taking hold. Externally the non-specific defence system is found in the form of unbroken skin. Like an unbroken castle wall this line of defence keeps attackers at bay. The outermost layers of skin consist of compacted, cemented cells impregnated with the insoluble protein keratin. ’7 Perspiration is an enzyme rich secretion that is needed to help destroy microorganisms and keep the skin free from infection. This barrier is usually impenetrable to attack but once it is breached it is easy for microorganisms to flood in. The main points of entry for attacking organisms are the body cavities that have external openings. The mucous membranes that cover the mouth, nose, eyes and line the vagina all produce chemical secretions to fight invaders.
The eyes and mouth are protected by tears and saliva that contain lysozyme; the secretions of the lining of the vagina are rich in lactic acid which, like the tears and saliva, begins to break down invaders. Internally, the cilia of the nasal lining trap particles and force them down into the pharynx where they are swallowed and digested by the acids within the stomach. The bodily fluids are also rich in the antibody Immunoglobulin G (IgG); this is the most common antibody. They, like all antibodies, are produced by plasma cells which are a type of white blood cell.
Other lines of internal non-specific chemical defence include spermine, a substance that restricts the growth of bacteria in the urogenital tract; and the action of phagocytes. Phagocytes are a type of general purpose white blood cell whose role it is to surround and destroy invaders. When microorganisms enter the body through a break in the skin chemical signals alert the phagocytes to their presence. The influx of phagocytic cells to the area causes swelling. The invading organisms are enveloped by the phagocytes which digest them using lysosomes.
It is this action that produces the heat often felt in the tissue surrounding a cut. Natural killer (NK) cells are also a line of non-specific defence. ‘Natural Killers are a unique set of cells which kill virus infested and cancer cells by a process called lysis. ’8 The NK’s use a protein called C9, which is cytotoxic, and creates a hole in the cell wall of the invading organism; it also prevents the hole from being repaired. This results in the cellular fluid being drained out and the cell dying. This is known as cell lysis. Diagram 9. The action of Phagocytes. Diagram 10.
Cell Lysis. Specific, or adaptive, defences are found in the form of B lymphocytes (B cells) or T lymphocytes (T cells). These are the specialised troops within the castle who are called into action once the besieged castle has been breached. T cells are divided into two groups; helper T cells (CD4+) and killer T cells (CD8+). Both B and T cells are produced in stem cells within the bone marrow and are a type of white blood cell. Where the lymphocytes remain in the bone marrow to mature they become a B cell. If the cell migrates to the thymus gland to mature it becomes a T cell.
The process of T cells attaining maturity is called ‘thymic education’ and it is during this process that the thymus identifies cells that will mature safely and those that may ‘evoke a detrimental autoimmune response and become potentially harmful to the body. ’9 When this occurs the thymus destroys the cells in question. Every cell in the body is marked with a specific protein marker known as major histocompatibility complex (MHC). ‘At the heart of the immune system is the ability to distinguish between self and non-self. Immune cells and other cells in the body usually coexist peaceably in a state known as self-tolerance. 10 As B and T cells travel around the body they are able to identify all the cells they encounter by reading these protein markers using specialised areas of receptors on their surface. This can be likened to every cell in the body having the same lock and the lymphocyte cells needing just one key, or the guards of a castle all knowing the password that is used to identify their own troops. When they encounter a cell whose marker they do not recognise, a lock that their key does not fit or a soldier that doesn’t know the password, they attack. The role of B cells is to identify foreign cells and tag them as intruders.
When a phagocyte has digested an invading cell it breaks down the proteins into peptide chains and uses them as a display marker to attract the attention of other cells. In doing this it is referred to as an antigen presenting cell (APC). These display markers are identified by receptor sites on the surface of the B cells which then lock on to the APC. When this is done they begin a reaction that requires a protein input from helper T cells, this is known as the activation phase. This is like an intruder being captured within the castle and being held by a guard until the intruder can be identified.
The B cell then begins to divide rapidly into plasma cells and memory cells, this is the effector phase. The plasma cells are responsible for the production of antibodies. When they are activated by the presence of a new antigen they will only produce antibodies that are capable of attaching to that particular antigen. Antibodies are Y shaped chains of protein; this shape allows them to attach to an antigen with one end and to bind with other antibodies using the other. As larger numbers of antigen carrying antibodies are formed they group together and will be consumed by phagocytes. Memory cells are produced by both B and T cells.
The specialised receptor sites on their surfaces ‘remember’ the distinct markers and know to attack immediately. They can carry out this action before the body develops any signs of illness. When a new antigen is first encountered there is no specific response immediately available, specialised troops need to be trained in order to best fight the invaders; this is known as the primary response. Infections take hold whilst this process is undertaken as it typically takes 5-10 days for the body to amass sufficient antibodies. During this time the elements of the non-specific defence system are utilised to ‘hold the fort’.
Secondary response is a term used in regard to the memory cells. When attackers who have been repelled before attempt to gain entrance again they are easily recognised and quickly overpowered. The memory cells identify the antigen and begin to duplicate themselves in order to provide a rapid response to the invaders. The actions and locations of B and T cells within the body can also be classified as humoral and cell mediated immunity. The antibody immunoglobulin M (IgM) is the largest antibody and is the first one to be produced when an antigen is detected.
The presence of antibodies secreted by B cells that circulate the body within the blood plasma and the lymph is referred to a humoral immunity. Cell mediated immunity (CMI) attacks organisms that have infected cells; it does this using cytotoxic T cells, known as CTC’s or Killer T cells. CMI does not use antibodies in its attack; instead it uses macrophages (a type of phagocyte), natural killers and cytotoxic killer cells. CTC’s are able to identify the infected cell because they display epitopes, an area on the surface of the antigen that elicits an immune response.
The types of cell open to attack are ‘virus-infected cells, cells with intracellular bacteria, and cancer cells displaying tumour antigens. ’11 Cytotoxicity refers to the death of cells. This can occur in several ways, cell necrosis is the destruction of the cell membrane which leads to cell lysis; a decrease or halting in the growth and division of cells; and apoptosis which is programmed cell death. The cell dies and fragments, the fragments are then consumed by phagocytes. ‘There are serious consequences when the immune system is compromised.
Three known disorders are allergies, severe combined immunodeficiency (T and B cells are not present or functional), and HIV/AIDS (severe decrease in the number of Helper T cells). ’12 Diagram 11. The action of B and T cells. Rather than suggesting that the body is like a castle under siege, although the skin and mucous membranes are exposed to countless pathogens each day, it would be more accurate to suggest that the body is like a castle whose defences are breached all too regularly with the invaders in a constant battle with the defenders of the castle.
Once the invaders have gained entry to the body they multiply swiftly to gain a foothold that will give them a numerical advantage over the body’s defences. They fight for an area and if they manage to secure it then they are able to push onwards to fight for more control over the areas they attack. There are times when the body’s defences are defeated easily. Diseases such as AIDS (acquired immunodeficiency syndrome), caused by HIV (human immunodeficiency virus) weaken the immune system to the point where bacterial and viral infections can easily take hold and ultimately defeat the body as a whole.
There are diseases like the Ebola virus which has a mortality rate of around 90%13 This is a viral infection that, in the vast majority of cases, the body cannot defeat. The effect of the virus is too strong for the body’s defences and kills before the body has time to create suitable antibodies. TAQ3 The difference between active, passive and natural immunisation. Active immunisation is the practice of injecting pathogens or fragments of them into the body to elicit an immune response. This is done by injecting a vaccine that helps the body gain immunity to a certain type of disease.
The vaccines are divided into two categories; live attenuated and inactivated. Live attenuated vaccines are made from weakened bacteria or viruses, depending in the disease to be immunised against. The viruses or bacteria are grown in a laboratory where the weaker, less virulent strains are isolated and repeatedly grown. It could be referred to as survival of the weakest. The virus or bacteria is suspended in a liquid solution and injected into the patient. This can be dangerous to individuals whose immune systems are weakened through illness.
Inactivated vaccines use either a whole virus or bacteria or part of one as a trigger for the immune system and can be divided into several categories. Where a whole virus or bacteria is used they have been killed, using heat or a chemical such as formaldehyde. These are far more stable than a live vaccine as there is no risk of organism mutating to a more virulent form. The vaccines are less effective than a live vaccine as they stimulate a weaker immune response and several additional injections, or boosters, may be required.
Fractional, or subunit, vaccinations use a fraction of the microbe to stimulate the immune response; this is done using a section of the polysaccharide coating from a bacteria or virus. The microbe is grown in the laboratory and chemically broken apart; the required sections of the coating are then taken and used. These sections of the cell ‘can contain anywhere from 1 to 20 or more antigens and identifying which antigens best stimulate the immune system is a tricky, time-consuming process. 14 Toxoid vaccines are used to fight the toxic secretions of some strains of bacteria. The bacteria are treated, usually with formalin, to render their toxins detoxified. They are then safe to be used as a vaccine. Conjugate vaccines are typically used in infants. They are used to immunise against a disease that the body has yet to encounter and that undiluted exposure to could prove fatal. The polysaccharide coating of the organism is able to disguise the presence of a harmful microbe to the immature immune system.
This technique is used to alter the coating to contain a small amount of antigen or toxoid that the body’s immune system can recognise. This enables the immune system to more easily recognise the threat. Experimental types of active immunisation include DNA vaccines and recombinant vector vaccines. DNA vaccines use the genetic code of a microbe’s antigen which is taken up by certain cells within the body. The DNA instructs the cell to create the antigens which are then displayed on the cells surface, this allows the body to react and produce antibodies.
Recombinant vector vaccines use attenuated bacteria or viruses as carriers of microbial DNA. The virus injects it into a cell; this mimics a natural infection and stimulates an immune response. In the case of bacteria the genetic material injected causes the bacteria to display antigens of a harmful microbe. ‘In effect, the harmless bacterium mimics a harmful microbe, provoking an immune response. ’15 The aim of all these vaccines is to stimulate the B cells and helper T cells into identifying and tagging the injected microbes.
As with unwanted microbial intruders the immune system produces plasma cells, to produce antibodies to fight the infection; and memory cells so that any future infection can be quickly identified and defeated. It is because the body’s immune system has to be able to identify the presence of a harmful pathogen that these vaccinations used tiny amounts of, or attenuated organisms. Passive immunisation differs from active immunisation in that the person requiring immunisation is injected with antibodies rather than antigens. This provides immediate protection from the threat of a specific disease.
Although the protection is instant it is only short lived. Antibodies are proteins that do not have a long lifespan and as they do not trigger a reaction from the immune system the body’s B cells do not learn how to produce them. Passive immunisation is used when there is a high risk of infection and it would be impossible for the body to produce its own antibodies in time to prevent serious illness. Travellers who are immunised against certain diseases receive a form of passive immunisation. The drawback to passive immunisation is that antibodies are difficult and time-consuming to produce.
Standard procedure is to harvest them from donated blood. In the body they are easily and quickly produced and now there are technological solutions to producing antibodies ‘such as recombinant systems using yeast cells or viruses and systems combining human cells and mouse cells, or human DNA and mouse DNA. ’16 and monoclonal antibodies, mono because they are designed to attach to a single site on a single type of pathogen and clonal because they are produced from a single parental cell. Monoclonal antibodies have been used to prevent ‘respiratory syncytial virus infection in high-risk infants. 17 A more fledgling technological approach is the ‘technique for constructing amino acid sequences, then linking them together to form a synthetic antibody, or synbody, that can bind with one or more protein molecules contained in the vast repository of human proteins. ’18 Maternal immunisation is a form of passive immunisation; this when antibodies, along with proteins, fats, minerals and other substances, are passed from the mother to the baby. Part of this action is done whilst the foetus is only a few months old. Maternal antibodies, or MatAb’s, pass through the placenta to the foetus at around three months.
IgG is the only antibody that the foetus receives in this way. Once the baby is born it is provided with the antibody IgA through the colostrum consumed during early breastfeeding. TAQ4 The lifecycle of influenza, plasmodium, vibrio cholera and trichophyto, how they develop and how they are transmitted to others. The influenza (flu) virus develops within the cells of the host organism. The cycle begins with the virus being inhaled into the respiratory tract where it lodges using surface proteins haemagglutinin (HA) and neuraminidase (NA) to latch on to the hosts cells.
The number of these proteins present is one of the ways in which the influenza virus is classified, i. e. H1N1. The proteins attach to receptor sites on the cell wall and are adsorbed through the cell wall using receptor mediated endocytosis. The virus is enclosed in a capture vesicle and taken towards the nucleus. The viral capsid is uncoated allowing its RNA/DNA become free; it is then guided to the nucleus by host proteins. Differing strains of flu will contain either RNA or DNA; RNA is less stable and more prone to mutation. The RNA/DNA enters the nucleus through protein channels and uses the cellular machinery to replicate itself.
This replicated viral RNA/DNA binds with viral proteins to create many new viruses; they move through the cytoplasm and leave the cell by budding. The new viral cells are then free to be transported further into the respiratory tract, spreading the infection further; or are combined with mucous and sneezed or coughed back out, in respiratory droplets, into the atmosphere where they can lodge on surfaces or can be inhaled by others. Diagram 12. Lifecycle of the Influenza virus. Influenza infection can develop and spread easily and become resistant or immune to antibodies.
The symptoms for flu include fever, muscle pains, weakness, shivering and loss of appetite. The flu virus is divided into three types; type A, type B and type C. All three types exhibit the same symptoms but with different level of severity. Type A is the most serious and is the only type of flu capable of antigenic shift. This is when two different strains of the same virus or two strains of different viruses combine to form a new disease. It is through antigenic shift that that a strain present in animals can jump species, either to an intermediate host or straight to a human host.
This occurs when two different strains infect the same cell and their genetic material is mixed to form a new strain that neither species will have immunity against. Diagram 13. Antigenic Shift. Infections can also spread due to antigenic drift. This is the mutation of a strain of flu. The vaccination against flu contains a mixture of flu types; this enables the body to produce memory cells to fight of any future infection. When a strain of flu mutates the genetic change alters the shape of the antibody binding sites on its surface, this inhibits the ability of the antibodies to kill them off. Diagram 14. Antigenic Drift.
Flu viruses are constantly changing. ‘A global flu pandemic (worldwide outbreak) can happen if 3 conditions are met: a new subtype of Type A virus is introduced into the human population, the virus causes serious illness in humans, the virus can spread easily from person to person in a sustained manner. ’19 Plasmodium are a species of protozoa and one of the eleven species that infect humans. They are introduced into the human body by the female mosquito and are responsible for the spread of malaria. They develop in the gut of the mosquito which is one of the two hosts that plasmodium will infect, the other being the human host.
Their life cycle can begin when a mosquito bites an infected human and drinks blood that contains microgametocytes and macrogametocytes. These are the male and female cells of the plasmodium, so named because the male is considerably smaller than the female. They have grown within the red blood cells of the host. When they are ingested by the mosquito they become microgametes and macrogametes, at this point the microgamete undergoes exflagellation, the flagella become detached and fertilize the macrogamete. ‘Mating between gametocytes produces embryonic forms called ookinetes. 20 The ookinetes penetrate the wall of the mosquito and develop over a period of up to two weeks into oocysts. After this time the oocysts ruptures releasing sporozoites (from sporozoan, a class of protozoa), these represent the second stage in the lifecycle of the plasmodium. The sporozoites migrate to the salivary glands of the mosquito where they mature. When the mosquito bites another human or animal the sporozoites are flushed out with the saliva and enter the bloodstream of the new host. The bloodstream carries the sporozoites to the liver where they lodge in the tissue and begin to grow.
This can take between nine and sixteen days and is known as exoerythrocytic schizogony. Schizogony refers to the manner in which the cell multiplies; the nucleus divides within the cell first then the cytoplasm divides into an equal number and surrounds the newly formed nuclei. Exoerythrocytic means that the schizogony takes place outside of the erythrocytic (red blood cell) cycle. The sporozoites mature into merozoites and are released from the liver into the bloodstream. Once in the bloodstream they attach to and invade the erythrocytes, red blood cells, using the proteins PfRh2a and PfRh2b.
Once inside the RBC they reproduce rapidly through erythrocytic schizogony, division within the red blood cell. Each individual merozoite with undergo division producing approximately 18 new merozoites. These burst out of the RBC, destroying it, and move on to invade other cells. ‘The parasite is in the bloodstream for roughly 60 seconds before it has entered another erythrocyte. ’21 The destruction of RBC’s can lead to anemia and fever. Because infected cells swell significantly before they burst it is possible for them to become lodged in the capillaries of the brain, this is known as cerebral malaria.
The lifecycle of plasmodium continues when the newly infected host is bitten again by another, uncontaminated mosquito. There are several species of plasmodium but it is Plasmodium falciparum that is responsible for the most serious cases of malaria and causes around 90% of malaria deaths. Once infected by this strain the mortality rate is around 20%. The majority of malaria cases are caused by Plasmodium vivax, although the most common it is also one the less dangerous strains. Diagram 15. Lifecycle of Plasmodium Vivax. Vibrio cholera is a water dwelling bacteria that is commonly found in estuaries where they can lie dormant in the silt.
These are ideal breeding grounds for the bacteria as agricultural run-off and high levels of algae provided a nutrient rich environment. There are over 200 serogroups of vibrio cholera, a serogroup is ‘a group of bacteria containing a common antigen, sometimes including more than one serotype, species, or genus. 22 The common shared antigen for this group is the O antigen which is found in the lipopolysaccharide layer of the cell wall. Of all the individual strains of bacteria that contain the O antigen it is O1 and O139 that cause cholera.
The bacteria enter into human hosts through contaminated water or foods that have been washed in water containing the bacteria; shellfish from waters that contain the bacteria are another potential source of infection. It is also possible for the bacteria to be present in ice cubes that have been made with non-purified water. Water that has not been treated or at least boiled carries the risk of cholera. ‘It is capable of running rampant in the water supply of almost any community where sanitation is anything less than rigorous. ’23 Poor hygiene and disposal of human waste is a key factor in the spread of this disease.
In many poorer countries human waste is used as a fertilizer for crops, this adds to the risk of transmission as the bacteria can be carried by flies and transferred to food. It can also enter the water supply or enter an individual’s body if they do not clean thoroughly. Once inside the body they enter the small intestine and attach to the cells of the intestinal wall. When the bacteria attach they release cholera toxin, this is known as an A-B toxin. It is comprised of a single A subunit and five B subunits. The B subunits have a specialised site on their surface that attaches to an area on the epithelial cells called the ganglioside GM1.
The A subunit is transferred inside the cell where it chemically activates a protein known as the G protein. In turn, this protein activates and enzyme that converts adenosine triphosphate (ATP) into cyclic adenosine monophosphate (cAMP). The A subunits activation of the G protein is permanent and this has a knock on effect to the production of cAMP, the levels of which increase up to 100 times. This system controls the pumping of water and electrolytes between the small intestine and the circulatory system. The action of the A subunit effectively locks the pump in the on position.
This results in large quantities of water, up to one litre per hour24, being pumped into the small intestine by the intestinal cells. The result is watery diarrhoea that can lead to dehydration and death. The mortality rate can be as high as 50% in less developed nations compared with around 1% when the disease occurs in countries where more modern treatment is available. Person to person contamination is a less common occurrence but in unsanitary conditions, where people are tending to those who are infected, contamination can easily happen.
Often the disposal of infected human waste is done near a water source which can easily contaminate water users further downstream. Diagram 16. Cholera toxins effect on intestinal cells. Trichophyton is one of the three fungi from the group dermatophytes, which translates as skin plants. Trichophyton is an anthrophilic species; this means that humans are its natural host. They are multicellular and cigar shaped with thin walls. Infection can occur in humans in a number of bodily areas, when it occurs on the feet it is called Athletes foot and is caused by Trichophyton Rubrum.
This parasitic fungus is a communicable disease and is easily transferred from person to person; this usually takes place in damp environments where people are barefooted; typically a locker room or shower. Infection can also spread via infected footwear. Trichophyton reproduce asexually using thin, membrane like hyphae that form spores. These filament structures are called conidiophores; they branch out into smaller strands which terminate in conidia. These are non-motile spores that are produced through cellular mitosis.
The conidia multiply until they breakout through a layer or the surface of the skin where they can settle and restart their lifecycle. When an infection begins, usually between the toes, the fungi attaches to the stratum corneum (the dead outer layer of skin cells). It gains nourishment from breaking down keratin, the key protein in skin, into amino acids. When the supply of keratin within the stratum corneum has been exhausted the layers of new skin beneath are attacked. The destruction of the new tissue and the immune response are what provide the characteristic pain and sores of athletes’ foot. Trichophyton uses a variety of acid proteases, elastases, and keratinases to invade the epidermis or skin cells. ’25 Elastases are enzymes that breakdown the proteins elastin and collagen, which together form connective tissue. Keratinases are enzymes that breakdown keratin and other proteins in the skin. Diagram 17. Lifecycle of Trichophyton (right-hand illustration). TAQ5 Main features in controlling infectious diseases. The control of infectious diseases began with the discovery of microorganisms and the subsequent understanding of how they were transferred.
This lead to improvements in sanitation, hygiene, the discovery of anti-biotics and vaccines; and improvements in water treatment. In order to control infectious diseases the chances of them coming into contact with the human population must be reduced wherever possible. Water treatment is key to the control of disease. Cholera is almost non-existent in the developed world and this is due to advances in water treatment. Not only is water used for drinking but also for cleaning and food preparation and if the water at any of these stages isn’t properly treated then disease can spread.
Water treatment involves physical, chemical and biological treatments in order to remove physical, chemical and biological contaminates. These processes include; pre-chlorination, aeration, desalination and disinfection. These actions eliminate any possible source of contamination. Vaccinations, in their modern form, have been used since the late 18th century and are considered a ‘a miracle of modern medicine. In the past 50 years, it’s saved more lives worldwide than any other medical product or procedure. 26 Vaccinations enable individuals to be immunised against specific diseases by injecting them with vaccines that contain a weakened version of the disease, this enables the body to create specialised memory cells to fight off any future attack of the same illness. Methicillin-resistant Staphylococcus aureus, more commonly known as MRSA is an infectious bacterial disease that is often associated with outbreaks in hospitals. This is a bacterium that is carried by approximately one third of the population and is no more aggressive than any other bacteria. What makes MRSA such a danger is that it is more resilient to penicillin based drugs.
Methicillin is no longer used clinically but the term MRSA is used to describe any strain of staphylococcus aureus that is resistant to these drugs. The best practice for combating MRSA in hospitals is personal hygiene in the form of handwashing. The hands of clinical staff interact with numerous people and pieces of equipment in the course of their work and a strict policy of handwashing before and after interacting with a patient is commonplace within medical settings. ‘Although poor handwashing is known to play a key role in the spread of infection, there is evidence that compliance with handwashing protocols is low in many hospitals. 27 Handwashing in hospitals is a vital step in controlling infectious diseases; typically patients are sicker and weaker and are therefore more susceptible to infection if they touch or are touched by someone whose hands are carrying disease. It is good practice within hospitals to keep patients who are MRSA carriers in an isolation ward. If the patients need to leave the ward to undergo treatment in another area of the hospital then there are strict guidelines surrounding the cleaning of any equipment used or touched by the patient. MRSA is not only present in hospitals, community acquired MRSA is also a threat.
This is a different strain of S. aureus and it produces a toxin called Panton-Valentine Lecocidin. This toxin kills white blood cells and can cause tissue death, this increases the bacteria’s ability to cause infection. Anti-biotics are not powerless against MRSA but mutation to become resistant to drugs is a common occurrence in bacteria. Prevention through handwashing is better than cure. Clostridium Difficile, or C. diff, is another infectious bacterial disease that is also often associated with outbreaks in hospitals. This is a bacterium that lives in the human gut of a small percentage of the population.
Their numbers are controlled by other bacteria. C. diff becomes harmful when a patient undergoes a course of anti-biotics. It is often the case that regardless of the bacteria being treated against, harmless bacteria numbers will also be reduced. When this occurs C. diff bacteria, which are naturally more resilient to anti-biotics, thrive. C. diff produces toxins that are harmless when they are present in small numbers but if they are able to flourish then the toxin levels increase and cause serious anti-biotic associated diarrhoea (AAD). Cross contamination usually occurs through the faecal-oral route.
The bacteria produce spores that are passed from the body in the faecal waste and can easily become airborne. It is important in controlling the infection that strict enteric precautions are followed. These are precautions used when dealing with infected faecal waste that are designed to ensure safe disposal of the waste and high levels of cleanliness in any area that may be affected. It is important to consider what situations allow C. diff to flourish. A course of anti-biotics reduces the effectiveness of the ‘good’ bacteria that control C. diff numbers, the longer the course of anti-biotics the more chance of the C. iff has of multiplying to dangerous levels. This is one of the dangers of reliance on anti-biotics; they can do wonders against one disease but over use can lead to problems from more resistant strains. TAQ6 Discuss the use of anti-biotic drugs to treat bacterial diseases and the problems posed by the emergence of strains of bacterial that are resistant to certain anti-biotics. Anti-biotics, which translates from the Greek ‘against life’, can be described as a selective poison. This is measured using the Therapeutic Index (TI). This is the ratio of toxicity of the dose, to the patient; against the therapeutic dose, against the infection.
The larger the ratio the safer it is for use. They are designed to act on specific bacteria and have no harmful effects on the cells of the body. They are prescribed if a bacterial infection has become too severe for the body’s immune system to counter. Anti-biotics are designed to work against bacterial, fungal and parasitic infections; they do not work against viral infections. This is because a virus is not a living organism; it is a strand of chemicals that hijacks living cells. Each species of bacteria will be affected by anti-biotics in different ways; different concentrations of anti-biotics will have differing effects.
When a dose of anti-biotics inhibits growth but does not kill the bacteria it is referred to as the minimum inhibitory concentration (MIC). Where a level is reached that it is fatal to the bacteria it is referred to as the minimum bactericidal concentration (MBC). ‘By understanding the concepts in determining antibiotic concentrations compared to the MIC and MBC, we can make rational decisions in determining how successful antibiotic treatment is likely to be. ’28 Anti-biotics are divided into two types; bactericidal (Bcidal) and bacteriostatic (Bstatic). Bactericidal anti-biotics are designed to kill the bacteria.
They do this by chemically altering how the bacterium constructs its cell wall. Penicillin and its derivatives act on the peptidoglycan layer of the cell wall; the anti-biotic reduces the ability of the peptidoglycan to withstand the pressures within the cell. When the cell divides the daughter cells will have weaker, thinner walls than the original parent cell. When the daughter cells divide further there is not enough peptidoglycan to hold the wall together so the cell bursts. Lysis occurs and the cell dies. ‘Penicillin antibiotics work in this way, as do the cephalosporins. 29 Other Bcidal anti-biotics work by binding to the ribosomes; this is part of the cellular structure which assembles amino acids into proteins. The anti-biotic restricts the ability of the ribosome to make efficient or correct proteins, this effectively starves the bacteria. Bacteriostatic anti-biotics work by halting the reproduction of bacteria. It can affect the DNA replication, the bacterial protein production or other areas of cellular metabolism. This significantly slows or halts the cells ability to reproduce, therefore numbers do not increase and the body’s defences are able to outnumber them.
Anti-biotics are also described as narrow and broad spectrum. This is a classification that refers to the species of bacteria that each is designed to destroy. Narrow spectrum anti-biotics are designed to target only a small number of bacteria species, in some cases a single species. ‘Narrow spectrum antibiotics tend to be very specific and act on a molecule in the metabolism of one particular type of bacteria that is special to that species. ’30 They are highly effective when the species of bacteria causing the infection is known. This is advantageous for two reasons.
Firstly there will be fewer of the body’s beneficial bacteria destroyed and secondly there is a reduced risk of non-targeted bacteria becoming drug resistant. Broad spectrum anti-biotics are effective against a wider range of bacteria species as they ‘act on structures or processes that are common to many different bacteria, such as the components of the cell wall. ’31 They are used prior to identification of the bacteria causing the infection where a delay in treatment could prove dangerous. This is an advantage that they have over narrow spectrum.
Broad spectrum anti-biotics are particularly useful in treating super-infections. This is when a patient is suffering from two or more bacterial infections; in these cases a broader approach is beneficial in the short term. The disadvantages with any prolonged course of anti-biotics, especially broad spectrum, is that there is an increased chance of the emergence of bacterial strains that are resistant to anti-biotics. Organisms that are resistant to one or more anti-biotics are commonly referred to as superbugs. Medically they are referred to as multidrug resistant (MDR) or multi resistant organisms (MRO).
In optimum conditions a bacteria such as S. aureus can divide once every thirty minutes. Within five hours a single bacteria will have grown into a colony of over one thousand and within ten hours the colony would number over one million. In these conditions a single cell that has a natural immunity to an anti-biotic could produce a substantial colony of anti-biotic immune bacteria within a day. Mutation rates per generation are low but with such a high rate of reproduction genetic mutations are not rare. Genetic information being passed from parental cell to daughter cell is known as vertical gene transfer.
Drug resistance can also occur through horizontal gene transfer. If a bacterium encounters other bacteria whose genetic material is different from its own, either through mutation or it is descended from a genetically different ancestor, it is able to share new genetic material with it. This can happen through conjugation, transformation and transduction. Conjugation, also known as type IV secretion system, is when genetic information is passed from one bacterium to another via cell to cell contact. Bacteria contain a plasmid, this is DNA separate to the nucleoid DNA and is able to replicate independently.
When two cells come into contact the one with the drug resistance, the donor, snares the second bacterium, the recipient, with a hair-like extension called a pilus. This forms the basis of a mating bridge between the two cells. A protein complex called a relaxosome enables the plasmid to cross the mating bridge into the recipient bacteria; this enables the recipient bacteria to use the new DNA to become immune to the anti-biotics and to act as a donor. Transformation is the process by which bacteria are able to absorb the DNA of other bacteria through their cell walls.
Bacteria that are capable of picking up free floating, or naked DNA, are described as competent. The DNA that they absorb, either fragments or a plasmid, is often obtained from bacteria that have destroyed through lysis. In order for this to occur the ‘bacteria requires that the freed DNA remain stable and that potential recipient cells become competent to take it up’32 Once absorbed the bacteria is able to assimilate the DNA into its own genetic make-up. If the absorbed DNA contains the codes to enable anti-biotic resistance then this will be passed along through vertical gene transfer and possibly horizontal gene transfer.
Transduction is the transfer of whole plasmids or pieces of bacterial chromosome between two bacteria. This is typically done by viruses that infect bacteria, known as bacteriophages. Usually it is the viral DNA that is transferred but on occasions it can be the genetic material of a bacterium that is resistant to anti-biotics. ‘Laboratory experiments indicate that some bacteriophages can apparently infect several species and even genera of bacteria, suggesting they might broadcast bacterial genes well beyond the locale where they first took up the genes. 33 These three occurrences show how a genetic mutation can occur and spread throughout a species of bacteria and can greatly increase the speed with which drug resistance can occur in bacterial infections. Diagram 18. Conjugation. Diagram 19. Transformation. Diagram 20. Transduction. . Staphylococcus aureus, or staph, are common bacteria that are largely harmless. However there are certain strains that have become resistant to drugs that had previously proved effective against MRSA. They are Vancomycin-resistant Staphylococcus aureus (VRSA) and Vancomycin-intermediate S. ureus (VISA). There are concerns that, like MRSA, VRSA and VISA could become more common in community settings. This refers to a setting that is not a hospital or other healthcare treatment centre. Whilst there are drug treatments available for VRSA and VISA these have proven to be costly and have serious side effects. They are also not suitable for use of children under 18 and can pose a risk to the elderly, two groups who are more susceptible to infection. Multi drug resistant tuberculosis (MDR-TB) is a disease that is on the increase in the world’s poorer countries.
Each year 440,000 people are being diagnosed with MDR-TB with 150,000 of them dying. Current TB medication is still having some impact on the condition, but in many cases first-line drugs such as isonictinic acid hydrazide (INH) is proving ineffective. There is a newer strain, extensively drug resistant TB (XDR TB) which is showing signs of being resistant to second and third-line drugs. This is proving fatal to many who are already suffering from diseases associated with weakened immune systems. New Delhi Metallobeta-lactamase or NDM-1 is one of the new breed of superbugs that poses a real health risk.
This is an enzyme that enables bacteria to destroy a type of anti-biotic called carbapenems, which is one of the key anti-biotics used in fighting infection. This enzyme is most commonly found in the bacteria E. coli and Klebsiella pneumonia but has been found to have shifted strain through horizontal gene transfer. The concern is that it may shift into a strain of bacteria that is already highly resistant to drug treatment. The most effective method of controlling this infection is ‘through surveillance, rapid identification and isolation of any hospital patients who are infected. 34 ‘Antibiotic resistance has been called one of the world’s most pressing public health problems. ’35 There is almost no species of bacteria that isn’t evolving to become stronger and more resistant to anti-biotics. Resistance can spread quickly through a colony of bacteria and the bacteria themselves can be spread quickly and easily from person to person, especially in healthcare settings where ‘bacteria proliferate in an environment filled with sick people who have poor immune systems and where antibiotics have eliminated competing bacteria that are not resistant. 36 Most hospital acquired infections are now strains of microorganisms that are drug resistant and given the speed with which these organisms mutate it is proving impossible for drug development to keep up. The risk is that more powerful anti-biotics may have to be used in order to eliminate bacterial infections; this would result in a depletion of the harmless bacteria that do so much to aid the human body and increase the risk of further infection. If an infectious disease reaches a point where there is no safe way to treat the patient with anti-biotics then the disease could spread unchecked with catastrophic results.
It is often said that a person is resistant to drug treatments but in reality it is the organisms that are causing the illness that are resistant. David Livermore, director of antibiotic resistance monitoring at the U. K. ‘s Health Protection Agency said in a statement, “So much of modern medicine–from gut surgery to cancer treatment, to transplants–depends on our ability to treat infection. If resistance destroys that ability then the whole edifice of modern medicine crumbles.
