Pathogenesis of Microbial Infection

• Symbiosis is the close and long-term interaction between two different biological species. There are 3 types of symbiotic associations:

  • Commensalism - one organism benefits, and the other derives neither benefit nor harm.
  • Mutualism - both organisms are benefited from the association.
  • Parasitism - one organism, the parasite, benefits at the expense of the other organism.
• Obligate intracellular parasites (such as intracellular bacteria, like Chlamydia, and all viruses) can only reproduce within host cells.

  Facultative parasites don't rely on its host to continue their life-cycle, as it can live and reproduce inside and outside cells. An example of a facultative parasite is Salmonella.
• Normal flora is the population of microorganisms that reside in the skin, mucus membranes, and intestinal tract of a healthy human body. The normal flora mainly constitutes bacteria; viruses, protozoa, and fungi are also present, but make up a minute proportion of the total normal flora.

  Functions of the normal flora are:

  • to help the development of mucosal immunity
  • to protect the host from colonisation with pathogenic microbes
  • to aid in the digestion of food.

  The human microbiome is the collection of genes of all the microbes in the normal flora.
• At specific sites of the body, a different set of microbes may perform the same function for different people.
• The human microbiome is the collection of genes of all the microbes in the normal flora. It can be considered a counterpart to the human genome. The genes of the microbiome outnumber the genes of the genome by about 100 to 1.
• Knowledge of bacteria are normally located can help work out when they're in the wrong place. This in turn, allows the prediction of the likely cause of disease in 2 main ways:

  • prediction of the pathogen causing an infection as bacteria tend to grow in specific body sites.
  • Investigation for underlying abnormalities in specific areas of the body when bacteria are isolated from normally sterile sites.
• Normal flora on the skin can be divided into resident flora or transient flora.
• Resident/normal flora of the skin consists of microorganisms that normally reside on the surface of the skin. Resident flora is generally less likely to be associated with infections, but it can cause infections in sterile body cavities, the eyes, or non-intact skin. Staphylococcus epidermidis is the most common species found in resident flora.
• Transient flora don't usually multiply on the skin and more easily removed by routine hand-washing than resident flora. Transient flora is often acquired during direct contact with patients or contaminated surfaces close to the patient. Transient flora is most frequently associated with hospital-acquired infections. Staphylococcus aureus is the most common species in transient flora.
• The normal flora of the human body begins to change after admission to a hospital or a long-term care facility. This is mainly due to:

  • exogenous environmental infections (such as the hospital flora found on linen, equipment, and the water supply).
  • increased risk of infection due to invasive techniques employed in treatment (such as urinary catheters and IV lines)
  • antibiotics.
• Normally, microorganisms that form part of the resident flora are non-pathogenic, but in some circumstances, they can become pathogenic and cause disease. Infections acquired in this way are known as opportunistic infections. Opportunistic infections can occur if the microorganism moved from the usual site to other areas of the body. For instance, UTIs are caused by intestinal normal flora, such as E.coli, finding their way into the urinary tract through the urethra. This is usually diagnosed by determining the presence of bacterial products in the urine.
• Another cause of opportunistic infections is a weak immune system. For example, chemotherapy will kill healthy leukocytes and will interfere with the normal turnover of epithelial cells, leading to mucosal injury. Both these side effects will predispose the patient to fungal and bacterial infections, such as candida aspergillus, or pseudomonas aeruginosa.
• Opportunistic infections can also appear due to the lack of competition from normal flora due to its loss from the body. For example, when antibiotics are used to treat infection in women, they can cause vaginal yeast infections because they disturb the normal balance between candida albicans and Lactobacillus acidophilus in the vagina.
• • Infection - the presence of microorganisms in the body.
  • Colonisation - when a new microorganism grows on superficial body sites, such as the skin, GI tract, and mucosal membranes, without invading the body.
  • Carrier - a person who harbours a microorganism that can be a source of infection for others.
  • Pathogen - a microorganism capable of causing disease.
  • Microbial pathogenesis - the process by which infection leads to disease.
• Exposure and invasion of the host leads to infection and the appearance of a clinical syndrome.

  An explanation as to why a microorganism ends up infecting their host and inducing a disease in the host is that, in some cases, the pathological response that microorganisms elicit enhance the efficiency of their spread and hence, clearly have a selective advantage for the the pathogen.

  For example, virus-containing lesions on the genitalia caused by herpes simplex facilitate the direct spread of the virus during sexual contact.
• Many signs and symptoms associated with infectious diseases are direct manifestations of the host's immune system. For example, ,some common signs of a bacterial infection include swelling, redness, and pus, result from the immune system cells attempting to destroy the invading pathogen.
• Each interaction between a particular microorganism and particular host is unique, and the outcome is depending on a constantly changing of microbial activity and host immunity function. The extend of damage caused to the host depends on the interplay of these factors.

  In extreme cases, the most severe and damaging consequences of an infection are directly caused by an overwhelming immune response. This is known as immunopathogenesis.
• Immunopathogenesis - when the primary cause of cell death is due to the killing of the infected cells by the hosts' immune system. Immunopathogenesis can be caused by:

  • a cytotoxic T-cell mediated attack to the tissue
  • antibody mediated damage to the host
  • antibody mediated complement fixation
• When talking about the clinical manifestations of a disease symptoms are the subjective features of a disease experience only by the patient. Infections can be asymptomatic (sub-clinical) or symptomatic.

  The signs of infection are objective manifestations of a disease that can be observed and measured by others.

  A syndrome is a group of symptoms and signs characteristic of a disease.
• Manifestations of infection may develop in only one body part or organ. These are called local effects, and include things such as inflammation, tissue necrosis, and nasal congestion.

  When the manifestation of an infection develops in multiple areas, or in multiple organ systems, then it's called systemic effects. These include fevers (the most common systemic effect), altered immune responses, and muscle pain (myalgia).

  Most manifestations resolve when the underlying infection is treated.
• Pathogenesis occurs when a pathogen causes damage to the host tissue. Pathogenesis is the result of complex microorganism-host interactions that can be summarised in 4 main steps:

  • entry and spread by avoiding the host's primary defences (skin barrier, stomach, cilia and mucus epithelium in airways)
  • evasion (evade the immune system long enough for a full cycle in to be completed in the host)
  • multiplication via rapid growth and replication
  • transmission, which is the microorganism exiting the body into the next portal of entry.
• There are several stages of infectious disease progression for the host:

  • incubation
  • prodrome
  • illness
  • recovery
• The incubation period is the time elapsed between exposure to the pathogen and the onset of specific clinical symptoms.

  Factors that affect the incubation period are

  • the virulence of the pathogen
  • the infective dose
  • the health of the patient's immune system
  • generation time of the pathogen
  • site of infection

  Because of all these dependent factors, incubation periods different depending on the pathogen involved.
• The incubation period can include a prodrome. In the prodrome phase, the number of infectious agents starts increasing and and the immune system starts reacting. This phase is characterised by non-specific, or constitutional, symptoms, such as fever, malaise, headache, and loss of appetite, These non-specific symptoms may indicate the start of a disease before specific symptoms occur.

  Not all infectious diseases have a prodromal stage.
• The illness period is characterised by active replication or multiplication of the pathogen in, ,quite often, a very short period of time. During the illness period, the clinical features of the infection start to manifest.
• Finally, in the recovery phase, the illness abates and the patient returns to the healthy state.
• An infection can be classified as communicable or non-communicable depending on how the disease spreads.

  A communicable infection is transmitted from host or host either directly (such as HIV) or indirectly (such as noroviruses). The term 'contagious' is applied to highly communicable diseases spread by contact.

  Non-communicable diseases are infections that aren't transmissible between humans, such as botulism.
• Infections can be classified based on their occurrence:

  • Sporadic infections are diseases that occur occasionally (tetanus).
  • Endemic infections are diseases that is continuously present in a population, community, or country (tuberculosis and chickenpox)
  • Epidemic infections are diseases that have a greater number of cases than normal in an area within a short period of time. In order words, when outbreaks of the disease occur (SARS in 2003)
  • Pandemic are epidemic diseases that have a global distribution (the flu pandemic in 1918 and 2009).
• Infections can be classified based on the site of infection:

  • Superficial infections are self-limited. They're caused when microorganisms replicate in the epithelium at the site of entry, which results in local damage. Immune responses to superficial infections can give rise to constitutional symptoms. Examples: folliculitis, impetigo.
  • Systemic infections are caused when microorganisms replication at multiple sites due to infection of deeper tissues. Systemic infection spread throughout the body, primarily via lymph and blood. Examples: chickenpox, measles, Salmonella typhi.
• Infections can also be classified based on its outcome. Outcome refers to the balance between microbial replication and spread, and the host's ability to respond/resit.

  • Acute infection is the rapid onset of disease with a relatively brief period of symptoms. The pathogen is cleared within days. Examples: influenza, poliovirus, measles.
  • Persistent infections
• Persistent infections is when the pathogen isn't cleared from the host following primary infection, but instead, remains in the tissue. Persistent infections can be:

  • Latent, which is when the microorganism persists after initial clearance. Latent persistent infections may have an asymptomatic or symptomatic reactivation. Examples: latent TB, herpes simplex virus.
  • Chronic, which is the continued production of the infectious organism and continued immune evasion. Infected hosts with chronic persistent infections are carriers. Examples: HIV, hepatitis B, chronic diabetic foot infection.
• Nosocomial infections are any infections acquired in a hospital or medical facility. They can affect both patients and healthcare workers, and are common because:

  1. they are easily transmitted around by staff, patient, or visitors
  2. they're not always prevented by proper hand-washing.
• Infections that can be prevented by handwashing are:

  • Staphylococcus aureus
  • Clostridium difficile (C-Diff)
  • Pseudomonas aeruginosa
  • Enterococcus spp
  • Respiratory syncytial virus (RSV)
  • Norovirus

  Infections that can't be prevented by hand-washing include:

  • influenza
  • chickenpox
  • measles.
• Many bacteria that cause nosocomial infections are resistant to antibiotics. Such bacteria include MRSA, VRE, and CPE.
• Some of the main factors that contribute to the appearance of antibiotic resistance are:

  • Mutation and transfer of resistance genes through plasmids.
  • Transmission of resistant bacteria via the hands of healthcare staff.
  • Incorrect and excessive use of antibiotics.
  • Transmission of resistant bacteria from surfaces within the healthcare facility.
• The traditional model to describe the causes of infectious disease is the epidemiological triad. According to the epidemiological triad, a disease occurs when an organism or pathogen meets the right host under conditions in the environment that favour disease development.
• In the epidemiological triad, the interactions between the pathogens, host, and environment can be viewed as a triangle with the 3 essential factors at the vertices, and the disease occupying the interior space of the triangle. Any effect on one side of the triangle will have effects on the other 2 sides and will affect the disease.

  The three essential factors necessary for disease development are host, pathogens, and environment, and they all interplay into each other.
• Factors affecting disease development in relation to the host:

  • age - infants and the elderly are more susceptible to infection. If the appropriate host isn't found, the disease won't occur.
  • underlying characteristics that increase susceptibility, such as asthma, obesity, diabetes, and malnutrition
  • genetic variation. The sickle cell trait provides protective to malaria.
  • Immunodeficiency; opportunistic infections occurring in patients with AIDS.
  • Immune response
  • Trauma/surgery. Surgical implants make it easier for bacteria to cause infection, and it harder to eradicate them.
• Iatrogenic infections are due to the activity of a physician or therapy. Iatrogenic infections are an example of how factors that disrupt the body's non-specific mechanical barriers to infection make it easier for microorganisms to cause infection.

  Injury associated with therapy, such as surgery, endoscopy, or radiotherapy, allow microorganisms to enter normally sterile parts of the body.
• Plastic and metal 'foreign bodies', such as prosthetics or IV lines, provide surfaces that microbes can colonise more easily than their natural equivalents. Infections that arise from these cases aren't easily treated, and the microorganism aren't easily eradicated, so the foreign body would need to be replaced to avoid risk of chronic infection and severe sepsis.