DR. KARABINYOSH S.O.

Infectious agents have probably always caused disease in humans.

Smallpox has been described in ancient Egyptian and Chinese writings and may have been responsible for more deaths than all other infectious diseases combined.

There is evidence that malaria and poliomyelitis have existed since ancient times.

In the 14th Century, the bubonic plague, or Black Death, killed about 20 million people in Europe alone.

In the 20th Century, the 1918 influenza may have killed up to 50 million people worldwide

Close to 20 million people have died of

Courtesy of CDC

Recreated 1918 Influenza virions. The 1918 Spanish flu killed more than 500,000 people in the United States and up to 50 million worldwide.

Koch developed four criteria to demon- strate that a specific disease is caused by a particular agent.

1. The specific agent must be associated with every case of the disease.

2. The agent must be isolated from a diseased host and grown in culture.

3. When the culture-grown agent is introduced into a healthy susceptible host, the agent must cause the same disease.

4. The same agent must again be isolated from the infected

Etiology - the study of the cause of a disease or abnormal condition (peculiarities of the causative agent described later in this presentation).

Pathogenesis - is the biological mechanism (process) that leads to the diseased state. The term can also describe the origin and development of the disease, and whether it is acute, chronic, or recurrent.

Pathomorphology - describes morphologic changes caused by a pathological condition.

Disease – a pathological condition of body parts or tissues characterized by an identifiable group of signs (syndrome) and symptoms.

Infectious disease – disease caused by an infectious agent such as a bacterium, virus, protozoan, or fungus that can be passed on to others.

Infection – is the invasion of a host organism's body tissues by disease-causing agents, their multiplication, and the reaction of host tissues to these organisms and the toxins they produce, in other words occurs when an infectious agent enters the body and begins to reproduce; may or may not lead to disease.

Pathogen – an infectious agent that causes disease.

Host – an organism infected by another

q Contagenicity – dangerous for surrounding people

q Specificity – every disease has the specific infectious agent

q Periodicity – § incubation period;

§ initial (prodromal) period;

§ period of acute illness;

§ period of convalescence or reconvalescence.

q Post-infection immunity

q Cyclicity – ability to epidemic spreading after some period of time

Synoikia – mutual being, when one species uses another as a living place without harming it

Mutualism – symbiosis, that is profitable for both organisms

Commensalism – one organism gets a benefit from other without harming it

Parasitism – microorganism (parasite) feeds with the saps or tissues of the host harming it. Most infectious diseases belong to this kind of symbiosis

Endogenous diseases (autoinfections) – caused by human own microflora (pathogenic or half-parasites) of the skin, respiratory or alimentary tracts, conjuctive, genitals

Exogenous diseases – caused after penetration of the microorganisms from the environment

Human demographics and behavior

Technology and industry

Economic development and land use

International travel and commerce

Microbial adaptation and change

Violation of public health measures

qSporadic

qEpidemic

qPandemic

I. Main symptoms (pathognostic) : symptoms which are characteristic

for one disease only.

II. Supporting or optional

symptoms: symptoms, which are may be present in some infectious diseases, they give possibility to differentiate diseases.

Clinical: investigation

epidemiological anamnesis

Laboratory: virological

bacteriological

parasitological

serological

allergic

biological

immunoenzyme etc,

Life style and living conditions of the patient

Patient’s occupation

Previous diseases and preventive vaccinations

1. Fever

2. Rash

3. Diarrhea

4. Respiratory syndrome

5. Jaundice

6. Meningeal signs

7. Lymphoadenopathy etc

Fast (acute) temperature rise – patient clearly fix the hour of the disease onset

Gradual rise

Ø Subfebrile (37,0 – 37.9 0C)

Ø Moderate (38,0 – 39,9 0C)

Ø High (40,0 – 40,9 0C)

Ø Hyperpyrexia (41 0C and higher)

Classification of fevers:

§ Constant fever (febris continua)

§ Remittent fever (febris remittens)

§ Intermittent fever (febris intermittens)

§ Recurrent fever (febris recurrens)

§ Undulant fever (febris undulans)

§ Hectic fever (febris hectica)

§ Distorted fever (febris inversa)

§ Acute undulating fever (febris undulans acuta)

§ Relapsing fever (febris recidiva)

Microbes may make harm by releasing toxins, for example, in food poisoning, a parasite Entameba hystolytica can release toxins, which can destroy colonic mucosa, resulting in bleeding ulcers and diarrhea.

Invasion of microbes triggers immune response of the body and attracts inflammatory cells, like leukocytes, and substances, like cytokines, which attack the microbes. Such a defense reaction regularly results in an inflammation of infected tissue, which can be observed, for example, as purulent discharge in common cold or swollen joint in bacterial arthritis. Toxins released by microbes often trigger fever.

Inflammatory response itself can be harmful. For example, Streptococcus pneumoniae , causing pneumonia, can trigger fluid collection in the lungs, impeding oxygen exchange between the air and the

Symptoms commonly appearing in all types of infections:

Fever in localized skin infections or food poisoning may be absent, in tuberculosis or viral pneumonia it is usually low-grade, in influenza moderate, and in bacterial pneumonia or sepsis high.

Pain in childhood viral infections and flu is usually general and vague, and in localized bacterial infections, like bacterial prostatitis, localized and intense.

Headache in sinusitis is facial, in meningitis on the back of the head and neck, and in viral infections general

Skin rash in bacterial skin infections is usually in the form of red bumps or patches; in viral infections, blisters and in fungal skin infections, scaly discolored patches usually appear

Discharge from the nose, eyes, ears, trachea, bronchi and lungs (phlegm, sputum), nipples, bowel (mucus in the stool), urethra, vagina and wounds may appear in all types of infections.

Three stages : effervescence fastigium deffervescence

Five kinds of fever: *Sustained fever.

*Remittent fever: one that shows significant variations in

24 hours but without return to normal temperature. ,

*Intermittent fever: an attack of malaria or other fever,

with recurring fever episodes separated by times of normal

temperature ,

*Relapsing fever: alternating periods of fever and apyrexia,

each lasting from five to seven days.

*Saddle type fever.

*Irregular fever.

Temperature i s u l t imate ly regu la ted in the

hypothalamus. A trigger of the fever, called a

pyrogen, causes a release of prostaglandin E2 (PGE2).

PGE2 then in turn acts on the hypothalamus, which

generates a systemic response back to the rest of the

body, causing heat-creating effects to match a new

temperature level.

A pyrogen is a substance that induces fever. These can be either internal (endogenous) or external (exogenous) to the body.

The bacterial substance lipopolysaccharide (LPS), present in the cel l wal l of some bacteria, is an example of an exogenous pyrogen.

Cytokines (especially interleukin 1) are a part of the innate immune system, are produced by phagocytic cells, and cause the increase in the thermoregulatory set-point in the h y p o t h a l a m u s . O t h e r e x a m p l e s o f endogenous pyrogens are interleukin 6 (IL-6), and tumor necrosis factor-alpha.

PGE2 acts on neurons in the

preoptic area (POA) through the

prostaglandin E receptor 3 (EP3).

EP3-expressing neurons in the POA

i n n e r v a t e t h e d o r s o m e d i a l

hypothalamus (DMH), the rostral

raphe pallidus nucleus in the

medulla oblongata (rRPa) and the

paraventricular nucleus (PVN) of

Fever signals sent to the DMH and rRPa lead to stimulation of the sympathetic output system, which e v o k e s n o n - s h i v e r i n g thermogenesis to produce body heat and skin vasoconstriction to decrease heat loss from the body surface.

I t i s p r e s u m e d t h a t t h e innervation from the POA to the PVN mediates the neuroendocrine effects of fever through the pathway involving pituitary gland and various endocrine organs

Rash eruption Date of eruption 1st: chickenpox 2nd: scarlet fever

3rd: smallpox 4th: measles

5th: typhus 6th: typhoid fever

Location of eruption Form of rash Exanthema : *maculo-papular rash: A maculopapular rash is a flat, red area on the skin that is covered with small confluent bumps e.g. measles.

*Petechia: * V e s i c u l o -

§ Roseola

§ Macula

§ Papula

§ Erythema

§ Tuberculum

§ Nodus

§ Urtica (hives)

§ Vesicula

§ Pustula

§ Herpes

§ Bulla (blister)

§ Hemorrhage (petechiae, purpura, ecchimosis)

§ Erosio

§ Ulcus

§ Dyschromia cutis

§ Squama

§ Crusta

§ Cicatrix

Red or purple-red

Diameter 2-5 mm

Spherical form

Similar to roseola

Diameter 5-20 mm

Color same as roseola’s

Red or purple-red

Diameter 1-20 mm

Proliferation of epidermis with vasodilatation

Result of large maculae joining

Inflammatory fields

Diameter from 2 cm and higher

Formations without cavities

Granulematous inflammatory infiltrate

Limited dense formation

Diameter 1-5 cm

Spherical or oval form

Small cavity formation containing serous or serouse-hemorrhagic fluid

Half-round element

Diameter from 1 to 5 mm

After damaged

Cavity formation

Dimension up to

10 cm

Extravasation into the skin

Different kinds and dimensions

A deep defect of the skin (epidermis, derma, underline tissues)

Enanthema – rashes on the mucous membranes

Ø Toxemic symptoms

Ø Mononuclear phagocyte system reactions

Hepato- splenomegaly

Lymph nodes enlargement

Ø Clinical types

acute, sub acute, mild, common, severe, fulminant, typical, atypical, abortive, ambulatory

The suffix “-emia”

A suffix meaning “presence of an infectious agent”

Bacteremia = Presence of infectious bacteria

Viremia = Presence of infectious virus

Fungemia = Presence of infectious fungus

Septicemia = Presence of an infectious agent in the

The suffix “-itis”

A suffix meaning “inflammation of”

Examples:

Pharyngitis = Inflammation of the pharynx

Endocarditis = Inflammation of the heart chambers

Gastroenteritis =

A cause of an infection can be often recognized from a combination of symptoms and signs. When in doubt, a doctor can take a sample of blood, urine, stool, sputum, nasal or other discharge and send it to laboratory, where microbes can be determined by serologic tests or a culture.

Medical diagnosis (DS or Dx) - is the process of determining which disease or condition explains a person's symptoms and signs, described by complaints and examination results.

The information required for diagnosis is typically collected from a history of illness and physical examination of the person seeking medical care. Often, one or more diagnostic procedures, such as

A fomite is an inanimate object or substance capable of transmitting infectious agents (microorganisms) from one object to another. Once contaminated, fomites may carry microbes for few minutes or several weeks, depending on the type of the microbe and certain circumstances, like air humidity and temperature.

Examples of fomites: Door knobs

Bus handles

Faucets, especially in public toilets

Computer keyboards-

Phones

Towels

Napkins

Used razors

Used needles (drug addicts)

Pens

Sport equipment

Clothes

Books

Paper

Money

Disease and Infectious Disease

Disease

Any deviation from a condition of good health and well-being

Infectious Disease

·A disease condition caused by the presence or growth of infectious microorganisms or

Endemic Disease

A disease condition that is normally found in a certain percentage of a population

Epidemic Disease

A disease condition present in a greater than usual percentage of a specific population

Pandemic Disease

An epidemic affecting a large geographical area; often on a global scale

Epidemiology

The study of the transmission of disease

Communicable Disease

A disease that can be transmitted from one individual to another

Contagious Disease

A communicable disease that is easily spread from one individual to another

Non communicable Disease

A disease that is not transmitted from one individual to another

Endemic/Enzootic: The constant presence of a disease or infectious agent within a given geographic area.

Epidemic/Epizootic: The occurrence in an area of a disease or illness in excess of what may be expected on the basis of past experience for a given population (in the case of a new disease, such as AIDS, any occurrence may be considered "epidemic").

Pandemic/Panzootic: A worldwide epidemic affecting an

Zoonosis

 is any process whereby an infectious disease is transmitted between different species of animals.

Antroponosis

 is an infectious disease in which a disease causing agent carried by humans is transferred to other animals. It may cause the same disease or a different disease

By duration

Acute – develops and runs its course quickly.

Chronic – develops more slowly and is usually less severe, but may persist for a long, indefinite period of time.

Latent – characterized by periods of no symptoms between outbreaks of illness.

By location

Local – confined to a specific area of the body.

Systemic – a generalized illness that infects most of the body with pathogens distributed widely in tissues.

By timing

Primary – initial infection in a

Acute infection vs. chronic infection

Acute Infection

An infection that is characterized by sudden onset, rapid progression, and often with severe symptoms

Chronic Infection

An infection that is characterized by delayed

Localized infection vs. systemic infection

Localized Infection

An infection that is restricted to a specific location or region within the body of the host

Systemic Infection

An infection that has spread to several regions or areas in the body of the

Clinical infection vs. subclinical infection

Clinical Infection

An infection with obvious observable or detectable symptoms

Subclinical Infection

An infection with few or no obvious symptoms

Opportunistic infection

An infection caused by microorganisms that are commonly found in the host’s environment This term is often used to refer to infections caused by organisms in the

Sporadic level: occasional cases occurring at irregular intervals

Endemic level: persistent occurrence with a low to moderate level

Hyperendemic level: persistently high level of occurrence

Epidemic or outbreak: occurrence clearly in excess of the expected level for a given time period

Pandemic: epidemic spread over several countries or continents, affecting a large number of people

Incubation period – time between infection and the appearance of signs and symptoms.

Prodromal phase – mild, nonspecific symptoms that signal onset of some diseases.

Clinical phase – a person experiences typical signs and symptoms of disease.

Decline phase - subsidence of symptoms.

Recovery phase – symptoms have disappeared, tissues heal, and the

1. Entry of Pathogen

Portal of Entry

2. Colonization

Usually at the site of entry

3. Incubation Period

Asymptomatic period

Between the initial contact with the microbe and the appearance of the first symptoms

4. Prodromal Symptoms

Initial Symptoms

5. Invasive period (depends on the state of the Host Immune System and Number of Pathogenic Cells encountered by the Host – infectious dose)

Increasing Severity of Symptoms

Fever

Inflammation and Swelling

Tissue Damage

Infection May Spread to Other Sites

Acme (Fastigium)

6.Decline of Infection

7.Convalescence

Chain of Transmission

Portal of exit

Portal of entry

Agent

Susceptible Host

Mode of transmission

Reservoir Person to person transmission

SOURCE OF INECTION

Reservoir of Infection The source of an infectious agent

CarrierAn individual who carries an infectious agent without manifesting symptoms, yet who can transmit the agent to another individual

FomitesAny inanimate object capable of being an intermediate in the indirect transmission of an infectious agent

Reservoir Human

Person with symptomatic illness

Carriers:

Asymptomatic

Incubating

Convalescent

Chronic

Animal: zoonosis

Environmental: soil, plant, water

Direct

Direct contact

Secretions, Blood, Faeces/urine

Droplet spread

Indirect

Food/water

Aerosol

Animal vectors

Fomites

Medical devices and treatments

Mode of Transmission

Human/animal

Respiratory tract

Genito-Urinary tract

Faeces

Saliva

Skin (exanthema, cuts, needles, blood-sucking arthropods)

Conjunctival secretions

Placenta

Environmental

Cooling towers

Portal of exit

Respiratory tract

Mouth (faecal-oral transmission)

Skin

Mucous membranes

Blood

Portal of entry

In medical terms, the incubation period is the time from when a person is exposed to an infectious agent (pathogenic microorganism) till the onset of signs and symptoms. Not every person who comes into contact with an infectious agent will become infected but once the infection is acquired, the micororganism will take a period of time during which it multiplies and spreads within the body until the point that signs and symptoms become evident.

Incubation periods can vary significantly for a number of reasons. This includes :

Method of transmission.

Site of entry.

Immune response.

Reproduction mechanism of infectious agent.

Action of infectious agent.

Nature of the disease.

For pathogens, there is safety and success (that is, infectivity) in numbers. In fact, the doubling time for some bacteria can be as little as 20 minutes.

This extremely high reproductive rate requires that the growth environment be satisfactory, and for most pathogens the tissues and fluids of the human body are an ideal environment. So the number of organisms required for successful infection can easily be achieved.

There is considerable variability among organisms with regard to the number required for success, and we can run specific experiments to establish the criteria for virulence for any given pathogen. The lethal dose 50% (LD50) is the number of organisms required to kill 50% of the hosts, and the infectious dose 50% (ID50) is the number of

Using these types of information, we can categorize organisms according to virulence. It is important to remember that bacteria divide by binary fission (one bacterium splits into two) and that a pathogen that has a low LD50 and a short doubling time could be extraordinarily dangerous, with the rapid increase in organisms quickly overwhelming a patient. Fortunately, attacking only rapidly growing bacteria is the way in which many antibiotics work, thereby preventing negative outcomes from infection.

In viral infections, the number requirement is easier to understand. A lytic virus is defined as one that functions by filling a host cell with viral particles called virions until the host cell bursts open and pours virions into the intercellular fluid. These new virions locate new host cells, and the process is repeated until there are no more host cells available. Infection

There is considerable variability among organisms with regard to the number required for success, and we can run specific experiments to establish the criteria for virulence for any given pathogen. The lethal dose 50% (LD50) is the number of organisms required to kill 50% of the hosts, and the infectious dose 50% (ID50) is the number of organisms required for 50% of the population to show signs of infection. Pathogens having the lowest LD50 and ID50 values are the most virulent.

Using these types of information, we can categorize organisms according to virulence. It is important to remember that bacteria divide by binary fission (one bacterium splits into two) and that a pathogen that has a low LD50 and a short doubling time could be

Most infectious agents that cause disease are microscopic in size and thus, are called microbes or microorganisms.

Different groups of agents that cause disease are:

Bacteria

Viruses

Protozoa (Protists)

Fungi

Helminths (Animals)

Bacterial infections are usually limited to one part of the body. Examples of bacterial infections: staphylococcal skin infections, pseudomonas folliculitis, streptococcal pharyngitis, osteomyelitis, pneumococcal pneumonia, bacterial meningitis, etc. Bacterial infections can be treated by antibacterial

Viral infections are often systemic and may cause fever, headache, runny nose, sore throat, muscle and joint pains, diarrhea, skin rash, etc. Examples of viral infections: influenza, childhood diseases like chicken pox, rubella, rubeolla and infectious mononucleosis, AIDS, viral hepatitis, viral hemorrhagic fever, etc. Examples of a localized viral infection are common cold and labial herpes.

Fungal (yeast) infections in a person with a healthy immune system usually affect only the skin. Patchy areas with a brownish or reddish scaly rash on the scalp (scalp ringworm), trunk, limbs or groin (jock itch), peeled skin on the hands or feet (athlete’s foot), or discolored or cracked nails are typical symptoms of a skin fungal infection. Effective over the counter or prescribed anti-fungal ointments and oral medications are available.

In a person with a weak immune system, fungal infections, commonly caused by a yeast Candida albicans, may appear in the mouth (oral thrush), esophagus,

Parasitic infections cause different symptoms, depending on the type of parasite and organ affected. Intestinal parasites cause bloating, diarrhea, mucus in the stool and eventual weight loss. Plasmodium malariae can cause episodes of fever, chills sweating and tiredness. Head and pubic lice, and scabies cause itchy skin. Treatment is with specific anti-parasitic drugs. Surgical removal of parasitic cysts, like in Echinococcus, from the liver, bones, brain or lungs is sometimes required.

Infestation (Latin infestare = to attack, disturb) is an invasion

Acute contagious disease caused by the influenza virus.

Respiratory tract infection, but symptoms felt throughout entire body.

Epidemics occur seasonally with low fatality; more deadly pandemics occur several times each century.

Highly changeable virus that can infect multiple species, including humans, pigs, and birds.

Concern exists that current avian flu will lead to a new pandemic.

Being contagious means being capable of carrying microbes or spreading an infection. In everyday speech, only infections transmitted directly from person to person (like flu) are considered as contagious.

A term contaminated is used for soil, water, food and surfaces that carry microbes.

An incubation period is the time elapsed between exposure to pathogenic microbes and symptoms appearance.

Sources and modes of transmission of

Infection can be transmitted from person to person by:

Skin-to-skin contact, clothes, towels, sport equipment, etc. (staphylococcal, including MRSA skin infections, like folliculitis; scabies, head lice)

Droplets during coughing, sneezing (common cold, flu, swine flu, pneumonia, tuberculosis, bacterial meningitis, chicken pox, measles, rubella, mumps), or kissing (infectious mononucleosis, cold sores)

Stool-to-mouth (fecal-oral) spread, usually via dirty hands or utensils (stomach flu, hepatitis A, Giardia, pinworms, Clostridium

Sexually transmitted (gonorrhea, Chlamydia, genital herpes, pubic lice, genital warts (human papillomavirus – HPV), AIDS, syphilis)

Blood-to-blood contact by:

contaminated needles, usually by drug addicts or health workers (hepatitis B, C, AIDS)

blood transfusion (hepatitis B,C, AIDS, viral hemorrhagic fevers)

mosquitoes (malaria)

Spread from mother to fetus during pregnancy (hepatitis B, C, AIDS, HSV-1, HSV-2, rubella, parvovirus, toxoplasma, varicella, syphilis, bird flu), or delivery (Chlamydia trachomatis, Neisseria gonorrheae, CMV, group B Streptococci)

An autoinfection – the spread of an infection from one body part to another,

Food poisoning is an infection of the gastrointestinal tract caused by microbes from contaminated food: bacteria, like Salmonella or E.coli, toxins from Staphylococcus aureus or Clostridium botulinum, parasites like Giardia or roundworm, viruses, like Enterovirus.

By drinking contaminated water, one can contract stomach flu, cholera, dysentery, typhoid fever, amebiasis, etc. Tap water in newly opened hospitals may contain Legionella.

By swimming in contaminated swimming or spa pools, or lakes, one can contract hot tub folliculitis, intestinal parasite Cryptosporidium, eye and middle ear infections. Certain parasites may enter through the skin.

Water in public showers may hold Legionella; the floor may be contaminated by Staphylococci (from human skin infections)

Industrial cooling or hot water systems, air condition and room-air humidifiers can be a source of Legionella, H. influenza.

During walking barefoot, Clostridium tetani, sandworms, or intestinal parasites, like Strongyloides stercoralis or hookworms can be contacted.

Eating with soil-contaminated hands can also

Infections acquired in hospitals can be dangerous, since causing microbes are often resistant to regular antibiotics, and patients infected are often already seriously ill. Common HAIs include:

Urinary tract infections from urinary catheters

Surgical-site infections

Staphylococcal skin, lung and heart valve infections

Fungal infections, like oral thrush in patients with low immunity system or cancer patients receiving chemotherapy

Animal Vectors

An animal (nonhuman) that can transmit an infectious agent to humans

Two types: mechanical and biological

Biological animal vectors: The infectious agent must incubate in the animal host as part of the agent’s developmental cycle; eg, the transmission of malaria by infected mosquitoes

Mechanical animal vectors: The infectious agent is physically transmitted by the animal vector, but the agent does not incubate or grow

Virulence factors help bacteria to (1) invade the host, (2) cause disease, and (3) evade host defenses. The following are types of virulence factors:

Adherence Factors: Many pathogenic bacteria colonize mucosal sites by using pili (fimbriae) to adhere to cells.

Invasion Factors: Surface components that allow the bacterium to invade host cells can be encoded on plasmids, but more often are on the chromosome.

Capsules: Many bacteria are surrounded by capsules that protect them from opsonization and phagocytosis.

Endotoxins: The lipopolysaccharide endotoxins on Gram-negative bacteria cause fever, changes in blood pressure, inflammation, lethal shock, and many other toxic events.

Exotoxins: Exotoxins include several types of protein toxins and enzymes produced and/or secreted from pathogenic bacteria. Major categories include cytotoxins, neurotoxins, and enterotoxins.

Siderophores: Siderophores are iron-binding factors that allow some bacteria to compete with the host for iron, which is bound to hemoglobin, transferrin, and

Virulence factors are molecules produced by pathogens (bacteria, viruses, fungi and protozoa) and contribute to the pathogenicity of the organism that enable them to achieve the following:

colonization of a niche in the host (this includes attachment to cells)

immunoevasion, evasion of the host's immune response

immunosuppression, inhibition of the host's immune response

entry into and exit out of cells (if the pathogen is an intracellular one)

obtain nutrition from the host

We can say that we classify virally caused cell damage or death as a cytopathic effect (CPE) and that the cytopathology associated with viral infections can occur in three ways.

The most obvious way is viral overload, a condition that causes the virus to explode out of the host cell and infect and lyse surrounding host cells. A second type of CPE occurs when host defense mechanisms

identify and kill virally infected cells. This is categorized as a cytocidal effect. The third type of viral cytopathology occurs when a virus shuts down the host DNA, RNA, and protein synthesis and thereby forces the

Viral cytopathology can be identified microscopically. In some cases, inclusion bodies filled with virus become visible inside the cell. For example, Negri bodies are inclusion bodies seen in rabies viral infections and can be diagnostic for the disease. Some viral infections cause breaks in the host chromosomes, and these breaks are easily identifiable.

The formation and appearance of syncytia (gigantic cells formed as a number of infected host cells merge) can also be a visual indication of viral infection. More subtle pathogenic effects, such as the

Bacteria produce various adhesins including lipoteichoic acid and trimeric autotransporter adhesins to attach to host tissue.

Capsules, made of carbohydrate, form part of the outer structure of many bacterial cells including Neisseria meningitidis. Capsules play important roles in immune evasion, as they inhibit phagocytosis, as well as protecting the bacteria while outside the host.

Another group of virulence factors possessed by bacteria are immunoglobulin (Ig) proteases. Immunoglobulins are antibodies expressed and secreted by hosts in response to an infection. These immunoglobulins play a major role in destruction of the pathogen through mechanisms such as opsonization. Some bacteria, such as Streptococcus pyogenes, are able to break down the host's immunoglobulins using proteases.

Adhesins are cell-surface components or appendages of bacteria that facilitate adhesion or adherence to other cells or to surfaces.

Examples:

Protein A (Staphylococcus aureus)

Protein M (Streptococcus

Some bacteria, such as Streptococcus pyogenes, Staphylococcus aureus and Pseudomonas aeruginosa, produce a variety of enzymes which cause damage to host tissues. Enzymes include hyaluronidase, which breaks down the connective tissue component hyaluronic acid; a range of proteases and lipases; DNases, which break

Examples:

Coagluase (Staphylococcus aureus)

Streptokinase (Streptococcus pyogenes)

Hyaluronidase (Many pathogens)

Collagenase (Many pathogens)

Leucocidin (Many pathogens)

Hemolysin (Many pathogens)

Leukocidins are enzymes that destroy white blood cells in the host. White blood cells are an important part of both the innate and the adaptive host defense systems. Two types of white blood cell are neutrophils and macrophages, which are powerful phagocytic cells. In addition, the white blood cells known as lymphocytes, which are responsible for the adaptive immune response to infection, are destroyed by leukocidins. Leukocidins are produced by staphylococcal and streptococcal pathogens, and it is easy to see how the ability to kill

Hemolysins are membrane-damaging toxins that disrupt the plasma membrane of host cells and cause the cells to lyse. These toxins can damage the plasma membrane of both red blood cells and white blood cells and are produced by a variety of bacteria, including staphylococcal species, Clostridium perfringens (which causes gas gangrene), and streptococcal species. Hemolysin produced by streptococcal bacteria is referred to as streptolysin and can be divided into different groups, such as group A and group O. The various groups of streptolysin differ from one another in the type of cell destruction that they

Coagulase is a pathogen-produced enzyme that causes fibrin clots to form in the blood of a host. Clot formation can be used by both host and pathogen during an infection. The host can use clotting as part of the defense against infection. This clotting occurs in blood vessels around the site of the infection, thereby closing in the pathogens and preventing the spread of the infection. An example of bacterial “walling off” is a boil resulting from a localized staphylococcal

Kinases are enzymes that break down fibrin and dissolve clots. These enzymes can be used by a pathogen to overcome attempts by the host to wall off the infection, thereby ensuring its spread. Staphylokinase is produced by staphylococcal species, and streptokinase is produced by streptococcal species.

Hyaluronidase and collagenase are enzymes that break down connective tissue and collagen in a host, thereby allowing infections to spread. Both are active, for instance, in the infection gas gangrene (caused by C. perfringens),

A major group of virulence factors are proteins that can control the activation levels of GTPases. There are two ways in which they act. One is by acting as a GEF or GAP, and proceeding to look like a normaly eukaryotic cellular protein. The other is covalently modifying the GTPase itself. The first way is reversible; many bacteria like Salmonella have two proteins to turn the GTPases on and off. The other process is irreversible, using toxins to completely change the target GTPase and shut down or override gene expression. One example of a bacterial virulence factor acting like a eukaryotic protein is Salmonella protein SopE it acts as a GEF, turning the GTPase on to create more GTP. It does not modify anything, but overdrives normal cellular internalization process, making it easier for the Bacteria to be colonized within a host cell. YopT from Yersinia is an example of modification of the host. It modifies the proteolytic cleavage of carboxyl terminus of RhoA, releasing RhoA from the membrane. The mislocalization of RhoA causes downstream effectors to not work.

A major group of virulence factors are bacterial toxins. These are divided into two groups: endotoxins and exotoxins.

Endotoxins

Endotoxin is a component (lipopolysaccharide (LPS)) of the cell wall of Gram-negative bacteria. It is the lipid A part of this LPS which is toxic. Lipid A is a very potent antigen and, as a result, stimulates an intense host immune response. As part of this immune response cytokines are released; these can cause the fever and other symptoms seen during disease. If a high amount of LPS is present then septic shock (or endotoxic shock) may result which, in severe cases, can lead to death.

A type of bacterial toxin having the following properties:

Produced only by gram-negative bacteria

Endotoxins are a component of the gram-negative cell wall

The action of endotoxin requires the presence of the bacteria in the host. The endotoxin may be released from the cell wall as the cells die and disintegrate

Endotoxin is composed of Lipid A: Part of the lipopolysaccharide layer

Mode of action: Irritation/inflammation of epithelium, GI irritation, capillary/blood vessel inflammation, hemorrhaging

Exotoxins

Exotoxins are actively secreted by some bacteria and have a wide range of effects including inhibition of certain biochemical pathways in the host. The two most potent exotoxins known to man are the tetanus toxin (tetanospasmin) secreted by Clostridium tetani and the botulinum toxin secreted by Clostridium botulinum. Exotoxins are also produced by a range of other bacteria including Escherichia coli; Vibrio cholerae (causative agent of cholera); Clostridium perfringens (common causative agent of food poisoning as well as gas gangrene) and Clostridium difficile (causative agent of pseudomembranous colitis). A potent three-protein virulence factor produced by Bacillus anthracis, called anthrax toxin, plays a key role in anthrax pathogenesis.

Exotoxins are also produced by some fungi as a competitive resource. The toxins, named mycotoxins, deter other organisms from consuming the food colonised by the fungi. As with bacterial toxins, there is a wide array of fungal toxins. Arguably one

A type of bacterial toxin with the following properties:

May be produced by either gram-positive or gram-negative bacteria

Is secreted by the bacteria

The action of the exotoxin does not necessarily require the presence of the bacteria in the host

Most exotoxins are peptide or protein

Most exotoxins are heat sensitive

Classes of exotoxins: Neurotoxic, cytotoxic, or enterotoxic exotoxins

Neurotoxins: Interfere with proper synaptic transmissions in neurons

Cytotoxins: Inhibit specific cellular activities, such as protein synthesis

Enterotoxins: Interfere with water reabsorption in the large intestine; irritate the lining of the gastrointestinal tract

Emerging diseases are those that have recently appeared within a population, or whose incidence or geographic range is increasing rapidly.

Diseases can emerge or re-emerge due to:

appearance of a previously unknown agent.

evolution of a new infectious agent.

spread of an infectious agent to a new host.

spread of an infectious agent to

Vaccines

Antimicrobial drugs

Good personal hygiene

and sanitation

Protection against mosquitoes

Quarantine

Please sign your papers:

Name:

Group #:

Date:

21 year old male student from Africa presented with ulcerative lesions of his tongue. Bacteriological test reveals: Strep. mutans and Strep. salivarius. Physician prescribed Amoxicillin. After a week of AB treatment patient complaints on white, “cottage cheese” like discharge with bad odor from ulcers, diarrhea and abdominal pain. Physician prescribed Nystatin for 2 weeks. AB and AF treatment was still unsuccessful.

After 2 weeks of diet and loratidine ulcers fully resolved.

From anamnesis: suffered for 3 years, symptoms started after first year of school in Ukraine. Patient indicates that he has changed to a healthy diet (fresh fruit and

Questions:

1) Which disease does the patient have?

2) Why is this case considered to be iatrogenic?

3) What mistake did the physician make?

4) Which complications did the physicians mistake cause?

A 15 year old male admitted with severe throat pain. Treated with Amoxicillin for a week.

After 2 months develops petechial rash. Was diagnosed with vasculitis. In 4 months started to experience swelling and pain in his index finger and thumb on both hands, toes and knee joints. Diagnosed with juvenile rheumatoid arthritis. Treated with methotrexate (10 mg) for 1 year and remained under supervision of rheumatologist.

Patient has got a consultation of the infectologist undergone throat swab test (Streptococcus Spp.) was recommended to get tonsillectomy and AB treatment. After surgery and AB treatment (Amoxicillin/clavulanic acid + Erythromycin) symptoms almost completely

Questions:

1) What was the causative agent that caused rheumatoid arthritis?

2) Was the decision to prescribe methotrexate reasonable? Why?

3) Why didn’t Amoxicillin didn’t help for strep throat?

4) Why did AB treatment and