Emerging Infections
Infectious disease causes significant death and morbidity due to:
Reemergence of old infections
Emergence of unknown infections
Development of antibiotic resistant infections
More than 40 unknown infections have arisen within 1 generation
Microorganism and Humans
have a mutual symbiotic relationship.
Consists of a normal biome
Normal microbiome
Resident microorganisms are found in different parts of body
Produces enzymes that help digestion
Produces antibacterial factors
Produces metabolites (vitamin K and B vitamins)
true pathogens
bypass normal defenses and cause infection
Infection is usually dependent on adequate numbers of microorganisms rather than a compromise of the host's defenses
Incubation stage of clinical infectious disease
Period from initial exposure to onset of first symptoms
Prodromal stage of clinical infectious disease
Occurrence of initial symptoms, usually mild with feelings of discomfort and tiredness
Invasion stage of clinical infectious disease
is farther and affects other body tissues
Convalescence stage of clinical infectious disease
Recovery occurs and symptoms decline, or the disease is fatal, or has a period of latency
What are the stages of clinical infectious disease?
Incubation, Prodromal, Invasion, Convalescence
Processes of infection
colonization, invasion, multiplication, and spread
Colonization process of infection
Infectious microorganisms are transmitted by (direct, indirect, droplet/airborne, vertical/horizontal transmission)
Adhere to tissues via specific surface receptors
Invasion Process of Infection
Invades surrounding tissues by evading host's defenses
Multiplication process of infection
Warm and nutrient-filled environment of human tissue causes most to multiply rapidly
Spread process of infection
May stay localized or enter other body areas
Spread is quick if immune system is compromised
Infectious Disease Clinical Manifestations
Variable, depends on the pathogen
Caused directly by pathogen or indirectly by its products
Manifestations include: fatigue, malaise, weakness, loss of concentration, generalized aching, loss of appetite
Fever: hallmark of infection, Body temperature is r
Factors for infection
communicability, infectivity, virulence, pathogenicity, portal of entry, toxigenicity
Communicability
the ability to spread disease from one to other
Infectivity
ability of pathogen to invade and multiply in host
Virulence
capacity of pathogen to cause severe disease
Pathogenicity
ability of an agent to produce disease
Portal of entry
route by which pathogenic microorganism infects host
Toxigenicity
ability to produce soluble toxins or endotoxins, factors that influence pathogen's virulence
endemic
Diseases with relatively high, but constant, rates of infection in a particular population
Epidemic
Number of new infections in a particular population that greatly exceeds the number usually observed
Pandemic
An epidemic that spreads over a large area such as a continent or worldwide
Infectious
infection spread from person to person
Pathogens successfully cause disease because they...
Compete with normal flora
Produce toxins
Produce enzymes to (Avoid phagocytosis, opsonization, destroy connective tissues)
Avoid lysis (Stop complement cascade by degrading C3b)
Paralyze ciliary activity
Bacterial Virulence and Infectivity
Important factors in determining these are:
Iron needed to multiply
Siderophores (iron receptors)
Presence of polysaccharide capsules
Suppression of complement activation
Bacterial proliferation rates surpassing protective response
Staphylococculs aureus
Life-threatening, major cause of nosocomial infection
Common on skin and nasal passages
Opportunistic, secretes endotoxins
Antibiotic resistance is major problem
Toxin production
Exotoxins (released from living microbe)
Enzymes that damage host cell plasma membranes or can inactivate enzymes critical to protein synthesis
Endotoxins (released from lysed gram-negative bacteria: LPS)
Activate inflammatory response and produce fever
Bacteremia (presence) or septicemia (growth)
Bacteria present in blood
Failure of the body's defense mechanisms
Caused by gram-negative bacteria
Endotoxins released in blood activate complement and clotting systems
Capillary permeability causes plasma to escape into surrounding tissues producing wid
Gram-negative bacteria
DO NOT retain crystal violet dye in Gram staining process
Lipopolysaccharide coat (endotoxin)
Gram-positive bacteria
DO retain crystal violet dye in Gram staining process
Countermeasures Against Pathogens
Antibiotic resistance
CDC: urgent, serious, concerning
Horizontal gene transfer
Enzymatic inactivation of antibiotics
Aminoglycoside-modifying enzymes (AMEs)
Multi-drug resistant transporters (MDRs)
Proteins that prevent antibiotic cell access
Target bypa
Methicillin-resistant Staphylococcus aureus (MRSA)
International healthcare crisis
Over use of antibiotics/not completing antibiotic regimen
Fusidic acid: binds to ribosome and prevents protein synthesis
Old treatment revisited: bacteriophages
Viruses that infect bacteria
Fungal infections
Large microorganisms with thick, rigid cell walls. Mold, yeast, dimorphic. Disease transmitted by inhalation or contamination of wounds. Dermatophytes if infection invade skin, hair, or nails
Systemic infection is usually from immunosuppression
Pneumocyst
Molds
filamentous grow as multinucleate, branching hyphae, forming a mycelium (example = ringworm)
Yeasts
grow as ovoid or spherical; single cells multiply by budding and division (example = Histoplasma)
Mycoosis
Disease caused by fungi
Candida albicans
Most common fungal infection
Resides in skin, gastrointestinal tract, mouth, and vagina
Local defense mechanisms and microbiome produce antifungal agents
Remains localized if:
Immune system is intact
Immune system is compromised, then infection can become
Parasitic and Protozoan Infections
Most common parasitic infections in US
Toxoplasma gondii and Trichomonas vaginalis
Are rarely transmitted from human to human; mainly through vectors
Malaria by mosquito bites
Trypanosomes by the tsetse fly
Leishmania spp. by sand flies
Others found in co
Viral Infections
Most common affliction of humans
Viruses are intracellular parasites; replication depends on ability to infect host cell
Usually self-limiting
Do not have organelles necessary for reproduction
Replicates by "taking over" the metabolic systems of host cell
Life cycle of viruses
completely intracellular
Translation of mRNA results in the production of viral proteins
For enveloped viruses, new virions are released through budding
Viral DNA is integrated in the host cell and transmitted to daughter cells by mitosis
Transmission
aerosol, infected blood, sexual contact, vector
Viral infection symptoms are mild
Fever, aches, nausea
Interferons
are effective against many viruses
Harmful effects of viruses
Inhibition of DNA, RNA, or protein synthesis
Disruption of lysosomal membranes
Promotion of cell apoptosis
Fusion of adjacent cells (giant cells)
Transformation into cancer cells
Alteration of antigenic properties (immune attacks normal cells)
Influenza Virus
Highly infectious
Virions attach to respiratory epithelial cells and enter by endocytosis
May be fatal for the very young and the very old
It is seasonal
Surface proteins undergo change each year
Can have antigenic drift or mutation
Mutation of genes that
Viral Infection stages
Attach to host cell via protein receptors
Penetrates host cell
Releases genetic information into host cytoplasm
Uncoating
RNA viruses enter host nucleus
Produce mRNA (new viral material)
May produce provirus DNA (retroviruses: HIV)
DNA viruses enter host
Viral Replication
Translation of mRNA results in the production of viral proteins
Assembly of new virions are released through budding
Viral DNA is integrated in host cell
DNA is transmitted to daughter cells by mitosis
Coutnermeasures
infection control, antimicrobials, antibiotic resistance, vaccines
Infection control
Environmental measures (food safety, water treatment/contamination prevention, insect control, insecticides)
Antimicrobials
Bacteriocidal vs. bacteriostatic
Antibiotic resistance
Lack of compliance with therapeutic regimen, overuse
Vaccines
Development, costs, reluctance to vaccinate, induction of long-lasting protective immunity
Acquired Immunodeficiency Syndrome (AIDS
Syndrome caused by viral human immunodeficiency virus (HIV)
Depletes the body's T helper (Th) cells
HIV is a form of secondary immunodeficiency
Is susceptible to life-threatening infections and cancer
Blood-borne pathogen (blood, vaginal fluid, semen, bre
Incidence of AIDS:
is and remains a major cause of morbidity and mortality; Africa is the epicenter of the AIDS pandemic
Types of AIDS
HIV-1: cause of HIV in Western hemisphere and Europe
HIV-2: cause of HIV in Africa and Southeast Asia
Routes of transmission for AIDS
Blood or blood products, IV drug use, heterosexual or homosexual activity, maternal-child transmission before or during birth
AIDS: Mechanism of Injury
Retrovirus (RNA virus)
Genetic information is in the form of RNA
Stores genetic material on single-stranded RNA rather than usual double-stranded DNA
Contains reverse transcriptase to convert RNA and creates a double-stranded DNA version of the virus
Inte
Human Immunodeficiency Virus (HIV)
Structure: gp120 protein binds to the CD4 molecule found primarily on surface of helper T cells
Destroys CD4+ Th cells
Typically 800 to 1000 cells/mm3
Reverses CD4:CD8 ratio
Co-receptors
CXCR4 and CCR5
Strains can be selective for these receptors; influen
Early Phase of HIV
Lasts about 1-6 weeks
Clinical latency ; active proliferation in lymph nodes
Headaches, fever, fatigue, non-specific flu-like
High virus in blood; serological antibodies against HIV may not yet be detected
Middle Phase of HIV
Lasts months to years
Virus dormant in host DNA; few in blood but many antibodies (basis of testing)
Few symptoms
Continuous infection, death, CD4+ T cells, likely by own Tc (CD8+ T cells)
Late Phase of HIV
Varies
Rapid decline in CD4+ T cells (normal = 800-1000/mm3)
< 400 /mm3 = start tx
Weak, opportunistic infections begin (herpes, varicella, mycobacterium (Tb), fungi, pneumocystis
< 200 /mm3
Lymphoma
Cancer (Kaposi sarcoma)
Often fatal within 1 yr
Treatment & Prevention
Antiretroviral therapy (ART)
Three or more drugs:
Reverse transcriptase (usually 2 are from this class)
Protease inhibitors
Integrase inhibitors
Fusion inhibitors
CCR5 antagonist
Death reduced significantly
Resistance variance identified
DOES NOT cure, it
HAART Treatment and Prevention
(highly active antiretroviral therapy) - current regimen
3 or more drugs combination that attacks different portions of viral replication pathway
Usually 2 target reverse transcriptase
Fools DNA into incorporating it into new strand, then halts DNA synthe
Problems with HAART
Not a cure; instead slows progression
Expensive: $7000 to $10,000 per year or more
Unpleasant side effects
Prior to HAART, those infected lived only a few years
With HAART, HIV infection is a chronic disease (basketball great Magic Johnson has been alive
Prevention & Ongoing Research
Prevention
Vaccines so far not very effective: progress is being made
Reduce risk behaviors
Research
Fusion inhibitors
Interferes with fusion of HIV and CD4+ cells
Integrase inhibitors
Worked in monkeys to slow disease progression; have undergone clinical
Pediatric AIDS
Transmitted during pregnancy, at delivery, or through breast-feeding
More aggressive in children
If untreated, child likely dies by second birthday
Neurologic involvement common
HIV encephalopathy
May be difficult to differentiate from other risk factors