Overview of bacterial and
viral infections
What are bacteria? Prokaryotic microorganisms
Size – 0.2-1.5µ diameter and 3-5µ length
Appear spherical, rod, spiral forms Actinomycetes- branching filamentous form Mycoplasma – cell wall deficient forms
Grow in culture media Normal flora – can become opportunistic pathogens
Infection: The lodgment and multiplication of the parasite in or on the tissues of the host
SOURCES OF INFECTION
a. Man b. Animals - carrier - plague by rats
c. Insects
d. Food
- dysentery , typhoid by domestic flies
- Staphylococcus
e. Soil and water - Cholera and tetanus
METHODS OF TRANSMISSION
a. Contact
- syphilis
b. Inhalation - tuberculosis
c. Ingestion - water borne (cholera)
d. Inoculation - Tetanus spores
PATHOGENECITY
Attachment of the bacteria by adhesins Invasiveness Toxigenecity - Exotoxins
- Endotoxins
Other toxins – Coagulase
- Fibrinolysins
- Hyaluronidase - Haemolysins
LOCALIZED INFECTIONS
Organism enters the body and reaches target site of infection Organism adheres to or enters host cells and multiplies at site of infection Infection spreads within the site (e.g., respiratory tract; intestines)
Symptoms of illness appear
Organism does not spread through the lymphatic system or reach the bloodstream Infection subsides due to host defenses (e.g., immunity) Agent eliminated from the body; infected cells replaced; "cure"
GENERALIZED INFECTIONS
Organism enters the body and reaches target site of initial infection Organism adheres to or enters host cells and multiplies at initial site of infection Infection spreads within site and to other sites via tissues, lymphatic system, bloodstream (bacteremia) and possibly other routes Symptoms of illness may appear Organisms infect other organs, tissues and cells; more spread via bloodstream Symptoms of illness become severe Host defenses eliminate organisms leading to cure or disease continues, possibly leading to irreversible damage or death
IMMUNITY TO BACTERIAL INFECTIONS
Innate immunity - intact skin, mucous membrane, tears - Compliment of blood - Polymorphonuclear leucocytes - Macrophages Active immunity - antibodies - vaccines and toxoids
Passive immunity - natural- mother to fetus Artificial - by administration of antibodies.
INFECTIONS
Respiratory tract infections
- Klebsiella, Haemophilus,
Mycobacterium. tuberculosis
Central Nervous System Alimentary tract infections Urinary tract infections - Meningococcus, St. pneumoniae – Escherichia. coli, Vibrio. cholerae - Proteus, E. coli
Sexually transmitted diseases - Neisseria. gonorrhoeae
TYPES OF SPECIMENS
Blood
Stool
- sepsis, endocarditis, meningitis
- Diarrhea
Throat swab - pharyngitis, thrush, diphtheria
Sputum
Urine Spinal fluid Pus
– Pneumonia, tuberculosis
- UTI, pyelonephritis - meningitis - abscesses, wound infection
Genital swab - abnormal discharge
BACTERIAL LAB DIAGNOSIS Includes two approaches
a. Bacteriological approach
Choosing appropriate specimen Specimen should be free from contamination Transport to the lab Staining of the specimens Inoculation on to a bacteriological medium Biochemical tests
b. Serological - Widal, VDRL
S. aureus
Pneumococci in sputum
M. tuberculosis
Treponema pallidum
Staphylococcus and Streptococcus growth on blood agar plates
Antibiotics test plate
Treatment
Antibiotics
Selective inhibition of growth of bacteria without damage to host Broad spectrum antibiotics – tetracycline Narrow spectrum antibiotics- Vancomycin Vaccines Killed vaccines – Vibrio cholerae, Yersinia pestis Live vaccine - tuberculosis, Francisella tularensis, Typhoid
bacilli
Subunit vaccines – Haemophlilus influenzae, Strep.
pneumoniae
VIRAL INFECTIONS
VIRAL EFFECTS ON HOST CELLS
Degeneration: Cytomegalovirus Cell lysis Cell fusion, syncytia formation: Respiratory Syncytial Virus Transformation: malignancy (Human Papilloma Virus)
ROUTES OF ENTRY
Horizontal transmission • skin • respiratory tract • gastrointestinal tract • genitourinary tract • conjunctiva
Skin May be penetrated by viruses as a result of
-mechanical trauma (HIV, Hepatitis B Virus, poxvirus)
-by injection (Hepatitis B virus, HIV) -by the bite of an infected mosquito (arboviruses) - by the bite of an infected animal (rabies) Viruses are carried away from site of infection: by bloodstream (Hepatitis B virus, arboviruses) or migration along nerves (rabies)
RESPIRATORY TRACT Viruses causing local respiratory infections – influenza virus, rhinoviruses generalized spread - measles, mumps, chickenpox, enteroviruses Transmission usually by droplet infection in aerosols GASTROINTESTINAL TRACT Entry via GI tract may involve • local infection (rotavirus, coronavirus, adenovirus) or • invasion of the host to produce systemic illness (Enteroviruses, hepatitis A) GENITOURINARY TRACT Tears or abrasions allow viral entry Sexually transmitted viruses • HIV • herpes simplex (mostly HSV II) • Papillomaviruses (genital warts) • hepatitis B virus.
VERTICAL TRANSMISSION- TRANSMISSION FROM MOTHER TO INFANT
Transplacental – leads to congenital infections- HIV, Hepatitis B, Rubella
At the time of birth – Hepatitis B, HIV, Human Papilloma virus.
Via Breast milk - HIV
LOCALIZATION AND SPREAD - many viruses multiply in epithelial cells at site of entry - produce a spreading infection - then shed directly to exterior • respiratory infections – influenza and rhinoviruses • gastrointestinal infections caused by rotaviruses • dermatologic infections of the papillomavirus
Rabies
Evasion of host defenses
Viral encoded proteins block host immune mediators by attaching to the receptors to the various immune mediators.
Reduce the expression of class 1 MHC proteins there by reduce
the ability of cytotoxic T cells – HIV
Inhibit complement – Herpes Simplex Virus
Blocks the synthesis of IL-2 thereby reducing the action of Th cells
- measles.
Multiple antigenic types - Rhinovirus
Latent infections In latent infections, overt disease is not produced, but the virus is not eradicated.
The virus may exist in a truly latent noninfectious occult form, possibly as a integrated genome or an episomal agent.
Herpes Simplex Virus Chicken pox virus Mostly reactivated by immuno-suppression
Viral Oncogenesis Oncogenic viruses causes malignant transformation of host cells Transformed cells show changes in morphology, behavior and biochemistry
Cells continue to divide and form masses of cells – tumors
Both DNA and RNA viruses cause cancer Papilloma virus 16 and 18 Hepatitis B virus
Antiviral Immunity Non-Specific Mechanisms a. Interferons: glycoproteins Inhibition of viral translation and transcription Enhancement of the ability of natural killer cells to lyse virally infected cells.
b. Natural Killer Cells Specific Mechanisms a. Antibody mediated -Neutralizing antibody -Enhance phagocytosis -Direct NK cells to kill virus -IgA: mucosal surface
b. Cellular immunity – CD8 cytotoxic T cells with class 1 MHC molecules
Overview of diagnostic methods 1. Direct Examination of Specimen Electron Microscopy morphology Light microscopy histological appearance - e.g. inclusion bodies Antigen detection immunofluorescence, ELISA etc. Molecular techniques for the direct detection of viral genomes
Electronmicrographs of viruses commonly found in stool specimens from patients suffering from gastroenteritis.rotavirus, adenovirus, astroviruses
Negri Body in rabies-infected cell
2. Indirect Examination Cell Culture - cytopathic effect, confirmation by immunofluorescence haemadsorption, etc. Eggs pocks on CAM - haemagglutination
Cytopathic effect of RSV Syncytia formation Cytopathic effect of Herpes Simplex Virus, Balloning of cells 3. Serology – CFT, RIA, ELISA
ANTIVIRAL CHEMOTHERAPY Obstacles to the use of vaccines include 1) multiplicity of serotypes e.g. rhinoviruses 2) Latent infections a. Nucleoside analogues – Inhibits nucleic acid replication Eg. Acyclovir –VZV, EBV
Lamivudine HIV1,HIV2 and HBV potent reverse transcriptase inhibitor
b. Protease inhibitor- inhibits viral protease required for late stage in replication cycle Eg Saquinavir for HIV
c. Amantadine molecules- treatment of Influenza A infection
VIRAL VACCINES.
Killed vaccines Live vaccines Subunit vaccines
- Hepatitis A, influenza A and B, Rabies - Measles, mumps, polio virus - Hepatitis B, HA vaccine for influenza A&B
Parasites: are living organisms that live in or on a host that provides physical protection and nourishment. The host suffers from injury. Parasitology: Is the study of parasites their hosts and the relationship between them Symbiosis: Association between two organisms, dependent upon each other that one can not live without the help of other. Commensalism: An association in which the parasite is only deriving benefit without causing harm to its host. Medical Parasitology: is the study of those parasites which infect humans. Parasitic diseases in humans are caused by protozoans and helminthes.
Classes of parasites 1. Ectoparaites – vectors transmitting pathogenic organisms 2. Endoparasites – live within the body of the host Life cycle of parasites
Sexual or asexual. Certain parasites sexual multiplication is immediately followed by asexual multiplication.
Direct life cycle:
Parasite requires one host to complete its development
– E. histolytica. Indirect life cycle:
Parasites require two or more species of hosts to complete its development – Filarial worms require both human and insect host
CLASSES OF HOSTS
Definitive host – adult stage of the parasites live or where the parasites utilizes the sexual method of reproduction.
Intermediate host – Larval stage of the parasite lives or the asexual multiplication takes place. Eg man in malaria
Reservoir host – animal or human host in which parasite usually resides or in which a parasite that infects man is able to be maintained in the absence of human host. Eg Hydatid disease of Echinococcus granulosus. – sheep, cattle.
METHODS OF TRANSMISSION 1. Faecal-oral route. Food and drink contaminated with infective forms of parasites Eg. cysts of E. histolytica and ova of Ascaris lumbricoides. Ingestion of undercooked meat of intermediate hosts E.g. pork containing the larval forms of Taenia. solium. By ingesting aquatic plants which contain encysted forms of parasites. 2. By skin penetration Filariform larva of Strongyloidis. stercoralis in fecally polluted soil Cercarial larva of Schistosoma. haemarobium in contaminated water 3. By agency of infected insects
Malaria-Anopheline mosquitoes, Trypanosoma-tse tse fly
4. Direct transmission- Trichomonas vaginalis 5. Inhalation of dust containing Ascaris
Medically Important Protozoa Protozoa is simple eukaryotic organism composed of single cell ranging from 2µm to 100µm. Protozoa can infect all the major tissues and organs of the body. Infect the tissues and organs as Intracellular parasites inside the red cells, brain, muscles -Plasmodium, Leishmania
Extra cellular parasites in the blood, intestine or urogenital system
Malaria parasites inside host red blood cells
Features of medically important protozoa
Location Species Mode of transmission Disease
Intestinal tract
Entamoeba histolytica Giardia lambia Cryptosporidium spp Cyclospora cayetanensis Microsporida
Trichomonas vaginalis Trypanosoma spp T. cruzi T. gambiense T. rhodesience Leishmania spp L. donovani L. tropica L brazliensis
Ingestion of cysts In food
Amebiasis Giardiasis Cryptosporidiasis Cyclosporidiasis microsporidiasis
Trichomoniasis Trypanosomiasis Chagas disease Sleeping sickness Visceral leishmaniasis Cutaneos leishmaniasis Mucocutaneous leishnaniasis
Urinogenital tract Blood and tissue
Sexual Reduvid bug Tsetse fly
Sand fly Sand fly
Plasmodium spp
Toxoplasma gondii
Anopheles mosquito
Ingestion of cyst in raw meat Contact with soil containing cat feces
Malaria
Toxoplasmosis
HELMINTHS
Multicellular organisms, worms
Most infections man serve as a definitive host Helminths
Nematoda Cestoda (tapeworms)
Trematoda (flukes)
Ascaris
Scolex of Tenia solium
Fasciola hepatica
INFECTIONS Skin Respiratory tract infections CNS Alimentary tract infections - Leishmania, Schistosomes - Ascaris, microfilariae of Wuchereria - Trypanosoma. brucei – Taenia. saginata
Genito-Urinary tract infections – Schistosoma .haematobium,
Trichomonas. vaginalis
Pathogenesis
Physical obstruction
Pressure effect Vascular or lymphatic obstruction
Allergic manifestation
Predisposition to malignancy
Innate immune responses.
HB-S deficient red cells offer resistance to Plasmodium. falciparum infections.
Gastric acidity gives some protection in Dracunculus and Giardia cysts. Intact skin offers some resistance to parasites entering by skin penetration
Acquired immunity
Antibody responses All the five classes of immunoglobulins are produced in parasitic infections
IgG - antiplasmodial effect
Malarial parasite
IgM - Phagocytosis
IgE – helminthic infections IgA – interstinal protozoa ( Entamoeba, Giardia)
T lymphocytes CD8+ T cells kill parasite infected host cells, e.g. Plasmodium infected liver cell. CD4+ T cells act as helper cells in antibody production.
Macrophages Activated macrophages effective against intracellular protozoa and worms e.g. Leishmania, Toxoplasma, Trypanosoma cruzi.
Granulocytes Neutrophils and eosinoplils The immune response mediated by eosinophils is particularly effective against invasive infections with certain types of parasites called helminths (roundworms).
Giardia lamblia Trophozoite, Giemsa stain Resembling "badminton racket" or "owl face" Two nuclei and four pairs of flagella
Trypanosoma brucei
Thin blood film, Giemsa stained Early trophozoite- "Ring form" containing a reddish chromatin "dot" and blue cytoplasm "ring"
Note infected red cell is larger than uninfected red cell
Plasmodium vivax
Taenia spp Wet mount.
Enterobius vermicularis
Treatment
4 aminoquinoline – antimalarial drug Tetrachlorethylene - antihelminthic
Fungal infections Species causing disease may be acquired from the environment or occur as part of the normal flora. Infections may be located superficially, in cutaneous or in deep tissues. Infections are most serious in immunocompromised individuals Cutaneous or subcutaneos – nails and deeper layers of the skin Systemic – involvement of deeper internal organs Opportunistic mycosis
Aspergillus
Candida albicans
Histoplasma capsulatum
Methods of transmission
Skin
Inhalation Normal flora Host defense Mechanisms
Innate and cell-mediated immunity
opportunistic mycoses occur in individuals with defective innate and/or adaptive cellular immunity.
Fatty acid content of the skin
Normal flora Cilia of respiratory tract
Fungal toxins and allergies
Mycotoxicosis – caused by ingested toxins
Amanitin and phalloidin are hepatotoxins Ergotoxin – vascular and neurological effects Aflatoxin – liver damage and tumors Allergies – caused by fungal spores Eg Aspergillus
Candida, oral thrush by candida
culture plate with Sabouraud's dextrose agar
Lab diagnosis Direct microscopic examination Fungal culture on Sabouraud Dextrose agar DNA probe Serological tests – PCR, latex agglutination test, ELISA
Treatment
Amphotericin B and various azoles Caspofungin