2. Viruses The smallest of the microbes that we will cover (excludes prions and agents of spongiform encephalopathies): 20 – 200nm
3. Viruses Classification Viral genome Size and shape of the capsid Enveloped or non-enveloped capsid Method of replication Pathophysiology Physical/chemical features
4. Classification Viral Genome DNA or RNA Single stranded or double stranded Linear or circular Segmented or non-segmented Genome capping
13. Classification Pathophysiology of the virus such as host range, antigenic composition, vectors, and tissue tropism Physical/chemical features, such as susceptibility to acid or lipid solvents
14. Viruses Structure Complete infectious virus is called a virion Composed of its specific nucleic acid, DNA or RNA, surrounded by a protein coat known as the capsid
17. Bacteria: Classification Shape and arrangement Cocci – round or spherical cells Bacilli – rod-shaped cells Curved, spiral forms
18. Bacteria: Classification Other classification metabolic and physiologic differences, as measured by the presence or absence of specific enzymes these identify bacteria that are able to use particular nutrients for growth, or metabolize particular substrates Genetic methods
20. Bacteria: Structure Flagella: Long, complex structures that are important for motility Non-essential An important antigen for identification and classification among those bacteria that possess them
21. Bacteria: Structure Pili or fimbriae: Short, non-flexible structures that surround the surface of the cell Responsible for adherence to host cell membranes through a very specific interaction that frequently determines the organotropism of a particular pathogen Non-essential Conjugation – the attachment and transfer of DNA between similar species of bacteria by way of the sex or F pili – this is process is the most common method for acquisition of antibiotic resistance determinants by bacteria
22. Bacteria: Structure Capsules: Secreted polysaccharides and, in some cases, proteins that surround some bacterial cells Non-essential In the environment, their primary function is to prevent dehydration of the cell, but in pathogens they are a major virulence factor through interference of the host’s phagocytosis
23. Bacteria: Structure Cell Wall: Essential component to all bacteria, with the exception of the mycoplasma Determines the size and shape of the cell Serves as an exoskeleton, preventing lysis of the cell Differences in structure provide the taxonomic designation of gram staining; peptidoglycan – this polymer forms the strong backbone for all other cell wall components
24. Bacteria: Structure Cell wall: Gram + Gram + bacteria are composed of a very thick layer of peptidoglycan This does not make the cell wall a permeability barrier for the bacteria’s cytoplasmic membrane, primarily because of teichoic acid Teichoic acid can activate host macrophages with the release of IL-1 and TNF-alpha
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26. Gram - bacteria have a much more complex cell envelop: the outermost portion of the gram-neg cell wall is a lipid bilayer known as the outermembrane, under which is the periplasmic space, which contains a variety of metabolic and transport enzymes
28. The outer leaflet of the outer membrane contains lipopolysaccharide, or endotoxin, which is a major virulence factor of gram-negative bacteria
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30. Fungi Characteristics Pathogenic fungi have two forms: Yeasts, which are unicellular and reproduce by extension of buds from the mother cell Molds, which are multicellular, with a division of function among individual cellular components, and grow as a filamentous, branching strand of connected cells, forming a hypha Many of the truly pathogenic forms fungi have two growth forms and can exist as either molds or yeast, depending on environmental conditions, i.e. they are dimorphic.
36. Fungi Systemic Mycoses There are those systemic mycoses that are caused by true, or primary, pathogens, which are capable of causing disease in healthy people There are those systemic mycoses that are opportunistic pathogens, which are marginally pathogenic and cause disseminated or deep-tissue infection in immunocompromised or debilitated hosts
37. Parasites Parasites: parasitic diseases are spread in conditions of poverty – substandard housing, poor water treatment, and crowding facilitate their transmission
39. Parasites: Protozoa Belong to a subkingdom (Protozoa) as they are neither plant nor animal Oval, spherical, or elongated cells that range in size from 1-300µm to 1-2 mm Cytoplasmic membrane that encloses cytoplasm containing membrane-bound nuclei, mitochondria, 80S ribosomes, and a variety of specialized organelles associated with higher life forms Majority of protozoa are aquatic, living in soil water, rivers, oceans, etc; there is a small subset that are obligate parasites of animals capable of producing both acute and chronic disease Can reproduce both asexually and sexually (like fungi) Some protozoa have complex reproductive cycles, in which different hosts are required for different stages of the life cycle Hosts in which sexual reproduction occurs is called the definitive host, while asexual multiplication occurs in the intermediate host, among Protozoa requiring multiple hosts to complete their life cycles Some protozoa can form cysts to survive in unfavorable environmental conditions (like spore-forming bacteria)
41. Protozoa: Classification Sarcomastigophora Sarcodinia – Amoeba generally confined to the intestine, but can occasionally be carried in the blood to other organs of the body, such as the liver, lungs, spleen, pericardium, and brain Do not possess complex organelles Do not reproduce sexually; multiply by binary fission Use of pseudo-podia (fingerlike projections) to acquire food, and for motility Many species are capable of forming cysts under adverse conditions
43. Protozoa: Classification Amoeba Entamoeba is the most prevalent genus associated with humans Most species of this genus exist as normal flora of the human intestinal tract However, Entamoebahistolytica is a potential pathogen in humans: infections with this species are referred to amebiasis and can be the cause of amebic dysentery:
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46. Protozoa Amoebic dysentery Actively growing organisms (trophozoites) invade the intestinal mucosa, resulting in lesions that can range in symptoms (few daily loose stools with small amounts of blood and mucous to numerous intestinal ulcers causing severe diarrhea and substantial amounts of blood and mucous; in some individuals these intestinal ulcers may erode into adjoining blood vessels, allowing the amoeba to spread to other organs, especially the liver and lungs, and eventually leading to abscess formation More prevalent in tropical and subtropical regions than in temperate regions Often associated with poor sanitary conditions In most cases, transmission is the result of ingestion of cysts from chronic carriers who shed the cyst form of the organism in their feces Unlike acute cases, which tend to shed the trophozoite forms in feces, cysts are relatively resistant to harsh environmental conditions and therefore survive long enough to establish new infections
47. Protozoa: Classification Mastigophora: flagellated protozoa commonly divided into those that cause intestinal or genital tract disease (intestinal flagellates) and those transmitted by blood-sucking insects (hemoflagellates)
51. Example: Trypanosomiasis Hemoflagellates Trypanosoma Trypanosomes are the causative agents for: West and East African trypanosomiasis (Sleeping Sickness) American trypanosomiasis (Chagas’s disease)
52. Example: Trypanosomiasis African trypanosomiasis (Sleeping sickness) Tsetse fly (Glossinia) is the vector The trypanosomes migrate through the blood to lymph nodes This triggers ongoing attacks of fever The attacks can be intermittent and recur over a period of weeks to months These sustained attacks can often result in heart damage As the disease progresses trypanosomes invade the central nervous system, causing meningoencephalitis
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56. African Trypanosomiasis Epidemiology West African versus East African T. bruceigambiense: disease progression is slow T. brucei rh0desiense: disease progression is very rapid Western sand fly: Riverine, very high density Eastern sand fly: Everywhere, by very sparse (1 fly per square mile) Importance of conflict and displaced communities Disease burden: widely varying estimates; very poor surveillance in remote areas; anywhere between 10, 000 and 500,000 new cases per year
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58. American Trypanosomiasis American trypanosomiasis (Chagas’ Disease) Reduviid bug is the vector The trypanosome is unable to multiply outside the cell of its vertebrate host, and therefore undergoes a change to the amastigote form and can be found multiplying in virtually every cell in every organ of the body Hollow organs The organ most often effected is the heart, wherein inflammation causes an enlargement of the heart
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64. American Trypanosomiasis Epidemiology Housing is a critical characteristic for reduviid bug control: thatched roofs; dogs and pigs close to or in the home Disease Burden: prevalence ~ 8 million across all endemic countries; incidence ~ 40 – 50,000 per year Chronic disease lasting decades is quite common, so humans are a critical reservoir as well
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66. Example: Leishmaniasis Leishmania spp. Causative agent of leishmaniasis Transmitted by the vector sand fly (Phlebotomusgenus in the Old World, Lutzomyia in the New World) The flagellated promastigote is the form that is in the vector gut and the form that is transferred to the human host The flagellated promastigotes then transform into nonmotileamastigotes that then proliferate in cells of the reticuloendothelial system, specifically, macrophages and endothelial cells Leishmania cause disease by co-opting the immune response
70. CutaneousLeishmaniasis Leishmania: 3 major species are of importance to humans (there are many others) Leishmaniatropica – Causes cutaneousleishmaniasis: occurs primarily in the Near East, Mediterranean, Africa, Southern Russia and South Asia; Characterized by a papule that appears at the bite site and eventually develops an ulcer, usually healing within a year and leaving a scar
73. MucocutaneousLeishmaniasis L. braziliensis – Causes mucocutaneousleishmaniasis: a variant of cutaneous form that involves the mucous membranes of the nasopharyngeal area; If untreated the nasal septum, lips, and soft palate may be destroyed, resulting asphyxiation due to airway collapse or secondary bacterial infection
76. Visceral Leishmaniasis L. donovani – Causes visceral leishmaniasis: the leishmania are able to invade the reticuloendothelial system throughout the body, especially the liver and spleen As a result, these organs become enlarged causing abdominal swelling and often result in death an average of two years after onset of initial symptoms
79. Leishmaniasis Epidemiology Again, poor surveillance, especially for VL Hundreds of millions are at genuine risk for infection. ~10 million infected, with ~1-2 million incident cases per year (includes all forms) Vector control has figured prominently: insecticide impregnated bed nets (similar to malaria)
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82. Back to ProtozoanClassification Apicomplexa – Only one class that is relevant for humans: Sporoza: These parasites cause malaria and toxoplasmosis, as well as intestinal infections
83. Protozoa: Classification Sporoza: Plasmodium vivax, P. ovale, P. malariae, and P. falciparum: Cause malaria Transmission by vector of the female mosquito (Anopheles) Clinical symptoms are variable across the different species, but in general include chills and fever at intermittent, regular intervals followed by profuse sweating
86. Parasites: Helminths Platyhelminthes (flatworms): Typically no digestive tract, or only a rudimentary one Typically flat Most are hermaphroditic Humans are often the definitive hosts for adult worms, though there are also often intermediate hosts in other animals in different developmental stages of the worm