Infectious Organisms

INFECTIOUS DISEASE EPIDEMIOLOGY

Infectious Organisms

Viruses

The smallest of the microbes that we will cover (excludes prions and agents of spongiform encephalopathies): 20 – 200nm

Viruses

Classification Viral genome Size and shape of

the capsid Enveloped or non-

enveloped capsid Method of replication Pathophysiology Physical/chemical

features

Classification

Viral Genome DNA or RNA Single stranded or

double stranded Linear or circular Segmented or non-

segmented Genome capping

Classification

Capsid Size and shape of the capsid Enveloped or non-enveloped

Classification

Method of replication

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

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

Viruses An example

Bacteria

Classification: Morphologic classification based on 1) staining characteristics, 2) shape and size of the organism

Bacteria: Classification

Gram stain reaction Cells that retain the

crystal violet-iodine complex appear blue/purple and are gram positive – cell walls are thicker

Cells that do not retain the crystal violet-iodine complex appear red/pink and are gram negative – cell walls are thinner

Bacteria: Classification

Shape and arrangement

Cocci – round or spherical cells

Bacilli – rod-shaped cells

Curved, spiral forms

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

Bacteria

Structure

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

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

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

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

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

Bacteria: Structure Cell wall: Gram – 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

The peptidoglycan layer of gram - bacteria is much thinner that that of gram + bacteria

The outer leaflet of the outer membrane contains lipopolysaccharide, or endotoxin, which is a major virulence factor of gram-negative bacteria

The cell wall of gram-negative bacteria is a permeability barrier, unlike gram-positive bacteria

Bacteria: Structure

Cytoplasmic membrane:

Essential Beneath the cell

wall of all bacteria Primary osmotic

barrier for the cell

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.

Fungi: Mold Structure

Fungi: Mold Structure

Fungi: Yeast Structure

Fungi: Yeast Structure

Fungi

Fungi of medical importance can be grouped according to the type or location of infection they cause:

Superficial mycoses or infections that involve only the outermost layers of the skin and hair

Cutaneous mycoses that involve primarily the epidermis

Subcutaneous mycoses that cause infections of the dermis and subcutaneous tissue

Systemic mycoses, which are infections of internal organ systems

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

Parasites

Parasites: parasitic diseases are spread in conditions of poverty – substandard housing, poor water treatment, and crowding facilitate their transmission

Parasites: Disease Burden

TDR

Disease Burden (DALYs)

(thousands)

Deaths (thousands)

Total Male Female Total Male Female

African trypanosomiasis

1 1598 1029 568 50 32 18

Leishmaniasis 1 2357 1410 946 59 35 24

Malaria 2 42,280

20,024

22,256 1124 532 592

Schistosomiasis

2 1760 1081 678 15 11 5

Chagas disease

3 649 333 316 13 7 6

Lymphatic filariasis

3 5644 4317 1327 0 0 0

Onchocerciasis

3 987 571 416 0 0 0

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)

Protozoa

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

Protozoa: Amoeba

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, Entamoeba histolytica is a

potential pathogen in humans: infections with this species are referred to

amebiasis and can be the cause of amebic dysentery:

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

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)

Flagellated Protozoa

Flagellate Life Cycle

Protozoa: Classification

Mastigophora: Intestinal (genital) flagellates

Giardia lamblia – causes giardiasis Trichomonas vaginalis – trichomoniasis

Hemoflagellates Trypanosoma Leishmania

Example: Trypanosomiasis

Hemoflagellates Trypanosoma Trypanosomes are the causative

agents for: West and East African

trypanosomiasis (Sleeping Sickness) American trypanosomiasis (Chagas’s

disease)

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

African Trypanosomiasis

Epidemiology West African versus East African T. brucei gambiense: 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

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

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

Example: Leishmaniasis

Leishmania spp. Causative agent of leishmaniasis Transmitted by the vector sand fly (Phlebotomus

genus 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 nonmotile amastigotes that then proliferate in cells of the reticuloendothelial system, specifically, macrophages and endothelial cells

Leishmania cause disease by co-opting the immune response

Protozoa: Leishmania

Cutaneous Leishmaniasis

Leishmania: 3 major species are of importance to humans (there are many others)

Leishmania tropica – Causes cutaneous leishmaniasis: 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

Cutaneous leishmaniasis

Mucocutaneous Leishmaniasis L. braziliensis – Causes mucocutaneous leishmaniasis: 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

Mucocutaneous leishmaniasis

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

Visceral leishmaniasis

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)

Back to Protozoan Classification Apicomplexa – Only one class that is

relevant for humans: Sporoza:

These parasites cause malaria and toxoplasmosis, as well as intestinal infections

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

Protozoa: Classification

Sporoza Toxoplasma gondii Cryptosporidium

Toxoplasma gondii: Life Cycle

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

Parasites: Helminths

Platyhelminths Cestodes (tapeworms) Trematodes (flukes)

Cestodes

Cestodes

Trematodes (liver fluke)

Trematodes (blood fluke)

Parasites: Helminths

Aschelminths (roundworms) Nematodes (e.g. Toxocara, pinworms)

Nematode

Nematode