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Epidemiology

the study of the distribution and causes of disease in populations

Contagious/communicable

an infectious disease that can be transmitted from one host to another
can be direct or indirect

Non-communicable disease

disease that typically cannot be transmitted from one host to another - usually caused by normal microbiota or the environment

Attack rate

the number of susceptible persons developing illness in a population exposed to an infectious agent

Incidence

number of new cases in a specific time in a given population (measure risk) per 100,000 people

Prevalence

Total number of cases at any time or for a specific period in a given population (overall impact)

Morbidity

Illness; most often expressed as a rate of illness in a defined population

Mortality

death; most often expressed as a rate of death in a defined population

case fatality rate

the proportion of persons diagnosed with a specific disease who will die from that disease

Microbial intoxication

Staph aureus produces toxins - cream pie at room temp - toxin is ingested - the toxin from the bacteria is what makes you sick

Microbial infection

Staph aureus (in nasal passageways) if transferred to wound then it multiplies and causes infection. Actual bacteria itself causes infection

Steps in pathogenesis

Entry - Attachment - multiplication - invasion/spread - evasion of host defenses - damage to host tissues

Virulence factors

Attachment, multiplication, invasion/spread, evasion, damage to host tissues \--- are facilitated by the bacteria own abilities

Incubation period

interval between initial infection and first signs and symptoms

Prodromal period

early symptoms that may indicate the onset of a condition or disease \-- no clinical signs of disease

Period of illness

symptomatic

Convalescent

person recovering from sickness

Infectious stages

Incubation period, Prodromal stage, full illness, convalescent period

Symptomatic

clinical signs and symptoms are present

Asymptomatic

Sub clinical no symptoms

Carrier

asymptomatic and sheading the pathogen - ex typhoid mary, gave it to her rich clients

Latent infections

Pathogen is not eliminated from body, but isn't actively replicating. Disease does not spread. Ex herpes simplex 1 and 2, TB, chickenpox

Koch's Postulates

1. survey population 2. evidence of disease - can isolate the germ from the infected 3. grow germ on pure culture 4. cultured germ must cause disease in healthy experimental host (animal/plant) 5. same germ must be re-isolated from the diseased experimental host

When can Koch's postulated not be used?

when the organism can't be cultured, ex obligate intracellulars
no animal host - not susceptible to disease
infection caused by more than one organism
healthy subjects can carry organisms that cause disease

Molecular Koch's Postulates

1. The phenotype under study should be associated with pathogenic strains of a species.
2. Specific inactivation of the suspected virulence gene(s) should lead to a measurable loss in virulence or pathogenicity. The gene(s) should be isolated by molecular methods.
3. Reversion or replacement of the mutated gene should restore pathogenicity.

What virulence factors are required for pathogen to be successful

Studying GENES

Bubonic Plage

occurred 541AD and the mid 20th century - compared DNA sequences, Bronze age- couldn't make the flies sick

Bubonic Plage strains

1 mild disease/limited infection
2 pneumonia disease
3 disseminated infection

Pestoides F - make people so much sicker has pla gene difference - missense causing amino acid change

Bubonic Plage Implications

Not eliminated. An orgnasim can go from mildly virulent to highly virulent with one small genetic change

chain of infection

Reservoir of infectious agent 1- portal of exit 2- transmission 3- portal of entry 4- susceptible

FLU - stay home/antibiotics, breaks at 1
antiseptics/disinfectants/hand washing, breaks at 3
vaccine, breaks at 4

Reservoir of infection

infected humans - ex smallpox, common cold, measles
vaccinated \>90% smallpox and measles can be eliminated

animals - ex rabies, plague, Lyme disease

environment - legionnaires disease (kind of pneumonia) legionella pneumophila, in pools of water goes in rooms by AC

Vertical transmission

from mother to infant ex HIV (cross placenta/in birth canal)

Horizontal transmission

person to person

Direct transmission

Indirect transmission

airborne, fomites (inanimate objects), food/water, vectors

Biological vector

non human animal ex mosquitoes carry malaria parasite
part of pathogens life cycle occurs in the vector

Mechanical vector

Just carries... houseflies, cockroaches - just picks them up

Disease triad

Agent
infectious dose, virulence, incubation period, antigenic stability, survival

Host
age, sex, genetic background, bahavior, nutritional status, socioeconomic status, culture

Environment
weather and season, housing, geography, occupational setting, air quality, food, population density

Herd immunity

The resistance of a group to an attack by a disease to which a large proportion of the members of the group are immune

Endemic

constantly present in a population - always there. ex common cold in MN, malaria is not in MN

Cholera in Haiti

Post 2010 earthquake, now it is an endemic.. if not treated it can be deadly. UN groups brought cholera with them (carriers). Shead it by using the bathroom, the sanitation wasn't good so it was spread into the rivers. Vaccinate? not many doses available. Doctors without boarders said no. It was given anyways, and vaccinating a portion of the population lead to a lower incidence of disease through herd immunity

Normal Urinary Tract

Basically sterile above urethra
flushing action of urine, low pH, urine composition, mucous, inhibitory peptides and antibodies, peristalsis, basic anatmony (males)

UTI

7 million in US

may include any or all the organs of the urinary system

any situations interfering with urine flow increases risk of infection

common cause E. coli (escherichia coli) GRAM -

behavioral issues in older people

cranberry juice - not much of a difference, makes urine more acidic - can't hurt

costs billions of dollars per year in health care burden

source is usually fecal flora

drug resistance is a huge problem

other bacteria - staphylococcus, klebsiella, proteus, pseudomonas, enterococcus, enterobacter

uncomplicated - age/female
complicated - age/male

Urethritis

(lower) dysuria (painful/or difficult urination), frequency and urgency of urination

Cystitis

(lower) In bladder, dysuria, frequency, urgency, tenderness and pain over bladder, bloody or cloudy (due to bacteria and or white blood cells) urine

biofilm forms

neutrophils invade

damage epithelial

Pyelonephritis

(upper) In kidneys, fever, lower back pain, lower UTI symptoms, nausea, vomiting, diarrhea, chills tachycardia, bacteremia - bacteria in blood stream

complications - sepsis, shock, death

release toxins

Ascending route of infection

bacteria colonize urethra, spread to bladder where they multiply, may move to ureter and kidneys

sources - intestines, sex, catheter insertion

Women UTI

more common due to anatomy - shorter distance

HAI

Healthcare-associated infection uropathogenic escherichia coli (UPEC)

Mirco UTI activity

cells that line bladder are facet cells

Uropathogenic E coli has bind sites and can grow on the inside of cells (type 1 pillus allows them to attach)

release cytokines

outer cells get sluffed off (exfoliation)
bacteria is still deep in and can come out later

acute infection cycle \-- attach - invade - early - middle (change shape/biofilm forms) - late - egress

acute cycle termination \-- exfoliate - invade - QIR

persisters
quiescence - not growing

Which of the following is NOT a virulence factor for uropatogenic E. coli

type 1 pillus
intracellular growth
filament formation
coagulase
quiescence in cells

coagulase

Diagnosis UTI

gram stain and look \>10^5 CFU/mL

examine for pyuria (white blood cells) \>8 PMNs/mL, leukocyte esterase (more likely for bladder infections, neurtrophils in urine)

enzymes - nitrate reductase

Culture and sensitivity

CNA - gram + selective, has blood so can look for hemolysis

McConkey Agar - gram - enteric selective, crystal violet and bile salts, pH sensitive

Antimicrobial sensitivity - rings on plate at different concentrations

HardyChrom HUrBI plates

urine diagnostic - one side grows gram +/- and has color indicators

quick diagnosis
EXPENSIVE

40 infectious diseases have been discovered since the 1970s

ex SARS, MERS, ebola, chikungunya, avian flu, swine flu, zika

Emerging infectious disease

previously undected or unknown infectious agents

known agents that have spread to new geographic locations ro new populations

previously known agents whose role in specific diseases has previously gone unrecognized

re-emergence of agents whose incidence of disease had significantly declined in the past, but whose incidence of disease has reappeared (ex measles)

CLIMATE CHANGE
expansion of population/extreme poverty
wars
deforestation

Which of the following is not an emerging infectious agent?

acinetobacter baumanni
antibiotic resistant gram - bacteria
hep A
antibiotic resistant gram \-- negative bacteria

Hep A - food borne, just stays, never really changes in rates

Opportunities for pathogens

agriculture - west nile, hantaan, argentine hemorrhagic fever

food handling practices - SARS, H5N1, influenza, enteropathogenic E coli

dams, changes in waste ecosystems - rift valley fever, vector born diseases

deforestation/reforestation - kyasanur forest, lyme disease (nice lawns??)

climate change - hantavirus, pulmonary syndrome, vector borne diseases

Zoonotic disease

disease that can be passed between animals and humans

emerging and reemerging infections are 70% vector borne or zoonotic

airborne, vectors, direct contact, close proximity, food borne

viruses \-- natural host (asymptomatic) \-- transmission hosts (moderate to severe symptoms) pigs/raccoons/horse etc. \-- spillover host (sever infection and high mortality rate) humans

Vector Borne

ex Zika - herd immunity?

Priority 1 CRITICAL

acinetobacter carbapenem-resistant
pseudomonas aeruginosa, carbapenem-resistant
enterobacteriaceae, carbapenem-resistant, ESBL-producing

Acinetobacter

gram negative bacilli

very stable, contaminates hospital equipment, patients, airborne - versatile

forms biofilms

very resistant

difficult to disinfect

cytotoxity

problem for immunosuppressed people

treat with phages from the army research labs

acinetobacter baumannii is difficult to control in a hospital setting because it

is easily spread
forms biofilm
can survive on dry surfaces
is resistant to many antibiotics
all the above

all the above

Methacillin Resistant Staphylococcus aureus (MRSA)

gram + bacilli - grapes/clusters

skin infections ex boules

systemic - pneumonia, endocarditis (heart infection)

community acquired - more now (wrestlers/ opioid epidemic - injections) 0.2-7.4%

hospital acquired

MRSA is a strain of staphylococcus aureus defined by its

clot forming ability
resistance to methicillin
ability to ferment mannitol
sensitivity to methicillin

resistance to methicillin

Gonorrhea

Neisseria gonorrhoeae, fastidious, gram - diplococcus

one of the most common STI
human specific pathogen

symptoms-
incubation period 2-5 days frequently asymptomatic
men have urethritis and thick pus containing discharge
women have painful urination, vaginal discharge

complications -
men - inflammation can produce scar tissue that obstruct urethra, slows urination, increase risk of UTIs, can spread to prostate gland and testes causing infertility

women - infection can spread to Fallopian tubes, cause pelvic inflammatory disease (PID), sometimes infertility

Drug resistant neisseria gonorrhoeae

1940s penicillin
1980s penicillin resistant
now even more resistant

top priority

disproportionately impacts youth 15-24yo, reportable disease

Chlamydia trachomatis

spherical obligate intracellular gram neg

75% women and 50% men asymptomatic

men - thin grey/white discharge from penis
women - increased vaginal discharge, sometimes painful urination, abnormal vaginal bleeding, abdominal pain, and pain during sexual intercourse

life cycle
infectious elementary body enters the cells - forms reticulate body - divides/binary fission of reticulate bodies in inclusion - reorganize themselves as an elementary body - can part off as extruded vesicles /or release elementary bodies

Syphilis - treponema pallidum

very slender, motile spirochete, gram -
transmitted almost exclusively by sexual or oral contact
only infects humans
lacks many metabolic abilities

incubation - 9 to 90 days
infections -
primary: 6 weeks to 6 months CHANCRE
secondary: 18 months RASH
latent - no signs
tertiary: many years later BENIGN GUMMATOUS, cardiovascular syphillis, neurosyhillis (dementia?)

treatment penicillin

congential syphilus - passed from mom and serious disfigurement

Tuskegee Study

an unethical study about syphilis in which black male subjects were denied treatment so that the effects of the disease could be studied

Viral STIS Human papllomavirus (HPV)

can cause gential warts and cervical,oral, penile, vaginal, and anal cancers

symptoms
most people with it can clear it
warts can appear 3 months after infection on head or shaft of penis and at vaginal opening or around anus

vaccine- gardasil and cervarix age 11

Herpes simplex 2 (HSV2)

genital herpes

symptoms -
2-20 days after exposure, genital itching and burning
in some cases severe pain
clusters of small, red bumps appear on genitalia or anus, depending on site of infection - worst in first 1-2 weeks, disappear within 3 weeks

recurrences less severe

Protozoan STI

Trichomoniasis vaginalis, protozoan
unmistakable jerky motility under microscope
can't survive without host
lacks mitochondria but had hydrogenosomes instead

treatment - metronidazole or tinidazole

most men are asymptomatic

women - itching, burning, swelling, vaginal redness, frothy discharge, burning urination

abstinence, monogamy, proper use of condoms

Lymphatic system

Lymph nodes, lymphatic vessels, lymph, thymus, spleen, and tonsils
Function: fluid balance, producing of immune cells, disease defense

sterile

Circulation of blood and lymph

supplies nutrients and O2 to cells, removes waste

heats and cools to maintain optimum temperature

infections can be serious, and become systemic/carried throughout the body

bacteremia
viremia
fungemia

\-- in blood

endocarditis

inflammation of the inner (lining) of the heart (particularly heart valves)

usually bacteria carried into bloodstream by flow of lymph from area of infection in tissues

Acute bacterial endocarditis

by virulent species usually staphylococcus aureus
quickly destroys heart valves
form abscesses in muscle that lead to heart failure

Subacute Bacterial Endocarditis (SBE)

by organisms with little virulence, proceeds more slowly
less likely to be fatal
usually normal microbiota of mouth or skin such as viridans streptococci and staphylococcus epidermidis

Virulent bacteria like staphylococcus aureus usually cause subacute endocarditis

true/false

false \-- ACUTE

Sepsis

potentially life threatening complication of an infection

resulting from infection of your skin, lungs, urinary tract elsewhere

causative agents --
systemic infection by any microorganism can result in sepsis
common causes - staphylococcus aureus, e coli, some types of streptoccocus

most fatal cases involve gram - due to endotoxin (LPS)

response to MAMPs and DAMPs yield devasting outcomes - full body inflammation

Four types of infections result in sepsis

lungs - pneumonia

kidney - UTIs

skin

gut

Stages of sepsis

systemic inflammatory response
- tachycardia, hypo/hyperthermic, high respiratory rate, decreased CO2, extreme WBC counts

Sepsis
- SIRS + infection

Severe sepsis
- sepsis + end organ damage

Septic shock
- severe sepsis + hypotension

Neutrophil

lethal bacteremia

Macrophage

multi organ failure

endotheial cell

death

thymocyte

immunodeficiency

Septic shock is characterized by all of the following except

increased coagulation
necrotic cell death
increase blood pressure
activation of complement
suppression of the adaptive immunity

increase blood pressure

Plague

yersinia pestis

enterobacteriaceae, facilitate anaerobe, gram - rod

non motile grows best at 28 degrees C

certain dyes stain ends more intensely - safety pin appearance

forms biofilms in digestive tract of infected fleas - starves, wants more blood - vomits bacteria into host

can be treated with antibiotics

rare in US

multiple virulence factors

infects macrophages with die and release bacteria

endotoxins cause septicemic plague shock

10-20% infect lungs leading to pneumonia plague - respiratory droplets can transmit fully virulent pathogen

EBV- infectious mononucleosis

epstien barr virus EBV, double stranded DNA virus in herpes family - can integrate into chromosome

carried to lymph nodes, infects B lymphocytes (TARGET ORGAN), B cell proliferation causes lymph node and spleen enlargement - can explode

T cells respond to infected B cells and are activated

symptoms
long incubation period 30-60 days
fever, sore throat covered with pus, marked fatigue, enlargement of spleen and lymph nodes

fever, sore throat gone in 2 weeks, others in 3 weeks

Malaria

Protozoa of Plasmodium genus - infect cardiovascular, lymphatic systems

leading cause of morbidity and mortality

millions infected worldwide

protozoa reproduces in mosquito gut and differentiates - mosquito bites - infection of liver and differentiates again - effect blood cells more differentiation -
new mosquito feeds on RBCs - gametocytes become gametes and fertilization occurs forming a zygote - zygote becomes motile and penetrates the gut wall - in gut wall it forms a oocyst and multiples asexually - oocyst releases sponozoitos that infect the mosquitos salivary glands

recurrent paroxysms (hot/cold/chills/sweat) followed by feeling healthy result from cycle of growth and release of merozoites from RBCs

infections in all the million of RBCs becomes synchronous

anemia

The characteristic cold, hot, wet paroxysms of malaria are the result of

lysis of millions of infected red cells at the same time
infection of the liver with malarial parasite
exposure to varying tropical climate
production of reproductive gametocytes
reaction to mosquito bites

lysis of million of infected red cells at same time

Malaria treatment

complicated since different stages of life cycle

chloroquine and mefloquine effective against erythrocytic (RBCs) stages of sensitive strains

combination therapy combats development of resistance
derivative of artemisinin plus traditional medications

prevention has become global focus

Lyme disease

Lyme Connecticut in 1970s

30,000 new cases each year

most common vector borne

borrelia burgdorferi, large, gram -, microaerophilic, spriochete with multiple copies of linear chromosome

spriochetes introduced into skin by bite of infected tick, enter bloodstream, flu like

early localized infection
early disseminated infection 2 to 8 weeks later, nervous system affected

late persistent - chronic nervous system impairments, pain, paralysis, depression, arthritis

no vaccine anymore - can vaccinate dogs

Lyme disease is caused by a \---- and transmitted by \----
protozoa, ticks
yeast, ticks
bacteria, ticks
virus, mosquitos

bacteria, ticks

HIV/AIDS History

NY San Fran - gay males were getting sick

people didn't really care

Gailo and luc Montagnier discovered it - only luc got the nobel prize DRAMa

Structure of AIDs

lipid envelope, receptor complex, structural proteins, enzymes (reverse transcriptase), two strands of RNA

attaches to CD4 T cells and coreceptor CXCR4 or CCR5

can't live without host, can be cleaned with antiseptics

Life cycle of HIV

1. Binding & fusion, 2. reverse transcription - can make mistakes - constantly can mutate and resist treatment, 3. integration, 4. Replication, 5. assembly, 6. budding

HIV infection targets

CD8 T lymphocytes
CD4 T lymphocytes
B lymphocytes
RBCs

CD4 T lymphocytes

HIV/AIDS

AIDS is caused by human immunodeficiency virus (HIV)

Acute retroviral syndrome: infection - few weeks
flu like symptoms, HIV infections spreads throughout body

Asymptomatic interval: years
clinical latency, CD4 lymphocytes decreasing, not cutlurable HIV

AIDS: years - death
lymph node enlargement, fever, weight loss, fatigue, diarrhea, etc
opportunistic infections, malignant tumors
culturable HIV

AIDS diagnosed

CD4 T cell count less than 200 cells/mm3
OR
illness with an AIDS defining condition - opportunistic infections

ex cytomegalovirus retinitis, pneumocystis jiroveci pneumonia, chronic intestinal crytpsporidiosis, HIV related encephalopathy, TB pulmonary or extrapulmonary, invasice cervical cancer

Main symptoms of AIDS

neurological - encephalitis, meningitis

eyes - retinitis

lungs - pneumocystis pneumonia, TB, tumors

skin - tumors

GI - esophagitis, chronic diarrhea, tumors