PH 162A Midterm II (Week 8-9)

definitive host*

an organism that harbors the adult, sexually reproducing form of a parasite

think sexual cycle

intermediate host*

an organism that harbors a sexually immature stage of a parasite

think no sexual cycle with gametes

vector*

an arthopod that transmits a disease-causing organism from one host to another

biological vector*

an arthropod that actively transmits pathogens that complete part of their life cycle within the organism

mechanical vector*

a vector in which the pathogen does not complete any part of its life cycle during transit

dengue virus

+ sense RNA genome

4 serotypes:

- ~65% genoome similarity

- primary infection with any of the dengue strains causes the same disease/range of symptoms

dengue fever (DF) clinical manifestations: primary infection

high fever

headache

retro-orbital pain

myalgias/arthralgias

fatigue

nausea, vomiting

cutaneous rash

dengue homorrhagic fever / dengue shock syndrome (DHF/DSS): secondary infection

increased vascular permeability

hemoconcentration

hypovolemic shock

hemorrhagic manifestations

thrombocytopenia

abdominal pain

cytokine storm (many cytokines elevated in serum)

little or no damage to vascular endothelium

4 DENV SEROTYPES: WHAT IS A SEROTYPE, WHAT IS A CROSS REACTIVE ANTIBODY?

a group of intimately related microorganisms distinguished by a common set of antigens

each has a different interactions with the antibodies in human blood serum because of variations on their surface

aedes aegypti and aedes albopictus*

both bite during the day

both species are small, black mosquitos with white stripes on their back and on their legs

they can lay eggs in any small, artificial, or natural container that holds water

zika virus*

an emerging + RNA flavivirus

also spread by aedes mosquitos; can also be spread from mother to child and can be sexually transmitted

infection during pregnancy associated with congenital birth defects (microcephaly) and Guillain-Barre syndrome

also enhances risk of future severe dengue infection

encephalitis

infection/inflammation of the brain

caused by a variety of viruses (in the US: togaviruses and flaviviruses)

West Nile Virus

widespread in the US; invade CNS, infect neurons

flavivirus related to zika and dengue

mosquito vector; mostly culex mosquitos

life cycle: mosquito - bird - mosquito

mosquito control

eliminate standing water, mosquito fish, standing water - larvicides, fogging (adults); public education, avoid mosquito bites

mosquito surveillance

mosquito traps/pool testing for viruses

sentinel chicken flock immuno-serological testing

dead bird testing for viruses (esp WNV)

arboNET

epizootic*

outbreak of disease affecting many animals/animal species at one time; however, doesn't include humans

enzootic

sustained prevalence of disease in a non-human animal population

ex. what part of the WNV transmission cycle is enzootic? the part with mosquito vectors and birds

lyme disease

caused by borrelia burgdoferi

transmitted by ixodes scapularis and ixodes pacificus ticks

nymphs responsible for most infections because borrelia need 48-72 hours to disseminate from tick to human and nyumphs are hard to detect

70-80% of patients get EM rash

lyme disease diagnosis

clinical; can be challenging in Stage 2/3

isolation of B. burgdoferi (especially from captured tick)

significant change in IgM and IgG antibody

lyme disease treatment

antibiotics: only early (6 weeks) after infection!

EM: doxycycline or amoxicillin

neurological: IV antibiotics

lyme disease prevention

repellent and barriers

immediate tick removal

malaria transmission (plasodium falciparum)

night time biting mosquitos

young children particularly at risk for severe malaria

used to be a problem in the US, but no longer the case

prevalent in many countries in Africa

malaria prevention

insecticide-treated bednets

indoor residual spraying

repellents

drain water

why is P. falciparum more virulent?*

can infect RBCs and erythropoetic (RBC) stem cells, exacerbating anemia

by adhering to capillaries and rosetting, infected RBCs can clog blood flow to viral organs

where the capillaries are obstructed leads to particular clinical manifestations

P. falciparum antigenic variation

avoid clearance from the spleen (survival strategy 1)

waves of malarial "variation" with each parasite clone, until parasite runs out of infected RBC surface antigens and matching endothelial cell receptors (survival strategy 2)

successive infections occur with different parasite clones until host has developed antibodies to virtually all Pfemp 1 variants -> natural immunity

zoonotic disease accidental host

humans are the accidental host - NEVER the definitive host

progression from spillover through evolving human host-pathogen relationship to uniquely human disease

infectious disease key factors: endemic

poverty

poor sanitation/hygiene

malnutrition

overcrowding

infectious disease key factors: emerging/re-emerging

international travel & trade

economic development and land use (de/reforestation, new roads, mines, and plantations, contact with wild animals)

ecological and climate change

behavioral and demographic change

microbial adaptation

breakdown of public health

susceptibility; lack of immunity

many emerging diseases are zoonotic infections

many infections with a human reservoir started out in the course of human evolution as zoonotic diseases

- a human host-parasite relationship evolved

- eventually it became a uniquely human disease

these are NOT zoonotic diseases because the parasite is now exclusively human

- smallpox, measles, mycobacterium, HIV

ebola

linear non-segmented single-stranded negative RNA genome

reservoir: fruit bats, monkeys, apes, forest antelope

ebola transmission

to people from wild animals: contact with blood secretions, organs, and/or bodily fluids

human to human: direct contact with blood/bodily fluids, needle exposure

healthcare settings: improper hygine and sterilization techniques, need for extensive PPE

ebola clinical manifestation

fever, aches & pains (severe headache, muscle and joint pain), weakness, fatigue, sore throat

ebola tretment and prevention

supportive care

new strategies:

balancing patient fluids and electrolytes

ring vaccination study

monoclonal antibodies

ring vaccination steps

1. Identify index case

2. Close contacts who had high risk of exposure are vaccinated, creating an immunological "ring" around the index case to interrupt chains of transmission

3. Rings can be expanded to include several degrees of contacts depending on the disease scenario

rabies reservoir and transmission

reservoir: wild & domestic animals (foxes, bats, racoons)

transmission: rabies is shed in saliva -> animals bite humans

may also be transmitted via exposure to bat feces

does NOT follow iceberg concept- most deadly infectious disease

rabies clinical manifestations

enters via animal bite or skin break, replicates locally, migrates to neurons, replicates slowly -> spinal cord, brain, acute encephalitis

infection to symptoms: usually 20-60 days

loss of control of movement, throat muscle paralysis

behavioral changes

coma

death approx. 3 months after exposure

rabies treatment

no established antiviral treatment available for either animals or humans

passive immunization injected around wound site

active immunization with inactivated vaccine (secondary); virtually 100% effective

toxoplasma life-cycle (toxoplasmosis)

cats are definitive host: sexual cycle occurs only in intestine of feline family; transmission occurs from ingestion of material contaminated with cat feces

birds, rodents, ungulates, humans are intermediate hosts; cycts form in their tissues

transmission can occur from eating undercooked beef

toxoplasmosis and behavior change

animals: greater predation of intermediate hosts by definitive hosts

toxoplasmosis and behavior change for infected rats and mice

increased nonspecific movements, more active

reduced neophobic behavior: less fear of new scents, sounds

reduced aversion (fatal attraction!) to cat urine

reduced learning behaviors

toxoplasmosis and behavior change for infected whales

less able to flee from attacks

draw attention of sharks due to abnormal movements

toxoplasmosis and behavior change for humans (chronic infection)

schizophrenia, suicide attempts, epilepsy

may reduce brainn function

loss of psychomotor performance

men became more jealous, emotionally unstable, suspicious, short-tempered, low self-esteem, disregard social rules

infected people become more anxious

plague

cause: yersinia pestis (gram - cocobacillus)

treatment: antibiotic IF given early enough, surveillance of rats, no feeding squirrels

transmission of yersinia pestis

requires the flea as a vector (biological vector)

bacteria multiply in flea gut and block it, causing flea to regurgitate infected material when the flea feeds on a new host

flea is in a starving state so bites frantically

pneumonic plague

dissemination to lungs, causing pneumonia; respiratory transmission

bubinic plague

lymph node, no human to human transmission (from flea)

anthrax (STOPPED HERE)

cause: bacilllus anthracis (gram + bacillus,, endospore forming)

herbivores: sheep, goats, cattle, reindeer - acquired from contaminated soil; carnivores infected from consuming meat

human cases in Africa, Asia, and the Caribbean

naturally acquired inhalation causes anthrax infected goat, sheep products (spores persist in soil for decades)

anthrax: mode of animal infection

when spores activate (thru being inside the body of an animal/person), the bacteria can multiply and spread out in the body, priduce toxins and cause severe illness and death

when infected animal dies, bacteria goes dormant/forms spores

anthrax clinical info: cutaneous anthrax

90% skin lesions, center black and necrotic

anthrax clinical info: intestinal anthrax

5%; symptoms mimic food poisoning

lesions/ulcerations in digestive tract

can lead to septicemia and death

outbreak in unpasteurized goat's milk cheese

anthrax clinical info: respiratory anthrax

5%; most deadly; most concern with bioterrorism

symptoms similar to flu

inhaled into lungs, spores germinate in alveoli, phagocytized by macrophages, replicate

swollen lymph nodes

swelling, blood clots within capillaries and lymph nodes -> airway obstruction

anthrax: diagnosis and reservoir

dianosis: blood culture, gram stain, and culture of external lesions; serological tests, molecular (PCR) assays

reservoir: animals (contaminated soil)

anthrax: treatment and prevention

treatment: ciprofloxacin; other more common antibiotics (penicillin, doxycycline, eryhtromycin)

prevention: human vaccines, reduce exposure to endospores; dispose of infected animals properly; vaccinate animals

defenses of the upper respiratory system

normal microflora

hairs in nose -> filters out large particles

mucus from membranes lining the nasal cavity, pharynx -> trap microorganism & contains lysozomes

ciliated epithelia -> trap and expel microbes

phagocytic cells (neutrophils, macrophages)

local production of antibodies: mostly IgA (secretory antibody) and IgG

lower respiratory tract

lungs

bronchiole

outer ear infection

otitis externa (“swimmer’s ear”)

middle ear infection

otitis media (with efusion)

passage of the pharyngeal organisms through the Eustachian tube (this connects the pharynx to the ear)

why do children get more ear infections than adults?

the Eustachian tube connects the pharynx to the ear

children have shorter and more level eustachian tube -> difficult for fluid to drain out the ear

inner ear infection

otitis interna (labyrintits)

streptococcal pharyngitis (strep throat): causatuve and pathogenesis

causative agent: steptococcus pyogenes (Gram +, cocci)

pathogenesis: M-proteins of bacterial capsule evade phagocytosis

streptococcal pharyngitis (strep throat): host response and treatment

host response: antibodies against the M protein -> phagocytosis

treatment: antibiotic (penicillin)

sequelae of S. pyogenes

a chronic condition with a different oathogenesis that occurs as a result of an acute disease being left untreated for about 2-3 weeks

occurs in

rheumatic fever

autoimmune disease

antibody produced to M protein cross reacts with components of heart muscle, and damages the heart, especially valves

glomerulonephritis

kidney function damaged by build up of immune cpmplexes of IgG and Igm complexed with M proteins and deposited in the glomerulus

kidney function is blocked -> inflammation

influenza

negative ssRNA, segmented virus, enveloped

highest mortaility in children and elderly

hemagglutinin (H)

envelope glycoprotein

attachment and entry to host cell receptor (also RBCs)

tropism

viral surface protein that mediates viral entry and membrane fusion

responsible for host cell attachment

neuraminidase (N)

envelope protein, enzyme → prevents viral particles from clumping together

mobility through respiratory tract mucus; budding of virus particles

nucleoprotein- 3 major types: A, B, C

influenza: antigenic drift***

mutations in hemagglutinin and neuraminidase genes

antibodies from previous infections are less effective in neutralizing virus

influenza: antigenic shift***

gene reassortment when two different viruses infect the same cell exchange segments

more dramatic changes

antibodies formed against one hemagglutinin are not protective against another type

antigenic shift generally precedes pandemic

community acquired pneumonia

typical pneumonia: sudden onset URT symptoms, 1 in 4 mortality rate

atypical pneumonia: cause: chlamydia (and others), generally less severe

hospital/ventilator-acquired pneumonia

nosocomial pneumonia

tuberculosis

causative agent: mycobacterium tuberculosis

slow growing (couple weeks to be visible on solid media)

epidemiology: airborne transmission, occurs worldwide

most people who are exposed are not infected, and most who are infected do not develop disease

tuberculosis: pathogenesis

infects macrophages (able to multiply)

primary disease: disease manifestation dependent on bacterial proliferation, dissemination and cell mediated immune response

latent TB: infection controlled but not cleared, no transmssion

reactivation: occurs when pathogen present and there’s no deteriotian in host immune function

tuberculosis: latent disease

some may form granulomas and control disease

granulomas can stay with individual for life

bacteria sometimes escape granuloma and cause disease -> reactivation TB

tuberculosis: treatment

last ~ 2 months

MDR TB: resistant to at least 2 firts-line drugs

extensively drug resistant: MDR + resistance to second line drugs

vaccine: BCG

SARS-CoV-2: COVID-19 pathogenesis

infects both upper and lower respiratory tract

can enter the Type II pneumocytes, which line the pulmonary alveoli

SARS-CoV-2: COVID-19 pathogenesis (2)

spike protein from virus binds to ACE2 receptor on these Type II pneumocytes -> infected cell death -> fluid leakage and loss of oxygen -> cytokine storm (strong inflammatory response) -> affects whole body

COVID-19 Therapies: antivirals

need to be administered early

ex. remdesivir, paxlovid, molnupiravir

COVID-19 Therapies: immunosuppressive therapy

tucilizumab: IL-6 inhibitor, monoclonal antibody therapy

MERS coronavirus (middle east respiratory syndrome)

reservoirs: camels, bats

transmission: person to person through close contact

no vaccine or chemoprophylaxis, only supportive treatment