Exam 4

Question 1

Antibodies

Answer 1

Blood serum proteins produced by animals

Made by injecting animal with specific protein antigen

Question 2

Nucleic acid probes

Answer 2

look for binding of labeled nucleic acid probe to DNA from specific colonies

Question 3

Gene fusions

Answer 3

Consist of segments from two different genes

Promoters can be changed

Used to study gene regulation if measuring natural levels is difficult, such as fusing regulatory region to B-galactosidase or GPF

Can investigate transcriptional control or translational control

Question 4

Operon fusions

Answer 4

coding sequence with its own translational start site and signals are fused to transcriptional signals of another gene

Question 5

Protein fusions

Answer 5

Genes encoding two proteins are fused to share the same transcriptional and translational start and stop and yield one hybrid polypeptide

Question 6

Recombinant vaccines

Answer 6

Vaccines elicit immunity to a disease when injected

Can modify a pathogen with genetic engineering to delete virulence factors and retain those that elicit immune responses, yielding recombinant, infective, attenuated vaccine

Can add genes from a pathogenic virus to genome of a harmless carrier virus, yielding vector vaccine

Question 7

Polyvalent vaccine

Answer 7

A single vaccine that immunizes against two different diseases

Question 8

Vaccinia virus

Answer 8

Widely used to prepare recombinant vaccines for people

Cloning requires selective marker: Thymidine kinase

Genes first inserted into E. coli plasmid containing thymidine kinase (TDK) gene, inactivating TDK

Transform recombinant plasmid into animal cells with inactivated TDK and also infected with wild-type vaccinia

Select for viruses whose TDK gene contains insert

Can be engineered to form polyvalent vaccines

Question 9

Subunit vaccines

Answer 9

Contain only a specific protein or proteins from a pathogenic organism (e.g. coat protein of a virus)

Popular because large amounts of immunogenic proteins are produced and can be administered at high dosage with less risk than attenuated or killed vaccines that may inadvertently contain viable pathogens/viruses

If glycosylation required, subunit vaccine is produced in eukaryotic host (yeast) (e.g. hepatitis B subunit vaccine)

Question 10

Many mammalian proteins have high pharmaceutical value but are costly to purify because of:

Answer 10

low amounts in normal tissue

genetically engineered microorganisms used instead

Question 11

Somatotropin

Answer 11

Human somatotropin (growth hormone) is a single polypeptide encoded by a single gene

Treats stunted growth

Cloned as CDNA from MRNA

Recombinant bovine somatotropin (RBST) is commonly used in the dairy industry –> stimulates milk production in cows

Mutated human somatotropin targets only growth, not milk production

Question 12

_______ was the first human protein made commercially by genetic engineering

Answer 12

insulin

Question 13

Transgenic organism

Answer 13

genetically engineered organism that contains a gene (transgene) from another organism

Question 14

Agrobacterium tumefaciens (plant pathogen) contains the ____________ responsible for virulence

Answer 14

TI plasmid

TI plasmid contains genes that mobilize DNA for transfer to plant

T-DNA = plasmid segment transferred to plant; sequences at ends essential for transfer

Question 15

Binary vector

Answer 15

Common TI-vector system for gene transfer to plants and consisting of cloning vector plus helper plasmid

Cloning vector contains multiple cloning site flanked by T-DNA ends, two origins of replication for E. coli and A. tumefaciens, two antibiotic resistance markers for plants and bacteria

Foreign DNA inserted into vector

Vector transformed into E. coli and conjugated into A. tumefaciens

Helper plasmid (D-TI) allows for transfer to plant

TI system works well with broadleaf plants (DICOTS); does not work with monocots, which need alternative methods (e.g. transfection by microprojectile bombardment with particle gun)

Question 16

Herbicide- and insect-resistant plants

Answer 16

Targets for improvement include herbicide, insect, and microbial disease resistance and improved product quality

Main genetically modified (GM) crops are soybeans, corn, cotton, canola

Herbicide resistance engineered to protect crop plants (e.g. soybeans) from herbicides that kill weeds, for example, glyphosate (roundup) inhibition of aromatic amino acid biosynthesis

Resistance to damage by some insects (ex: BT toxin from bacillus thuringiensis is toxin to moth, butterfly, beetle, and/or fly larvae and mosquitos

Question 17

Transgenic fish

Answer 17

Many foreign genes have been expressed in research and commercially important animals

Microinjection and recombination of foreign DNA into fertilized egg genomes

Aquadvantage salmon - reach market size in 18 months instead of 3 years; growth promoter for growth hormone was replaced with another fish’s promoter

Question 18

Metagenome

Answer 18

Genomes of an environment

Question 19

Gene mining

Answer 19

Process of identifying and isolating potentially useful genes from the environment without culturing the organisms that contain them

Question 20

Environmental gene mining

Answer 20

DNA (or RNA, then CDNA) is directly isolated from the environment and cloned into appropriate expression vectors to construct a meta genomic library

Screening has identified novel genes encoding pollutant-degrading and antibiotic biosynthetic enzymes

Bacterial artificial chromosomes (BACs) needed for entire pathways because they carry large DNA inserts, especially useful for screening samples from rich environments (e.g. soil) with large numbers of unknown genomes and genes

Question 21

Genome editing and CRISPRs

Answer 21

Sequence targeting by Cas9 protein

Also requires protospacer adjacent motif (PAM) on target DNA for complete endonuclease activity

Various methods of CRISPR system delivery by injection (plasmid; sgRNA and mRNA can be made in-vitro)

Homologous recombination can be used to incorporate new DNA (insertion)

Nonhomologous double-stranded DNA break repair pathway can ligate after deletion

Question 22

Cas system can be used as _____________ to spread mutations throughout generations of ____________________ organisms

Answer 22

gene drive; sexually reproducing

Occur naturally via transposons but difficult to control

heterozygotes become homozygous due to double-stranded breaks in wild-type copy

Question 23

Gene drives

Answer 23

a natural process and technology of genetic engineering that propagates a particular suite of genes throughout a population by altering the probability that a specific allele will be transmitted to offspring (instead of the Mendelian 50% probability)

Gene drives can arise through a variety of mechanisms

They have been proposed to provide an effective means of genetically modifying specific populations and entire species

Question 24

Epidemiology

Answer 24

the study of the occurrence, distribution, and determinants of health and disease in a population

Question 25

Targeted control of common vehicles and reservoirs (universal improvement of living conditions)

Answer 25

Access to safe water and food

Improved public sewage system

Less crowded living conditions

Lighter workload

Vaccination (humans and domestic animals)

Many formerly prevalent infectious diseases could be controlled (measles, typhoid fever, diphtheria, brucellosis, poliomyelitis), or even eliminated (smallpox)

Question 26

Disease surveillance (role of epidemiologists)

Answer 26

Identify the origin

Identify the mode(s) of transmission

Collect data from local and national health authorities

Data analysis

Report trends and signals for disease outbreak or containment

Form policies for outbreak control and public health

Question 27

Epidemic

Answer 27

Disease occurs in a large number of people in a population at the same time

Question 28

Pandemic

Answer 28

disease is widespread, usually worldwide

Question 29

Endemic

Answer 29

disease is constantly present in a population, usually at low incidences

Question 30

Incidence

Answer 30

number of new cases of a disease in a given period of time

Question 31

Prevalence

Answer 31

total number of new and existing cases of a disease in a population in a given time

Question 32

Herd immunity

Answer 32

resistance of a group to infection due to immunity of a high proportion of the group

If a high proportion of individuals are immune to an infection, then the whole population will be protected

Immunized people protect non immunized people because the pathogen cannot be passed on, and the cycle of infectivity is broken

Question 33

Disease reservoir

Answer 33

sites in which infectious agents remain viable and from which individuals can become infected

a number of infectious diseases are caused by pathogens that propagate in humans and animals (ebola in fruit bats, avian flu)

For other pathogens, nonliving matter serves as reservoirs

Question 34

Zoonosis

Answer 34

Any disease that primarily infects animals but is occasionally transmitted to humans

Control of a zoonotic disease in the human population may not eliminate the disease as a potential public health problem

Certain infectious diseases have complex life cycles involving an obligate transfer from a nonhuman host to humans followed by transfer back to the nonhuman host

Question 35

Carriers

Answer 35

Pathogen-infected individuals showing no signs of disease

May be individuals in the incubation period of the disease or asymptomatic

Can be identified using diagnostic techniques, including culture and immunoassays

Typhoid Mary is an example of a carrier

Question 36

Emergence factors

Answer 36

Human demographics and behavior

Technology and industry

Economic development and land use

International travel and commerce

Microbial adaptation and change

Breakdown of public health measures

Abnormal natural occurrences

Question 37

Diseases via droplet-infections (aerosolization)

Answer 37

Sneezing, coughing, talking, breathing, singing

Respiratory infections are the most common of all human diseases

Clearly, infections can also occur via direct contact with respective fluids or mucus, even on fomites

Question 38

Upper respiratory tract infections are _______________

Answer 38

acute, but not life-threatening

Upper respiratory tract = nasal cavity to larynx

Question 39

Lower respiratory tract infections are ____________

Answer 39

severe, e.g. pneumonia

lower respiratory tract = trachea to alveoli (essentially everything below the trachea)

Question 40

Staphylococcus aureus infections

Answer 40

resistant to drying and high salt concentrations

depending on the “port of entry”; skin/wound infections, food-
poisoning when ingesting toxins, pneumonia when inhaled

normal skin and upper respiratory tract flora of many (asymptomatic) people, transfer to susceptible person

cause acne, boils, pimples, impetigo (pustules and yellow crusty
sores); can also go deeper inside: carditis (infection of the heart), arthritis (inflammation and stiffness of the joints)

VF: coagulase - clotting of fibrin, leucocidin (destruction of white blood cells), hyaluronidase (destruction of hyaluronic acid between epithelial cells MSA)

Diagnosis: vigorous pus-formation, culturing, PCR, special MRSA medium, agglutination

Treatment: antibiotics; clindamycin, tetracyclines against MRSA

Prevention: virtually impossible; identifying of health care workers as MRSA carriers

Question 41

Streptococcus pyogenes infections

Answer 41

normal mouth and upper respiratory tract flora of many (asymptomatic) people, transfer to susceptible person

causes pharyngitis (strep throat), middle ear infections, or impetigo infections of superficial skin layers

rapid differentiation of strep vs. viral infection necessary, because group A streptococci can cause severe post-infection diseases, e.g. scarlet fever, rheumatic fever or toxic shock syndrome

group A can encode pyrogenic (fever-inducing) lysogen encoded exotoxins and superantigens (make T cells secrete cytokines, upscaling inflammatory reaction), or, have host-resembling antigens

Diagnosis: rapid antigen detection, culturing for more accurate drug testing

Treatment: antibiotics

Prevention: virtually impossible

Question 42

Rheumatic heart disease

Answer 42

life-threatening heart condition which results from damage to heart valves caused by one or several episodes of rheumatic fever

Rheumatic fever is caused by an abnormal response of the body to infection with streptococcal bacteria, which usually begins as a sore throat or tonsillitis in children

children 5-15, children who suffer repeated strep throat infections, people in low-income, people in certain indigenous communities, and people who’ve immigrated from countries where RF is more common are the most at risk

Treatment: anti-inflammatory drugs may be used to reduce inflammation and lower the risk of heart damage, other medications may be needed to manage heart failure, in severe cases treatment may include surgery to replace or repair a badly damaged valve

Prevention: prevent any strep throat infections, treat infections with antibiotics (such as penicillin) to prevent rheumatic fever, prevent additional streptococcal infection, long-term antibiotics can reduce progression to more severe disease

Question 43

Diphtheria

Answer 43

a severe respiratory disease that typically infects children

Caused by corynebacterium diptheriae, a bacterium that forms irregular rods during growth

Preventable and treatable by antitoxin for acute cases, previous infection or immunization provides resistance

Spreads by airborne droplets and enters the body via respiratory route

Pathogenic strains lysogenized by bacteriophage beta produce a powerful exotoxin that causes tissue death and the appearance of pseudomembrane in the patient’s throat

Question 44

Pertussis (whooping cough)

Answer 44

An acute, highly infectious respiratory disease

Caused by infection with bordetella pertussis

Observed frequently in school-age children

Characterized by a recurrent, violent cough

There has been a consistent upward trend in infections since the 1980s

Inadequately immunized children, adolescents, and adults are at high risk of acquiring and spreading pertussis

Diagnosis: Made by fluorescent antibody staining of a nasopharyngeal swab specimen, also made by actual culture of the organism

Prevention through vaccine soon after birth, treated by antibiotics (but elimination is helped by the immune response)

Question 45

Typically, any type of viral infection is more difficult to avoid or treat than bacterial infections because:

Answer 45

Viruses can often remain infectious for long periods of time in dried mucus or on fomites

Viruses require a host cell to replicate, so killing the virus means usually also killing the host cells

No antibiotics work at all (anti-viral drugs are available, and only inhibit their development, cannot “kill” them)

Question 46

Hepatitis

Answer 46

Liver inflammation

A, B, C, D, and E are all different viruses

transmitted in blood and other body fluids: transfusions, hypodermic needles, mother-to-child during birth, sex

liver infections can be acute: liver failure, death, or, chronic: destruction of functional liver anatomy (enlargement) and cells (cirrhosis), and even oncogenic (cause cancer)

Diagnosis: yellowing of the eyes, liver biopsy and enzyme tests, PCR, ELISA, immunofluorescent

Treatment: supportive to increase life quality with anti-viral drugs

Prevention: vaccination, but not routinely performed, “universal precaution”

Question 47

Incurable STDs

Answer 47

HSV herpes, HPV, HBV hepatitis, HIV

Congenital syphilis up 235% since 2016, can be cured with access to testing and penicillin

Question 48

The common cold

Answer 48

caused by rhinoviruses (3/4 of cases, 100 different, SS(+)RNA) but also other viruses

most common infectious disease

usually short duration (~1 week) and self-healing

droplets, fomites, direct contact

infects upper respiratory tract, especially nose

rhinitis: inflammation of mucous membranes of
nose, nasal obstruction, watery nasal discharge, muscle aches, general feeling of malaise, typically no fever

Diagnosis: symptomatic

Treatment: none, or, antihistamines or decongestants

Prevention: “universal precaution”

Question 49

Influenza

Answer 49

caused by influenza A virus (SS(-)RNA)

two unique surface glycoproteins, each consisting of multiple proteins (hemagglutinin and neuraminidase)

slight mutations, causing as little as one amino acid replacement, can leave new virus infection unrecognized (antigenic drift)

packaging of random RNA segments into virions: when two viral strains infect same host their genomes can get mixed (reassortment), alters entire outer protein signature, typically trigger strong clinical symptoms (antigenic shift)

Diagnosis: symptomatic, rapid influenza (antigen) diagnostic tests

Treatment: neuraminidase inhibitors block release of virions (Tamiflu)

Prevention: world-wide surveillance, sampling, annual vaccine design

Question 50

Hemagglutinin

Answer 50

unique surface glycoprotein of influenza, consists of multiple proteins

attaches virus to host

Question 51

neuraminidase

Answer 51

unique surface glycoprotein of influenza, consists of multiple proteins

releases virus from host

Question 52

Influenza pandemics

Answer 52

Occur every ~40 years

Time when major antigenic shift usually occurs (hemagglutinin and neuraminidase composition)

Often, reassortment in swine (immune system very similar to humans)

Question 53

Antigenic shift

Answer 53

an abrupt, major change in a flu A virus, resulting in new HA and/or new HA and NA proteins in flu viruses that infect humans

Question 54

Chicken pox and shingles

Answer 54

caused by varicella-zoster virus, dsDNA herpesvirus

goes into bloodstream and travels to skin, manifests as a papular rash

inhaling virus particles, or direct contact with chicken pox blisters

typically self-healing, no scarring unless constantly scratched

like all herpes viruses, VZV establishes a life-long latent (permanent) infection in nerve cells - virus can stay dormant indefinitely

can migrate to skin decades later, causing painful skin eruptions (shingles) on neck, head and upper torso

“break out” usually when body is becoming immunocompromised

Diagnosis: symptomatic

Treatment: none; or, calamine lotion and cooling gels to ease itching

Prevention: vaccination, becoming routine for children; shingles vaccine for people >50

Question 55

HIV/AIDS

Answer 55

caused by human immunodeficiency virus

80 million people infected world-wide

replicates in macrophages and T helper cells, lyses them, eliminates key immune cells

can exist in dormant stage as provirus

death from AIDS is usually the result of a secondary infection, typically from an opportunistic pathogen (most common: fungal pneumonia)

eukaryotic pathogens are generally difficult to treat (strong side-effects) because cells have more similar machinery to body cells

also a certain type of cancer is often developing: cancer of the cells lining the blood vessels - seen as red/purple splotches on skin (human herpesvirus 8)

Diagnosis: low CD 4 T cell count, or, list of typical secondary (unusual) infections

Treatment: decrease viral load, e.g. reverse-transcriptase inhibitors

Prevention: condoms, monogamy, abstinence, public education

Question 56

How do we know that HIV causes AIDs?

Answer 56

HIV isolated from virtually every patient with AIDs; has been cultured or confirmed by molecular techniques (PCR)

Accidental exposure to HIV in lab workers resulted in development of AIDs (no other risk factors present)

Animal models of human AIDs

HIV is the only factor that predicts whether a person will develop AIDs (disease found in individuals from diverse backgrounds)

Question 57

Sexually transmitted diseases

Answer 57

Body fluids of the genitourinary tract

Sometimes also in blood

Agents require protected, moist environment

Spread can be “controlled”

Many diseases have only minor symptoms

Many can be cured with antibiotics

But, people often reluctant to seek help

Remain untreated can lead to infertility, cancer, heart disease, birth defects

Bacterial ex: gonorrhea, chlamydia
Viral ex: herpes, HIV/AIDs

Question 58

Tamiflu

Answer 58

Neuraminidase inhibitor, virions can’t leave the cell

Treatment against influenza types A and B

Shortens symptoms by 1-2 days

May be important for older people (65+) and/or with chronic conditions (lessens risk to develop complications like pneumonia)

Also halts lytic cycle, influenza does not do lysogeny

Question 59

Acyclovir Against Cold Sores

Answer 59

Synthetic nucleoside analog to guanosine, inhibits DNA synthesis

Highly potent inhibitor of herpes simplex virus (HSV), types 1 and 2, and varicella zoster virus

Host cell thymidine kinase has very low affinity for the molecule as substate for mono-phosphorylation (no harm)

Only halts lytic cycle, provirus remains in host

Question 60

Anti-retroviral Therapy Against HIV

Answer 60

Needs to be taken daily (“HIV treatment regimen”)

Live longer, healthier and reduce risk of transmission

Prevents any more T cells getting harmed, goal is to keep virus as provirus, so viral load is undetectable in blood via lab test

Only halts lytic cycle, provirus remains in host

Question 61

Dysplasia (pap smear morphology)

Answer 61

a higher nuclear to cytoplasmic ratio

this means the nucleus is larger than it should be for the size of the cell

Question 62

Mild Dysplasia (pap smear morphology)

Answer 62

The nucleus is about 3-4 times larger than it should be

Question 63

Moderate dysplasia (pap smear morphology)

Answer 63

The nucleus is 5-6 times larger than it should be

Question 64

Severe dysplasia (pap smear morphology)

Answer 64

The nucleus is taking up most of the cell

Question 65

HPV

Answer 65

Cause most warts (not toads) including genital warts

Is a sexually transmitted virus that at leads to the majority of cervical, anal, vulva and orthopharnygeal (throat) cancers

50% of the sexually active population will be infected with oncogenic versions of HPV

Untreated HPV infection leads to cervical cancer and kills ~ 300,000 women every year worldwide

HPV vaccination is recommended prior to sexual activity

PAP smear screening is the most effective cancer screening test developed so far

In the US each year HPV causes ~27 K cervical cancers and ~21K throat cancers in males

Question 66

Gardasil

Answer 66

Name brand of vaccine against HPV infection is not a virus, recombinant VLP (virus like particle)

contains 9 antigens corresponding to the most oncogenic HPV variants

Question 67

COVID-19/SARS-COV-2 envelope structure

Answer 67

S (spike) glycoprotein, gives the virus its corona(crown)-like morphology in the electron microscope

HE = hemagglutinin-esterase glycoprotein (smaller spikes)

M = highly hydrophobic transmembrane protein

Angiotensin-converting enzyme II (ACE2) is cell receptor for SARS-CoV, and also for some SARS-like bat coronavirus

Receptor-binding domain of SARS-CoV-2 virus has even higher binding affinity than SARS-CoV

Target: certain progenitor cells that normally develop into respiratory tract cells lined with cilia that sweep mucus and bacteria out of the lungs

Question 68

Paxlovid

Answer 68

Antiviral treatment for SARS-COV-2 (COVID-19)

Mechanism of action very similar to HIV protease inhibitor

Some viruses make all their proteins linked together as a polypeptide

Question 69

How does the immune memory work?

Answer 69

Antigens are encountered in blood, lymph (nodes) or spleen

Each antigen-stimulated B cell divides and differentiates to form plasma cells (live ~1 week), excreting antibodies (remain ~3 months)

Memory cells get antigen-stimulated, divide, and differentiate into plasma cells, do NOT need T helper cells

Most efficient antibodies are produced: IgG in serum IgA in mucous membranes

Titer only slowly decreases without antigens present, may never cease in life

Question 70

After vaccination, our body produces _______________

Answer 70

polyclonal antibodies

Each phagocyte presents a DIFFERENT epitope of the spike protein

A variety of B cells get activated, each one recognizing a different epitope of the antigen (of spike protein)

Slight changes in antigen (mutations) should still allow for adequate memory/immunity; DNA-containing vs. RNA containing pathogens

Question 71

Omicron had more than expected mutations in spike protein, which lead to:

Answer 71

increased binding of ACE2 receptor (more contagious), and evaded immunity by 30-50% overall

Question 72

One antigen contains multiple ___________________

Answer 72

regions/epitopes for recognition:

one antigen reacts with several different B cells

one antigen activates a multitude of B cells

each B cell clonal population generates their own specific antibody

Question 73

Properties of mRNA vaccines

Answer 73

Studied since 1970s (current research: HIV, ebola, flu, rabies)

mRNA molecules are not biologically produced, but via chemical synthesis

mRNA is in vitro transcribed from a DNA template in a cell-free system

mutations = differences in the sequence of the viral RNA genome, mRNA sequence can be easily modified in the solid phase synthesis process

no need to cross nuclear membrane for expression, no risk of viral genes integrating into host DNA (there is no DNA)

Long-time problem: mRNAs have high natural destruction rate, and, low transfection efficacy (uptake efficiency by eukaryotic cells)

Nanotechnology helped: vaccine is packed in catatonic, lipid nanoparticles (LNPS)

Question 74

How do mRNA vaccines work?

Answer 74

1. lipid bubble around the mRNA molecule allows vaccine to enter cells
2. mRNA molecule becomes free and ribosomes translates it into antigenic (Spike) protein
3. the protein is excreted in high amounts and can now serve as antigen
4. encountering phagocytes, it is being digested and presented via MHC II to T helper cells
5. this initiates the regular immune answer to the B cells and production of polyclonal serum

Question 75

What is the goal of a vaccine?

Answer 75

activate B and T cell

establish immune memory

Question 76

Live attenuated vaccines

Answer 76

Uses closely related strain with reduced pathogenicity

Share epitopes = elicit immune response that cross-react with the “real” pathogens

These strains can still replicate and ensure prolonged exposure/stimulation (fewer booster shots)

Made from successive passaging in cells and screening/selection for attenuated pathogenicity

Time consuming, lots of variation, not ideal to react quickly to pandemics

Question 77

Inactivated vaccines

Answer 77

When no known strains have lower pathogenicity

Triggers immune activation but only for a short period of time (these strains don’t replicate)

More boosters required

No risk of reversion of virulence

Inactivated by heat or chemical treatment

Question 78

Rabies

Answer 78

Rhabdovirus (SS(-)RNA)

in U.S. main carriers are raccoons, skunks, coyotes, foxes and bats

transmission via saliva in wounds (bite) or through mucous membranes

incubation time in animals <14 days, much longer in humans up to 9 months

infects cells of the central nervous system, especially in the brain

symptoms: fever, first phase of excitation (restlessness, nervousness, irritability), then, dilation of pupils, excessive salivation, depression/anxiety, spasms, and ultimately (respiratory) paralysis

once symptoms show, death is evitable

research on post-exposure vaccine: recombinant parainfluenza virus (harmless) carries a strong antigenic protein of rabies virus

Diagnosis: symptomatic, tissue examination for virus (fluorescent immunostaining)

Treatment: none for animals; purified human antibodies (passive), and vaccination (active)

Prevention: routine vaccination of domestic animals and high-risk persons

Question 79

Hantavirus infections

Answer 79

Hantaviruses (SS(-)RNA), related to Ebola virus

local outbreaks when poor rodent control (China, Korea, Russia, Desert SW USA)

main carriers are mice, rats, lemmings, and voles

transmission via contact with saliva, or, inhalation of excrements (urine, feces)

incubation time 1-5 weeks, mortality rate ~40%

two diseases:
1. hantavirus pulmonary syndrome (HPS), symptoms: fever, muscle pain, lung congestion, shortness of breath, fluid in the lungs

2. hemorrhagic fever with renal syndrome (HFRS), symptoms: intense headache, back and abdominal pain, kidney failure, spontaneous bleeding, red-shot eyes, photophobia

Diagnosis: X-ray of the lungs, agglutination (antibodies + blood sample)

Treatment: only supportive (intubation and mechanical ventilation, rehydration)

Prevention: avoiding rodent contamination

Question 80

Diseases via arthropods

Answer 80

insects, spiders, crustaceans

main transmission: bites

humans are “accidental hosts”

diseases are often devastating, fatal

Bacterial ex: rickettsial (typhus, RMSF), Lyme disease, plague

Viral ex: yellow fever, zika

Question 81

Rickettsiales

Answer 81

Very small cell morphology

obligate parasites (bacterial)

often associated with blood-sucking arthropods, such as fleas, lice, ticks

Have not been cultured in artificial culture media, but can be grown in the lab animals, ticks, lice, and mammalian tissue culture

Can replicate inside macrophages

Three groups based on the diseases they cause: typhus group (rickettsia prowazek II), spotted fever group (rickettsia rickettsia), ehrlichiosis group (ehrlichia cheffeensis)

Question 82

Lyme disease

Answer 82

Borrelia burgdorferi

first incidents in Old Lyme, Connecticut, “borreliosis”

most prevalent arthropod-borne disease in U.S.

transmission in ticks, especially (very small) deer ticks

symptoms: headache, back pain, chills, fatigue

if untreated weeks after bite disease becomes chronic

arthritis, neurological problems (weakness in limbs or one
side of the face), heart damage

bacteria infect cells of the central nervous system, can stay dormant and cause later ongoing muscle, vision or nerve damage, seizures

Diagnosis: bull’s eye rash ( <65%), fluorescent immunostain

Treatment: antibiotics in first 1-2 weeks

Prevention: removal of ticks before they bite, DEET insect repellent

Question 83

Typhus

Answer 83

Rickettsia prowazek II

transmitted by common body or head lice

was generally main cause of death among troops during war time:
during world war I epidemic in eastern Europe killing 3 million people

bite wound gets infected with lice feces

incubation time 1-3 weeks

bacteria replicate inside cells lining small blood vessels

symptoms: fever, headache, weakness, rash starts in armpits and spreads leaving out the head

damage of central nervous system, lungs, kidneys, heart

mortality 30%

Diagnosis: fluorescence immunostain on skin biopsy from rash

Treatment: antibiotics

Prevention: vaccination, but only when travelling to endemic regions

Question 84

Rocky Mountain spotted fever

Answer 84

Rickettsia rickettsia

about 2000 cases in U.S. per year

mainly in Southeast U.S.

transmitted by dog ticks, in their saliva

mortality <1% when treated, 30% untreated

incubation time: 3-12 days

symptoms: fever, severe headache, followed by systemic rash, gastrointestinal problems (diarrhea, vomiting)

damage of blood vessels, post-infection amputation, paralysis

Diagnosis: symptomatic, blood testing poor, takes weeks

Treatment: antibiotics

Prevention: removal of ticks before they bite, DEET insect repellent

Question 85

Plague

Answer 85

Yersinia pestis

transmitted by fleas of rats (commonly believed by rats themselves)

today, endemic in many countries, esp. sub-Saharan Africa

cells replicate in lymph nodes, capsule protects from phagocytosis

bacteria fill lymph nodes, large swelling (bulbonic plague)

cells enter blood stream and cause septicemia, uncontrolled bleeding, visible as dark blotches on skin, tissue necrosis/ gangrene (“Black Death”), delirium

mortality >90% in 48 hours

Diagnosis: sample from swollen lymph nodes, agglutination test, culturing

Treatment: antibiotics (greatly decreases mortality to 5%)

Prevention: good sanitation and rodent control, quarantine (droplet infection)

Question 86

Yellow fever

Answer 86

Flavivirus (SS(-)RNA), related to dengue fever, west nile, and zika virus

endemic in tropical and subtropical climate, esp. Latin and South America, and Africa

transmitted by mosquitoes

virus replicates in immune system cells in lymph nodes and then
travels on to liver

symptoms: headache, mild fever and chills, back pain, nausea

1 in 5 enter “toxic phase”: jaundice (yellow coloring of skin, eyes, and
mucous membranes due to bilirubin, formed when red blood cells break down), bleeding from mouth, eyes, and gastrointestinal tract, bloody vomit, multiple organ failure; 20% mortality

Diagnosis: antibody detection in blood sample

Treatment: supportive, and, isolation of patient so no mosquitoes can transfer the virus

Prevention: vaccination, recommended when travelling to endemic regions

Question 87

Zika

Answer 87

Flavivirus (SS(-)RNA)

emerged ~65 years ago in Zika forest, Uganda

in 2015 appeared in Brazil; 2016 in Puerto Rico and southern USA

vector is also mosquito

mild symptoms, disease typically self-healing

symptoms: fever, back pain, joint pain, red eyes, rash

but very severe for pregnant women (or wanting to get pregnant)

virus infects cells in special region of the brain

microcephaly in newborns: the head (circumference) is smaller than normal, also other brain problems - intellectual disability, speech delay

Diagnosis: symptomatic, RT-PCR from blood or urine in pregnant women

Treatment: none; both, people and unborns

Prevention: insect repellents, general measures to avoid mosquito bites

Question 88

Soilborne diseases

Answer 88

Direct contact or aerosolized

Soil particles with attached bacteria

Animal fur or hides in the ground

These pathogenic bacteria are usually free-living, do not require host for replication or for any other aspect of their metabolism

Bacterial ex: anthrax, tetanus, gas gangrene

Question 89

Tetanus

Answer 89

Clostridium tetani, endospore

> 150,000 deaths in Africa and South-east Asia

spores enter body through (deep) soil-contaminated wound (typically puncture or cut)

incubation time: days - weeks

after germination, bacteria grow but are essentially non-invasive, however, produce exotoxin tetanus toxin

affects inhibitory signaling molecules in nervous system

paralysis of the voluntary muscles, first in face (“lockjaw”)

symptoms: proceeding spasms and body paralysis, respiratory failure; mortality 10-50%

Diagnosis: symptomatic, rarely blood or tissue tests

Treatment: antibiotics; vaccine; antitoxin (cannot un-paralyse)

Prevention: routine vaccination

Question 90

Cholera (water/vehicle borne)

Answer 90

Vibrio cholerae; salt tolerant

disease with pandemic proportions, WHO: >1 million cases/year

severe gastrointestinal diarrheal disease

natural reservoir: fresh and saltwater

also ingestion via undercooked shellfish (main source in U.S.)

disease requires high dose of bacteria (>108), because only 0.01% survive stomach acid

cells attach to epithelial cells in small intestine

produce AB-toxin, enterotoxin

causes massive secretion of fluid into the intestinal lumen (20 L per day)

mortality 25-50% by dehydration

Diagnosis: culturing on special medium with bile salts and citrate

Treatment: antibiotics, rehydration drink (glucose, NaCl, NaHCO3, KCl)

Prevention: adequate sewage treatment & drinking water purification procedures

Question 91

Legionellosis (water/vehicle borne)

Answer 91

Legionella pneumophila; resistant to chlorine and heating

main disease-causing agent linked to drinking water in the U.S.

transmitted via aerosols in showers and evaporative cooling systems

natural reservoir: freshwater and soil

persist in biofilms in water distribution pipes

high cell numbers in warm, stagnant water, e.g. water tanks

invade the lungs and grow in macrophages

mild symptoms in healthy people (sore throat, headache, fever)

cause pneumonia in elderly, mortality 10%

Diagnosis: immunostaining of bronchial washings or pleural fluid

Treatment: antibiotics

Prevention: major problem, heating water above 63°C

Question 92

Norovirus

Answer 92

Norovirus (SS(+)RNA)

world-wide, leading cause of gastrointestinal illness

feces-contaminated food or water

short but intense state of vomiting, diarrhea, fatigue (“24-hour-bug”)

only rarely does the dehydration become severe

very easily transmitted person-to-person or to food by fecal-to-oral route

often mass occurrence on cruise ships, in nursing homes, or other spatiotemporally confined group settings

Diagnosis: symptomatic, RT-PCR, enzyme immunoassay of vomit or feces

Treatment: none (necessary), rehydration/electrolytes

Prevention: good sanitary behavior, boiling water, wash/heat foods

Question 93

Clovibactin

Answer 93

an antibiotic from an uncultured bacterium binds to an immutable target

Similarity to Texiobactin and Vancomycin natural product from “incurable” bacteria

Mechanism binds phosphate group of membrane phospholipid