Exam 4 Flashcards
Antibodies
Blood serum proteins produced by animals
Made by injecting animal with specific protein antigen
Nucleic acid probes
look for binding of labeled nucleic acid probe to DNA from specific colonies
Gene fusions
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
Operon fusions
coding sequence with its own translational start site and signals are fused to transcriptional signals of another gene
Protein fusions
Genes encoding two proteins are fused to share the same transcriptional and translational start and stop and yield one hybrid polypeptide
Recombinant vaccines
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
Polyvalent vaccine
A single vaccine that immunizes against two different diseases
Vaccinia virus
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
Subunit vaccines
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)
Many mammalian proteins have high pharmaceutical value but are costly to purify because of:
low amounts in normal tissue
genetically engineered microorganisms used instead
Somatotropin
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
_______ was the first human protein made commercially by genetic engineering
insulin
Transgenic organism
genetically engineered organism that contains a gene (transgene) from another organism
Agrobacterium tumefaciens (plant pathogen) contains the ____________ responsible for virulence
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
Binary vector
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)
Herbicide- and insect-resistant plants
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
Transgenic fish
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
Metagenome
Genomes of an environment
Gene mining
Process of identifying and isolating potentially useful genes from the environment without culturing the organisms that contain them
Environmental gene mining
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
Genome editing and CRISPRs
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
Cas system can be used as _____________ to spread mutations throughout generations of ____________________ organisms
gene drive; sexually reproducing
Occur naturally via transposons but difficult to control
heterozygotes become homozygous due to double-stranded breaks in wild-type copy
Gene drives
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
Epidemiology
the study of the occurrence, distribution, and determinants of health and disease in a population
Targeted control of common vehicles and reservoirs (universal improvement of living conditions)
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)
Disease surveillance (role of epidemiologists)
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
Epidemic
Disease occurs in a large number of people in a population at the same time
Pandemic
disease is widespread, usually worldwide
Endemic
disease is constantly present in a population, usually at low incidences
Incidence
number of new cases of a disease in a given period of time
Prevalence
total number of new and existing cases of a disease in a population in a given time
Herd immunity
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
Disease reservoir
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
Zoonosis
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
Carriers
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
Emergence factors
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
Diseases via droplet-infections (aerosolization)
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
Upper respiratory tract infections are _______________
acute, but not life-threatening
Upper respiratory tract = nasal cavity to larynx
Lower respiratory tract infections are ____________
severe, e.g. pneumonia
lower respiratory tract = trachea to alveoli (essentially everything below the trachea)
Staphylococcus aureus infections
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
Streptococcus pyogenes infections
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
Rheumatic heart disease
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
Diphtheria
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
Pertussis (whooping cough)
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)
Typically, any type of viral infection is more difficult to avoid or treat than bacterial infections because:
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)
Hepatitis
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”
Incurable STDs
HSV herpes, HPV, HBV hepatitis, HIV
Congenital syphilis up 235% since 2016, can be cured with access to testing and penicillin
The common cold
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”
Influenza
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
Hemagglutinin
unique surface glycoprotein of influenza, consists of multiple proteins
attaches virus to host
neuraminidase
unique surface glycoprotein of influenza, consists of multiple proteins
releases virus from host
Influenza pandemics
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)
Antigenic shift
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
Chicken pox and shingles
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
HIV/AIDS
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
How do we know that HIV causes AIDs?
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)
Sexually transmitted diseases
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
Tamiflu
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
Acyclovir Against Cold Sores
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
Anti-retroviral Therapy Against HIV
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
Dysplasia (pap smear morphology)
a higher nuclear to cytoplasmic ratio
this means the nucleus is larger than it should be for the size of the cell
Mild Dysplasia (pap smear morphology)
The nucleus is about 3-4 times larger than it should be
Moderate dysplasia (pap smear morphology)
The nucleus is 5-6 times larger than it should be
Severe dysplasia (pap smear morphology)
The nucleus is taking up most of the cell
HPV
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
Gardasil
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
COVID-19/SARS-COV-2 envelope structure
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
Paxlovid
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
How does the immune memory work?
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
After vaccination, our body produces _______________
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
Omicron had more than expected mutations in spike protein, which lead to:
increased binding of ACE2 receptor (more contagious), and evaded immunity by 30-50% overall
One antigen contains multiple ___________________
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
Properties of mRNA vaccines
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)
How do mRNA vaccines work?
- lipid bubble around the mRNA molecule allows vaccine to enter cells
- mRNA molecule becomes free and ribosomes translates it into antigenic (Spike) protein
- the protein is excreted in high amounts and can now serve as antigen
- encountering phagocytes, it is being digested and presented via MHC II to T helper cells
- this initiates the regular immune answer to the B cells and production of polyclonal serum
What is the goal of a vaccine?
activate B and T cell
establish immune memory
Live attenuated vaccines
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
Inactivated vaccines
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
Rabies
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
Hantavirus infections
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
- 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
Diseases via arthropods
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
Rickettsiales
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)
Lyme disease
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
Typhus
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
Rocky Mountain spotted fever
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
Plague
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)
Yellow fever
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
Zika
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
Soilborne diseases
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
Tetanus
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
Cholera (water/vehicle borne)
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
Legionellosis (water/vehicle borne)
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
Norovirus
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
Clovibactin
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
