People, Parasites, and Plagues Exam #1

parasitism

A relationship between two organisms of different species where one benefits and the other is harmed (one organism lives on or in the host)

variolation

The technique of enhancing immunity by exposing patients to dried smallpox scabs taken from those already infected

inoculation of smallpox into the skin

definitive host

the host in which the sexual reproduction of a parasite takes place

intermediate host

obligate but transient (lasting for short time) host required for completion of a parasitic life cycle, but NO sexual reproduction occurs

an organism that supports the immature or non-reproductive forms of a parasite

incidental/accidental host

host where parasite infection occurs but is a dead end for the normal life cycle

when a parasite establishes itself in a host in which it does not usually live

reservoir host

typically, wildlife species that maintain parasite populations that intermittently cause outbreaks in humans (zoonoses)

infected organism (usually an animal) which makes the parasite available for transmission to other hosts

the deadliest arthropod borne disease

malaria

number of deaths per year due to mosquitoes

725,000

THREE different mosquito species

1. Anopheles spp.

2. Aedes spp.

3. Culex pipiens

Anopheles spp.

malaria; lymphatic filariasis (damage to lymph system); O'nyong'nyong virus (fever, joint pain, and usual symptoms-resembles Dengue fever)

***less harsh

Aedes spp.

Dengue virus; Yellow Fever virus; Zika virus; West Nile virus; Chikungunya Virus; EEE virus (brain inflammation-very severe); lymphatic filariasis

***very invasive

Culex pipiens

West Nile virus; EEE (brain inflammation) virus; Japanese Encephalitis virus (brain swelling, fever, headache, vomiting); lymphatic filariasis

***"house mosquito"

malaria is caused by FIVE types of...

plasmodium

1. plasmodium falciparum

2. plasmodium vivax

3. plasmodium ovale

4. plasmodium malariae

5. plasmodium knowlesi (NEW-in primates)

plasmodium

a genus of unicellular eukaryotes that are obligate parasites of vertebrates and insects

deadliest plasmodium

plasmodium falciparum

global burden of malaria

-249 million cases

-608,000 deaths

-95% of deaths in sub-saharan africa

-80% in children under age 5

plasmodium falciparum

one of five species of plasmodium that infect humans

eukaryotic, apicomplexan parasite (obligate, intracellular)

causes symptoms through human blood stream; must pass through mosquito

anopheles gambiae

-major african vector of malaria parasites

-night biting with strong preference for human blood

life cycle of plasmodium

1. In the liver

2. sporozoites reproduce asexually in liver

3. Merozoites enter the bloodstream and reproduce

4. Female mosquito sucks in infected blood.

5. In gut of mosquito, plasmodium zygotes develop into sporozoites in salivary glands.

The malaria parasite life cycle involves two hosts. During a blood meal, a malaria-infected female Anopheles mosquito inoculates sporozoites into the human host . Sporozoites infect liver cells and mature into schizonts , which rupture and release merozoites

has intermediate host and definitive host

anautogeny

necessity of taking a blood meal in order to produce eggs.

eggs --> larvae --> pupae

brief aquatic larval stage lasting 5-8 days

nectar stage

male and female mosquitoes drink nectar from plants for nutrients to power flight

adult stage

(2-3 weeks) mating occurs

1. feed on sugar

2. male/female mate

3. female feed on blood

mosquito blood feeding characteristics...

-vertebrate blood feeding

-females only feed on blood

-provides essential protein and lipid for egg production

anopheles complex larval habitat

larvae live in swampy or marshy environments that are nutrient poor

anopheles gambiae habitat

females: live by blood sources and humid microenvironment; close to sugar

males: difficult to know

anopheles location

found everywhere; anopheles gambiae have been eradicated from North America and Europe

7 types of anopheles species

1. An. gambiae

2. An. coluzzi

3. An. arabiensis

4. An. quadriannulatus A and B

5. An. melas

6. An. merus

7 An. bwambae

-morphologically indistinguishable

-different geographic distribution and different biology

-different chromosomal rearrangements

-adaptation to environmental conditions like climate

where are anopheles arabiensis found?

arid regions throughout africa (sub-saharan)

where are anopheles gambiae found?

congo rainforest; reliant on humidity; sub-saharan africa

where are anopheles melas and merus found?

costal parts of africa; reliant on brackish water

where are anopheles bwambae and quadriannulatus A and B found?

sub saharan africa

how many times do female insects (including anopheles gambiae) mate in their life? When do they mate?

only 1!!!!! mate early in life and store sperm

how do anopheles gambiae mate

through a behavior called "swarming," where male mosquitoes gather in large, visible groups in the air, and females fly into the swarm to mate with a male; this usually happens around dusk near specific landmarks, with the female typically only mating once in her lifetime

females must mate with the correct species of male to ensure...

viable offspring

males transfer ______ and _______ during mating

1. sperm

2. seminal secretions

***males are capable or reproducing/mating again

why can females only mate once?

when they mate, males transfer sperm resulting in a gelatinous plug with nutrients that blocks the reproductive tract of females

MATING

1. induce refractoriness to remating (behavioral, physiological)

2. promotes host seeking behavior in females

3. enhances egg production post blood feeding

4. promotes egg laying

5. promotes immune tolerance to malaria

order of mosquito feeding

sugar meal-->mate-->blood feeding

NON-BLOOD FEEDING INSECTS

autogenous arthropods--> long larval stage (nutrient aquisition) --> adult emerges (adult uses nectar feeding for flight and uses larval energy reserves for egg production)--> mating

1. most insects are autogenous

2. larval stage is focused on nutrient acquisition

3. adult stage focused on mating, producing offspring

4. adults take nectar meals to power flight

5. TENERAL reserves are larval energy stores

6. IMAGO is the adult insect

AUTOGENY

use of macromolecule reserves from larval stage to produce eggs

why has blood feeding evolved so many times?

it provides a readily available, nutrient-rich meal, particularly high in protein and lipids, which is crucial for many insects, especially females, to produce eggs, making it a significant evolutionary advantage despite the risks involved in feeding on a much larger animal like a vertebrate

Arthropod-Borne Diseases

-Generally rare

-Some are of historical interest (such as plague and typhus)

-Some newly emerged (such as Lyme disease and erlichiosis)

phlebotomus "sand fly"

Leishmania

(leshmania major)

lxodes "deer tick"

Lyme Disease (+++)

(borrelia burgdorferi)

simulium "black fly"

River Blindness

(oncocerca volvulus)

glossinia "tsetse fly"

Trypanosomiasis

(trypanosoma brucei)

rhodnius "kissing bug"

Chagas Disease

(trypanosoma cruzi

blood feeding induces ______ to rapidly produce eggs

a cascade of hormone signaling

***lipid/protein transporters that play role in egg development; steroid hormone (20-hydroxyecdysone 20E); produce about 1500 offspring

what is the relationship between oogenesis in anopheles and the plasmodium parasite development in female mosquitoes?

the two events happens at the same time (they are physiologically and temporally tied)

when and where do oogenesis and parasite production occur?

in the mosquito midgut after blood meal from infected host

if anopheles is everywhere, why isnt malaria?

-mosquitoes in north/south america tend to feed less on humans than those in africa; tend to feed more on livestock in the US and livestock are more tolerant

-environment (climate) and human intervention

malaria started as _____ and is now ______

an amoeba; is now blood borne

malaria transmission is a _____ process

2 week process

***most mosquitoes dont live long enough

mosquito life cycle traits that impact malaria transmission

1. mosquito density (# of mosquitoes)

2. biting habit (bite frequency)

3. probability a mosquito becomes infected

4. mosquito daily mortality

5. life expectancy

6. infectious mosquito surviving to bite

7. proportion of human infectious bites

8. successful human infection

9. duration of human infection

most important factor

mosquito daily mortality

mosquitoes have a very _____ biting patter

variable

vector competence "probability a mosquito becomes infected"

-ability of a vector to transmit a pathogen; determines malaria transmission efficiency; significant variability in vector competence within An. gambiae

-describes how malaria moves through population

-human malaria originated in africa and spread with humans to asia, europes and americas

-necessitated to co-adaptation between local vectors and invasive plasmodium

vector/parasite incompatibilities between mosquito and within parasite species are mediated by _____

a SINGLE gene

3 ways to control/prevent malaria

1. (PREVENTATIVE) prophylaxis drugs to prevent sickness; incompatible with liver stage

2. (REACTIVE) if INFECTED, therapeutic drugs can treat

3. (PREVENTATIVE) insecticides to kill off females mosquitoes

***easier to PREVENT than treat

best preventative method

insecticide treated nets; neurotoxic insecticides repel or kill susceptible mosquitoes; physical barrier or "baited trap" where they are attracted to net then killed

artemisinin

destroys malarial parasites by releasing free radicals in red blood cells

the problem with insecticide nets

1. mosquito resistance

2. lack of novel and safe chemistries (must be safe to be in contact or sleeping under one)

insecticide resistance causes

1. BEHAVIORAL resistance- changes in biting behavior from night to day time; increased exophagy vs endophagy

2. METABOLIC resistance-upregulation of excretion and detoxification enzymes (cytochrome P450s; glutathione-S-transferases)

3. CUTICULAR resistance-thickening of outer waxy layer of the mosquito cuticle

4. TARGET SITE resistance-pyrethoids and organochlorides share a target site, the sodium channel protein (resistance to one class confers resistance to both)

alternatives to insecticide control

1. gene drives (supression/replacement)

2. sterile insect technique (eradication or sterilization of males)

3. mosquito targeted anti malarials

4. attractive targeted sugar baits

5. ivermectin and other endectocides

6. wolbachia can control mosquito population and reduce disease spread

ENDECTOCIDES

drugs that are effective against both endo- and ectoparasites

how is mosquito density reduced

gene drives, sterile insect technique, and wolbachia

how is probability of mosquito becoming infected reduced?

gene drives, wolbachia, antimalarial nets

how is daily mortality reduced?

ivermectin and sugar baits

how is infectious mosquito surviving to bite reduced?

antimalaria nets

_______ blocks transmission of P falciparum

ATOVAQUONE (expose to mosquitoes and they cannot pass on parasite); very lipophilic; penetrates mosquito cuticle and rapidly accumulates in midgut lumen

helps because even with resistance to insecticide, they will not be able to transmit the parasite

adding _____ to nets would greatly reduce malaria prevalence

plasmodium (parasite) inhibitors

MICROBIOLOGY

A branch of biology dealing especially with microscopic forms of life (as bacteria, protozoans, viruses, and fungi).

most life is _____

prokaryotic (bacterial); life also contains archeal and eukaryotic forms

eukaryotes include

protists, fungi, plants, animals; microbes and vertebrates

MICROBES are important for

global health; food production; nutrient and energy cycling

DNA replication

highly conserved and easy to grow quickly; the process of making a copy of DNA; foundational discoveries; better to work with microbes because no one cares if you kill them

microorganism viruses

staph; herpes simplex virus; brugia malayi

Robert Koch

Developed the culture plate method to identify pathogens; 1st real clinical microbiologist

1. grew pure cultures of organisms and experimented with different growth media to grow different cells

2. attributed specific organisms to specific diseases (bacillus anthracis=anthrax; vibrio chloerae=cholera; mycobacterium tuberculosis=TB)

"Germ Theory" of Disease

-idea that infectious diseases are caused by microorganisms

-bacteria are known and can be isolated and attributed to disease

Koch's Postulates

Set of rules for proving that a microorganism causes a specific disease

1. organism must be present in every disease case

2. organism must be isolated from host containing diseases and grown in pure culture

3. samples of organism taken from pure culture must cause same diseases with inoculated into healthy, susceptible animal in lab

4. organisms must be isolated from inoculated animal and identified as the same original organism that caused disease

important clinically relevant microbes

-bacteria (gram negative and positive); viruses

-EUKARYOTES: yeasts/fungi; unicellular parasites; multicellular parasites

viruses are diverse meaning

made up of DNA or RNA and can be single or double stranded; can be anti-sense or sense

eukaryotic microbial pathogens

1. yeast/fungi (spores infections)-aspergillus fumigatus (aspergillosis); cryptococcus neoformans (cryptococcosis)

2. protozoa (unicellular)-plasmodium falciparum (malaria); toxoplasma gondii (toxoplasmosis); naegleria fowleri (brain eating)

3. multicellular- brugia malayi (lymphatic filariasis

old methods of finding out what caused disease

phenetic

PHENETIC

based on phenotype, or expression of traits

new way of determining what caused disease

phylogenetic and genotypic

PHYLOGENETIC

The study of evolutionary relatedness among various groups of organisms

post-evolution classification scheme; ordered via evolutionary relationships (evolved organisms share processes and DNA sequence)

molecular determinations

***rapid clinical trials

1. G + C content-more GC content is stronger and more stable

2. higher organisms have 30-50 GC (prokaryotes vary)

3. 10% change in GC content means no close relationship

HYBRIDIZATION

cutting and combining 2 genomes and labeling with radioactivity to determine homology

16S or 18S rRNA sequencing

-useful for easy genus classifications

-slow to change, essential

-not subject to lateral gene transfer (important)

***amplifies and sequences DNA regions to determine microorganism

Genomic Fingerprinting

-analysis of genes that evolve more quickly than rRNA encoding genes; needed for SPECIES classifications because it follows multiple loci

-multilocus sequence analysis (MLSA)

-uses restriction enzymes and separates by electrophoresis

-restriction length polymorphism analysis

Illumina sequencing

-allows you to get billions of bases on something the size of a microscope slide

-lots of DNA molecules read at the same time

-relies on short sequences of starting DNA; fragmentation and adapter additions

"sequence by synthesis"

-Cyclic detection of fluorescent nucleotides sequentially incorporated into DNA molecules

-fluorescently labeled nucleotides are added; 3' end blocked

-addition of nucleotide is read by lasers and measuring glow

-fluorescent blocker removed, next round begins

-repeat (millions of potential clusters, containing thousands of similar DNAs in one area)

-relies on sequence overlap to assemble sequences

SPECIES

collections of strains that share properties and are measurably different from other species

STRAIN

descendants of a pure microbial culture (clonal)

BIOVAR

strains that differ in biochemical or physiological differences

MORPHOVAR

strains that differ morphologically (shapes)

SEROVAR

strain variants via antigenic properties

BIOVAR examples

1. chlamydia trachomitis

2. biovar trachoma vs biovar LGY

TRACHOMA: limited and localized in ocular or genetic infections

LGY: systemic infections