W2P1 Flashcards
Vector of Malaria
Anopheles mosquitoes
Vector of Dengue
Aedes mosquitoes
Vector for Chikungunya
Aedes mosquitoes
Vector for ZIKA
Aedes mosquitoes
Vector for Lyme disease
Ixodes ticks
Vector for Leishmaniasis
Sandflies
Vector for African Tryp
Tse Tse flies
Vector for American Tryp
Triatomine
Vector for Rickettsia
Lice
Ticks
Other arthropods
Arthropods
Arthropods are members of the phylum Arthropoda, which means “jointed leg.” Arthropods include insects, arachnids, and crustaceans
Anopheles Mosquito
- what is the life cycle**
Parasite of human RBCs- MALARIA
THE parasitic killer of human beings
90% of deaths in sub-Saharan Africa*
Transmitted by Anopheles mosquitoes
LIFE CYCLE
A. infection, a bite
B. Sporozoites released and invade hepatocytes = LIVER STAGE, they multiply
C. Meroziotes get released into the blood = BLOOD stage, they for a ring, asexual reproduction cycle. they they burst/hemolytic and infect other RBCs
D. Small percentage will enter sexual stage: gemtocytes which will then be passed on to next mosquito that bites infected host = TRANSMISSION stage
At what stage of Malaria cycle does the infected host start to feel symptoms?
During the LIVER STAGE there are NO symptoms, this is the incubation period it takes to mature
only once it enters the BLOOD stage (7-30 days later) do we get symptoms: high fever + shaking chills
Anopheles Mosquito
- Vector for which illness
- When does it bite?
- Inactive in what conditions
vector for Malaria
Bite dusk to dawn
Only females
Inactive below 18°
Altitude sensitive
Anopheles Mosquito
- vector for what
- What are the known effective repellents?
- don’t like what type of environment?
Vector for Malaria
DEET and picaridin are the ONLY effective repellents
Permethrin-treated clothes/nets/curtains
Don’t like cities*
Why are there prevalence differences in the areas where falciparum malaria occurs?
even though falciparum malaria exists in many places, only the places with EFFICIENT VECTORS lead to endemics and threats to human
so the TYPE OF VECTOR plays an important role**
Aedes Mosquito
- vector for
- what environment is is emerging in
- what are the two types
- overtaking malaria as the…
Vector for DENGUE/CHIK/ZIKA/YF
Emerging URBAN VECTOR-BORNE disease
- Very infectious* = Incidence 30X in last 50 years
Dengue vs dengue hemorrhagic fever
Overtaking malaria as leading cause of fever in returning travellers from several places
Dengue Fever vs Dengue Hemorrhagic Fever (DHF)
Despite the name, the critical feature that distinguishes DHF from dengue fever is not hemorrhaging, but rather plasma leakage resulting from increased vascular permeability
Aedes Mosquito
- vector for
- time it bites
- inactive when
- what are the ONLY effective repellents ?
- where do they thrive
Vector for: DENGUE/CHIK/ZIKA/YF
DAYTIME BITERS Only females Inactive below 18° *DEET and picaridin are the ONLY effective repellents* Permethrin-treated clothes/nets/curtains Thrive in cities and elsewhere
Anopheles vs Aedes Mosquito, what are the
- Differences
- Similarities
Differences:
- Time it bites
Anopheles - bites dusk to dawn, night time
Aedes - bites in the DAYTIME - Area of preference
Anopheles - DON’T like cities
Aedes- THRIVE in cities. #citygirls
Similarities 1. only females bite, hehehe 2. INACTIVE below 18 degrees 3. DEET and picaridin are the ONLY effective repellents Permethrin-treated clothes/nets/curtains
ZIKA
- what is it’s vector
- which virus
- why did it get attention
Aedes mosquitos
Flavivirus closely related to Dengue, YF, JEV, SLE
2015-2016: Exploded onto the scene, Americas
Association with rise in microcephaly cases, Brazil
1 Feb 2016: “Public Health Emergency of international concern” WHO
mid-2016: Causal link established for CONGENITAL syndrome
ZIKA infection in adults
Incubation usually 2 to 14 days
Resolves spontaneously
Approx 80% asymptomatic
ZIKA most severe in which type of patients?
- symptoms in these patients
- similar to rubella because…
CONGENITAL ISSUES, i.e. VERTICAL TRANSMISSION
mother infected can have baby with
- seizures, microcephaly, facial distortions, delays in cognitive development
First time we face infectious epidemic teratogen since rubella
How is ZIKA transmited
Primarily vector borne transmission
HOWEVER can also be transmitted SEXUALLY so important to use protection after travelling to high risk countries for atleast 6 months
Where should you check for ticks
- In and around the hair
- in and around the ears
- under the arms
- bra lin
- inside belly button
- groin area
- back of the knees
- any creases
Lyme disease Life Cycle
- what season is risk of human infection greatest?
- In late spring and summer
- these are the BLACK LEGGED ones
This life cycle is more complex
- eggs
- Larva : a distinct juvenile form many animals undergo before metamorphosis into adults in BIRDS AND MICE
- Nymph: dear and other mammals
- Adults: in dear and humans
What is the #1 vector borne disease in NA
Lyme Disease
- southern border of Canada, along american border*
Clinical manifestations of Lyme disease in UNTREATED infections
these are experts at evading immune system so they will manifest as MULTIPLE stages of infection
Early infection
a. localized stage = Erythema Migrans
b. disseminated stage, if untreated = meningitis, bell’s palsy
Late infection
- prolonged arthritis attacks
Treatment of Lyme disease
- word on retreatment?
Give Oral antibiotics THEN Treat symptomatically*
- if they have meningitis give X, carditis give Y, arthritis give Z etc
10% of treated pts continue to have subjective symptoms
MSK, neuro, fatigue, etc.
4 dbpc-RCT = NO BENEFIT FROM MORE ABX
- no such thing as chronic lyme disease? no point in giving MORE treatment, it is ineffective
High complication rate (line infections, PE, allergy, GB, c.diff)
Methods to PREVENT ticks
- to prevent i.e. Lyme disease
Preventing tick bites
- extra vigilance in the summer months
- habit to scan body for ticks latched on
- Avoid direct contact
- Avoid wooded and busy areas with high grass and leaf litter
- walk in the center of trails - Repel Ticks with DEET or PERMETHRIN
- Find and remove ticks from your body
- bath and shower right away
- full body scan
- examine gear and pets
- tumble clothes in a dryer on high heat to kill remaining ticks
Lyme should be considered as able to cause many ______
Lyme should be considered as able to cause many NEUROPATHOLOGIES
Seropositivity is the sine qua non of diagnosis
Antibiotic-Refractory Lyme
- when does it occur
- chronic symptoms?
Antibiotic-refractory Lyme occurs rarely
- No ongoing infection in these cases*
- Strong evidence support auto-immunity (HLA associations, demonstrable sterilization, strain-dependent)
Post-Lyme syndrome (among proven treated cases) must be distinguished from other “Chronic Lyme” suspicions
Lyme Disease is a real infection with:
- known cause
- well characterized diagnostic methods
- effective treatments
Intestinal Nematodes
- list all 5 we learned about
Trichuris Enterobius Ascaris Strongyloides* hookworm
What is special about strongyloides
Stronglyoides needs special consideration
All these nematodes have a life span, if you don’t get re-infected, the worm will get old and just DIE, you’ll be rid of it.
Strongyloides is the EXCEPTION, it will multiply in the human host and NEVER go away. Can become a high burden, especially if you are immunosuppressed
Systemic nematodes
- List the ones we’ve learned about
- Trichinella
- Toxocara
- Filaria
- lymphatic
- Loa loa
- Onchocerca
Intestinal Helminths are what kind of worm?
I THINK
Roundworms
Round Worm Characteristics
- how many larval stages
Round in cross section
Digestive system complete – mouth to anus
Acellular cuticle
Four larval stages
Subcuticular layer of muscle
Separate sexes
Terms: egg (ova)
embryo
larva
adult
Alternative name for Trichuris Trichiuria
Whipworm
(head is the thinner part)
[This is an intestinal nematode under Helmints]
Trichuris trichiura
- Geography
- route of transmission
- Presentation in what organ
Clinical presentation in
Canada VS Tropics
Geography: tropical esp. SE Asia, Phillipines, Dominica
Risk: fecal oral transmission
Presentation: colon
Presentation in
CANADA:
asymptomatic
no eosinophilia
TROPICS [worm load dependent] diarrhea hypertrophic osteoarthropathy * dysentery * prolapsed rectum * iron deficiency anemia
- because: We get eosinophilia when worms are migrating through tissues but NOT when worms are just chilling and livin in the lumen
Life Cycle of Trichuris Trichiura
- Human feces used as fertilizer in soil
- 2-3 weeks in soil before it becomes infective
- humans eat plants the grew in that fecal contaminated soil and get infected themselves
- trichuris then lives in our colons* until we poop again and the cycle continues
Enterobius vermicularis
is what kind of worm
pinworm
Enterobius vermicularis
Geography
Risk
Presentation
Symtpoms in
Canada vs Tropics
Geography…universal
Risk……… small children
Presentation… colon, anus
THE SAME
Canada
asymptomatic
perianal itch
recurrent UTIs
in female children
Tropics asymptomatic perianal itch recurrent UTIs in female children
life cycle of Enterobus
lays eggs at night in perianal folds
eggs become infective in 4-6 hours
eggs can survive in carpet for 2 weeks
eggs laid by adult after 2 months in colon
adult female lives 2-3 months
What can be used to diagnose Enterobius Vermicularis?
aka pinworm
you can use the pinworm paddle
Ascaris lumbricoides
- what type of worm
roundworm
Ascaris lumbricoides
Geography
Risk
Presentation
symptoms in Canada Vs the Tropics
Geography…. World wide in the tropics
Risk………… Fecal oral
Presentation.. small intestine
Symptoms
Canada asymptomatic
Tropics abdominal pains ? malnutrition? small intestine obstruction biliary tree obstruction perforation of intestine suture
Life cycle of Ascaris lumbricoides
18-24 days to embryonate
2-3 mo to start egg production
live 1-2 years
What are the two Hookworms we learned about
Ancylostoma duodenale
Necator americana
Ancylostoma duodenale/ Necator americanum
Geography…. worldwide in tropics
Risk….. Contact with feces contaminate soil
Presentation….
Canada
: asymptomatic
eosinophilia
Tropics
minor abdominal pains
iron deficiency
anemia
malnutrition
Life cycle of Ancylostoma duodenale/ Necator americanum
eggs in human feces
grow in soil
human steps in contaminated soil and gets infected
Difference between roundworms, whipworms and hookworms in terms of AGE of peak intensity
The first two: roundworms and whipworms are feceal oral, so as kids your at higher risk…. as you get older, adults eat less poop so the infection rate is lower in adults
However, hookworms is through contact in the soil, and in this case, adults are as likely to walk bare foot as are children so the risk relative to age is still high in adults.
Strongyloides stercoralis
Geography…scattered tropical
Risk……contact with feces contaminated soil immunocompromised (not AIDS)
HTLV1
Presentation….. Canada asymptomatic dyspepsia cutaneous larva currens eosinophilia disseminated strongyloides
Tropics asymptomatic dyspepsia cutaneous larva currens eosinophilia disseminated strongyloides *chronic diarrhea, weight loss* [the only difference]
Diagnosis for Strongyloides Stercoralis
Diagnosis
Agar plate culture
Serology * [The other ones don’t have serology cause they stay in the lumen ]
THIS ONE does have serology
The actuall disease has to do with disseminating into other parts of the body but its home is the intestine
Treatment
Ivermectin
Albendazole
Disseminated Strongyloidiasis in the Immunocompetent vs immunosuppressed (HTLV1, Steroids etc)
Immunocompetent
limits adults and larvae to submucosa of small intestine
severely limits autoinfective cycle
Immunosuppressed (HTLV1, steroids etc.)
no limit to dissemination of larvae (wandering through body)
larvae carry intestinal bacteria
peritonitis
pneumonitis
meningitis
necrosis of intestine wall
Which two are the larger nematodes that you’d actually be able to SEE passed in the stool?
Ascaris Lumbricoides and pinworm [Enterobius Vermicular]
Trichinosis
NOT a tropical disease. due to poor animal food hygiene
Trichinosis is a food-borne disease caused by a microscopic parasite called Trichinella. People can get this disease by eating raw or undercooked meat from animals infected with the parasite. Often these infected meats come from wild game, such as bear, or pork products.
Two Types of Trichinella
Trichinella spiralis
Trichinella nativa
Trichinella Life cycle
Starts through CONSUMPTION of contaminated food. It multiplies in the small intestine and travels to the STRIATED MUSCLE
(where we bite into when we eat animals) - walrus, pig, human- ANY CARNIVORE
- cooking the meat/vegetables reduces infectivity
Trichinella spp. Reservoir Location Longevity Biology Transmission
reservoir…muscles of all carnivorous
animals (bear, walrus, rat, man, pig)
location…encysted in individual striated
muscle cells
longevity…years
biology…T. nativa resists freezing
transmission…raw meat ingestion
Trichinella spp.
reservoir…muscles of all carnivorous
animals (bear, walrus, rat, man, pig)
location…encysted in individual striated
muscle cells
longevity…years
biology…T. nativa resists freezing
transmission…raw meat ingestion
Trichinella spp.
Classic vs Diarrheic Symptoms
Myopathic (classic)
muscle pain, weakness
fever
edema
CK eosinophils trichinella IgG trichinella IgM positive muscle biopsy EMG abnormal
Diarrheic
diarrhea
no fever*
no edema*
normal CK
eos
trichinella IgG
neg muscle box
EMG normal
Diagnosis of Trichonella
DIAGNOSIS Symptoms Eosinophilia CK Serology biopsy
TREATMENT
albendazole
prednisone
Which is a zoonosis?
Trichinellosis Strongyloides stercoralis Trichuris trichiura Ancylostoma duodenale Enterobius (pinworm) Ascaris lumbricoides
How are HOOKWORMS different form the other ones we learned about?
Most of the other worms mentioned are commensal, they just occupy space and share your meals
HOOKWORM however is DIFFERENT: it bites into the mucousa and LIVES IN YOUR BLOOD
Hence why you get iron deficiency anemia
Why do you get Dyspensia and Eosinophillia with Strongyloides
Eosinophilia: OFTEN present, because it is a continious cycle where it leaves the small bowel (unlike others where it stays in one place
same reason it causes dyspensia
Toxocara canis
- Distribution
- Presenation
visceral larva migrans weakness pruritis rash/uriticaria dyspnoea abdominal pain dizziness cough weight loss fever and EOSINOPHILIA
Toxocara canis (visceral larva migrans) CT Laparoscopy Biopsy Serology
CT…………..scattered hypodense abscess-like
1-7 cm lesions
Laparoscopy…gray/yellow/tan round to “sinuous”
nodules on liver surface
Biopsy……..necrotic eosinophilic granulomas
Serology……sensitivity ~78 %
Which Nematodes have SEVER eosinophil levels
Trichinella
Ancylostoma/Necator Americanum
Toxocara
Fasciola
Which nematodes have NO eosinophil levels
giardia
amoeba
Filariasis
- location
- require WHAT?
Nematoda
Systemic round worms
I.E. Loa, onchocerca, Wuchereria
a roundworm
Adult filaria live in body cavities, lymphatics,
and subcutaneous tissues
larvae (microfilaria) live in blood or dermis
all require an insect or crustaean vector
microfilaria (150-350 µ long) (4 – 10 µ wide)
adults 2 cm – 120 cm, 1mm wide or less
River blindness is caused by?
Filaria- Onchocerca Volvulus
vector: black fly
(all require an insect or crustaean vector)
Wuchereria bancrofti
Brugia malayi
These are a COMMON type of FILARIA that leads to
- lymphatic filariasis elephantiasis
and their vector is mosquito
Clinical presentations of Wuchereria bancrofti
- assymptomatic
- inflammatory - lymphangitis - arms 25%
- legs 11%- epididimitis, funiculitis 42% - ‘filarial fevers’ - orchitis - filarial abscess - Obstructive - elephantiasis
- chyluria
- hydrocoele
- Tropical pulmonary eosinophilia
blood microfilaria
1 – direct examination (thick or thin smear)
2 – Knotts concentration technique
3 – millipore filtration
4 – antigen capture (Wb), PCR
serology
Loa loa
- presentation
Type of Filaris (the blood inhabiting one)
called the “eye worm”
Calabar swelling
Immune tolerance: Age at first infection
Infected as a child, human worm, you develop tolerance
Then it develops as a lot of worms in the blood but immune system does NOTHING because fool us to think it is host
So you get no symptoms. When you get infected as a visitor to endemic area, you develop immune response and symptoms
So we see the infections in adults
But not in kids who have developed tolerance and no symptoms
Onchocerca volvulus
Type of Filaris
“ River Blindness”
VECTOR: black fly
- you get nodules
Hyphae
Filamentous tubular structure with and with or without internal septae
Mycelium
Mycelium
Group of hyphae, often used interchangeably with hyphae
Yeast
Yeast
Unicellular round fungal cells that reproduce by budding
Conidia
Asexual spores of ascomycetes (most pathogenic phylum)
Conidiophore
Specialized hyphae that produce conidia
The Big Two Morphologies
Yeast vs. Mold
Antifungal agents
Antimicrobial agents must exploit differences between microorganisms and humans
Much greater challenge than with bacteria as fungi are eukaryotic and closely related to humans
Ribosomes and DNA replication enzymes are too similar for targetting
First antifungals developed were highly toxic
The three targets of Antifungal Therapy
Cell membrane
Fungi use principally ergosterol instead of cholesterol
DNA Synthesis
Some compounds may be selectively activated by fungi, arresting DNA synthesis.
Cell Wall
Unlike mammalian cells, fungi have a cell wall
List Cell Membrane Active Antifungals
Azoles
Allyamines
Polyenes
Azoles
Inhibit 14 alpha demethylase
Key enzyme to synthesize ergosterol
Toxic intermediates accumulate in the membrane
Allylamines
Inhibit squalene epoxidase early in ergosterol pathway
Polyenes
Binds to ergosterol in membranes
Forms pores allowing cell contents to leak out
Polyenes
Nystatin
Highly toxic – topical only
Amphotericin B deoxycholate
Slightly less toxic but binds cholesterol
Renal failure, severe infusional toxicity
Lipid-based formulations of
Amphotericin
Reduced toxicity by using a lipid carrier intermediate in solubility between ergosterol and cholesterol
VERY expensive but broadest spectrum agents available
Azoles
Yeast only activity
Fluconazole. Very non-toxic.
Yeast and mold activity
Itraconazole is oldest, but has poor absorption and erratic kinetics
Voriconazole, isavuconazole and posaconazole are newest and have excellent anti-mold activity, particularly Aspergillus species.
Toxicities
Hepatitis – all agents – VORI>ITRA>ISA>POSA>FLU
Visual hallucinations and skin cancer with voriconazole
Allylamines
Terbinafine (lamisil)
Primarily used for superficial fungal infections
Most common topically
Oral is also available for extensive infections or nail infections
Can be used synergistically with azoles
Side effect – hepatitis
Antifungal that targets DNA synthesis
5-Flucytosine (5-FC)
A prodrug converted by fungal cytosine deaminase into 5-flourouracil
Inhibits DNA chain synthesis
Type of chemotherapeutic
Toxicity is bone marrow suppression
Only useful in combination therapy for Cryptococcus
Antifungal that targets Cell Wall Active Agents
Echinocandins
Caspofungin, micafungin, anidulafungin
Inhibit synthesis of cell wall β-glucan
Cause cell wall fragmentation
Not active on fungi with low levels of β-glucan
No significant toxicities or differences between agents
IV only
Which antifungals are toxic to the liver?
azoles
Which is the safest antifungal?
the ones that acts against the cell wall: Echinocandins
