Protozoa Flashcards
Life stages of protozoa
Cysts
Trophozoites
Ciliated protozoan infecting humans
Balantidiasis (A pig with hairy balanitis)
Big signet ring shaped protozoan cyst
Blastocystis (Blastoise with a signet ring)
Intracellular gut protozoa
Microsporidiosis (small to fit into cell)
E. hystolytica (and dispar) cyst description
smooth outer membrane
1-4 nuclei
10-15um
chromidial bar or glycogen in immature cells
E.coli cyst description
(coli = cool guy = big)
15-25um
1-8 nuclei
irregular peripheral chromatin
E.nana cyct description
(na na - little kid)
round or oval
1-4 hole like nuclei
7.5-10 um
Giardia egg description
oval shaped
10-15um
2-4 nuclei at one end
S shaped axostyle in middle
Adult giardia description
Falling leaf motility
8 flagella
sucking disc
Which gut protozoa is not killed by chlorination
Cryptosporidium (and similar)
Giardia
Amoebiasis symptoms
Dysentery
Perianal ulceration
Tenesmus
Perianal abscess
Amoebic liver abscess - many smaller abscesses join with chocolate brown pus
(Amy has an anal ulcer and likes chocolate)
Diagnostics for amoebiasis
- microscopy
- PCR
- Antigen detection test
- Serology (only in non-endemic areas)
Treatment for amoebiasis and giardia
Metronidazole + Nitazoxanide (for cyst treatment in non-endemic areas).
Parmomycin (if pregnant) (has mom in it)
Giardia symptoms
- eggy taste and eggy burps
- chronic diarrhoea
- pale greasy stools
Special test for giardia
string test
special test for cryptosporidia
Acid fast - Ziehl-Neilson stain –> bright red appearance
Cryptosporidia treatment
Nitazoxamide, Paromomycin
Relationship between Cryptosporidia and HIV
- HIV blocks TLR4 receptors for innate immunity, worsening Cryptosporidia infection
- Cryptosporidia infected cells express CXCL10 which attracts more T cells to the area, increasing the number of T cells with HIV
Cryptosporidia symptoms in HIV
Chronic (rather than self limiting)
Severe
Extra-intestinal manifestations ( cholecystitis, pancreatitis)
Cause of diarrhoea in Asia/Americas and its treatment
Cyclosporidia/Isosporidia
Can be severe and chronic in immunosuppressed
Can test with duodenal string test
Treat with Bactrim
Source of Toxoplasmosis infection
Cats
Infected meats
Symptoms of toxoplasmosis (in immunosuppressed only)
Neurological symptoms predominant - particularly basal ganglia disease
Pneumonia
EBV like illness (early)
Toxoplasmosis treatment
6 weeks of pyrimethamine, sulphadiazine, folic acid
Vector for Human African Trypanosoma (HAT) aka sleeping sickness
Tsetse fly
Lifecycle of T. Brucei
?No amastigote stage
Epimastigote in tsetse fly
Becomes trypomastigote in tsetse mouth
Trypomastigote is injected into human –> divides in lymph and blood.
Short and stumpy form –> reuptake to tsetse
long and slender form –> sexual reproduction
Can progress to meningoencephalitic stage
Symptoms of T.Brucei
(1st stage) Haemolymphatic stage:
- Chancre develops at the site of the bite -may ulcerate - is a painful lesion
- Fevers, severe pruritis, lymphadenopathy, myalgia, arthralgia, facial oedema, headaches.
- Lymphadenopathy in neck is known as Winterbottoms sign
- Organ symptoms - cardiac, liver, spleen, eyes, endocrine.
(2nd stage) Meningoencephalitic stage
- Convulsions
- Psych symptoms
- Movement disorders
- Sleep disturbance
- Coma
Difference between Gambiense and Rhodeiense subtypes
Rhodeiense = rapid (1 week), high fevers, chancre, more organ symptoms, more trypanosomes in blood. Has zoonotic reservoir.
Gambiense - gradual (weeks-months), low fevers, less chancre, lymphadenopathy, more trypanosomes in LN. NO zoonotic reservoir.
Cause for T.Brucei not being cleared by immune system
- reservoir in skin
- immune evasion methods with variant surface glycoproteins (VSG) which keep changing
- mosaicism
ALSO cannot have vaccine for these reasons
Diagnostics for T.Brucei
- thick and thin film
- LN biopsy
- LP + CSF
- BMAT
- chancre biopsy
- centrifuge - microhaematocrit - trypanosomes in buffy layer
- Quantitative buffy coat
- Card agglutination test
(Buffy the trypanosome slayer)
Treatment for T. Brucei Gambiense
Non-CNS and >6yrs - Fexinidazole
CNS - NECT (combination therapy)
<6 years - Pentamidine (less than 6 is 5 (pent))
Treatment for T. Brucei Rhodeiense
Non-CNS - Suramin
CNS - Melarsoprol (Arso - Arsenic)
Follow up for stage 2 HAT
6 monthly LPs for 2 years
Tsetse fly description
hatchet cell wings
upward probiscus
striped thorax
Vector for Chagas disease and method of innoculation
Rudviig bug - Triatomine
Another host is mammals/ Sylvanian creatures
Bug defecates after biting - scratching faecal matter into wound or touching eye causes disease.
Distribution of Chagas
Central and South America (also worldwide)
Lifecycle of T.cruzi
Epimastigote within Triatomine bug
Trypomastigote enters human
Trypomastigote moves intracellularly and differentiates into amastigotes which replicate
Amastigotes maturing into trypomastigotes causes cell lysis and release if infection
T. cruzi appearance
C-shaped
darker
larger
large kinetoplast
Chagas symptoms
Acute:
- Romana sign (eye)
- Chagoma
- fever, fatigue, headache, diarrhoea
Chronic:
Silent cardiomyopathy
mega-oesophagus
mega-colon
Diagnostics for T.Cruzi
PCR
Buffy coat microscopy
Serology
Treatment for T.cruzi (including who and why)
Benznidazole or Nifurtimox
- only treat asymptomatic patients, women of child-bearing age and children
- symptomatic patients have high risk of drug side effects - derm reactions, peripheral neuropathy.
Vector for leishmaniasis
Biting sandfly (bites at night)
Life cycle of Leishmaniasis
Promastigote in sandfly
Enters human - moves intracellularly (PHAGOCYTIC CELLS ONLY)
Becomes amastigote form and divides in cell
NO trypomastigote form
many animal reservoirs
Types of leishmaniasis
Cutaneous (and mucocutaneous) Leishmaniasis - Baziliensis and Mexicana
Visceral Leishmaniasis - Donovani
Symptoms of cutaneous Leishmaniasis
Incubation is months
Lesion with raised edges and satellite lesions
Distant lesions from lymphatic spread
10% have highly destructive mucocutaneous lesions (braziliensis)
Chiclero’s ear - mexicana type
Which type of cutaneous leishmaniasis relapses?
Mexicana
Investigations for cutaneous leishmaniasis
Skin scraping/biopsy
Histology
PCR - genus specific testing available
Reservoir for Visceral Leishmaniasis
Zoonotic reservoir
Human skin reservoir - infection can be present in skin without visceral involvement - can later become active. May have false negative tests.
Incubation for visceral leishmaniasis
Can be up to 2 years - more acute in migrants
Symptoms of visceral leishmaniasis
Fever
Weight loss/ cachexia
Massive hepatosplenomegaly
lymphadenopathy
diarrhoea
cough
pigmentation changes
Investigations for visceral leishmaniasis
organ biopsy
histology
culture
PCR
DAT - direct agglutination
Immunofluorescence - becomes negative 9 months post treatment
Major complication of Visceral Leishmaniasis
Post Kala Azar dermal leishmaniasis
- occurs due to the dermal reservoir
- leads to large nodular lesions - usually on the face
- mainly seen in Sudan and India
Cutaneous Leishmaniasis treatment
Sodium stibogluconate or Miltefosine
IM or IV for 10-20 days
Visceral Leishmaniasis treatment
PO miltefosine
IV liposomal amphotericin
IV/IM pentavalent antimony
Distribution of each type of malaria
Falciparum - Africa + the tropics
Vivax - South america, SE asia
Ovale - West Africa
Malariae - tropics and sub tropics
Knowlesi - SE asia
Which cell type is infected in malaria
erythrocytes
Malaria life stages
Sporozoite = parasite stage - passes from mosquito to human
Schizont = host cell containing mature parasites
Merozite = parasite released from liver cell
Trophozite = developing parasite in blood cell
Gametocyte = sexual stage of parasite life
Hypnozoites = dormant stage
Malaria life cycle
- Exo-erythrocytic stage
- sporozoites infect liver cells
- schizonts form (some dormant hypnozoites)
- cells burst releasing merozoites - Erythrocytic stage
- immature trophozoite
- mature trophozoite –> then becomes:
a) schizont - bursts RBC and merozoites release to restart the cycle
b) gametocytes form which are taken up by mosquito blood meal - Sporogonic stage
- within mosquito
Symptoms of malaria
cyclical fevers - usually every 3 days
rigors
myalgia
headaches
Signs and symptoms of severe malaria
Prostration (exhaustion) / CNS symptoms
respiratory distress
Acidosis/AKI
Jaundice/hyperbilirubinemia
Bleeding / Severe anaemia <70 / splenomegaly/ splenic rupture
Hypoglycaemia
High lactate
High parasitemia
Malaria treatment
Falciparum:
Non-severe: ACT = Artesunate-mefloquine
Severe: IV artesunate (Quinine is 2nd line)
Non falciparum:
Chloroquine (only in non-falciparum)
PO or IV 3 days
2nd line (in resistance areas):
artemether-lumefantrine (Coartem)
OR
dihydroartemisinin-piperaquine
Hyponozoites: Add Primaquine day 3 (avoid in G6PD and pregnancy)
1st trimester pregnancy - Quinine
May also need to consider supportive therapies, ABx
Complications of malaria in pregnancy
- pregnancy increases attractiveness to mosquito (more CO2 release)
- more severe disease - mild pregnancy related immunosuppression.
- anaemia
- reduced foetal growth/ low birth weight
- specific malaria parasites grow in the placenta - causes vascular changes and reduced O2/ nutrient transfer. Parasites in the placenta have variable surface antigens (VSG) so avoid immune detection and clearance. (1st pregnancy with malaria most severe)
- increase risk of foetal loss (3-8%)
WHO treatment frameworks for malaria in pregnancy
High incidence
1. Case management
2. ITNs
3. IPTp (intermittant preventative treatment in pregnancy)
- Sulfadoxine/pyrimethamine (SP) monthly (Bactrim if HIV+)
Low incidence
1. Case management
2. ITNs
3. Screen and treat
How does malaria cause disease
Malaria parasites change the cell structure to something more rigid with outer nodules - this leads to sequestration of the RBCs and consequent cytoadherence and microvascular coagulopathy.
There may also be further involvement of cytokines - unclear.
Malaria diagnostics
Thick and thin microscopy
Buffy coat
Rapid antigen tests
PCR - finger prick is best due to most parasites in the capillaries
ELISA
Features of thin film in Falciparum
- delicate structure
- double chromatin
- multiple infection
- normal sized RBC
- crescent shapes gametocytes
- single stage
- Maurer’s clefts
- accole forms
Features of thin film in vivax
- schuffners dots
- enlarged RBCs
- amoeboid cytoplasm
- single infections
Features of thin film in ovale
- schuffners dots
- enlarged RBCs
- single infections
- fimbriae
- 8-12 merozoites
Features of thin film in malariae
- normal sized RBC
- single infections
- band forms (streaky bacon form)
Retinal changes in malaria and their importance
Retinal changes are important as it reflects what may be occurring in the CNS.
Malaria pathology is largely due to RBC sequestration and microhaemorrgahes.
Retinal changes
- papilloedema
- vessel whitening
- retinal cotton wool spots
- retinal haemorrhages
When should you give a blood transfusion in malaria
Low transmission setting: Hb <70 or any Hb if decompensated
High transmission setting: Hb <50 or any Hb if decompensated
Complication of malaria
black water fever
Which drug(s) work on stages of malaria besides the blood stage?
Artesunate - works on gametocytes
Primaquine - works on hypnozoites
Anti-folates - work on liver stage
Artesunate MOA
Iron binding leads to endo-peroxide bridges and free radicals
Chloroquine side effects
- arrhythmias
- neurotoxicity
- avoid in epilepsy
Quinine Side effects
- QT prolongation
- deafness
- HYPOGLYCAEMIA
Artesunate side effects
post artesunate delayed haemolysis
Whats is the ABCD of malaria prophylaxis
A - awareness
B - bite prevention
C - chemoprophylaxis
D - Diagnosis
Which malaria prophylaxis can be used in pregnancy?
Mefloquine
Chloroquine
Malarone pros and cons
Cant be used in pregnancy currently
GI upset
LFT derangement
Mefloquine pros and cons
Have to take for 28 days post
Neuro psych SE
cant be used in epilepsy
doxycycline pros and cons
Cant be used in children or pregnancy
photosensitivity
GI upset
take 28 days post return
Chloroquine pros and cons
epilepsy
psoriasis
Primaquine pros and cons
IPT (intermittant preventative treatments) for malaria
Pregnancy (IPTp) - 3 doses of sulfadoxine-pyrimethamine - 4 weeks apart in 2nd and 3rd timesters
Infants (IPTi) - SP at the time of 2nd and 3rd DTP and MMR vaccines
Seasonal malaria chemoprevention (SMC) - for children <6 year - SP given monthly during season.
Difference between stable and unstable malaria
Stable malaria = unaffected by natural and man-made changes
- is VERY difficult to control as moderate changes to mosquito populations do not make a difference
Unstable malaria = very sensitive to environmental changes and man-made controls.
Retinal changes in malaria
Retinal whitening
cotton wool spots
retinal haemorrhage
vessel changes
Difference in hospital admissions/severe malaria in high transmission settings and low transmission settings
High transmission - hospitalisation mostly in children <5
Low transmission - hospitalisation/severe malaria spread throughout the age groups.
How is malaria controlled in the body
infected RBCs are taken up by dendritic cells.
Dendritic cells present infected RBC proteins in lymph node
Adaptive immunity activated.
Malaria largely controlled by antibody response
How does malaria avoid elimination
- Sequestration prevents infected RBCs being destroyed by the spleen.
- Plasmodium falciparum erythrocyte membrane protein 1 (PFEMP1) has high antigenic variation - body must keep adapting its antibody strains.
- Merozoite antibodies only have a very small window of time.
Current malaria vaccine mechanisms
Uses circumsporozoite protein (CSP) bound to Hep B antigen
Concentration methods for trypanosomes
Thick film
Woo concentration - centrifuge then buffy coat
Quantitative buffy coat
CNS Toxoplasmosis presentation
Retinal changes
Ring enhancing lesions on MRI
Treatment for toxoplasmosis CNS disease
Pyrimethamine + Sulphadiazine or Clindamycin + Folic acid
Antiepileptics
Steroids
when to treat iron deficiency anaemia in Malaria
After malaria has been treated - iron replacement can make malaria worse.
Haemaglobinopathies protective in malaria
G6PD
Sickle cell
Drugs which trigger G6PD
Triggering drugs - primaquine, sulfa drugs, nitrofurans.
What are the stages in making an area malaria free?
- Control
- A. Optimise vector control and case management
- Pre-elimination
- B. Increase sensitivity and specificity of surveillance
- Elimination
- Reduce transmission through population wide parasite clearance strategies
- Investigate and clear individual cases and manage follow up
- Prevention of reintroduction
What is SUFI
Sufi = scaling up for impact
Is a method implemented to reduce malaria by scaling up existing control measures.
The amastigotes of which species is found in muscle tissue?
T. cruzi
Periodicity in malaria
all are 48hrs except malariae which is 72hrs
