Malaria Flashcards
Which disease transmission intensity can be measured by rates of splenomegaly? Other infections commonly causing massive splenomegaly?
- Malaria - hyperreactive malarial splenomegaly (due to recurrent infections)
- Schistosomiasis, visceral Leishmaniasis
hyperreactive malarial splenomegaly pathophysiology? Sx? Who is it dangerous in?
- Repeated infections -> overproduction on IgM. These removed by spleen which enlarges
- Spleen >10cm below costal margin, anaemia, abdo discomfort
- Pregnant - may get acute haemolysis
Hyperreactive malarial splenomegaly diagnosis? How to differentiate from lymphoma? Rx?
- Spleen >10cm below costal margin and reduces in size by 40% on antimalarial treatment
- Younger (usually <40) lymphocyte count more normal
- Chloroquine
Where has >90% vivax? Falciparum?
- Central America/ West Coast South America/ China
- Falciparum - Sub saharan Africa
Malaria life cycle. Form injected and what do these do?
Which infects RBCs?
Which is taken up by other mosquitos? Life cycle within mosquitos? How long does it last?
What form in only vivax and ovale?
- Sporozoites - infect hepatocytes and mature into schizonts (containing merozoites) which rupture.
-[Vivax and ovale some from this initial infection form hepatic hypnozoites] - Merozoites infect RBCs (as these mature in RBC form immature ring shaped trophozoites which go on to either
Produce:
- Gametocytes (male and female) taken up by mosquitos ) - to form ookinite then oocyst then oocytes in anopheles gut wall
- 10 days
Or Form mature trophozoite in RBC which turns into RBC shizon which then ruptures releasing more merozoites
- Hypnozoites
Why is falciparum more severe?
- Cytoadherance - Bind to endothelial cells in capillaries of organs -> prevents effective removal of infected cells by spleen
- Increased sequestration
- Also replicates faster
Which rbc antigen protects against vivax
- Duffy negative
Aspects of severe Malaria
Any 1 of:
- Anaemia <70g/L together with parasite count>10,000/µL
-or <50g/L in kids - Acidosis pH <7.3, bicarb <15, lactate >5
- Hypoglycaemia <2.2 mmol (<40 mg/dl)
- seizures >2,
- GCS <11
- Renal impairment Cr >265µmol/L (3 mg/dL)
- Bilirubin >50 µmol/L (3 mg/dL) together with a parasite count>100,000/µL
- Pulm oedema
- Shock (<80mmHg)
- Bleeding
- Hyperparasataemia >10%
- Black urine
Name 2 contributing factors for hypoglycaemia in Malaria
- Impaired hepatic gluconeogenesis
- Glucose consumption by parasites
- Quinine - stimulates pancreatic insulin secretion
Seen on fundoscopy of cerebral Malaria
White patches on retina (due to focal ischaemia) and haemorrhage
white-centred haemorrhages, a superficial blot haemorrhage at the fovea, mild macular whitening (black arrow) and cotton wool spot (white arrow)
Which Malaria can cause malarial nephrosis in children?
- P malariae
- Immune complex - Causes nephrotic syndrome that Doesn’t respond to steroids or Malaria eradication
Rbc on slide - looks like pair of headphones inside is typical of ?
Falciparum - actually 2 chromatin dots
Thick and thin blood films mainstay of dx for Malaria. Rapid diagnostic test can be used. What might a RDT look for? Which one specific to falciparum?
- pLDH (plasmodium LDH)
- HRP-2 (histidine rich protein 2) - falciparum
Which antimalarial most potent (fastest drop in parasite count)? Why often given in combination? Example Combination?
- Artensunate
- Can be given IV PR or oral
- Short half life *1hr and so often used in combination with other drugs ‘arteminism combination therapy’ as otherwise would need 7 day course.
- Artemether-lumefantrine
Which Quinine no longer recommended for p falcipaum
Chloroquinine - high levels of resistance
Which antimalarial for vivax and ovale in addition to choroquine? What do you need to screen for
- Primaquine 30mg for 14 days (15mg for ovale)
- G6PD
Rx of uncomplicated faciparum?
Artemisinin combination therapy 3-days
Eg Artemether/Lumefantrine
Rx severe falciparum
IV artesunate
Malaria in pregnancy rx
Still ACT
A-Lumefantrine first line
[But not A-co-trimox or A-pyronaridine]
Best evidence vector control for Malaria (2 things)
- Insecticide treated nets
- Residual indoor spraying
Malarone is? How does it work? How does this affect length of treatment when used for prophylaxis?
- Atovaquone-proguanil
- Prevents formation of schizonts ‘causal prophylaxis’
- Most other agents kill blood stage schizonts - ‘suppressive prophylaxis’
- Therefore only need Malarone for 1 week after leaving but others need to keep taking for 1 month
Malaria vector
Anopheles
Malaria reservoir
Humans
Where does the sexual multiplcation of malaria take place
In mosquitos -> form sporozoites
Called when fusion of male and female gametocyte in malaria ? type of genome
Zygote (diploid genome)
[This penetrates gut wall and produces oocyst]
Trophozoites which mature in RBCs which type causes:
-Schüffner’s dots:
- Ziemann’s stippling:
- Sinton and Mulligan’s stippling:
- Maurer’s clefts:
Schüffner’s dots: P. vivax and P. ovale; enlarge RBC
- Ziemann’s stippling: P. malariae
- Sinton and Mulligan’s stippling: P. knowlesi
- Maurer’s clefts: P. falciparum
What is the brown pigment seen in RBCs infected by malaria
haemozoin
Types of malaria and how often fevers after initial attack?
[all are daily at first)
Knowlesi - Daily
Vivax, falciparum, ovale - every 2 days
P malarea - every 3 days
Fever causes the synchronisation of erythrocytic schizogony
Which Malaria has trophozoites which disappear from blood after 16-24hrs?
Faliparum - sequestered in endothelial capillaries via cytoadherence due to PfEMP-1
[You will still see ring trophozoites and gametocytes]
2 parts of sequestration and proteins
Adherence between endothelial lining cells (ICAM-1,
intercellular adhesion molecule-1)
[I cam adhere]
knob-like projections on infected RBC surface (PfEMP-1, Pf-erythrocyte membrane protein-1): Cytoadherence.
[Pfemp through]
how many parasites to see malaria on thick film
50/microL
What 2 things can merozoites become
majority → schizonts (merozoites) (asexual)
- few → gametocytes (sexual)
Define
Patent parasitemia.-
Sub-patent parasitemia.-
Pre-patent period.-
Patent parasitemia.- Parasitemia detected by optic microscopy
(≥50 p/µL)
Sub-patent parasitemia.- Parasites present in the blood but not detected by optic microscopy (<50 p/µL)
Pre-patent period.- Time between infection and patent parasitemia
Recrudescence is? Seen in?
Renewed detection of parasitemia arising from
survival of undetectable erythrocytic parasites (persistent
undetectable parasitemia):
P. malariae, P. falciparum, P.knowlesi, drug resistant P.vivax.
What are hypnozoites also called?
exo-erythrocytic malaria parasites
What is pyrogenic density? Who is it lower / higher in?
Level of parasitemia at which fever occurs
Lower in nonimmunes (<10 000 Pf/µL)
- Higher in immunes (tolerate up to
100 000 Pf/µL).
As infection continues your PD will increase slightly - ie will have asymptomatic parasitaemia
2 ways of malaria transmission
Bite from anopheles
Inoculated with RBC eg transfusion / needles …
Congenital
Malaria Hypo vs meso vs hyper vs holoendemic
Hypoendemic: Spleen rate (SR) or parasite rate (PR)
≤ 10% in children 2-9 yo.
Mesoendemic: SR or PR 11-50% in children 2-9 yo.
Hyperendemic: SR or PR consistently over 50% in children
2-9 yo.
Adult spleen rate is also high (>25%).
Holoendemic: SR or PR consistently over 75% in children
2-9 yo.
Adult spleen rate is low.
Parasitaemia rate in infants < 1 yo is high (> 75%)
What is introduced malaria
Secondary cases acquired locally, but derived from imported cases. ie malria traveller infects mosquitos in new area
What is Authochthonous malaria
contracted locally
Premunition in malaria is? how long does it last?
State of partial immunity
- Due to continuous exposure of infective bites
- Tend to have asymptomatic parasitaemia
After 6m loss of exposure -> loss of this partial immunity
Why do babies not tend to get malaria for first 3-6 months
Maternal IgG protects
Then risk of high levels parasitaemia and death while still an infant
OR develop premunition
Which deficiencies protect against malaria ? relevance
Iron KEY [riboflavin and PABA]
Iron supplementation in people who DONT have iron deficiency is assoc with increased risk of malaria
Ie STILL GIVE iron if iron deficient
Duffy is
Duffy NEGATIVE genotype: RBC lacking Ags Fya and Fyb
Resistance to Vivax [very little vivax in west Africa]
name 3 protections against severe malaria
Hb S
Hereditary ovalocytosis
Duffy negative antigen
Thalassemia
G6PD deficiency
Hemoglobinopathies
HLA changes
Protect against cerebral/severe malaria
Flight range of anopheles
2-3km - Bit may end up on plane or ship
What affects sporogony in malaria
- Duration of the sporogony:
Optimum conditions: 25o- 30oC
Mean relative humidity ≥ 60%.
Sporogony: Ceases at To < 16oC
Slows down considerably at To > 35oC
Needs rainfall
2 key features of vivax in infected RBC
Enlarged as only invades reticulocytes
Caveolae in RBC membrane: Schüffner’s dots.
2 people who cant get primaquine
Need to screen for G6PD
[doesn’t occur much in Peru and so just given Rx]
Also don’t give during pregnancy
Pregnancy and malaria risk which pregnant women have the worst time? What happens
Young and primigravid
Increased severe anaemia
Sequestration in placenta
Key issue with falciparum and preg? why? Why not in multigravida?
Sequestration in placenta
Parasites in placenta express variant surface Ags
(VSAs) → cytoadhere to chondroitin sulphate A (CSA)
Multigravids - Develop antibodies to VSA
How long does risk of severe malaria last for pregnant women
8-10 weeks post-partum
Issues for babies with malaria-infected pregant mothers
70% of IUGR
35% of preterm delivery worldwide
Stillborn / Miscarriage
Anaemia of newborn
Long term risk of chronic diseases in later life
Uncomplicated P malariea Rx
3 days chloroquine
Uncomplicated P vivax rx
3 days chloroquine
7 days primaquine
In G6PD how can you give primaquine
Low dose 45mg instead of 210mg and only given weekly for 8 weeks
Why combination therapy in p falciparum
More effective
Less development of resistance
How long in ACT for p faliparum uncomplicated
3 days usually
[When combined with rapidly eliminated compounds
(tetracyclines, clindamycin), a 7-day course of treatment is
required.]
Why primaquine in flaciparum
Kills gametocytes
Most common ACT for uncomplicated falciparum
Artesunate
Lumefantrine OR Mefloquine
for 3 days
[+ Single dose primaquine often used for gametocytes]
1st trimeter uncomplicated falciparum
ACT
Why only primaquine after 6m old
hypnozoites only if infected by bite - Ie not from maternal blood
Falciparum Malaria in returning traveller Rx options
Atovaquone/proguanil 4 tabs qd X 3 or
Artemether/lumefantrine bid X 3 days
[or Quinine x 3 days, + doxycycline x 7 days]
P vivax in returning traveller Rx uncomplicated ? When different?
Chloroquine for 3 days + Primaquine 30 mg (base) po X 14d.
Papa new guin/ Indonesia -> treat as falciparum
Drug that can be used as a single dose for vivax Hypnozoites (but rarely available
Tafenoquine
When does anopheles bite
Night
When does anopheles bite
Night
When does anopheles bite
Night
What stage of malaria life does Malarone act on when used for prophylaxis?
Atovaquone-proguanil acts on hepatic schizonts during initial infection
When do doxycycline, mefloquine, and chloroquine act on malaria life cycle
Blood-stage schizonticides interrupt schizogony within red cells
[malarone does too but also on shizonts]
What is reccomended first line test in US for malaria
RDT: Binax card test - Antigen detection
[Only good sensitivity is for falciparum]
Which Malaria fever
Quotidian
Tertian
Quatan
Quotidian - knowlesi (daily)
Tertian - vivax falciparum ovale
Quatan - malariae 3 days
P. knowlesi usually georgraphy? mistaken for? rx?
South east asia [Monkey malaria]
Looks similar to p malariae on blood film
VERY sensitive to all antimalarials
Which malrial prophlyaxis can be used 1/week? Side effects?
Mefloquine (and for 4 weeks post travel)
Insomnia, vivid dreams, and anxiety in some patients
Where are 95% of malaria deaths? Who makes up loads of them?
Africa
Children <5 80%
Malria definitive vs intermediate host
Def - mosquito
Intermediate - human
Which malaria commonly has chronic infection (doesn’t kill you)
Plasmodium malariae
P falciparum affects what age RBC ?
Whats found in peripheral circulation
Key things found on RBC?
Pre-patent / incubation period
All ages of RBCs infected - normal size
- Usually only rings and gametocytes in the
peripheral circulation Ie Shizonts are rare
-unless very heavy burden - Characteristic Maurer’s clefts and appliqué forms
- Prepatent period 9-11 days
- Incubation period 9-14 days
What does vivax require to bind
duffy antigen
Prepatent perior of vivax
11-13 days
Pre patent period ovale
10-14 days
P malaria infects which RBCs? Parasitaemia ?
Fever cycle?
Associated with?
- Infects old RBCs - smaller
Parasitemia less than 1% - Quartan cycle (72 hours)
Long-lasting, chronic infection of senescent RBCs
Nephrotic syndrome
Which malarias have high parasitaemia
Falciparum
Knowlesi
Knowlesi infects which rbcs ? looks similar to? differentiate?
All RBCs
24 hour fevers
Looks like p malaria (mature trophozoites)
PCR
What temp is too cold for anopheles
<18
How does p faliparum get in and cause adhereance?
- RBC surface knobs (PfEMP1: major protein)
- Adhesion of RBC to the endothelium of capillaries &
venules (receptors: CD36, ICAM-1, CSA…)
Formation of rosettes with uninfected cells
What does cytoadherance and rosetting lead to?
poor tissue perfusion
organ dysfunction, anaerobic glycolysis and lactic acidosis
immune evasion
What is a rosette? Significance?
binding of two or more uninfected red blood cells (rbc) to an infected rbc
promotes RBC sequestration in the microvasculature and is associated with severe malaria
Rings of P. falciparum in a thick blood smear
Rings of P. falciparum in a thick blood smear
Rings of P. falciparum in a thin blood smear.
Rings of P. falciparum in a thin blood smear.
Malaria life cycle
Rings of P. falciparum in a thin blood smear.
iRng-form trophozoites of P. falciparum in a thin blood smear, exhibiting Maurer’s clefts.
Ring-form trophozoites of P. falciparum in a thin blood smear, exhibiting Maurer’s clefts.
Ring-form trophozoites of P. falciparum in a thin blood smear, exhibiting Maurer’s clefts.
Trophozoites of P. falciparum in a thick blood smear…
Apparently
Trophozoite of P. falciparum in a thin blood smear
Trophozoite of P. falciparum in a thin blood smear
Trophozoite of P. falciparum in a thin blood smear. In this figure, a gametocyte can also be seen in the upper half of the image.
Trophozoites of P. falciparum in a thin blood smear.
Gametocyte of P. falciparum in a thick blood smear. Note also the presence of many ring-form trophozoites.
Gametocytes of P. falciparum in a thick blood smear.
Gametocyte of P. falciparum in a thin blood smear. Also seen in this image are ring-form trophozoites exhibiting Maurer’s clefts.
Gametocyte of P. falciparum in a thin blood smear. Also seen in this image are ring-form trophozoites and an RBC exhibiting basophilic stippling (upper left).
Gametocyte of P. falciparum in a thin blood smear, showing Laveran’s bib. Also seen in this image are ring-form trophozoites exhibiting Maurer’s clefts.
Schizont of P. falciparum in a thin blood smear.
Schizont of P. falciparum in a thin blood smear.
Ring-form trophozoites of P. knowlesi
Band-form trophozoite of P. knowlesi
[looks same as malariae]
Mature schizont P knowlesi
Ring-form (lower right) and developing (upper left) trophozoites of P. malariae
[Just need to be able to spot there’s something there on thick film]
“Birds-eye” trophozoite of P. malariae in a thin blood smear.
Ring-form trophozoite of P. malariae
Band-form trophozoite of P. malariae
Band-form trophozoite of P. malariae
Basket-form trophozoite of P. malariae
Gametocyte of P. malariae in a thin blood smear.
Schizont of P. malariae in a thick blood
Schizont of P. malariae in a thick blood
Schizont of P. malariae in a thin blood smear.
Ring-form trophozoites of P. ovale in a thin blood smear. Note the multiply-infected RBC
Trophozoite of P. ovale in a thin blood smear. Note the fimbriation
Trophozoite of P. ovale in a thin blood smear. Note the fimbriation and Schüffner’s dots.
Trophozoite of P. ovale in a thin blood smear. Note the fimbriation and Schüffner’s dots.
Trophozoite of P. ovale in a thin blood smear.
Just need to spot there’s Malaria here as its a thick film
[Gametocyte of P. ovale (red arrow) nestled between two white blood cells in a thick blood smear.]
Microgametocyte of P. ovale in a thin blood smear. Note the elongated, oval shape and the Schüffner’s dots.
Macrogametocyte of P. ovale in a thin blood smear. Note the fimbriation.
Macrogametocyte of P. ovale in a thin blood smear, showing Schüffner’s dots.
Macrogametocyte of P. ovale in a thin blood smear. Note the fimbriation
Schizont of P. ovale in a thin blood smear. Notice the fimbriation.
Ring-form trophozoites of P. vivax in a thin blood smear
Ring-form trophozoites of P. vivax in a thin blood smear.
Trophozoites of P. vivax in a thin blood smear. Note the amoeboid appearance, Schüffner’s dots and enlarged infected RBCs
Trophozoites of P. vivax in a thin blood smear. Note the amoeboid appearance, Schüffner’s dots and enlarged infected RBCs
Trophozoite of P. vivax in a thin blood smear. The infected RBCs are also noticeably larger than the uninfected RBCs.
Trophozoite of P. vivax in a thin blood smear. Note the band-like appearance of the trophozoite in this figure that may be mistaken for a band-form trophozoite of P. malariae. Note, however, the fine, light brown pigment that is distributed throughout the cytoplasm (pigment in P. malariae is usually darker and coarser and distributed on the periphery of the cytoplasm). The infected RBCs are also noticeably larger than the uninfected RBCs.
Macrogametocytes of P. vivax in a thin blood smear. Note the enlargement of the gametocytes compared to uninfected RBCs.
Macrogametocytes of P. vivax in a thin blood smear. Note the enlargement of the gametocytes compared to uninfected RBCs.
Macrogametocytes of P. vivax in a thin blood smear. Note the enlargement of the gametocytes compared to uninfected RBCs.
Macrogametocytes of P. vivax in a thin blood smear.
Ookinete of P. vivax in a thin blood smear.
Ookinete of P. vivax in a thin blood smear.
Schizont of P. vivax in a thin blood smear.
Schizont of P. vivax in a thin blood smear.
Ruptured schizont of P. vivax in a thin blood smear, showing free merozoites and pigment.
Vivax male gametocyte
Chromatin pulled together
Falciparum - Rings and Maurer’s cleft on a thin smear
shizont falciparum
vivax - Ameboid trophozoite and Schüffner’s dot
vivax shizont
vivax gametocyte
Ovale Trophozoite and Schüffner’s dot, fimbriated RBC
Ovale Schizont and Schüffner’s dot
ovale - Gametocyte and Schüffner’s dot
malariae - Trophozoites band basket forms
malariae Schizont, rosette pattern
malariae - gametocyte
Really sick
knowlesi - Mature trophozoite band form
knowlesi - Schizont, rosette pattern
Babesia microti
- Pleomorphic (vary in shape and size) and do not produce pigment.
* Tetrad forms (Maltese cross)
* Extracellular forms
