Malaria Flashcards
In endemic countries for malaria, if a patient presents with complicated malaria, what do you suspect?
HIV
What is terminal prophylaxis?
P.Vivax prophylaxis in its entirety
Take malarone or equivalent when abroad, and then when get home take 14 days of primaquine (no G6PD def) to kill the hypnozoites
Which species is most prominent in Malaysia?
P. knowlesi.
Primate malaria, Zoonosis, All ages of RBCs infected, Increasingly reported in SE Asia. Most cases are mild, Appearance similar to P. malariae
What is the WHO recommendation for a slide to be pronounced negative for malaria?
Slide can be pronounced negative only when a minimum of 100 fields have been carefully examined for the presence of parasites (THICK) and 800 fields (THIN)
What is the definitive host for malaria? What is the intermediate host? What is the reservoir?
Female mosquito. Human. Male mosquito.
What information do you need to know before starting somone on treatment for malaria?
Strain, clinical status of patient, previous Rx, pregnant or not, resistance
Why can ACT not be used for prophylaxis and why is it effective as a treatment for malaria?
act rapidly on blood phase - has a very short half life and so not appropriate as propylaxis
What protective factors are there against malaria?
Iron deficiency, Hbopathy
What types of recurrence are there in malaria?
- Recrudescence - Ineffective initial treatment. Renewed detection of parasitemia arising from survival of undetectable erythrocytic parasites
- Relapse - Renewed detection of parasitemia arising from survival of exo-erythrocytic parasites (Hipnozoites) (no surviving erythrocytic parasites): P.vivax, P. ovale.
- Reinfection- Renewed detection of parasitemia arising from a new infected mosquito bite.
What are the advantages of a RDT for malaria?
Quick - 20mins, does not need expertise, got sensitivity for falciparum
Which drug should you give patient who Is pregnant to Rx uncomplicated falciparum?
Artemethur-lumefantrine
Why is missing one single dose of doxy significant?
Short acting drugs, so miss a day the sporozoites can get into the liver and wait there (doxy only works in blood stream)
Antimalarial prophylaxis if a person is travelling and has HIV?
Doxycycline or chloroquine
Child on efavirenz/nevirapine or zidovudine - which anti malarial not to use?
artesunate/amodiaquine - risk of hepatitis and severe neutropenia
WHO GUIDELINE
Name the 6 species of malaria
vivax, ovale curtisi, ovale wallikeri, malariae, knowlesi, falciparum
What other tests can be used in malaria?
Serology - not routine
PCR - good for low parasitaemia and differentiate species
LAMP - good in non endemic setting
Alternative to primaquine in P.Vivax?
Tafenoquine
What are HIV patients at increased risk of with severe malaria?
Severe anaemia
What level parasitaemia is characterised as severe malaria?
> 2% in non immune, >10% in endemic, CDC says >5%
Which structure and species is this?
Schizont with Schuffners Dots, P.Ovale. Note Pacman ghost appeatance and irregular RBC outline
Child with suspected severe malaria - management immediately?
Pre-referral treatment with rectal artesunate in children
Apart from antimalarials, what else do you give in severe malaria?
IV antibiotics to cover gram negatives (gut translocation)
What are these?
P.Vivax Gametocyte (also here)
Why is Vivax not in Africa?
Duffy antigen
At what level parasitaemia does mortality start to increase?
low transmission setting: mortality begins to increase at
a parasitaemia of 100 000/ul (2%)
Artemethur-lumefantrine interacts with which HIV drugs? Which HIV drug does not interact with A-L?
Efafivinz, nevirapine
Liponavir/riponavir
USE DOLUTEGRAVIR!
HIV test when patient has malaria, problem? What to do?
False positive!
Test for HIV when doesn’t have malaria
What is induced malaria?
Acquired by blood transfusion/needles/transplant
What structure is taken up by mosquito during a blood meal from a malaria infected patient?
Gametocytes - reproduce sexually (sporogony) in intestine of anopheles. Microgametocytes and macro gametocytes taken up. Becomes ookinete then oocyst -> ruptures into lots of sporozoites. Sporozoites then move to salivary gland, and can be transmitted to humans when mosquitos take a blood meal
What is the pyrogenic density?
level of parasitaemia at which fever occurs
Lower in nonimmunes (<10 000 Pf/µL)
Higher in immunes (tolerate up to 100 000 Pf/µL).
What is introduced malaria?
Secondary cases acquired locally but derived from imported cases
What is the Rx for severe (complicated malaria)?
IF ONLY ORAL AVAILABLE: Artemether-lumefantrine (Coartem®) because of its fast onset of action. Other oral options include atovaquone-proguanil (Malarone™), quinine, and mefloquine.
IV artesunate: 2.4 mg/kg. A dose of IV artesunate should be given at 0, 12, and 24 hours.
After the initial course of IV artesunate is completed, if parasite density is ≤1% (assessed on a thin blood smear collected 4 hours after the last dose of IV artesunate) and patient can tolerate oral treatment, a full treatment course with a follow-on regimen must be administered. Artemether-lumefantrine (Coartem®) is the preferred follow-on treatment but adequate alternatives are atovaquone-proguanil (Malarone™), quinine plus doxycycline or clindamycin, or mefloquine
If, after the third IV artesunate dose, the patient’s parasite density is >1%, IV artesunate treatment should be continued with the recommended dose once a day for a maximum of seven days until parasite density is ≤1%
For those patients with parasite density ≤1% but who still cannot tolerate oral medications after completing IV artesunate treatment, clinicians can continue IV artesunate, one dose daily not to exceed a total course of seven days.
Following invasion of a RBC, what happens to merozoites?
Trophozoites -> schizonts -> may rupture and release 8-24 merozoites - causes inflammatory response and fever. Some may then form gametocytes.
What is the vector for malaria? Name some features of this vector.
female anopheles mosquito, night biting
How would you treat uncomplicated P.malariae?
Chloroquine base. 0 = 10mg/kg, 24 = 10mg/kg, 48 = 5mg/kg
3 days, orally
Treatment of uncomplicated malaria caused by P. vivax, P. ovale, P. malariae, P. knowlesi is chloroquine.
Can also use ACT in chloroquine resistant areas.
Who would you not administer primaquine to?
Pregnant women, children <6 months, breastfeeding to children <6 months, G6PD deficiency
Name 2 complications/risks of falciparum in pregnancy?
Stillbirth
LBW
Severe anaemia
What is uncomplicated hyperparasitaemia?
Uncomplicated hyperparasitaemia is present in patients who have ≥ 4% parasitaemia but no signs of severity. They are at increased risk for severe malaria and for treatment failure and are considered an important source of antimalarial drug resistance.
What structure is this?
Schizont, P.malariae (Rossett appearance)
What is severe malaria?
What is a Schuffners dot? Which species
Schuffner’s dots: Caveolae in RBC membrane
Caveola-vesicle complexes in cellular membrane of erythrocytes.
P.Vivax and P.Ovale
What is a hypnozoite?
Malaria dormant in the liver
Why do a thick smear for malaria?
increases sensitivity of parasitic detection (always do both)
HIV and malaria, what to avoid in Rx of malaria?
Avoid artesunate+ amodiaquine if patient is receiving efavirenz
or zidovudine
Which phase of the malaria life cycle are you most likely to see with falciparum?
Usually only see rings trophozoites and gametocytes unless very high burden of infection will see schizonts. Maulers clefts and appliqué forms characteristic.
What is imported malaria?
Acquired outside a specified area in which it is found
What is indigionous malaria?
Naturally present in an area or country
Malarias impact on HIV?
Specificity HIV RDTs decreased
Transient viral load increased
Transient CD4 increased
Progression to AIDS - no impact
HIV transmission may increase
What is an incubation period?
Time between infection and the onset of symptoms
What are the causes of false negative rapid diagnostic testing for malaria?
Low parasitaemia
Non falciparum species
High parasitaemia (prozone)
Gene deletion - HRP2 - more so in South America
Interpretation error
What are the disadvantages for RDTs in malaria?
Still need microscopy, possibility of false positives and false negatives, poor performance in species other than Falciparum
How do you treat uncomplicated P.Vivax in areas of high chloroquine resistance?
Artemisin compounds (artesunate, arthemeter, artemotil, dihydroartemisinin) containing artesemin AND a 2nd shizontocidal drug 3 days
Primaquine base 3 days
Co-trimoxazole prevents which conditions?
Toxoplasmosis
Malaria
Pneumocystis Jirovecii
Criteria for severe malaria in low resource settings?
- Prostration
- Resp distress
-Decreased GCS
Why do you give a partner drug with artemisinin?
Longer acting
Clears remaining parasites to prevent resistance to artemisinin
Post Rx prophylaxis
What is Ziemann’s stippling?
Eosinophilic dots in cytoplasm found in P.Malariae
What Is PART?
Presumptive Anti Relapse Therapy - primaquine for 2 weeks when come home from high vivax country
What is the definition of uncomplicated malaria?
Symptomatic malaria with a positive parasitological test, without signs of severity or evidence of vital organ dysfunction
What is cytoadherence? Which species?
Falciparum expresses the PfEMP1 protein, causes RBCs to adhere to each other and endothelium - causes end organ damage
Options for Rx of falciparum uncomplicated? Alternatives?
ACT - 1st line
Alternatives: malarone (atorvaquone and proguanil), doxycycline 7/7 and quinine 3/7 (cheap option but may be all you have, cannot use if quinine resistance) and mefloquine you can use but OUT of FAVOUR!
Prophylaxis in SE Asia which drug can you not use?
Mefloquine
Which antimalarials are ABSOLUTELY contraindicated in pregnancy?
Tetracyclines
primaquine
What constitutes an area being high risk of chloroqune resistance?
Chloroquine resistance: treatment failure rate is > 10% at day 28 -> recommend Rx with ACT first line
How often do patients get fever in the differing species of malaria?
P.malariae - 72 hrs - Quartan
P.Vivax and P.Ovale and P.Falciparum - 48 hrs - Tertian
What are maurers clefts?
Eosinophilic dots in cytoplasm - coarser than Schuffners dots - found in P.Falciparum
How do you do prophylaxis for P.Vivax?
Either primaquine prophylaxis during trip 1 day before of 7 days after
OR
14 days of primaquine prophylaxis WHEN RETURN FROM TRIP IN HIGH P.VIVAX AREA
How is malaria quantified on thick and thin films?
Thick - number of parasites/microlitre of blood determined by number of parasites in relation to standard number of WBCs. Inaccurate in high parasitaemia.
Thin - % - number of infected RBCs in relation to uninfected RBCs - minimum 800 counted. Inaccurate in low parasitaemia.
What activity of G6PD do you need to have to receive primaquine and tafenaquine?
> 70% tafenaquine
30% primaquine
What are the causes of false positive rapid diagnostic testing in malaria?
Persistence of HRP-2 (lasts for weeks after infection)
Delayed reading
Buffer substitution
Cross reactivity between species
Other conditions e.g. schisto, toxo, leish
What structure is this?
Trophozoite, Vivax (can see vacuole)
How does treament change in a recurrence?
Within 28 days - classed as treatment failure - use alternative treatment
After 28 days - can use the same Rx
If patient is on co-trimoxazole, which anti malarial not to use?
Artesunate + sulfadoxine/pyrimethamine (similar drugs, increases resistance)
WHO GUIDELINE
How does malaria impact HIV viral load? and CD4?
Increases it
Increased risk of transmission
Decline in CD4 (reversible)
What rapid tests can be used for P.falciparum?
Histidine-rich protein 2 - PfHRP2 (produced by gametocytes of Falciparum) - most sensitive
Parasite lactate dehydrogenase pLDH (less sensitive, all species)
Plasmodium aldolase - all species
Where do you use ACT for Vivax? Why?
Indonesia
PNG
What structures is this?
Male Gametocyte, Falciparum. Note laveran’s bibs (white part). Male - chromatin is more diffuse
Why use a partner drug in the Rx of uncomplicated Falciparum with the Artesemin containing compound?
Partner drug: longer acting, clears remaining parasites
If using mefloquine for malaria prophylaxis, why would you start it 3 weeks early?
If develop side effects, takes 3 weeks so you know.
What structures is this?
Female Gametocyte, Falciparum, Note laveran’s bibs (white part). Female - chromatin is compact
What is sporogony?
Sexual reproduction inside the mosquito, with produces sporozoites
Prozone effect occurs with which RDT and which species?
Falciparum
HRP-2
What treatment would you administer a pregnant patient with P.Vivax malaria?
Chloroquine pre delivery
Primaquine after delivery (if G6PD def risk low/test neg)
If vertical transmission to baby from mother, therefore no hypnozoites, so don’t need primaquine
Alternative to doxycycline in patient you are giving quinine to if pregnant for uncomplicated malaria (ACT and others not available)?
Clindamycin!
Malaria in first trimester - uncomplicated falciparum. Rx?
ACT but only certain ones - Artemethur - lumefantrine
Quinine + clindamycin if other formula not available
Treatment of uncomplicated malaria in pregnancy 2nd and 3rd trimester?
ACT
But if artesunate-SP is used, avoid high doses of folate
Which RBC cells does P.Vivax preferentially invade, and how is this recognised on a blood film?
Reticylocytes - large RBCs
What is the incubation period for the different malaria species?
P.Vivax - 15 days or up to 6-12 months
P.ovale - 17 days or longer
P.Falciparum - 9-14 days
P.malariae - 28 days or longer
What is patency?
The first microscopic detection of the asexual parasites (>50p/µL)
What is the Duffy antigen?
Surface antigen on RBC needed for vivax to enter erythrocyte (why there is limited Vivax in Africa)
Complications of cerebral malaria in children?
Cognitive deficits
Raised ICP
Retinal haemorrhages
Seizures
Postural abnormalities
What is the classic relapse time for P.Ovale and P.Vivax?
Varies depending on location
8-9 months - temperate strains of vivax
1 month - tropical vivax
How would you treat uncomplicated P.Vivax malaria?
Chloroquine base. 0 = 10mg/kg, 24 = 10mg/kg, 48 = 5mg/kg
3 days, orally
Treatment of uncomplicated malaria caused by P. vivax, P. ovale, P. malariae, P. knowlesi is chloroquine.
Can also use ACT if chloroquine resistance very high.
Give primaquine otherwise you will get a relapse - to kill hypnozoites in Ovale and Vivax. 15-30mg/kg primaquine for 7-14 days (14 days WHO)
Problem with Tafenoquine as prophylaxis for malaria?
Have to make sure patient does not have G6PD def
Which anti malarial can you give in pregnant patients?
Chloroquine and proguanil are safest.
Mefloquine probably safe.
What is the pre/sub patent period?
The time from inoculation of sporozoites from mosquitoes until asexual erythrocytic-stage parasites are detected by microscopy in the bloodstream (<50p/µL)
How would you treat uncomplicated P.Falciparum?
Artemisin compounds (artesunate, arthemeter, artemotil, dihydroartemisinin) containing artesemin AND a 2nd shizontocidal drug (mefloquine (ASMQ), amodiaquine (AS+AQ), Lumefantrine (AL), piperaquine (DHAP), sulfadoxine-pyrimethamine (AS+SP)
3 days orally
Alternative is
- doxy or clinda plus quinine (7 days)
- malarone
When you give NNRTI and PI with ACT, what happens to the concentrations of ACT?
-Artesemin concentration goes down
-Partner drug concentration goes up
What is this?
Immature schizont - P.vivax
What is link between HIV and malaria?
-Higher parasitaemia
-Higher incidence of clinical malaria
- increased severe malaria
- increased placental malaria
**inversely correlated with CD4 count
When would you Rx P.Vivax with ACT first line instead of chloroquine?
In areas of high chloroquine resistance
Change to ACT when the
treatment failure rate is >
10% at day 28.
What option for pregnant patients for malaria prophylaxis? problem with it?
Sulfadoxine-
pyrimethamine (SP) - 3 tablets. STILL beneficial however Falciparum is growing resistant!
What are the symptoms of malaria and why?
- That of the haemolysis of RBCs (headache, jaundice, headache, fatigue) and fever from inflammatory response to merozoites being released. Fever every 48 hrs.
- Cytoadherence of RBCs cause organ failure - kidneys, spleen, brain, lung
What is autochthonous malaria?
Locally contracted disease
-Indiginous and imported
Which species administer primaquine to and why?
P.Ovale and P.Vivax to kill hypnozoites
P.Falciparum single dose to kill gametocytes and stop transmission - only in non endemic area where vector exists to stop transmission.
What are the criteria for severe malaria in Knowlesi and Vivax?
Symptoms making malaria more likely?
splenomegaly, thrombocytopenia, high bilirubin
When combining and artemethur compound with doxy or clinda, how does the regime change and why (for uncomplicated, falciparum)?
Give 7 days instead of 3 days as doxy/clinda are rapidly eliminated
What are the requirements of a rapid diagnostic test in malaria?
- P. falciparum Panel Detection Score ≥ 75% at 200 parasites/μL
- P. vivax Panel Detection Score ≥ 75% at 200 parasites/μL
- False-positive rate < 10%
- Invalid rate < 5%
(WHO says needs to have ≥ 95% sensitivity with parastiaemia > 500/μL)
What is this?
Schizont - containing merozoites - P.Vivax
How much malaria in Peru Is Vivax vs Falciparum?
75% vs 25%
What is the prozone effect?
The prozone effect consists of false-negative or false-low results in immunological tests, due to an excess of either antigens or antibodies - clump together
What structure is this?
Gametocyte, P.Ovale. Irregular RBC outline, big cells.
In stable malaria, how long are babies protected from malaria and why?
Infants partially protected for first 3-6 months of life
Maternal IgG
What is tafenoquine, what is the advantage?
Long half life of 14 days, only have to take once a week
What strucutre is this?
Trophozoites - P.falciparum
What is a schizogony?
Asexual reproduction in both mosquito and human (liver), producing schizonts containing lots of merozoites.
What is the purpose of prophylaxis of malaria in terms of the life cycle?
kill sporozoites before they infect hepatocytes
When can you use tafenoquine?
Need to have >70% activity of G6PD on quantitative testing (primaquine need G6PD >30%)
Which strain is in Malaysia (99%) and also in Thailand and surrounding countries?
P.Knowlesi - monkey malaria!
Blood film mistaken for malariae
Transmitted from monkey -> human
What is the characteristic feature of P.Malariae on smear?
Older RBCs get infected - smaller cells
What option for pregnant patients for malaria prophylaxis?
sulfadoxine/pyrimethamine
What to do once initial 3 doses of artesunate given in severe malaria?
treat with oral ACT for 3 days (need this regardless of length of Rx of IV)
What are the patterns and definitions of endemicity for malaria?
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 are Sinton and Mulligans Stippling?
Eosinophilic dots in cytoplasm found on gram stain for P.knowlesi
Which artesemin containing compounds cannot be used in pregnancy?
Artesunate +sulfadoxine pyrimethanine and Artesunate-pyronaridine - 1st trimester.
2nd trimester - avoid high doses of folate with ASP, resistance also to this
USE AL IF POSSIBLE
Quinine and Clindamycin if no alternative available
What is premunition?
State of partial immunity (semi-immune) in an endemic area
What structure is this?
Ring Trophozoite, Falciparum
Infective stage of life cycle of malaria?
Sporozoites
What happens to sporozoites?
Become merozoites in schizonts by schizogony (asexual reproduction)
How many types of schizogony can occur in human?
2
-Exoerythrocytic
-Erythrocytic
What happens when a merozoite invades an RBC?
Becomes a trophozoite
which species get schuffners dots/ziemanns stippling/stinton/mulligans dots/maurers 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
Definition and cause of recrudescence
Recurrent clinical malaria due to infection falling below level of detection and then rising above level of detection.
Resistance, incomplete treatment, unusual PK, immunodeficiency
Thick smear and thin smear how to quantify?
Thin- % - quantity of infected RBCs in comparison to number of uninfected RBCs
Thick - no. of parasites per micro litre - no. of parasites in comparison to number of WBCs
Drugs which treat
-liver schizonts
-trophozoites
-gametocytes
-hypnozoites
Schizonts: primaquine (T), atorvaquone/proguanil
Hypnozoites: primaquine(T)
Blood trophozoites->gametocytes: doxy, mefloquine, atorvaquone/proguanil, chloroquine, ACT
Gametocytes: ACT, primaquine(T)
When is a pregnant patient in an endemic area most at risk? Why?
First pregnancy
After this - develop variable surface antigen
Criteria of severity in knowlesi
> 20,000p/microml plus jaundice
200,000p/microml
What causes cytoadherence?
pFEMP1 protein on RBC
What do you do if <30% G6PD activity and get Vivax? What about 30-80%? what about only qualitative testing?
Low dose weekly primaquine for 8 weeks
30-80% normal dose primaquine
<30% only detected - low dose primaquine
What is different about Babesia sp? What animal does it infect (definitive host, intermediate host, accidental host) and what does it look like on a blood smear? Rx?
Babesia - northern USA
Def - tick
Intermediate - mounse
Accidental - human
Blood smear - cross/tetrad
Rx: azithromycine atorvaquone
