Malaria Flashcards
What type of pathogen is malaria? What cells does it infect?
Protozoan paracyte that infects RBC and hepatocytes
What are the two key clues that highly indicate malaria?
Fever + travel
What are the major risk factors for severe malarial disease?
Non immune pts: children < 5 OR pregnant woman
Asplenic pts
How long does one have to be in a malaria endemic area to acquire disease?
All it takes is one bite
What are the five different malaria species?
Plasmodium falciparum P. vivax P. ovale P. malarial P. knowlesi
What is the vector for malaria?
Anophelene mosquito
What is the non human reservoir for malaria? Which one?
Macaques- P. Knowlesi
Where is P. Knowlesi located?
Borneo
What is the maturation pathway of malaria?
Enters as a sporozoite=> liver schizont => burst release merozoites (infect RBC) => ring, trophozoites => schizonts (then burst) OR gametocytes
What is the dormant form of malaria? Which specific malaria paracite has it?
Hypnozoite? Only seen in P. Ovale and P. Vivax. Releases parasites weeks to months after primary infection
What is the typical time frame between initial infection and symptoms?
Coincides with start of erythrocytes cycle 1-2 weeks after infection.
What are three possible evolutionary defenses against malaria?
- Duffy antigen negative: P. Vivax requires Duffy to enter RBC
- Sickle cell trait: selective suckling of p. Falciparum infected RBC cells
- Glucose-6-phosphate dehydrogenase deficiency- malaria grows poorly in G6PD deficient RBC
What are the classical symptoms of malaria?
Fever Chills Headache Fever Splenomegaly Abdominal pain
What are some clinical laboratory signs seen with malaria?
Low platelets (<12) High total bili (1.95)
What are the different clinical types of malaria?
Acute uncomplicated malaria
Severe malaria
Hyper reactive malarial syndrome (tropical splenomegaly)
What causes mild uncomplicated malaria? What are the key symptoms? How do the periodicity change with each type of malaria?
All plasmodium can cause uncomplicated malaria
Classic paroxysms: first cold stage then hot stage then sweat with reduction of fever
Episodes last 6-10 hrs
P. Vivax/ovale: every 2 days (tertian fever) and P. Falciparum
P. Malaria: every 3 days (quartan fever)
What is so bad about P. Falciparum that makes it have such a bad disease?
It infects RBC at any stage of the RBC life cycle
Complicated malaria (P. Falciparum high parasitemia)
Cerebral malaria
Respiratory distress
Severe anemia
Renal failure
What are the two main prognostic factors in a patient with malaria?
Degree of acidosis
Degree of parasitemia
What is the major cause of tissue hypoxia and lactic acidosis in malaria?
SEQUESTRATION. Parasites creates knobs on RBC => RBC stuck in capillaries => blockage of tissue
Cerebral malarial- causes?
Acute encephalopathy not attributable to other causes in pt with malaria
SEQUESTRATION hypothesis
- obstructed vessels => hetergeneous (some blocked some not)
- sequestered RBC => mass effect => swollen (not from cerebral edema)
INFLAMMATION hypothesis
- malaria toxin => cytokines storm but anti inflammatories do not help
HEMOSTASIS DYSFUNCTION hypothesis
- Coagulation dysfunction
Malaria dx
Blood smear (thick/thin)
Antigen testing: binax
CPR
What is the key morphology of P. Vivax and P. Ovale?
- Schuffners dots
- enlarge cells
P. Vivax: Lots of merozoites compared to P. Ovale
Key morphology of P. Malariae on microscope?
- band form
- owl eye teophozoite
- smaller infected cells (does not get bigger)
Key morphological features of p. Falciparum?
Multiple ring shaped tropozoites
Banana shape gametocyte
Key prevention of malaria?
Personal protection
Chemotherapy
What are the classes of anti-malarials?
- Quinolone
- Artemisin.
- Antifolates
- Other- tetracyclines, atovaquone/proquanil
What are a few key things to do when treating a malaria pt?
1 admit all pts with p. Falciparum
- Watch them take the meds
- Watch for respiratory compromise, hypoglycemia, neurological change
- Depressed sensorium? Vomiting? Organ problems or high paracitemia (>5%) =need I’ve tx
- Pts with p.vivax or p. Ovale: need primaquine to eradicate hypnozoites
A 3 yr old in Ghana presents with fever headache cough for 3 days and positive for P. Falciparum. He is tolerating PO. What is the recommended medication?
Artemeter-lumefantrine (coartem)
A 25 yo AD female plans a two week safari in western Kenya. What is the most appropriate chemo prophylactic?
Atovaquone-proguanil
How do quinolone and quinolone-like drugs work?
Impairs intra-parasitic heme polymerization into hemozoin (parasites die on their own poop)
What is the resistance mechanism against quinolones?
Efflux pump: P. Falciparum chloroquine resistance transporter (PfCRT)
When are quinolone used?
Therapy (use with other agents as well)
PART/radical cure: Primaquine
Primary prophylaxis: chloroquine/mefloquine
* mefloquine can cause crazy dreams
What is cinchonism?
Overdose of quinine- causes tinnitus, headache, nausea, bitter taste, dysphoria
What is a side effect of quinine to watch out for?
Hypoglycemia
How do you treat severe p. Falciparum? Uncomplicated?
Severe- quinine/quinidine
Uncomplicated- oral quinine and doxy/clindamycin
**resistance to quinine in SE Asia
Where can you use chloroquine?
Only for p. Falciparum in Central America, Haiti, Dominican Republic.
Good for P. Vivax, p. Ovale, p. Malariae in most locations
Mefloquine- indications? Side effects? Contraindications? Who is best to use this?
Use in locations of chloroquine resistant P. Falciparum. Weekly chemo - due to 3 wk half life. Use for long term travelers/children/ preggers
Neuropsychiatric side effects -crazy dreams
Cardio toxic if used with quinine, quinidine, halofantidine
Mefloquine resistance?
Plasmodium falciparum multidrug resistance protein 1 (PfMDR1)
- ATP cassette
- effluent pump
- polymorphisms
- primarily in SE Asia.
Primaquine- use? Things to worry about?
Radical cure of P vivax, or P. Ovale
PART
- print relapse in ppl who have had long exposure
test for G6PD deficiency: especially for preggers as we don’t know if fetus is g6pd.
Recommended for artemisinin resistance or elimination areas
How are preggers with p. Vivax or p. Ovale treated?
Chloroquine
Antifolate/sulfa derivatives
- pro guano
- prime thiamine
Resistance?
Dihydroperase synthase or dihydrfolate reductase point mutations
Atovaquone - mechanism of action? Resistance?
- inhibits mitochondrial electron transport (even better potentiated when paired with proguanil (Malarone)
- use as therapy and prophylaxis
- resistance- single point resistance in parasite cytochrome b gene
Antibiotics for malaria: which ones? Target? Things to consider?
Doxycycline, tetracycline, clindamycin, azithromycin, fluoroquinolones
- all target ribosomal functioning
- if these drugs are used for other purposes, it may mask or change the typical presenting signs of malaria.
Artemisinins- how do they work, where?
Used in what clinical setting?
Effective against wide range of stages of parasite
Mechanism: endoperoxide => free radicals
Use in artemisinin combined therapy
- artemisinin-lumefantrinev(coartem). First line tax of uncomplicated p. F
IV form: artesunate
Tx of severe malaria
IV quinidine
IV artesunate
Oral tax of uncomplicated malaria
Atovaquone-proquanil (Malarone)
Artemether-lumefantrune (coartem)
Quinine+ doxy or clindamycin
If pregnant, malarone and coartem become second line
