malaria

Question 1

Plasmodium falciparum is responsible for ~500,000 deaths yearly

Answer 1

yeppp; major cause of morbidity and mortality in the developing world

most aggressive

Question 2

Causes of Human Malaria:

1. Plasmodium falciparum (Pf)
2. P. vivax (Pv)
3. P. ovale (Po)
4. P. malariae (Pm)
5. P. knowlesi (Pk)

Answer 2

1. Plasmodium falciparum (Pf)
   Occurs worldwide
   Responsible for greatest morbidity + mortality
2. P. vivax (Pv)
   Occurs in Latin America, Asia, Middle East, North and East Africa
3. P. ovale (Po)
   Only found in Central-West Africa
4. P. malariae (Pm)
   Limited worldwide distribution
5. P. knowlesi (Pk)
   Recently identified cause of human malaria in Malaysia, Borneo, other parts of SE Asia

Question 3

what are we looking in a parasite smear in malaria?

Answer 3

trophozoites (ring forms)

Question 4

some forms of parasites in malaria are latent in the

Answer 4

liver

Question 5

Parasites reduce RBC membrane deformability resulting in hemolysis and increased splenic clearance leading to

Answer 5

anemia

Question 6

Once within RBCs, parasites digest hemoglobin

Answer 6

toxic metabolite (hemozoin) is stored in the parasite’s food vacuole

Question 7

why is P. falciparum so mean?

Answer 7

no latent stage goes directly to do the RBC and invades them alllllll.

Question 8

No latent stage (no hypnozoites)
Only invade senescent (old) RBCs
Mildest form of malaria, can persist at low levels for years
No sequestration

Answer 8

P. malariae

Question 9

After the initial liver stage, some parasites remain dormant as hypnozoites for weeks-years, allows for clinical relapses
Only invade reticulocytes (young RBCs)
Generally less severe disease
No sequestration

Answer 9

P. vivax/Ovale

Question 10

increased disease severity for malaria (4)

Answer 10

1. children
2. pregnancy
3. non-immune host
4. HIV infection

Question 11

decreased severity for malaria (4)

Answer 11

1. premunition- sustained repeated infection but last only a couple of months
2. sickle cell trait
3. absence of Duffy blood group- no infection
4. certain HLA types and thalassemia traits

Question 12

Mean incubation period for malaria

Answer 12

= 10-15 days

Question 13

Acute malaria attack classically has three stages:

Answer 13

1. Chills or rigors (30-60 mins)
2. High fever with diaphoresis, HA, GI symptoms
3. Period of intense sweating

Question 14

Do we see some enlargement of an organ in malaria?

Answer 14

yep, splenomegaly and hepatomegaly is seen

Question 15

severe malaria

Answer 15

badddddd, mortality is >20%, there is an intense cytokine response to parasite proteins released during shizont rupture and there are metabolic derangements

** pregnancy is a risk for severe disease

Question 16

cerebral malaria

Answer 16

cuased by P. falciparum that results in sequestration and resultant host immune response

We see Sludging of Capillaries.

it leads to confusion, seizures and coma and about 10% of children who survive will have long term neuro-psychological deficits

Question 17

malaria diagnosis

Answer 17

use a thick and thin smear; where the thick is more sensitive but thin is more specific

**stained with Giemsa/Wright’s

Question 18

Normal size RBCs; Small ring forms (”stereo headphones”);
Multiply infected cells; High grade parasitemia
Rare banana shaped gametocytes;
Developing forms almost never seen

Answer 18

P. falciparum:

Question 19

Rapid Antigen Detection Tests (RDTs)

Answer 19

Detect parasite proteins (histidine rich protein-2 of Pf and parasite specific LDH or aldolase antigens) in finger prick blood samples

• Advantage: easy to use, require minimal equipment/ skill
• Disadvantage: cannot quantify parasitemia, cannot pick up low level infection, remain positive for 7-14 d post-Rx

Question 20

other diagnostic tests for malaria

Answer 20

1. PCR
   Can detect <10 parasites per 10L of blood; species specific
   >90% sensitive; ~100% specific
   Turnaround time is slow and testing is expensive
   Can remain positive for several weeks after curative treatment
   Can be done at CDC for free (along with resistance testing)
2. Serology
   Detects Ab against malaria parasites
   Does not detect current infection per se, but rather measures past exposure

Question 21

Principles of Management: Definitions:

Prophylaxis
Medication taken at regular intervals to kill one or more life stages of the parasite to ______ clinical illness
Critical to prophylactic treatment is administration _______________; dosing/duration is drug dependent

Treatment
1. __________ eradication of RBC trophozoites and schizonts

2. ________ eradication of RBC trophozoites, schizonts and hepatic schizonts(hypnozoites)

Answer 21

Principles of Management: Definitions:

Prophylaxis
Medication taken at regular intervals to kill one or more life stages of the parasite to prevent clinical illness
Critical to prophylactic treatment is administration before, during and after exposure; dosing/duration is drug dependent

Treatment
1. Clinical cure: eradication of RBC trophozoites and schizonts

2. Radical cure: eradication of RBC trophozoites, schizonts and hepatic schizonts(hypnozoites)

Question 22

active against blood stage; used for treatment and prophylaxis

Answer 22

Blood schizonticide:

Question 23

active against liver stages of parasite; used for treatment and prophylaxis

Answer 23

Tissue schizonticide:

Question 24

active against sexual forms of parasite, interrupts transmission to mosquito

Answer 24

Gametocide:

Question 25

malaria treatment caviat

Answer 25

requires more than 1 drug regimen.... resistance occurs

Question 26

Arylaminoalcohols: Quinine and Quinidine

Answer 26

not really used clinically but for boards yes, this is a treatment choice. it needs to be combined with another drug. contraindication is QT prolongation and a classic SE is tinnitus/deafness

Question 27

Oral agent for prophylaxis for sensitive Pf (taken weekly) and treatment of sensitive malaria species, particularly Pv Resistant Pf strains widespread Must be given with primaquine or tafenoquine for treatment of Pv/Po to prevent recurrence Classic Side Effects: Pruritis (w/o rash) in dark skinned persons; exacerbation of psoriasis Irreversible retinopathy if prolonged exposure to high doses

Answer 27

chloroquine

Question 28

Oral agent for prophylaxis for Pf (taken weekly) and treatment of malaria Resistant falciparum seen in SE Asia Classic Side Effects: Neuropsychiatric: seizures, abnormal dreams, psychosis, anxiety, depression CV: QT prolongation Contraindication: if hx any of the above issues at baseline

Answer 28

mefloquine

Question 29

Oral agent active against hypnozoite forms of Pv/Po Prevention of relapse after infection with Pv/Poradical cure Presumptive therapy against relapse after possible exposure to Pv/Poterminal prophylaxis Resistance: Pv resistance in some areas Classic side Effects Acute hemolysis if G6PD deficiency—Must check G6PD prior to use Contraindication: G6PD deficiency; pregnancy (because cannot know G6PD status of fetus)

Answer 29

primaquine

Question 30

primaquine

Answer 30

treatment for latent phase of P. ovali

Question 31

FDA approved 2018 for prophylaxis of Pf AND Pv in adults AND for radical cure of Pv First new antimalarial approved in >60 years Kills dormant liver stage of P. v Side effects: generally well tolerated; occasional delayed hemolytic anemia Contraidication: G6PD deficiency, pregnancy; history of mental illness

Answer 31

tafenoquine

Question 32

Oral fixed dose combination for prophylaxis (taken daily) and treatment of Pf Resistance: develops rapidly to either agent when used alone; seen in parts of SE Asia Side effects: generally well tolerated Contraindication: significant renal dysfunction

Answer 32

atovaquone/proguanil

Question 33

PO, IM, IV, PR: used in combination with other agents for treatment of Pf Artemether-Lumefantrine fixed dose combination for uncomplicated Pf IV Artesunate Not FDA approved, but is recommended as first line choice for severe malaria Available from CDC Must be given with a second agent to prevent resistance Superior to quinine: better efficacy and tolerability Resistance: in parts of Asia Side Effects: generally well tolerated

Answer 33

Artemisinin derivatives

Question 34

Artemisinin derivatives

Answer 34

not FDA approved but it is main one for severe malaria

Question 35

Always used in combination with another antimalarial drug, for treatment of Pf usually a rapidly active agent Can also be used for prophylaxis

Answer 35

doxycyline

Question 36

Always used in combination with another antimalarial drug for treatment of Pf, usually a rapidly active agent (e.g. artemesinin)

Answer 36

clindamyicin | usually to treat infection above the diapghram

Question 37

recurrence of initial infection due to dormant liver stages (P. vivax and ovale)

Answer 37

Relapse:

Question 38

incomplete eradication of initial parasitemia, most likely due to resistance or inadequate levels of antimalarials

Answer 38

Recrudescence:

Question 39

in areas of intense transmission, new infection with a different malaria parasite, from additional mosquito bites

Answer 39

Re-infection:

Question 40

loss of susceptibility to therapeutic levels of antimalarials

Answer 40

Resistance: