malaria Flashcards

(40 cards)

1
Q

Plasmodium falciparum is responsible for ~500,000 deaths yearly

A

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

most aggressive

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2
Q

Causes of Human Malaria:

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

what are we looking in a parasite smear in malaria?

A

trophozoites (ring forms)

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4
Q

some forms of parasites in malaria are latent in the

A

liver

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5
Q

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

A

anemia

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6
Q

Once within RBCs, parasites digest hemoglobin

A

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

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7
Q

why is P. falciparum so mean?

A

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

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8
Q

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

A

P. malariae

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9
Q

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

A

P. vivax/Ovale

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10
Q

increased disease severity for malaria (4)

A
  1. children
  2. pregnancy
  3. non-immune host
  4. HIV infection
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11
Q

decreased severity for malaria (4)

A
  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
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12
Q

Mean incubation period for malaria

A

= 10-15 days

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13
Q

Acute malaria attack classically has three stages:

A
  1. Chills or rigors (30-60 mins)
  2. High fever with diaphoresis, HA, GI symptoms
  3. Period of intense sweating
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14
Q

Do we see some enlargement of an organ in malaria?

A

yep, splenomegaly and hepatomegaly is seen

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15
Q

severe malaria

A

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

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16
Q

cerebral malaria

A

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

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17
Q

malaria diagnosis

A

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

**stained with Giemsa/Wright’s

18
Q

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

A

P. falciparum:

19
Q

Rapid Antigen Detection Tests (RDTs)

A

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
20
Q

other diagnostic tests for malaria

A
  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
21
Q

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

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

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

  1. Radical cure: eradication of RBC trophozoites, schizonts and hepatic schizonts(hypnozoites)
22
Q

active against blood stage; used for treatment and prophylaxis

A

Blood schizonticide:

23
Q

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

A

Tissue schizonticide:

24
Q

active against sexual forms of parasite, interrupts transmission to mosquito

25
malaria treatment caviat
requires more than 1 drug regimen.... resistance occurs
26
Arylaminoalcohols: Quinine and Quinidine
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
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
chloroquine
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
mefloquine
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)
primaquine
30
primaquine
treatment for latent phase of P. ovali
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
tafenoquine
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
atovaquone/proguanil
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
Artemisinin derivatives
34
Artemisinin derivatives
not FDA approved but it is main one for severe malaria
35
Always used in combination with another antimalarial drug, for treatment of Pf usually a rapidly active agent Can also be used for prophylaxis
doxycyline
36
Always used in combination with another antimalarial drug for treatment of Pf, usually a rapidly active agent (e.g. artemesinin)
clindamyicin | usually to treat infection above the diapghram
37
recurrence of initial infection due to dormant liver stages (P. vivax and ovale)
Relapse:
38
incomplete eradication of initial parasitemia, most likely due to resistance or inadequate levels of antimalarials
Recrudescence:
39
in areas of intense transmission, new infection with a different malaria parasite, from additional mosquito bites
Re-infection:
40
loss of susceptibility to therapeutic levels of antimalarials
Resistance: