Malaria

Question 1

There are many risk factors for getting Malaria. Which ones double your chances of getting Malaria?

Answer 1

• Missing ANY prophylaxis
• Not using bed nets regularly
• Junior enlisted rank
• Failure to keep sleeves down
• Guard duty along river more than 7 nights

Question 2

Who is at risk for getting severe disease if they contract Malaria?

Answer 2

• Non-immune individuals (yea no shit)
• Children under 5 years old
• pregnant women
• asplenic patients

Question 3

Why was Malaria referred to as the hidden plasmodia in the 1930s and 40s?

Answer 3

The fact that after infection of volunteers with mosquitoes, the sporozoites circulated free for only about half an hour, and then vanished for several days (based on classic experiments by Fairley in Australia)

Shortt and Garnham solved this in 1948: infected monkeys with P. cynomolgi, did thorough autopsies a few days later, and found parasites in liver cells

Question 4

Discuss the forms of Malaria once it is in you.

Answer 4

Merozoites infect RBCs where they form ring-stage trophozoites .
(these mature into schizonts which rupture and release merozoites, which infect more RBCs)

Question 5

What is a hypnozoite?

Answer 5

Dormant liver stage in P. vivax and P. ovale

Release blood stage parasites weeks to months after primary infection

Question 6

How long after infection does one develop symptoms?

Answer 6

P. falciparum: 8-11 days
P. ovale: 10-17 days
P. vivax: 10-17 days
P. malariae: 18-40 days

Question 7

What determines the time between infection and onset of symptoms

Answer 7

Onset of symptoms coincides with the start of the erythrocytic cycle.

P. ovale and P. vivax, if untreated, will cause repeated bouts of fever due to eruption of hypnozoites from hepatocytes

incubation period with P. malariae can be up to 20 years (due to chronic, subclinical erythrocytic stage)

Question 8

One way some people have evolved against malaria is to become Duffy Antigen negative.

The fuck is Duffy antigen, and which malaria uses this

Answer 8

Duffy antigen/chemokine receptor (DARC), also known as Fy glycoprotein (FY) or CD234 (Cluster of Differentiation 234), is a protein that in humans is encoded by the DARC gene. The Duffy antigen is located on the surface of red blood cells, and is named after the patient in which it was discovered.

P. vivax uses Duffy Ag to enter RBCs

Question 9

What trait helps us not get Malaria and why

Answer 9

Sickle cell trait (increases survival during P. falciparum infection, perhaps by selective sickling of infected RBCs)

Question 10

G6PD deficiency is bad. How does it help though with malaria?

Answer 10

malaria parasites grow poorly in G6PD deficient RBCs, perhaps b/c this results in an overall increase in reactive oxygen species in RBCs

Question 11

How do symptoms for Malaria begin?

Answer 11

Fever
Chills
Headache

RARELY does it cause sore throat, lymphadenopathy, or rash

Question 12

What signs on exam will we see for Malaria?

Answer 12

1/3 of patients will have a temp greater than 39 degrees and 1/4 of patients will have splenomegaly

Question 13

Typical lab values for Malaria

Answer 13

Platelets down, Hgb down.

Question 14

Classic presentation of uncomplicated (mild) malaria

Answer 14

1. cold stage with shaking
2. hot stage with high temperature (>104°F)
3. sweating stage with resolution of fever

episodes last 6-10 hours, and then recur:

• every 2 days with P. vivax and P. ovale (tertian fever) and for P. falciparum (malignant tertian fever)
• every 3 days with P. malariae (quartan fever)

Question 15

Which strand gives us complicated malaria and how does it present?

Answer 15

• Cerebral malaria (change in mental status, coma)
• Respiratory distress
• Severe anemia (hct 2%

Question 16

Two most important prognostic factors for a patient with malaria

Answer 16

Degree of acidosis and degree of parasitemia

Question 17

Why is falciparum so bad?

Answer 17

Can grow and replicate in RBCs of ANY age, not just mature ones. So there is NO limit to the amount of parasitemia

Question 18

Wait, why do we get hypoxia and lactic acidosis with malaria?

Answer 18

Sequestration

Erythrocytes containing mature P. falcip. parasites develop “knobs” and express adhesion molecules that bind to endothelial cells of capillaries and post-capillary venules.

Additionally, there is decreased deformability of infected AND non-infected RBCs, contributing to sludging, rosetting, aggregation, and eventual blockage of blood vessels.

This causes tissue hypoxia and organ failure.

Question 19

What defines cerebral malaria?

Answer 19

acute encephalopathy not attributable to other causes in a patient with malaria

• decreased consciousness
• delirium
• seizures

cerebral malaria is driven by sequestered RBC in brain blood vessels

Question 20

What are the outcomes of cerebral malaria

Answer 20

mortality: 100% without Rx, 20% with Rx

gross neurologic sequelae in 10% of survivors

–>2/3 of neurologic sequelae in children occur in large vessel distributions (ex. hemiplegia)…a bit of a mystery.

Question 21

What 4 hypotheses outline the drive of Cerebral Malaria symptoms

Answer 21

venous obstruction hypothesis
- Sequestered RBCs in post-capillary venules cause vascular obstruction leading to vascular congestion

inflammation and vasogenic edema hypothesis
- Malaria toxin (probably glycophosphoinositol) activates monocytes to secrete proinflammatory cytokines such as IL-1, IL-6, M-CSF, and TNF, disrupting blood-brain barrier

cytotoxic edema hypothesis
- Impaired perfusion causes metabolic injury & cell death, disrupting BBB.

hemostasis dysfunction hypothesis
- Coagulation dysfunction contributes to pathology.

Question 22

How good is Antigen capture for diagnosing Malaria?

Answer 22

antigen capture
BINAX Now malaria card test (tests for malaria antigens)

• approved by FDA in 2007
• sensitivity 95%

Question 23

P vivax and ovale have two histological features of smear. What are they?

Answer 23

• Schuffner’s dots

- enlarged infected cells

Question 24

P Malriae has two histological features all to itself, what are they?

Answer 24

• Band forms
• Owl eye trophozoite

Smaller infected cells with yellow brown pigment

Question 25

P Falciparum has special feature on histology, you guessed it, two in particular. What do they look like?

Answer 25

• Multiple ring-shaped trophozoites

- Banana shaped gametocyte

Question 26

How do we prevent Malaria?

Answer 26

Personal protection measures

Chemotherapy

• doxycycline
• atovaquone/proguanil
• mefloquine
• Primaquine
• Chloroquine (in chloroquine-sensitive areas)

Question 27

What antimalarials can we use to treat someone who now has Malaria?

Answer 27

• artemesin compounds
• quinoline derivatives (incl. quinine, chloroquine, mefloquine, and primaquine)
• antifolates (incl. proguanil and pyrimethamine/sulfadoxine)
• other (incl. tetracycline, atovaquone/proguanil)

Question 28

Something to consider when treating patients with P vivax or P. ovale

Answer 28

Patients with P. vivax and P. ovale should receive therapy (primaquine) to eradicate any remaining hypnozoites after treatment for intraerythrocytic stage.

Question 29

When do we shift to IV therapy in those with Malaria?

Answer 29

In the presence of depressed sensorium, vomiting, organ dysfunction or parasitemia more than 5%, intravenous therapy should be used

Question 30

First thing you do in regards to care for someone with P. Falciparum

Answer 30

Admit all patients with P. falciparum.

Question 31

What mosquito transmits Malaria?

Answer 31

source: vector transmitted by the female Anopheles mosquito.

Question 32

Review: Discuss the life cycle of Malaria

Answer 32

Lifecycle: Anopheles mosquitoes carry sporozoites in saliva → infect human host → travels to liver to become trophozoites → become schizonts (ring shaped) → divide into merozoites (form sex gametocytes). → burst from hepatocytes → infect RBCs