by Meredith Maxey [Honors Tutorial college/BIOS]          

HEALTH HOME                                                               REFERENCES

Malaria

Page 1 of 3

Medieval Italian: mala aria or “bad air”               

Thought to have been a link to the smell of swamps, where there were many mosquitoes

Malaria is an infectious disease common in tropical and subtropical regions.  It is responsible for 1 to 3 million deaths annually and is caused by a protistan parasite – Plasmodium.

Picture: Painting of a swamp - malaria's namesake Source

Brief Recap of Life Cycle

• Anopheles injects Plasmodium into human host when feeding…

• Plasmodium infects cells, replicates, and wreaks further havoc…

• Some RBCs carrying Plasmodium can be transmitted back to a mosquito seeking a blood meal…

Symptoms                                                             

Picture: Man with malaria being examined Source

Generally, the infected person will be asymptomatic for 10-28 days.  Then the infected person may experience…

• Characteristic waves of fever and chills (lasting 4-10 hours)

  • 2 day cycle for P. vivax and P. ovale

  • 3 day cycle for P. malariae

  • None for P. falciparum (malignant tertian)

• Anemia - hemolysis

• Hemoglobinuria

• Convulsions

• Vomiting

• Tingling of skin (P. falciparum)

• Splenomegaly

Image: Note shape of enlarged spleen (splenomegaly)

• Coma (“sticky” RBCs affect integrity of blood brain barrier)

• Death

 Consequences of infection   

Young children with cerebral malaria may have severe neurological deficits.  Pregnant women may experience increased infant mortality, stillbirths, and babies with low birth weights.

Preferred Diagnostic Method

Microscopic examination of blood films allows for identification of the species of Plasmodium.

P. falciparum

• visible gametocytes

• visible trophozoites

P. vivax

• parasitized RBCs = 2x normal

• schizonts have up to 20 merozoites

P. ovale

• schizonts never have > 12 merozoites

P. malariae

• parasitized RBCs appear smaller than normal

• visible band forms across infected RBCs

 <<Previous Page                              

Microscopic examination of blood films

Thin films are similar to usual blood films and allow for species identification.  Thick films, on the other hand, screen a larger volume of blood and are 11x more sensitive than thin (.0000001%).  However, the parasite appearance is distorted.

Problems with blood films                                      

Picture: Common examples of "bad" blood films Source

Films MUST be made shortly after sampling            

or sample can be altered by…

Warm temperatures (schizonts rupture à P. falciparum)

EDTA (P. vivax and P. ovale à P. malariae size)

Cool temperatures (gametocyte divisions mistaken for other organisms)

If no microscopes…

Antigen detection tests can be used

• OptiMAL-IT ®

  • P. falciparum to 0.01%

  • Non-falciparum to .1%

• Paracheck-Pf ®

  • Detects parasites to 0.002%

  • Won’t distinguish between species

• Rapid assays are being developed for the field

 Treatment           

Several families of drugs used for treatment of prophylaxis based on the dosing. Chloroquine is the standard, but Plasmodium falciparum is resistant.

Drugs for therapy                                                 

Picture: Sample treatment instructions Source

Artemether-lumefantrine (Coartem)

Artesunate-amodiaquine

Artesunate-mefloquine

Artesunate-sulfadoxine

Quinine – toxic to the malaria parasite by interfering with the bug’s ability to break down and digest hemoglobin.

Primaquine (P. vivax and P. ovale only!)

Drugs for therapy and prophylaxis

Atovaquone-proguanil (Malarone)

Chloroquine

Cotrifazid

Doxycycline                           

Mefloquine (Lariam)

Sulfadoxine-pyrimethamine

 Chloroquine as a model drug

Mechanism

• Caps hemozoin molecules

• Leads to heme build up

• Toxic to cell                                      

Picture: Areas of chloroquine resistance Source  

P. falciparum Resistance

• They can efflux chloroquine at 40x normal the normal rate. 

• This gets rid of the toxic buildup of heme that chloroquine causes. 

• Mutations in the Plasmodium falciparum

• Chloroquine Resistance Transporter (PfCRT) gene are thought to be responsible for this.

Standards for Treatment

The WHO (2001) recommends using artemisinin-based combination therapy (ACT) which costs up to 20X as much as older meds.  There are still problems with availability and cost -- even in the United States.  These problems are especially evident in developing nations.   It only costs between a quarter and $2.40 (USD) to treat these people; the problem is largely one of availability (vs expense).

  Next Page>>