General Goal: To know the major causes of malaria, the life cycle of these parasites, the most common modes of transmission and the major manifestations of this disease.
Specific Educational Objectives: The student should be able to:
1. identify the infectious form of this parasite.
2. identify the cause of this disease that results in the most pathology.
3. identify the most common means of transmission of this disease. Know the most common cause of malaria.
4. identify a patient with this disease based on clinical manifestations. There are other diseases with fever that come and go. Knowing the length, severity, and time period between fevers would be very helpful.
5. identify the current prevention strategies.
Reading: MEDICAL MICROBIOLOGY by P.R. Murray, K.S. Rosenthal, G.S. Kobayashi and M.A. Pfaller, 3rd Edition. pp. 632-636.
Mosby's Color Atlas and Text of Infectious Diseases by Christopher P. Conlon and David R. Snydman. pp. 217-221.
Lecture: Dr. Neal R. Chamberlain
References:
Other websites: Malaria Research
Malaria is caused by obligate intracellular protozoan parasites of the genus "Plasmodium". They are members of the class Sporozoa, thus alternating asexual and sexual reproductive cycles are observed.
There are four species of human malarial parasites:
The general features of the following infective cycle apply to all Plasmodium life cycles.
Sporozoites: the infective form; transmitted during the blood-meal feeding of a female Anopheles mosquito on a human. The sporozoites invade and reside within hepatocytes where they increase in numbers.
Merozoites: several days after the initial infection, some of these sporozoite progeny in the liver enter the bloodstream and infect erythrocytes. (ring-cell stage)
Erythrocyte stages: begin when merozoites infect the red blood cells. The parasites attach to specific red blood cell receptors and are endocytosed to initiate infection. Asexual reproduction (schizogony) proceeds through a series of stages resulting in the rupture of the erythrocyte and the release of up to 25 parasites, still called merozoites.
Gametocytes: after one or more of these asexual cycles, some merozoites, within erythrocytes, develop into male and female gametocytes, which are the sexual forms of the parasite.
Zygote: gametocytes which are ingested by the mosquito can fuse within its gut to form a zygote which initiates the sexual reproductive cycle (sporogony), which produces the sporozoites that invade humans via mosquito saliva.
Anemia: results from erythrocyte destruction, and indirectly from increased phagocytosis of red cells, capillary hemorrhage, thrombosis, and decreased marrow function; the most anemia is associated with P. falciparum.
Pigmentation of organs: occurs when the malarial pigment, hemozoin is ingested by phagocytes in lymphoid tissue, liver, spleen and bone marrow.
Hepatomegaly and splenomegaly: results from dilation of the sinuses and increased numbers of macrophages (esp., spleen).
Capillary occlusions: parasitized red cells involved in immune complexes occlude capillaries, cause local hemorrhaging and anoxia in many tissues; the brain is most severely affected.
Intravascular hemolysis in the kidney: hemoglobinemia and hemoglobinuria results in very dark urine; Blackwater Fever.
Dormant sporozoites: after the immune response has terminated the erythrocytic cycle, vivax and ovale sporozoites can remain dormant in the liver and cause a relapse months to years later.
RBC antigen Duffy negative individuals are resistant
to P. vivax infections. Sickle cell individuals develop less
severe P. falciparum malaria.
Incubation period of 2 weeks or longer
A brief prodromal period
Cold stage: (consisting of a shaking chill)
Fever stage: (41-42°C) lasts about 24 hours
Wet stage: several hours after the fever, the body temperature drops quickly to normal, and profuse sweating begins; the patient is exhausted but well until the next cycle of paroxysms begin.
Splenomegaly
Anemia
Three basic types of malaria:
Blood smears: Thick and thin smears are prepared with Wright or Giemsa staining to detect and determine the malaria species involved.
Malaria-specific antibody: not detectable until after the patient first presents symptoms.
Serological tests: include agar diffusion, passive hemagglutination, immunofluorescence, and the ELISA.
Useful for: Patients that have negative blood smears
Detecting carriers of P. vivax and P. malariae in blood used for transfusions.
The primary goal is to eliminate the merozoite stages and erythrocyte destruction.
Chloroquine: Kills all of the different malarial merozoites Kills most of the gametocytes Does not kill P. falciparum gametocytes Does not kill the dormant sporozoites of vivax or ovale.
Primaquine: Can be administered with chloroquine to rid patients of sporozoites in the liver and falciparum gametocytes. Need to screen for glucose-6-phosphate dehydrogenase deficiency.
Quinine sulfate, Mefloquine, or Malarone (a newer (July 2000) fixed combination of atovaquone and proguanil hydrochloride): for chloroquine-resistant P. falciparum
Fansidar: a long-acting sulfonamide has been used prophylactically against P. falciparum, but is not recommended for other species.
Chloroquine prophylaxis in chloroquine-sensitive endemic areas. In areas with chloroquine-resistant P. falciparum Quinine sulfate, Mefloquine or Malarone (a newer (July 2000) fixed combination of atovaquone and proguanil hydrochloride) is suggested.
Primaquine when leaving endemic areas.
A good place for advice on prevention is the "CDC".
Vaccines against P. vivax are being developed and include a number of blood-stage candidates, a transmission-blocking candidate (directs immune response to Duffy binding protein on parasite) and a liver-stage candidate - which could reach clinical trial in 3-5 years. A number of vaccine candidates have also been identified for P. falciparum. Unfortunately, no malaria vaccine is currently available for widespread use.
