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Plasmodium falciparum (True Pathogen – Malignant Tertian Malaria)

Organism:
This organism belongs to the phylum Apicomplexa, is a true pathogen, and causes malaria.  In general, the ring forms, the gametocytes, and occasionally a mature schizont can be found in clinical specimens (thick and thin blood films). Other forms are sequestered in the deep tissue capillaries.

Description: C:\Users\User\Desktop\Old Data\Photoshop\NEW BLOODS, OLYMPUS\P. falciparum rings lg color2x2.jpg Description: C:\Users\User\Desktop\Old Data\Photoshop\NEW BLOODS, OLYMPUS\P. falc rings applique 2 inGOOD.jpg Description: C:\Users\User\Desktop\Old Data\Photoshop\NEW BLOODS, OLYMPUS\P. falc gameto.2x2.jpg
Plasmodium falciparum ring forms Plasmodium falciparum gametocyte

Life Cycle:
Within an hour of infection, sporozoites from the mosquito are carried via the blood to the liver, where they penetrate parenchymal cells, thus initiating the preerythrocytic or primary exoerythrocytic cycle.  The sporozoites become round or oval and begin dividing, resulting in large numbers of liver merozoites.  The merozoites leave the liver and invade the red blood cells (RBCs), initiating the erythrocytic cycle.
P. falciparum tends to invade all ages of RBCs, and the proportion of infected cells may exceed 50%. Schizogony occurs in the internal organs (spleen, liver, bone marrow, etc.) rather than in the circulating blood. Ischemia caused by the plugging of vessels within these organs by masses of parasitized RBCs will produce various symptoms, depending on the organ involved. It has been suggested that a decrease in the ability of the RBCs to change shape when passing through capillaries or the splenic filter may lead to the plugging of the vessels.

Acquired:
Bite:  female anopheline mosquito; blood, shared needles, congenital infections
Epidemiology:
Tropics, mosquito to human, human to human transmission
Clinical Features:
Early Infection:  Onset of a P. falciparum malaria attack occurs from 8 to 12 days after infection and is preceded by 3 to 4 days of vague symptoms such as aches, pains, headache, fatigue, anorexia, or nausea. The onset is characterized by fever, a more severe headache, and nausea and vomiting, with occasional severe epigastric pain. There may be only a feeling of chilliness at the onset of fever. Periodicity of the cycle will not be established during the early stages, and the presumptive diagnosis may be totally unrelated to a possible malaria infection. If the fever does develop a synchronous cycle, it is usually a cycle of somewhat less than 48 h.  An untreated primary attack of P. falciparum malaria usually ends within 2 to 3 weeks. True relapses from the liver do not occur, and after a year, recrudescences are rare.           
Complications:  Severe or fatal complications of P. falciparum malaria can occur at any time and are related to the plugging of vessels in the internal organs, the symptoms depending on the organ(s) involved. Severe complications may not correlate with the parasitemia seen in the peripheral blood.

Clinical Specimen:
Blood:  Multiple draws (EDTA).  Malaria is one of the few parasitic infections considered to be immediately life‑threatening, and a patient with the diagnosis of P. falciparum malaria should be considered a medical emergency because the disease can be rapidly fatal. Any laboratory providing the expertise to identify malarial parasites should do so on a 24‑h basis, 7 days/week.

Laboratory Diagnosis:
Although malaria is no longer endemic within the United States, this infection is life threatening, and laboratory requests for blood smear examination and organism identification should be treated as “STAT” requests.  Frequently, for a number of different reasons, organism recovery and identification may be more difficult than the textbooks imply.  It is very important that this fact be recognized, particularly when one is dealing with a possibly fatal infection with P. falciparum.
            Both thick and thin blood films should be prepared on admission of the patient (clinic, emergency room, in-house), and at least 300 oil immersion fields should be examined on the thick and thin film before a negative report is issued.  Since one set of negative films will not rule out malaria, additional blood specimens should be examined over a 36 h time frame.  Although Giemsa stain is used for parasitic blood work; the organisms can also be seen with other blood stains such as Wright’s, Wright-Giemsa, or any of the rapid blood stains.  Blood collected with EDTA anticoagulant is acceptable; however, if the blood remains in the tube for any length of time, true stippling may not be visible within the infected RBCs (P. vivax as an example), organisms will change their morphology, and some of the parasites will disintegrate (after 4-6 h).  Also, it is important to remember that the proper ratio between blood and anticoagulant is necessary for good organism morphology.

Organism Description:
Ring Forms:  Although ring forms of P. falciparum have been described as small, when the blood is collected in EDTA (venipuncture), the rings continue to grow; thus their size may mimic the other species.
Gametocyte:  The gametocytes have been described as crescent-shaped; however, in patients with an early infection, the gametocytes have not yet appeared in the blood.  This is a critical feature of immunologically naïve patients (travelers with no prior exposure to malaria) who present to the ER with symptoms, but very light parasitemias and no gametocytes in the blood.

Laboratory Report:
A number of reports can be relevant – remember to add the appropriate report comments.
Report 1:  No Parasites Seen:  The submission of a single blood specimen will not rule out malaria; submit additional bloods every 4-6 hours for 3 days if malaria remains a consideration.
Report 2Plasmodium spp. Seen:  Unable to rule out Plasmodium falciparum or Plasmodium knowlesi
Report 3Plasmodium spp., possible mixed infection:  Unable to rule out Plasmodium falciparum or Plasmodium knowlesi
Report 4:  Negative for parasites using automated hematology instruments.  Automated Hematology instruments will not detect low malaria parasitemias seen in immunologically naïve patients (travelers)

Treatment: 
Garcia, L.S. 2007.  Diagnostic Medical Parasitology, 5th ed., ASM Press, Washington, D.C.

Control:
Improved mosquito control, impregnated bed nets, potential vaccines, prophylaxis

Comments:
It is important to remember that the malarial parasites remain viable in the tube of blood collected using EDTA.  If the blood cools and the cap is removed (blood becomes aerated), the organisms then begin the life cycle seen in the mosquito.  Thus exflagellation of the male gametocyte can mimic spirochetes when they separate from the gametocyte (see below):

Description: C:\Users\User\Desktop\Old Data\Photoshop\NEW BLOODS, OLYMPUS\P. falc exflagellation 3002x2.jpg Description: C:\Users\User\Desktop\Old Data\Photoshop\Old Blood Parasites\P. falc exflagg full slide.jpg Description: C:\Users\User\Desktop\Old Data\Photoshop\NEW BLOODS, OLYMPUS\Plas exflagellation single.jpg