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Abstract:

and are intraerythrocytic apicomplexan parasites that cause malaria and babesiosis, respectively. Both organisms can cause severe, life-threatening disease. Malaria is transmitted through the bite of an mosquito primarily in the tropics and subtropics while babesiosis is transmitted through the bite of an ixodid tick and is mostly found in temperate regions. The most common species to infect humans are , , , , and . Of these, is responsible for the greatest morbidity and mortality worldwide. and are the most common causes of human babesiosis in the United States and Europe, respectively. Diagnosis of both is traditionally accomplished through microscopic examination of conventional Giemsa-stained thick and thin blood films. The thick film provides the greatest sensitivity for parasite detection and is preferred for screening, while the thin film provides the best morphology for differentiation of and parasites and species determination. Antigen detection methods are also widely used for detection of malaria and molecular amplification methods have been described for both organisms.

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
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Image of FIGURE 1
FIGURE 1

The parasite is transmitted to humans when an infected female mosquito takes a blood meal and inoculates sporozoites into the bloodstream ( ). Sporozoites infect hepatocytes ( ) and undergo asexual reproduction to form schizonts ( ) in a process called exoerythrocytic schizogony (A). After 5 to 15 days, liver schizonts rupture to release hundreds of thousands of merozoites into the blood ( ) which then infect erythrocytes ( ). and have a dormant hypnozoite stage, which may remain in the liver and cause relapsing disease weeks to months later, while other human species do not have this stage. In erythrocytes, merozoites undergo asexual reproduction to form trophozoites and then schizonts in a process called erythrocytic schizogony (B). Schizonts rupture to release merozoites, which then infect other erythrocytes ( ). This process is repeated every 1 to 3 days, resulting in the production of thousands to millions of infected erythrocytes in several days. Some merozoite-infected erythrocytes do not undergo asexual reproduction but instead develop into male microgametocytes and female macrogametocytes ( ). When ingested by a female mosquito during a blood meal ( ), microgametocytes exflagellate to release microgametes, which penetrate macrogametes and form zygotes ( ) via sexual reproduction in the sporogonic cycle (C). Zygotes become motile and elongated to form ookinetes ( ) which invade the mosquito’s midgut wall and develop into oocysts ( ). Over a period of 8 to 15 days, oocysts grow, rupture, and release thousands of sporozoites ( ), which travel to the mosquito’s salivary glands to be inoculated into a new human host during the mosquito’s next blood meal ( ). Life cycle courtesy of the CDC DPDx (http://www.cdc.gov/dpdx/). doi:10.1128/9781555817381.ch136.f1

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
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Image of FIGURE 2
FIGURE 2

morphology on thick blood films encompasses the entire spectrum of forms including trophozoites, schizonts, and gametocytes. Shown are early trophozoites in a moderate ( ) and heavy ( ) infection; early trophozoites ( ); ( ) and ( ) schizonts; and ( ), ( ), and ( ) gametocytes. Neutrophils are shown for size comparison in panels 4 and 7. (Giemsa, ×1,000.) doi:10.1128/9781555817381.ch136.f2

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
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Image of FIGURE 3
FIGURE 3

The ideal location for microscopic examination of a thin film is the region of the feathered edge where the erythrocytes have minimal overlap and maintain their central pallor (middle). In this location, the erythrocyte infected with is clearly enlarged and ovoid. When examining similar cells in regions of the film that are too thin (left) or thick (right), the morphology is distorted and may be misleading. doi:10.1128/9781555817381.ch136.f3

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
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Image of FIGURE 4
FIGURE 4

, successive developmental stages in Giemsa-stained thin blood films: early stage trophozoites/rings with a “headphone” form ( ), rings with Maurer’s clefts ( ), rings with appliqué forms and Maurer’s clefts ( ), maturing trophozoites ( ), early stage schizont ( ), mature schizont ( ) (courtesy of the CDC DPDx), macrogametocyte ( ), and microgametocyte ( ). Rings ( ) and, less commonly, gametocytes ( ) are found in peripheral blood, while other stages ( ) are typically sequestered in the microvasculature. doi:10.1128/9781555817381.ch136.f4

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
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Image of FIGURE 5
FIGURE 5

, successive developmental stages in Giemsa-stained thin blood films: early stage trophozoite/ring ( ), “bird’s eye” ring form ( ), mature trophozoites with “basket” form ( ), mature trophozoite with “band” form ( ), mature schizont ( ), mature schizont showing rosette form with central pigment ( ), macrogametocyte ( ), and microgametocyte ( ). doi:10.1128/9781555817381.ch136.f5

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
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Image of FIGURE 6
FIGURE 6

, successive developmental stages in Giemsa-stained thin blood films: early stage trophozoite/ring, ( ), maturing ring ( ), mature amoeboid trophozoites ( ), mature schizonts ( ), macrogametocyte ( ), microgametocyte ( ). Note the Schüffner’s dots ( ) and frequent molding of infected cells to neighboring erythrocytes. The infected erythrocytes are slightly larger than noninfected cells. doi:10.1128/9781555817381.ch136.f6

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
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Image of FIGURE 7
FIGURE 7

, successive developmental stages in Giemsa-stained thin blood films: early stage trophozoite/ring ( ), developing trophozoite ( ), mature trophozoite with “comet cell” morphology ( ); early stage schizont ( ), mature schizont ( ), macrogametocyte ( ), microgametocyte ( ). Note the Schüffner’s dots ( ) and oval/elongated shape of the infected cells ( ). The infected erythrocytes are slightly larger than noninfected cells. doi:10.1128/9781555817381.ch136.f7

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
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Image of FIGURE 8
FIGURE 8

, successive developmental stages in Giemsa-stained thin blood films: early stage trophozoites/rings ( to ), developing trophozoite ( to ), mature trophozoite with “band” form ( ), early stage schizont ( and ), mature schizont ( and ), immature gametocyte ( ), mature microgametocyte ( and ), mature macrogametocyte ( ). (Images reproduced from figures in with permission.) doi:10.1128/9781555817381.ch136.f8

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
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Image of FIGURE 9
FIGURE 9

Cerebral malaria due to on tissue section (hematoxylin and eosin, ×400). The capillary in the center of the image contains multiple infected erythrocytes, seen primarily by their brown-black hemozoin pigment. doi:10.1128/9781555817381.ch136.f9

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
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Image of FIGURE 10
FIGURE 10

life cycle. The normal zoonotic life cycle involves a rodent (primarily , the white-footed mouse) and an tick. The rodent becomes infected when an infected tick introduces sporozoites when taking a blood meal ( ). Sporozoites enter the rodent erythrocytes and most undergo asexual reproduction ( ), while some differentiate into female and male gametes ( ). Ticks become infected when ingesting gametes in the blood of an infected rodent ( ). Within the tick (A), the gametes undergo sexual reproduction to produce sporozoites ( ). As with rodents, humans become infected through the bite of an infected tick ( ). Sporozoites enter human erythrocytes (B) and undergo asexual replication ( ). Less commonly, humans are infected via blood transfusion ( ). doi:10.1128/9781555817381.ch136.f10

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
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Image of FIGURE 11
FIGURE 11

morphology on thick blood film consists of ring forms resembling trophozoites of . Some pleomorphism is apparent. doi:10.1128/9781555817381.ch136.f11

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
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Image of FIGURE 12
FIGURE 12

morphology on thin blood film. Note the presence of small intraerythrocytic ring forms resembling early trophozoites of , as well as thicker and markedly pleomorphic ring forms. Characteristic extracellular forms (arrow) and a tetrad form (arrow head) are also seen. doi:10.1128/9781555817381.ch136.f12

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
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Tables

Generic image for table
TABLE 1

Characteristics of infections

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
Generic image for table
TABLE 2

Comparative morphology of spp. in Giemsa-stained thin films

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
Generic image for table
TABLE 3

Comparison of malaria diagnostic direct methods

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136
Generic image for table
TABLE 4

Comparative morphology of spp. and

Citation: Pritt B. 2015. and *, p 2338-2356. In Jorgensen J, Pfaller M, Carroll K, Funke G, Landry M, Richter S, Warnock D (ed), Manual of Clinical Microbiology, Eleventh Edition. ASM Press, Washington, DC. doi: 10.1128/9781555817381.ch136

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