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Chapter 20 : Human Babesiosis

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Human Babesiosis, Page 1 of 2

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Abstract:

Babesial organisms are tick-transmitted intraerythrocytic parasites that are collectively called piroplasms, because they form pear-shaped figures within infected red blood cells. The piroplasms are almost universally transmitted by ixodid ticks and are capable of infecting a wide variety of vertebrate hosts that serve as reservoirs within the transmission cycle. Babesiosis is caused by infection with intraerythrocytic parasites of the genus . Most of what is known about the natural history of babesial infections comes from observations of vertebrate hosts other than humans, although the advent of new diagnostic tools has resulted in recent recognition of human babesiosis as an important tick-borne zoonosis. Human babesiosis was first described only in 1957 but is now known to have a worldwide distribution. The increase in reported cases is likely due to both increases in actual incidence and increased awareness of the disease. Despite improved understanding of the disease, babesiosis continues to have significant medical impact. It can also be a confounding variable in the diagnosis and treatment of Lyme disease and as a potential threat to the blood supply, especially in the United States. Diagnostic advances, including the development of PCR assays, have resulted in increased sensitivity of detection as well as the discovery and characterization of new babesial species. Further studies using the molecular tools available and those under development will lead to a better understanding of the natural history of this disease and its pathogenesis in humans.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20

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Figures

Image of Figure 1
Figure 1

Phylogenetic tree representation of a neighbor-joining analysis of several species of piroplasms. Five hundred nucleotides of the nss-rRNA were aligned using the Pileup program (Genetics Computer Group, University of Wisconsin). Phylogenetic analysis of the alignment was performed as described previously ( ) using the Molecular Evolutionary Genetics Analysis (MEGA) computer program, version 1.01 ( ), to make a Jukes-Cantor distance measurement and perform a neighbor-joining analysis with 500 bootstrap replicates. The Phylogenetic Analysis Using Parsimony (PAUP) computer program, version 3.1.1, was used to confirm the order observed by the neighbor-joining analysis (using a branch-and-bound algorithm with 100 bootstrap replicates).The percentage of neighbor-joining bootstrap replications (>50%) is shown above each node. This tree is consistent with previously published analyses. Species known to infect humans are marked with asterisks. The groups of large and small species are bracketed and labeled.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Figure 2
Figure 2

Life cycle of spp. in the tick and vertebrate hosts. Events in the tick begin with the parasites still visible in consumed erythrocytes. (A) Some are beginning to develop Strahlenkörper forms. (B) The released gametes begin to fuse (note that only one of the proposed mechanisms is pictured; one gamete has a Strahlenkörper form whereas the other does not). (C) The zygote then goes on to infect other tissues within the tick and migrates to the salivary glands. (D) Once a parasite has infected the salivary acini, a multinucleate but undifferentiated sporoblast is formed. (E) After the tick begins to feed, the specialized organelles of the future sporozoites form. (F) Finally, mature sporozoites bud off from the sporoblast. (G) As the tick feeds on a vertebrate host, these sporozoites are inoculated into the host. (H) Sporozoites (or merozoites) contact a host erythrocyte and begin the process of infection by invagination. (I) The parasites become trophozoites and can divide by binary fission within the host erythrocyte, creating the various ring forms and crosses seen on stained blood smears.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Figure 3
Figure 3

Model of the cells and effector molecules involved in immunity to species. Different immune mechanisms contribute to resistance during each stage of the babesial infection. (A) During the establishment stage antibodies (IgG) play a role in preventing erythrocyte infection by binding the free sporozoites. (B) During the progression stage the organisms succeed in invading the erythrocyte, and the resulting merozoites proliferate and lyse the infected cell. After lysis has occurred, parasites reach the bloodstream again to initiate a new round of invasion. Several rounds of this cycle cause parasitemia levels to increase. Cells of the innate immune system, especially NK cells and macrophages, have been implicated in antibabesial activity and are thought to control the growth rate of the merozoites. The inhibition seems to rely on the production of soluble factors: IFN-γ by NK cells, and TNF-α, nitric oxide (NO), and ROS by macrophages. (C) In the resolution stage parasitemia reaches a maximum and then declines. The decrease in parasites seems to be due at least in part to intracellular degeneration inside the erythrocyte, as evidenced by the appearance of “crisis forms.” T lymphocytes seem to be the cells responsible for parasite clearance, specifically the subpopulation of CD4 IFN-γ producers, although the specific role of IFN-γ is uncertain.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Map 1
Color Map 1

Approximate geographic distributions of tick-borne encephalitides caused by Central European encephalitis virus (CEE) (red), Kyasanur Forest disease virus (KFD) (blue), louping ill virus (LI) (green with horizontal lines), Omsk hemorrhagic fever virus (OHF) (back slashes), Powassan encephalitis virus (PWE) (green), and Russian spring-summer encephalitis virus (RSSE) (yellow with horizontal lines).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Map 2
Color Map 2

Approximate geographic distributions of (green with horizontal lines). (red with horizontal lines), (red), (green), (blue), (yellow with horizontal lines), and (yellow with vertical lines).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Map 3
Color Map 3

Approximate geographic distributions of (yellow with black slashes), (green), (red), (green with forward slashes), and (blue).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Map 4
Color Map 4

Approximate geographic distributions of (vertical lines), (red). (blue), (red with horizontal lines), (yellow with horizontal lines), and (green).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Map 5
Color Map 5

Approximate geographic distributions of (red), (green), (green with vertical lines), (red with vertical lines), (yellow with vertical lines), (red with horizontal lines), (yellow with horizontal lines), (forward slash), and (blue).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Map 6
Color Map 6

Approximate geographic distributions of (red), (green with horizontal lines), (red with horizontal lines), (blue), (red with vertical lines), and (yellow with horizontal lines).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Map 7
Color Map 7

Approximate geographic distributions of human cases of Crimean-Congo hemorrhagic fever (CCHF) (red), type A tularemia caused by (back-slashed lines), and type B tularemia caused by (yellow with forward-slashed lines).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Map 8
Color Map 8

Approximate geographic distributions of (back slashes), (red), (green), (blue), and (yellow with vertical lines).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Map 9
Color Map 9

Approximate geographic distributions of human cases of tick-borne spotted fevers caused by (Rocky Mountain spotted fever [RMSF]) (red with spots), (Mediterranean spotted fever [MSF]) (blue), (North Asian tick typhus [NATT]) (red), (African tick bite fever [ATBF]) (yellow with horizontal lines), (Flinder's Island-Thailand tick typhus [TTT] (green), and (Queensland tick typhus [QTT]) (red with horizontal lines).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Map 10
Color Map 10

Approximate geographic distributions of Lyme borreliosis caused by sensu stricto (ss) (red), (horizontal lines), and (vertical lines) ( overlaps ).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Map 11
Color Map 11

Approximate geographic distributions of (red), (green), (yellow), (blue), and (yellow with horizontal lines).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 1
Color Plate 1

(A) Adult female lone star tick (). The lone star tick is broadly distributed throughout the southeastern quadrant of the United States, with range extensions into New England and midwestern states. All three stages bite humans. is a recognized vector of several pathogens that cause diseases in humans, including ehrlichioses caused by and , and has been implicated as a vector of southern tick-associated rash illness believed to be caused by “.” Other pathogens or potential pathogens have been detected in this tick, including various spotted fever group rickettsiae, , and , although the role of in the transmission of these agents to humans is not well characterized. (B) Adult female American dog tick (). This tick is abundant in the southeastern United States and coastal New England, with limited distribution in several midwestern states, southern Canada, and western coastal regions. The tick is best known as the primary vector of Rocky Mountain spotted fever in the eastern United States. (C) Adult female blacklegged or deer tick (). As a member of the greater group that also includes , , and , this tick is an important vector of several infectious agents that cause disease in humans, including Lyme borreliosis, (granulocytic) anaplasmosis, and babesiosis. ticks elsewhere in the world may also transmit tick-borne flaviviruses capable of causing encephalitis, encephalomyelitis, and even hemorrhagic fevers (including tick-borne encephalitis virus, louping ill virus, Russian spring-summer encephalitis virus, Powassan virus, Kyasanur Forest disease virus, and Langat virus). Images courtesy of G. Maupin.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 2
Color Plate 2

(A to E) Soft tick morphology. (A) The soft tick is long lived and feeds repeatedly on humans and other mammals. (A and E) Dorsal aspect of an engorged female: the cuticle has a leather-like texture, lending to the name “Lederzecke” (leather tick), the German vernacular for argasid ticks. (B, C, and D) The capitulum is located in a subterminal, ventral position. The unfed argasid ticks are flat and highly mobile. When inactive, they hide in cracks and crevices. Each blood meal takes minutes to a few hours. In contrast, adult ixodid females feed for several days. (F to I) Hard tick morphology. (F) Engorged female tick. (G) Closeup of mouthparts nymph. C, chelicerae; P, palps; H, hypostome. The mobile distal cheliceral teeth reach beyond the hypostome. (H) During feeding, the palps are splayed laterally (female tick). (I) A feeding couple; the female tick is in front. (J) Tick feeding lesion. Adult female (below) feeding on a sensitized rabbit (above). Predominantly mixed inflammatory infiltrate cells line the feeding cavity. Discrete dermal swelling and dilated venules are found in the proximity. The mouthparts are anchored deep into the dermis, just reaching the cavity from which the tick feeds as indicated by the imprint of the hypostome contours (trichrome stain). Photographs courtesy of S. Archibald and E. Denison.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 3
Color Plate 3

Anatomy of a tick bite. This series of images was obtained from a single feeding adult female tick removed by biopsy from a patient in Maryland. The images show the partially engorged tick embedded in the skin (A) and the tick and skin sectioned en block (B) (hematoxylin and eosin [H&E] stain; original magnification, ×8). (C to E) Positioning of the tick capitulum and hypostome with relation to the epidermis (H&E stain; original magnification ×16) (C and D), the positioning of the hypostome into the dermis with the inflammatory vascular pool at its distal end (H&E stain; original magnification, ×16) (E), and the inflammation and edema present in the dermal blood pool upon which the tick feeds (H&E stain; original magnification, ×40). (F) Anatomical structures of importance in acquisition and transmission of pathogens by ticks with subsequent molts include the midgut into which pathogens pass with the blood meal and the hemocele into which pathogens pass after penetration of the midgut epithelium (H&E stain; original magnification, ×40). (G) Pathogens that are transmitted by tick bite gain access to the tick salivary gland before passing into the dermal vascular pool in tick saliva (H&E stain; original magnification, ×40). Not shown is the tick ovary, into which some pathogens may invade to allow transovarian transmission.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 4
Color Plate 4

Colorado tick fever virus (family ) (see Chapter 8) propagated in BHK-21 cells produces viral particles approximately 80 nm in diameter with a 50-nm core. (A) Thinsection electron microscopy; original magnification, ×30,500; (B) negative stain electron microscopy, original magnification, ×118,800. Images courtesy of F. A. Murphy.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 5
Color Plate 5

(A) Crimean-Congo hemorrhagic fever virus (family ) (CCHF) (see Chapter 10) causes liver injury characterized by diffuse microvesicular steatosis and hepatocyte necrosis (H&E stain; original magnification, ×133). (B) Immunohistochemistry for CCHF virus demonstrates localization of viral antigens to the cytoplasm of swollen, degenerating hepatocytes and to endothelial cells lining hepatic sinusoids (original magnification, ×133). Images courtesy of S. R. Zaki.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 6
Color Plate 6

(A) Erythema migrans rash in Lyme borreliosis (Chapter 11). Note the distinctive and well-defined erythematous border of this large lesion. Also, note the relative central clearing and central punctate (“bull's eye”) lesion at the site of tick attachment. Image courtesy of P. G. Auwaerter. (B) Acrodermatitis chronica atrophicans, a late skin manifestation of infection, shown affecting the legs of an elderly woman where the skin has become thinned and atrophic. Image courtesy of R. Muellegger. (C) Photomicrograph of skin biopsy of erythema migrans lesion (as seen in panel A) from a patient with early-stage Lyme disease (H&E stain), showing perivascular lymphocytic and plasma cell inflammatory infiltrates. (D) Modified Dieterle silver stain of spirochete in perivascular area of an erythema migrans lesion. Images in panels C and D courtesy of B. Berger.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 7
Color Plate 7

The ulceroglandular form of tularemia (see Chapter 12) may present with a striking ulcer, such as that seen here on a finger (A) or with lymphadenitis, which may also occur independently without evidence of an ulcer (so-called glandular tularemia) or in oropharyngeal tularemia (B). (C) Affected lymph glands are characterized by multiple granulomas and geographic necrotizing inflammation (H&E stain; original magnification, ×12.5). (D) The lymph node shows granulomas and granulomatous inflammation with palisaded histiocytes surrounding an extensive central region of suppurative and necrotizing inflammation (H&E stain; original magnification, ×100). (E) can be demonstrated by immunohistochemistry within histiocytes in the necrotic tissue (original magnification, ×100). Images in panels D and E courtesy of S. R. Zaki.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 8
Color Plate 8

Human granulocytic anaplasmosis (HGA, formerly known as human granulocytic ehrlichiosis or HGE) (see Chapter 13) caused by . (A) A cluster of bacteria, called a morula, is visible in the cytoplasm of a peripheral blood neutrophil (Wright stain; original magnification, ×400). The morula is differentiated from other leukocyte inclusions by the presence of dark blue to violaceous punctate staining, confined to one or few vacuoles. (B) Mild to moderate liver injury is frequent, and the underlying histopathology illustrates the frequent presence of mild lobular hepatitis with focal inflammatory lesions, apoptotic hepatocytes, and Kupffer cell hyperplasia (H&E stain; original magnification, ×40). (C) Opportunistic infections may occur as severe complications of HGA (H&E stain; original magnification, ×8); in this case, a gastroesophageal ulcer caused by infection occurred, resulting in fatal gastrointestinal bleeding (panel C inset, Gomori methenamine silver stain; original magnification, ×160). (D) Photomicrograph of Giemsa-stained HL-60 cells infected in vitro with isolated directly from the blood of a patient with HGA. Note multiple colonies of organisms in the cytoplasm of infected cells. Image courtesy of J. L. Goodman.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 9
Color Plate 9

spp. infections include human monocytic ehrlichiosis (HME) () (see Chapter 14) and infection by (see Chapter 15). (A) Typical morula with pale blue violaceous bacteria in a circulating blood monocyte (Wright stain; original magnification, ×400). Image courtesy of Aileen Marty. (B) Morulae of isolated from the blood of a patient with HME growing in the DH82 canine macrophage cell line. (C) As with human granulocytic anaplasmosis (HGA), HME frequently involves the liver and may be severe. The image shows necrosis and moderate lobular hepatitis (H&E; original magnification, ×16). (D) Small noncaseating granulomas typical of those frequently seen in tissues of patients with HME, including the bone marrow (H&E stain; original magnification, ×16). (E) Meningitis and meningoencephalitis occur in approximately 20% of patients with HME but are rare in HGA. Shown is a mild infiltration of the meninges by lymphocytes and histiocytes in a patient who died after contracting HME (H&E; original magnification, ×16). (F) As with , propagates in neutrophils in peripheral blood (modified Wright's stain; original magnification, ×400); (G) it may also occasionally be identified in inflammatory infiltrates in various organs, as in this bronchoalveolar lavage specimen of a patient with pulmonary manifestations associated with infection (modified Wright's stain, original magnification, ×400).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 10
Color Plate 10

Relapsing fever borreliae () (see Chapter 16) in peripheral blood can accumulate to quantities as high as 10 to 10/ml, sufficient for easy identification on Romanovskystained films (Wright-Giemsa stain; original magnification, ×336). Note the long (15 to 30 µm) and narrow (0.2 to 0.5 µm) spiral shape (arrows), typical of and other spirochetes. Blood smear courtesy of T. G. Schwan.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 11
Color Plate 11

Rocky Mountain spotted fever (RMSF). infects and damages endothelial cells and may cause profound vascular leakage. A macular or maculopapular rash that blanches with pressure is typically detected in the first several days of illness. (A) Petechiae frequently develop as the rash evolves, as a result of extravasation of erythrocytes into the dermis where vasculitis (C) may also be observed (H&E stain; original magnification, ×8). (C, inset) The rickettsiae alone are sufficient to cause vascular leakage, but their presence also elicits lymphohistiocytic and leukocytoclastic vasculitis, occasionally associated with fibrin deposition or non-occlusive thrombus formation (H&E stain; original magnification, ×16). (E) Vasculitis may involve all organs, and the most significant complications include pulmonary and central nervous system involvement ( immunohistochemistry; original magnification, ×260). (B) Pulmonary involvement may lead to bilateral interstitial infiltrates seen on chest radiographs. (D) Markedly increased microvascular permeability in the lung, believed to be due to rickettsia-mediated endothelial cell damage (H&E stain; original magnification, ×16) may lead to noncardiogenic pulmonary edema ( immunohistochemistry in skin; original magnification, ×260) (F). Meningoencephalitis and rickettsia-induced endothelial cell damage and inflammation can lead to cerebral edema and herniation. (G to I) Meningeal vasculitis (H&E stain; original magnification, ×100) (G) and one of many scattered mononuclear inflammatory cell infiltrates in the brain called microglial or typhus nodules (H&E stain; original magnification, ×100) (H). Immunohistochemical staining for shows widespread rickettsial infection of cerebral microvascular endothelial cells (original magnification, ×160) (I).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 12
Color Plate 12

Double-stained (F-actin and spotted fever group rickettsiae) immunofluorescence photomicrograph of utilizing actin tail formation for mobility in and cellto- cell spread between mouse (L-929) host cells. Image created by dual excitation of appropriate wavelengths for Texas red phalloidin and fluorescein isothiocyanate-conjugated antibodies to . Bar, 10 µm. Image courtesy of J. A. Simser and T. J. Kurtti.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 13
Color Plate 13

Mediterranean spotted fever (MSF) (boutonneuse fever) caused by (see Chapter 18). (A) The hallmark lesion of MSF is an eschar (tache noir) at the site of tick attachment. Image provided courtesy of P. E. Fournier and D. Raoult. (B and C) The tache noir is characterized by epidermal and dermal necrosis with extensive mixed inflammation, dominated by lymphocytes and histiocytes, with admixed endothelial cell injury, vasculitis, edema, and fibrin deposition or thrombosis. H&E stain; original magnification, ×8 (B) and ×100 (C). (D) Immunohistochemical staining for shows the scattered presence of organisms in cells in areas of necrosis and inflammation (original magnification, ×160). (E) In disseminated MSF, vasculitis and maculopapular skin lesions similar to those seen in Rocky Mountain spotted fever can be observed. Image courtesy of P. E. Fournier and D. Raoult.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 14
Color Plate 14

Other spotted fever group rickettsiae frequently elicit eschars at the site of tick bites. (A) African tick-bite fever caused by (see Chapter 18) is associated with one or more eschars, but the disease is often milder than Mediterranean spotted fever (MSF) and may include vesicular skin lesions. Image courtesy of P. E. Fournier and D. Raoult. (B) Similar to the histopathologic changes in MSF, eschars demonstrate an intense lymphohistiocytic infiltrate in the deep dermis extending into the panniculus (H&E stain; original magnification, ×25). (C) Immunohistochemical staining identifies intact rickettsiae and rickettsial antigens (red) in the infiltrate, distributed predominantly in perivascular locations (original magnification, ×25; inset original magnification, ×158). Panels B and C courtesy of R. Zaki. (D) Although rarely recognized, , a close relative of , is a proven cause of eschars in the Americas (see Chapter 17). Image courtesy of C. A. Ohl. (E) In this case, immunohistochemical staining (original magnification, ×250) demonstrates in the cytoplasm of a mononuclear cell. (F) This infected cell was identified subjacent to the eschar in the intense perivascular lymphohistiocytic infiltrate surrounding a dermal vessel with swollen endothelial cells (H&E stain; original magnification. ×158). Images in panels E and F courtesy S. R. Zaki. (G) Eschar and lymphangitis observed in a febrile patient in Marseille, France, possibly due to () (see Chapter 18).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 15
Color Plate 15

Tick-borne lymphadenitis (TIBOLA) (also called wood scar or -borne necrosis-erythema lymphadenopathy [DEBONEL]), likely due to (see Chapter 18). Inoculation eschar to the scalp (arrow) (A) and resultant enlarged cervical lymph nodes (B, arrow) in a patient with TIBOLA (see Chapter 18).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 16
Color Plate 16

causes both acute and chronic Q (query) fever (see Chapter 19). While typically transmitted via the respiratory route, it is rarely transmitted to humans by ticks. Acute manifestations range from moderate to severe pneumonia with airspace involvement and mild interstitial pneumonitis (A) (H&E stain; original magnification, ×16). (Inset) replicates to enormous levels in infected macrophages that often are localized within alveolar spaces ( immunohistochemistry; original magnification, ×100). (B) Acute infection can result in dissemination and formation of noncaseating granulomas in many organs, including the liver and bone marrow (H&E stain; original magnification, ×40). Chronic Q fever, usually manifested as endocarditis (C) or infection of vascular prostheses, does not typically cause an immune response that results in granulomas. Q fever endocarditis progresses slowly resulting in cardiac valves dominated by lymphohistiocytic inflammation with necrosis and fibrin deposition (H&E stain; original magnification, ×16). (Insets) can be visualized within macrophages of the inflammatory infiltrate of the damaged valve ( immunohistochemistry; original magnification, ×16 and ×100).

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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Image of Color Plate 17
Color Plate 17

Human babesiosis (see Chapter 20) can be caused by several different protozoan species in the genus . In North America, most cases of human babesiosis are caused by . (A) forms pleomorphic and amoeboid intraerythrocytic rings that can be difficult to differentiate from other babesial species and from spp. (Wright stain, original magnification, ×160). (B) Rare examples of infection by -like piroplasms called WA-1 (Wright stain; original magnification, ×160) have been documented in the Pacific northwest and in California. Image courtesy of D. H. Persing. (C) -like piroplasms are found in Europe and have also been observed in an infected person in Missouri in the south-central United States (Wright stain; original magnification, ×160). Image courtesy of E. Masters. When present, a helpful finding differentiating spp. from spp. is the presence of tetrads of merozoites, termed Maltese crosses (B). (D) in a peripheral blood smear from an infected patient detected by acridine orange staining and fluorescent microscopy. Image courtesy of D. H. Persing.

Citation: Homer M, Persing D. 2005. Human Babesiosis, p 343-360. In Goodman J, Dennis D, Sonenshine D, Tick-Borne Diseases of Humans. ASM Press, Washington, DC. doi: 10.1128/9781555816490.ch20
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