Rickettsia Coxiella Orientia and Ehrlichia Typhus Spotted Fever Q Fever Ehrlichioses

■ The genera of the Rickettsiaceae and Coxelliaceae contain short, coccoid, small rods that can only reproduce in host cells. With the exception of Coxiella (aerogenic transmission), they are transmitted to humans via the vectors lice, ticks, fleas, or mites. R. prowazekii and R. typhi cause typhus, a disease characterized by high fever and a spotty exanthem. Several rickettsiae species cause spotted fever, a milder typhuslike disease. Orientia tsutsugamushi is transmitted by mite larvae to cause tsutsugamushi fever. This disease occurs only in Asia. Coxiella burnetii is responsible for Q fever, an infection characterized by a pneumonia with an atypical clinical course.

Several species of Ehrlichiaceae cause ehrlichiosis in animals and humans. The method of choice for laboratory diagnosis of the various rickettsioses and ehrlichioses is antibody assay by any of several methods, in most cases indirect immunofluorescence. Tetracyclines represent the antibiotic of choice for all of these infections. Typhus and spotted fever no longer occur in Europe. Q fever infections are reported from all over the world. Sources of infection include diseased sheep, goats, and cattle. The prognosis for the rare chronic form of Qfever (syn. Qfever endocarditis) is poor. Ehrlichiosis infects mainly animals, but in rare cases humans as well. ■

Classification. The bacteria of this group belong to the families Rickettsiaceae (Rickettsia and Orientia), Coxelliaceae (Coxiella), and Ehrlichiaceae (Ehrlichia, Anaplasma, Neorickettsia). Some of these organisms can cause mild, self-limiting infections in humans, others severe disease. Arthropods are the transmitting vectors in many cases.

Morphology and culture. These obligate cell parasites are coccoid, short rods measuring 0.3-0.5 im that take gram staining weakly, but Giemsa staining well. They reproduce by intracellular, transverse fission only. They can be cultured in hen embryo yolk sacs, in suitable experimental animals (mouse, rat, guinea pig) or in cell cultures.

Pathogenesis and clinical pictures. With the exception of C. burnetii, the organisms are transmitted by arthropods. In most cases, the arthropods excrete them with their feces and ticks transmit them with their saliva while sucking blood. The organisms invade the host organism through skin injuries. C. bur-netii is transmitted exclusively by inhalation of dust containing the pathogens. Once inside the body, rickettsiae reproduce mainly in the vascular en-dothelial cells. These cells then die, releasing increasing numbers of organisms into the bloodstream. Numerous inflammatory lesions are caused locally around the destroyed endothelia. Ehrlichiae reproduce in the monocytes or granulocytes ofmembrane-enclosed cytoplasmic vacuoles. The characteristic morulae clusters comprise several such vacuoles stuck together.

Table 4.13 summarizes a number of characteristics of the rickettsioses.

Diagnosis. Direct detection and identification of these organisms in cell cultures, embryonated hen eggs, or experimental animals is unreliable and is also not to be recommended due to the risk of laboratory infections. Special laboratories use the polymerase chain reaction to identify pathogen-specific DNA sequences. However, the method of choice is currently still the antibody assay, whereby the immunofluorescence test is considered the gold standard among the various methods. The Weil-Felix agglutination test (p. 295) is no longer used today due to low sensitivity and specificity.

Therapy. Tetracyclines lower the fever within one to two days and are the antibiotics of choice.

Epidemiology and prevention. The epidemic form of typhus, and earlier scourge of eastern Europe and Russia in particular, has now disappeared from Europe and occurs only occasionally in other parts of the world. Murine typhus, on the other hand, is still a widespread disease in the tropics and subtropics. Spotted fevers (e.g., Rocky Mountain spotted fever) occur with increased frequency in certain geographic regions, especially in the spring. Tsutsugamushi fever occurs only in Japan and Southeast Asia. The bloodsucking larvae of various mite species transmit its pathogen. Q fever epi-

Table 4.13 Pathogens and Clinical Pictures of the Rickettsioses and of Q Fever

Pathogen Vector/host Disease

Clinical picture

Typhus group

Rickettsia prowazekii

R. typhi

Body louse/humans

Rat flea/rat

Epidemic typhus Incubation 10-14 days; high

Brill-Zinsser disease

Murine typhus fever; 4-7 days after onset maculous exanthem; lethality as high as 20% if untreated

Endogenous secondary infection by rickettsiae persisting in the RES; results from reduction of immune protection; milder symptoms than ET

Symptoms as in ET, but milder

Spotted fever group

R. rickettsii Hard tick/

rodents, tick

R. conori Hard tick/ rodents

R. sibirica

R. akari

Hard tick/ rodents

Rocky Mountain spotted fever (RMSF)

Incubation: 6-7 days; continuing fever 2-3 weeks; maculopapu-lous exanthem on extremities

Fievre bouton- Symptoms as in RMSF, necrotic neuse (Mediterra- lesions sometimes develop at nean fever) bite locus

North Asian tick fever

Mite/rodents Rickettsial pox

Symptoms as in RMSF, necrotic lesions sometimes develop at bite locus

Fever; exanthem resembles that of chicken pox

Tsutsugamushi fever

Orientia tsu- Mite larvae/ tsugamushi rodents

Japanese spotted fever

Symptoms similar to ET plus local lesion at bite locus and lymphadenitis

Q fever (Query fever)

Coxiella Dust/sheep, burnetii cattle, goats, rodents

Q fever Incubation 2-3 weeks; interstitial pneumonia (clinical picture often atypical); chronic Q fever (endocarditis) with onset years after primary infection, poor prognosis

Table 4.14 Pathogens and Clinical Picture of the Ehrlichioses

Pathogen

Vector/host

Disease

Ehrlichia

Ticks/deer,

Human mono-

chaffeensis

dog

cytotrophic

ehrlichiosis

(HME);

monocytes are

main target of

pathogen

Ehrlichia

Ticks/dogs,

Human granulo-

ewingii

horse, other

cytotrophic

animals

ehrlichiosis

and

(HGE); granulo-

Anaplasma

cytes are main

phagocytophi-

target of

lum

pathogen

Neorickettsia

Host unknown;

Sennetsu fever;

sennetsu

perhaps fish.

occurs in South-

Transmission

east Asia (Japan)

from eating raw

fish

Clinical picture

All ehrlichioses present as mild to occasionally severe mono-nucleosis-like multisystem disease with headache, fever, myalgias leukopenia, thrombocytopenia, anaemia, and raised transaminases. 20-30% show various symptoms in the gastrointestinal tract and/or respiratory tract and/or CNS.

Incubation time between 5-10 days.

Antibiotics of choice are the tetracyclines.

Cultivation from blood using cell cultures exhibits low sensitivity. Molecular techniques (PCR) better for pathogen detection. Use indirect immunofluorescence for antibody titers.

demics are occasionally seen worldwide. The sources of infection are diseased livestock that eliminate the coxiellae in urine, milk, or through the birth canal. Humans and animals are infected by inhaling dust containing the pathogens. Specific preventive measures are difficult to realize effectively since animals showing no symptoms may be excreters. Active vaccination of persons exposed to these infections in their work provides a certain degree of immunization protection.

Until 1987, ehrlichioses were thought to occur only in animals. Tickborne Ehrlichia infections in humans have now been confirmed.

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