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His mouth was dry and sticky; a heavy fog weighed down his brain.

—Anton Chekhov: Typhus


The agents covered in this chapter are all small, gram-negative, if they stain at all, intracellular coccobacilli that are arthropod-borne to humans. Their epidemiology, however, is determined largely by the distribution and habits of their arthropod vectors (ticks, fleas, mites, and sandflies). Clinical features also differ by pathogen, but all respond to doxycycline therapy. The rickettsioses fall into two categories: spotted fever group (SFG) and typhus group (TGR). With molecular tools, including sequencing, many new rickettsia are being described in both groups, but only the most important currently or historically are presented here.

In the SFG are tick-transmitted Rickettsia rickettsii that causes Rocky Mountain spotted fever (RMSF) and mite-borne Rickettsia akari that causes rickettsialpox. In the TGR are louse-borne Rickettsia prowazekii that causes epidemic typhus, flea-transmitted Rickettsii typhi that causes murine typhus, and mite-borne Orientia tsutsugamushi that causes scrub typhus. By far the most important rickettsiosis in the United States in both incidence and severity is RMSF, whereas epidemic typhus ranks foremost historically in Europe. Both RMSF and typhus are characterized by fever, headache, myalgia, and rash. In RMSF, the rash appears first on the palms and soles, wrists, and ankles and migrates centripetally; whereas in epidemic typhus, the rash moves in the opposite direction beginning on the trunk and spreading to the extremities. Both diseases may be fatal as the result of severe vascular collapse. Ehrlichia and Anaplasma are both transmitted by ticks. Ehrlichia chaffeensis primarily infects monocytes and causes human monocytic ehrlichiosis (HME) and Anaplasma phagocytophilum infects polymorphonuclear granulocytes and causes human granulocytic anaplasmosis (HGA). Both HME and HGA manifest with fever, headache, malaise, leukopenia, and thrombocytopenia. A rash may be seen, but is neither common nor prominent. Bartonella species are louse-borne Bartonella quintana that causes trench fever, sandfly-borne Bartonella bacilliformis that invades red blood cells and causes Oroya fever and verruga peruana, and Bartonella henselae (bacillary angiomatosis and cat-scratch disease) that is transmitted by scratches or bites of cats or their fleas.

This chapter takes up four groups of gram-negative bacilli whose obligate or preferred growth is inside eukaryotic cells where they rely on the host cell for some essential nutrients. They are animal pathogens transmitted by arthropods to humans who are in the wrong place at the wrong time. The diseases vary depending on whether the target is endothelial cells, phagocytes, or erythrocytes. Most have prolonged fevers, often with vasculitis. These include classic ones like RMSF, typhus, and cat-scratch disease, as well as recently recognized infections like human ehrlichiosis and anaplasmosis.

Obligate intracellular parasites




Rickettsiae are small coccobacilli (Figure 40–1), which measure no more than 0.3 to 0.5 μm. Although the Gram reaction is negative, rickettsiae take the usual ...

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