Introduction to Rickettsioses, Ehrlichioses, and Anaplasmoses

Bacteriology

Originally, all small gram-negative bacteria, associated (or not) with arthropods and strictly or facultatively intracellular, were considered Rickettsiaceae. The advent of 16S ribosomal RNA gene sequencing and phylogeny has deeply challenged this classification. The controversy has centered on how much difference between strains should constitute a subspecies. Among the agreed-upon changes, Orientia was created from an independent branch of its phylum. The Ehrlichia group has been reclassified into four genera, with Ehrlichia and Anaplasma being associated with ticks, Neorickettsia with helminths, and Wolbachia with both arthropods and helminths. This chapter is limited to the Rickettsiales. All are intracellular Alphaproteobacteria associated with eukaryotic hosts (arthropods or helminths). Based on antigenic and genetic data, pathogenic rickettsiae are traditionally divided into three groups—the spotted fever group, the typhus group, and the scrub typhus group ( Table 185.1 ). The spotted fever group accounts for most tick-borne rickettsioses. The typhus group comprises Rickettsia prowazekii, the agent of epidemic typhus that is transmitted by the human body louse, and Rickettsia typhi, causing murine typhus, which is transmitted by rat and cat fleas. The scrub typhus group comprises Orientia tsutsugamushi only, which is transmitted by chiggers (Trombiculidae).

History and Emerging Diseases

The development of polymerase chain reaction (PCR) and DNA sequencing, as well as the use of cell culture assays, has allowed the description of many new rickettsioses and ehrlichioses during the past 30 years ( Table 185.2 ). Seven ehrlichioses and 14 rickettsioses have been described since 1980. Three major conditions determined the description and separation of these species. Some were discovered after clinical description in countries where spotted fever had been unknown ( Rickettsia japonica in Japan, Rickettsia honei on Flinder's Island, and Astrakhan fever in Russia). Some were recognized by bacterial identification based on culture and PCR in places where the new pathogen was confounded with another known rickettsial pathogen ( Rickettsia africae with Rickettsia conorii, Rickettsia heilongjiangensis with Rickettsia sibirica, R. sibirica subsp. mongolitimonae and Rickettsia aeschlimannii with R. conorii, Rickettsia felis with R. typhi, and Anaplasma phagocytophilum and Ehrlichia ewingii with Ehrlichia chaffeensis ). Some were identified through association by physicians and microbiologists when an atypical unknown disease ( E. chaffeensis, Rickettsia slovaca, Rickettsia raoultii, and Rickettsia helvetica ) was being explored.

In addition to the description of new species, old rickettsioses, such as epidemic typhus or scrub typhus, reemerged apparently because of lack of social control or ecologic changes. These diseases, which were the more deadly rickettsioses for the human species, remain a threat. Studies in Asia identified rickettsioses such as murine typhus and scrub typhus among the most common causes of fever.

Wolbachia, an essential symbiont of human filarial worms, has been shown to play a major role in the pathology and clinical manifestations of filariasis. It introduces a completely new concept in infectious diseases. It appears that inflammatory reactions of patients during the disease and during the treatment of filariasis are caused by the release of lipopolysaccharide-like molecules from the symbiotic Wolbachia.

Many rickettsiae were found in their vectors long before a particular disease could be associated with them. However, the denomination nonpathogenic rickettsiae, which is used for bacteria found only in ticks, is misleading. Among famous pathogens first classified as nonpathogenic rickettsiae are Legionella pneumophila; Coxiella burnetii, the agent of Q fever; Rickettsia parkeri ; and R. africae. Several rickettsiae have been found in ticks throughout the world, the pathogenic potential of which remains unknown. A rarely recognized febrile disease caused by Neorickettsia sennetsu, acquired by eating raw infected fish, has been described in Laos and may be present throughout Southeast Asia.

Pathophysiology

Rickettsia, Ehrlichia, and Anaplasma species are host-associated pathogens. These pathogens depend on their environment for the supply of many nutriments. Rickettsia species escape rapidly from the phagosome to multiply within the cytoplasm. Spotted fever rickettsiae, which are motile in the cytoplasm through actin polymerization, invade neighboring cells. Rickettsia prowazekii is devoid of such motility and is released only by destruction of the host cell. Phospholipase D may play a key role in cellular invasion.

The target cell of Rickettsia is the vascular endothelial cell, except for Rickettsia akari and O. tsutsugamushi, which multiply in monocytic cells. Ehrlichia chaffeensis and Ehrlichia muris subsp. eauclairensis multiply in monocytic cells; A. phagocytophilum and E. ewingii multiply in polymorphonuclear cells. Some animal ehrlichiae multiply in blood platelets.