Ehrlichioses

Introduction

Bacteria of the genera Ehrlichia and Anaplasma are obligate intracellular bacteria with ultrastructural characteristics of Gram-negative bacteria. They reside in cytoplasmic vacuoles of their target cells, called morulae, and have evolved in close association with arthropods and a eukaryotic host.

Human ehrlichioses comprise three different diseases: (1) the most common human monocytotropic ehrlichiosis (HME), caused by E. chaffeensis ; (2) human granulocytotropic anaplasmosis (HGA), which has similar signs and symptoms, caused by A. phagocytophilum ; and (3) ehrlichiosis ewingii, caused by E. ewingii ( Table 24-1 ). The lone star tick, Amblyomma americanum , as well as Ixodes scapularis and I. Ricinus , are the main transmission vectors. The number of cases in the USA increased steadily from 200 cases in 2000 to 961 cases in 2008. It is also becoming an emerging disease elsewhere in the world.

Usually presenting 5 days after onset of illness, macular and papular eruptions, as well as petechiae and erythema involving the trunk and extremities, can occur in up to 33% of cases with HME. In children their occurrence can be as high as 67%. Occasionally, edema, vesicles, and purpuric plaques have been reported.

Infections typically present with flu-like symptoms. Individuals with outdoor lifestyles, coupled with laboratory abnormalities such as leukopenia, thrombocytopenia, and transaminitis, should prompt the clinician to suspect recent infection by ehrlichioses. PCR analysis should be performed, as serologies can be negative in the acute setting.

Doxycycline for 5–14 days is the recommended regimen. Delayed treatment can result in progression to longer hospi­talizations, ICU admission, and fatalities.

Ehrlichia and Anaplasma have been known for almost a century as veterinary pathogens. The target cells for these three pathogens are monocytes / tissue macrophages for E. chaffeensis and polymorphonuclear neutrophils (PMN) for A. phagocytophilum and E. ewingii .

History

Ehrlichial pathogens have been known for almost a century as causes of disease in animals. In 1987, the first case of HME was described in the USA and its pathogen cultivated, sequenced, and characterized as a new Ehrlichia ( E. chaffeensis ) in 1991. In 1994, a second ehrlichiosis was described based on 16S rRNA sequencing. Its pathogen was cultivated later and named human granulocytotropic ehrlichiosis (HGE) agent. A new classification of all ehrlichial organisms based on genetic sequencing was published and the HGE agent was reclassified as A. phagocytophilum . In 1999, a third uncultivable agent named E. ewingii was associated with a second form of granulocytotropic ehrlichiosis in humans (ehrlichiosis ewingii). The history of human ehrlichioses continues to evolve as new information becomes available in both North America and around the world.

Epidemiology

E. chaffeensis , A. phagocytophilum , and E. ewingii are part of zoonotic cycles in which they are transmitted transstadially through all maturation cycles of the tick vectors (larvae, nymphs, and adults). The larval and nymphal forms of tick vectors acquire a blood meal for molting, during which they can acquire ehrlichiae from an ehrlichiemic mammal. There is no evidence of transovarial transmission of ehrlichiae in which larval progeny would be infected by an adult female tick.

Human Granulocytotropic Anaplasmosis

HGA has been well described in the USA and Europe. Endemic areas in the USA include the northeastern states and the upper Midwest, where the tick vector is most abundant ( Fig. 24-1 ). In Europe, HGA has been described in several countries, including the Netherlands, Norway, Slovenia, Spain, Sweden, Switzerland, and the UK. The main vectors in the USA and Europe are Ixodes scapularis and I. ricinus , respectively. Well-described mammal reservoirs in Europe include sheep, goats, deer, and mice. In the USA, the main reservoirs are mice, cotton-tail rabbits, white-tail deer, and rats. The presence of A. phagocytophilum in nymphal and larval forms is as high as 25% in areas of high endemicity. As of 1997, a total of 449 cases had been reported to the Centers for Disease Control (CDC). However, this number is probably an underestimate of the true prevalence. The male-to-female ratio is approximately 4 : 1 and HGA has a definite seasonal distribution, with most cases being diagnosed during the spring and summer, when tick vectors are most actively looking for blood meals.