Ehrlichiosis represents a group of infections that are caused by obligate intracellular bacteria from the bacterial family Anaplasmataceae (chiefly belonging to the genus Ehrlichia and Anaplasma). These infections are transmitted by ticks (mostly between May and August) and are potentially fatal.
The early manifestations of human ehrlichiosis are relatively constant but are shared by a large number of other infectious and noninfectious states (with several exceptions). The involvement of multiple organs that is typical as the disease progresses further complicates the course of the condition and may result in life-threatening scenarios.
Pathophysiology of the Disease
Infection with bacterial species causing ehrlichiosis occurs when the extracellular infectious form of the organism is taken up by the host cell. These infectious forms are either the elementary body or the dense core, and are taken up by the cell via a process known as endocytosis. Once inside the cell, the infecting organism divides and matures until it forms a reticulate body/reticulate core, and then a morula; these are then redifferentiated again into an elementary body/dense core so it can leave the infected host cell and spread further.
During this process, Ehrlichia and Anaplasma utilize a range of immune evasion mechanisms, such as suppression of apoptosis in host cells, down-regulation of recognition receptors in the host that could enable clearance of the infection, as well as modulation of cytokine and chemokine responses. Some species have a preference for granulocytic cells (Anaplasma phagocytophilum and Ehrlichia ewingii), while others target mononuclear phagocytes (Ehrlichia chaffeensis and Ehrlichia canis)
Furthermore, multisystem involvement is also a potential consequence, as microorganisms are found in the spleen, bone marrow, lymph nodes and peripheral blood. In fact, all the clinical manifestations are thought to be a result of a host inflammatory response to disseminated infection, rather than because of direct bacteria-induced damage.
Patients with ehrlichiosis (regardless of the putative organism) clinically present with fever, chills, severe headache, confusion, malaise, nausea, vomiting, and generalized body aches. Respiratory symptoms such as cough may also be observed, but they are more common in adults than in children.
Symptoms are typically seen one to two weeks following a tick bite, with a median of nine days. The problem with tick bites is that they are usually painless, and therefore many people do not even remember being bitten. Due to immune suppression, secondary infections (usually caused by cytomegalovirus or fungi) are also frequent in severely diseased patients.
In approximately one-third of individuals with ehrlichiosis there is a visible rash that is maculopapular or petechial. The rash is more commonly observed in children and typically develops five days after fever ensues. If present, the rash typically spares the palms, soles and the face.
Akin to rickettsial infections, central nervous system involvement may occur in up to 20% of affected individuals, including dangerous manifestations like meningoencephalitis. Moreover, in some patients the disease may advance to acute respiratory distress syndrome or a shock-like presentation coupled with bleeding disorders and cardiovascular instability.
However, the overall death rate is substantially lower in ehrlichiosis when compared to rickettsial diseases. According to the data published by U.S. Centers for Disease Control and Prevention (CDC), the mortality rates in patients who are seen by a healthcare professional due to ehrlichiosis range from 1% to 3%.
On the other hand, a large number of patients may be infected with Ehrlichia and Anaplasma, but do not come for medical evaluation; therefore, these percentages may be overestimations of mortality. Naturally, immunocompromised individuals, elderly and those previously treated with sulfonamide antibiotics are at higher risk of more severe disease.
Since ehrlichiosis is a multisystem disease characterized by protean manifestations (i.e. without pathognomonic and highly characteristic clinical features), the differentials are often quite broad. Initial symptoms are often generalized and somewhat vague, which is why the illness may first be diagnosed as a possible “viral syndrome” in the context of upper respiratory infection, gastroenteritis and/or meningoencephalitis.
A history of tick exposure or tick bite in the recent past can be elicited from a majority of patients, but it is important to emphasize that this feature may be absent in up to 30% of all cases. Therefore, pursuing other appropriate diagnostic procedures to confirm this disease is of the utmost importance.
- Vanderhoof-Forschner K. Everything You Need to Know About Lyme Disease and Other Tick-Borne Disorders. John Wiley & Sons, 2004; pp. 104-132.
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Last Updated: Nov 21, 2018
Dr. Tomislav Meštrović
Dr. Tomislav Meštrović is a medical doctor (MD) with a Ph.D. in biomedical and health sciences, specialist in the field of clinical microbiology, and an Assistant Professor at Croatia's youngest university – University North. In addition to his interest in clinical, research and lecturing activities, his immense passion for medical writing and scientific communication goes back to his student days. He enjoys contributing back to the community. In his spare time, Tomislav is a movie buff and an avid traveler.
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