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1.0 Introduction and definition of terms
Ehrlichiosis is a general term used to refer to a collection of arthropod-borne diseases that are particularly spread by ticks (Vector). Arthropods refer to invertebrates with external skeleton (exoskeleton), jointed appendages and segmented body. They include arachnids, insects and crustaceans. On the other hand, a vector is an organism (usually an arthropod) that transfers a pathogen from one organism (host) to another. Biological vectors are those that harbor the infective agent in their bodies and the agent multiplies and develops in the vector before being actively transferred. In this case, the vector is essential to the pathogen’s lifecycle, classical examples are ticks, mosquitoes, lice and fleas. In contrast, the mechanical vector is not vital for the pathogen’s lifecycle because it merely picks the pathogen on the surface of its body and transfers the pathogen passively. A typical example is a housefly which may pick pathogens on its appendages upon landing on feces and transfer it to food before consumption (Farlex, Inc.). Ehrlichiosis is mainly transmitted by four tick species Dermacentor variabilis, Amyblyomma americanum (lone star tick), Ixodes scapularis and I. pacificus which are widely distributed in the United States, Latin America, New England and Africa(Keesing, Hersh, & Ostfeld, 2012)

2.0 Etiology and Microbiology of the pathogen
The etiology of Ehrlichiosis in humans has been linked to five bacteria species of the Anaplasmataceae family i.e. Ehrlichia/Anaplasma phagocutophilium (causes human granulocytic ehrlichiosis/anaplasmosis), E. chaffeensis (associated with human monocytic ehrlichiosis), E. ewingii (responsible for human ewingii ehrlichiosis), E. canis and E.sennetsu (linked to sennetsu fever) (Dumler, et al, 2005a; Goddard, 2008). However, only the first three have been elaborately studied. Recently, another species (provisionally refered to as E. muris-like wasisolated from a few patients travelling from Wisconsin and Minnesota but the vector for this species has not been identified (CDC, 2013). The pathogens responsible for ehrlichiosis target circulating leucocytes and thus the corresponding diseases are named as per the leucocytes infected by the specific bacteria. For instance, the human monocytic ehrlichiosis (HME) is caused by E. chaffeensis which infects monocytes while human granulocytic anaplasmosis (HGA), formerly HGE (ehrlichiosis) is caused by A.Phagocytophilum which attacks granulocytes. E. ewingii infects neutrophils and is serologically similar to E. chaffeensis (Dumler, et al, 2005a).

The bacteria responsible for ehrlichiosis are gram-negative coccobacilli (ellipsoidal in shape) (Ismail, Bloch, & McBride, 2010; Lyme and Tick-Borne Diseases Research Center , 2011). That means that in the decolorization with alcohol they lose the primary crystal violet-iodine stain but retain the safranin counter stain and they have a thinner cell wall (with only 10% peptidoglycan). In addition, gram-negative bacteria have an outer lipid membrane separated from the cell wall by a periplasmic space (Aneja, Jain, & Aneja, 2009). In addition, the bacteria are obligate intracellular parasites, meaning that they rely on the cellular resources of the host for their growth and reproduction and thus can only grow and reproduce in the host (Aneja, Jain, & Aneja, 2009). The bacteria occupy cellular cytoplasmic vacuoles in the host in microcolonies referred to as morulae which can be observed under a microscope as below (figure 1 and 2)

3.0 Reservoir, Transmission, epidemiology
The Ehrlichia genus is found in many vertebrate reservoirs, in which it multiplies without causing disease. The most common vectors include the white tailed deer, goats, domestic dogs, red foxes and several bird species (Ganguly & Mukhopadhayay, 2008). A study aimed at establishing the vector competence of A. phagocytophilum assessed 4,640 ticks that were collected over a period of 3 years from 254 animals. The study found that small mammals were the most competent reservoirs and identified more reservoirs including eastern chipmunks, white-footed mice, short-tailed shrews, opossums, skunks and southern flying squirrels (Keesing, Hersh, & Ostfeld, 2012).

Ehrlichiosis is transmitted through tick bites. The larvae stage of the ticks pick the causative bacteria from a vertebrate reservoir during a blood meal and maintain it through the nymphal stage which may transmit the bacteria to another reservoir or to humans during a blood meal. In addition, an adult tick may acquire the bacteria from infected nymphal stage through trans-stadial transmission or during a blood meal and pass it to another host (Ganguly & Mukhopadhayay, 2008). Below is the transmission cycle of the disease.

Figure 3: Transmission cycle of Ehrchiosis

As earlier implied there are three main diseases that form the collection of ehrlichiosis and of the three earlier mentioned, human monocytic ehrlichiosis (HME) and human granulocytic anaplasmosis (HGA) are the most common in the United States. The former was first described in humans in 1987 while the latter was described in 1990s (Dumler & Walker, 2009; Vorvick, 2011). However, A.phagocytophili, causative agent for HGA, had been identified as a veterinary pathogens as early as 1932 and was common in horses, dogs, sheep, cats and goats (Dumler, et al., 2005b). Currently, HME is found in 30 states mainly in the mid-Atlantic, southeast and south-central states as well as in parts of Africa and Europe. On the other hand, HGA is found in the mid-Atlantic, northeast, Midwest states, many parts of Europe and northern California. Unfortunately, because of inaccurate reporting and difficulties in diagnosis, the actual prevalence of the disease is unknown but is estimated to be between 15% and 36% in the endemic areas goats (Dumler, et al., 2005b). Some researchers have found that E.chaffeensis is endemic in the south central and south eastern states and of great public health significant thus a reportable disease with about 0.7 HME cases per million population being reported every year. If untreated or treated late, HME is fatal with a mortality rate of about 2.7%. Of the reported cases of HME. 75% are men at an average age of 44 years and mostly living in the rural areas. On the other hand, HGA is endemic in north central and pacific states and New England. 1.6 cases of HGA per million population are reported every year. E. ewingii (responsible for human ewingii ehrlichiosis) is more common in dogs and only found in a few immunocompromised individuals. E. ewingii is endemic in south Atlantic and south central states and causes mild illness that is similar to HME and has not been linked to any fatality (Goddard, 2008).

4.0 Pathophysiology, pathogenesis, symptoms, Diagnosis and treatment
Unlike most of the other common human bacteria pathogens, Ehrlichia lack pili and thus they bind to the specific host cells, mentioned earlier, through their membrane and enter (infect) the cells (Paddock & Childs, 2003). Once in the cell the bacteria form 1or 2 endosomes (membrane bound compartments) referred to as morulae, but they can be as many as 15 in an immunocompromised patient (Ganguly & Mukhopadhayay, 2008; Ismail, Bloch, & McBride, 2010). Though Ehrlichia mainly infect monocytes, they have been reported to infect lymphocytes, metamyelocytes, neutrophils and promyelocytes (Nicholson, et al., 2010). They multiply within the endosome and survive by suppressing the host immune system hence they are often linked to immunosuppression which in turn may lead to multi-organ infection and failure. Infections in the lymph nodes, bone marrow, liver, pariearteriolar sheaths and splenic chords have been reported in humans (Paddock & Childs, 2003). The multiple systems and organ infection, particularly in the bone marrow, is common in late stages of the disease and in immunocompromised individuals). (Paddock & Childs, 2003; Ganguly & Mukhopadhayay, 2008; Shipo, Klement, Tagar, Waner, & Harrus, 2008; Ismail, Bloch, & McBride, 2010; Nicholson, et al., 2010).

My cousin was diagnosed with HME and displaye the following symptoms rushes, muscle aches, fatigue, hedaches, chills, confusion, red eyes, nausea, diarrhea and vomitting associated with include. The same symptoms are associated with HGA and others include myalgia, malaise, respiratory, GI and CNS abnormalities. The disease is also associated with immunosuppression and thus opportunistic infections such as candidiasis are common (Goddard, 2008).

Several diagnostic tests for ehrlichiosis are available and include micrsoscopy, PCR amplification, serological tests such as western blotting and indirect immunofluorescence assay (IFA) (Ganguly & Mukhopadhayay, 2008). Blood cultures may also be used for diagnosis. Once the disease has been identified as ehrlichiosis it is treated with doxycycline or rifampin. Other treatments include chloramphenical and tetratcyclines. Tick control, avoiding long grass and bushes, tick removal, using insect repellants and protective cloths when handling animals are the main preventive strategies (CDC, 2013).


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