**2.6 Togaviridae Family: Old and New World Alpha Viruses**

Alpha viruses have been delineated as either New or Old World, depending on their geographical distribution; New World being primarily in the Americas, while Old World is in the Africa, Europe, Asia and Australia (Paredes et al., 2005). Besides their spatial differences, these viruses typically manifest different disease characteristics. Old World infections usually are more benign, with rash and arthritic symptoms, while the New World alpha virus infections can result in febrile disease with possible encephalitis onset (Paredes et al., 2005). However, several Old World viruses have showed to develop into encephalitis, with Chikungunya virus (CHIKV) and a variant of Semliki Forest virus (SFV) as such examples.

#### **2.6.1 Old World: Chikungunya, Me Tri and Ross River Virus**

Chikungunya Virus (CHIKV) was first isolated in Africa, with outbreaks reported in the Congo and Senegal (Diallo et al., 1999; Pastorino et al., 2004). CHIKV is transmitted by gallery forest mosquitoes, from wild forest primates and rodents (genus *Aedes*) (Diallo et al., 1999). Outbreaks of the virus in La Réunion, an island in the south Pacific followed by wide spread infection in India, Sri Lanka and Indonesia, resulted in considerable central nervous system involvement, including encephalitis (Rampal et al., 2007; Robin et al., 2008; Rajapakse et al., 2010), with human-human transmission facilitated mainly by *Aedes aegypti* in urban areas (Lahariya & Pradhan, 2006). A similar Old World Virus that has shown encephalitis onset is Me Tri virus, first isolated from *Culex tritaeniorhynchus* mosquitoes in the Me Tri Village of North Vietnam (Ha et al., 1995), though later it was classified as a Semliki Forest Virus (SFV) variant that had undergone homologous recombination, though this is the first variant of SFV outside of Africa (Tan et al., 2008). Ross River Virus is also an Old World alpha virus, suspect of encephalitic onset, though causation is lacking as to whether or not those isolated incidents were truly caused by Ross River virus (Harley et al., 2001).

#### **2.6.2 New World Alpha Viruses: Eastern, Western and Venezuelan Equine Encephalitis Virus**

Eastern Equine Encephalitis Virus (EEEV) is primarily found the Atlantic and Gulf Coast states, but cases have been reported further north into Canada, and into South America (Argentina and Peru) (Hansen & Docherty, 1999). Passerine birds serve as the amplification

One of the lesser known viral encephalides is the Chandipura virus (genus *Vesiculovirus*). Even though it is not well reported in the literature (Van Ranst, 2004), it was responsible for considerable encephalitic outbreaks in India in the last decade, in 2003 and again in 2007 (Rao et al., 2004; Narasimha Rao et al., 2008; Gurav et al., 2010). Viral transmission is through Phlebotomid sandflies (genus *Sergentomyia)* (Mavale et al., 2005) and is mainly found in India, but has also been isolated from sand flies in West Africa (Fontenille et al., 1994). The potential and need for further research in this emerging human pathogen is great

Australian bat lyssavirus (ABLV) is another encephalitic virus found in Pteropid bats, and as the name implies, this rabies-like virus is found in Australia (Warrilow et al., 2002). Two fatal encephalitis cases were confirmed to be caused by ABLV. The first in 1996 from an animal handler (Allworth et al., 1996); the second had been bitten by a flying fox (Hanna et al., 2000). Serologic testing done in the Philippines suggest that this virus is also present there, though no active infections were found in the bats sampled (Arguin et al., 2007).

Alpha viruses have been delineated as either New or Old World, depending on their geographical distribution; New World being primarily in the Americas, while Old World is in the Africa, Europe, Asia and Australia (Paredes et al., 2005). Besides their spatial differences, these viruses typically manifest different disease characteristics. Old World infections usually are more benign, with rash and arthritic symptoms, while the New World alpha virus infections can result in febrile disease with possible encephalitis onset (Paredes et al., 2005). However, several Old World viruses have showed to develop into encephalitis, with Chikungunya virus (CHIKV) and a variant of Semliki Forest virus (SFV) as such examples.

Chikungunya Virus (CHIKV) was first isolated in Africa, with outbreaks reported in the Congo and Senegal (Diallo et al., 1999; Pastorino et al., 2004). CHIKV is transmitted by gallery forest mosquitoes, from wild forest primates and rodents (genus *Aedes*) (Diallo et al., 1999). Outbreaks of the virus in La Réunion, an island in the south Pacific followed by wide spread infection in India, Sri Lanka and Indonesia, resulted in considerable central nervous system involvement, including encephalitis (Rampal et al., 2007; Robin et al., 2008; Rajapakse et al., 2010), with human-human transmission facilitated mainly by *Aedes aegypti* in urban areas (Lahariya & Pradhan, 2006). A similar Old World Virus that has shown encephalitis onset is Me Tri virus, first isolated from *Culex tritaeniorhynchus* mosquitoes in the Me Tri Village of North Vietnam (Ha et al., 1995), though later it was classified as a Semliki Forest Virus (SFV) variant that had undergone homologous recombination, though this is the first variant of SFV outside of Africa (Tan et al., 2008). Ross River Virus is also an Old World alpha virus, suspect of encephalitic onset, though causation is lacking as to whether or not those isolated incidents

**2.6 Togaviridae Family: Old and New World Alpha Viruses** 

**2.6.1 Old World: Chikungunya, Me Tri and Ross River Virus** 

were truly caused by Ross River virus (Harley et al., 2001).

**Encephalitis Virus** 

**2.6.2 New World Alpha Viruses: Eastern, Western and Venezuelan Equine** 

Eastern Equine Encephalitis Virus (EEEV) is primarily found the Atlantic and Gulf Coast states, but cases have been reported further north into Canada, and into South America (Argentina and Peru) (Hansen & Docherty, 1999). Passerine birds serve as the amplification

(Potharaju & Potharaju, 2006).

host for the virus (Chamberlain et al., 1954; Komar et al., 1999) and *Culiseta melanura*, a mainly ornithophic mosquito, maintains the lifecycle in endemic areas between bird hosts, though other genera have be able to become infected (Armstrong & Theodore, 2010). The virus starts its replication in the mid-gut epithelial cells and maintains a persistent infection in the mosquito, eventually reaching the salivary glands to ensure viral transfer (Georgiev, 2009). Mosquito with a wider range of hosts (*Coquillettidia, Culex, Ochlerotatus, Aedes, spp.*) serve to infect dead-end hosts (humans and horses) (Pfeffer & Dobler, 2010), with often fatal consequences for both (Pfeffer & Dobler, 2010).

Western Equine Encephalitis virus undergoes a similar endemic cycle in birds as EEEV does, with *Culex tarsalis* as the maintaining mosquito vector, although there is a cycle between rodents and *Ochlerotatus melanimon* in South America (Pfeffer & Dobler, 2010). WEEV can be found in North, South and Central America (Weaver et al., 1997), though *C. tarsalis* is well sustained in the Western U.S. in areas of agriculture and stream drainages (Zacks & Paessler, 2010).

Unlike the previous alpha viruses, the Venezuelan Equine Encephalitis Virus (VEEV) is maintained mainly in a mosquito/rodent cycle and amplification and further amplification is seen in horses and humans (Pfeffer & Dobler, 2010). *C. Melanoconion* serves as the enzootic strain vector among rodent hosts. The key to epidemic/epizootic transmission is through a the selection of the E2 envelope protein mutation of ID or IE subtypes (Pfeffer & Dobler, 2010), from which the IAB and IC subtypes emerge, and go on to infect equines and humans through *Ochlerotatus taeniorhynchus* (Georgiev, 2009). For additional details of the VEEV virus, mosquito vectors (both enzoonic and epizoonic), as well as the transmission cycle, please see the review by Weaver et al. (2004).

#### **3. Bacterial Encephalitides**

#### **3.1 Brucellosis:** *Brucella*

There are six 'classical' strains of *Brucella* genus, found in specific animals*, Brucella ovis, Brucella canis, Brucella neotomae, Brucella abortus, Brucella melitensis, and Brucella suis* (Moreno et al., 2002), with the latter three strains capable of infecting humans and human producing brucellosis (de Jong et al., 2010). These three strains are also able to infect reticuloendothelial tissues as well as reproductive tract cells, which results in abortions or sterility (de Jong et al., 2010). Neurological affects can manifest into Neurobrucellosis, with meningoencephalitis as a potential complication, though a rare occurrence among those affected (Shakir et al., 1987; Al Deeb et al., 1989). *Brucella* has also been detected in terrestrial wildlife populations (Godfroid, 2002), as well as marine mammals (Foster et al., 2002) and has been shown to jump from wildlife reservoirs to domestic herds in close proximity to each other. The study done by Beja-Pereira et al. (2009) showed that elk were the origin species for the *Brucella* outbreak in cattle herds in the greater Yellowstone area. For the greater population, human infection is usually caused by consumption of dairy products contaminated with the bacterium (De Massis et al., 2005). The risk of infection increases with animal contact, especially around periods of perturbation, which puts farm workers/ranchers, veterinarians and meat-packing employers at greater risk of infection (Seleem, Boyle et al. 2010).

#### **3.2 Leptospirosis:** *Leptospira*

Leptospirosis is caused by two species of *Leptospira*; *L. interrogans* and *L. borgpetersenii*. *L. interrogans* is effective in surviving in the environment, while *L. borgpetersenii* is host

Zoonotic and Animal Vector Mediated Encephalitides 11

(similar to neuroborreliosis in animal models (Steere, 2001)), which can result in

Scrub Typhus, or tsutsugamushi disease, is caused by *Orientia tsutsugamushi*, grouped into a separate genus in the Rickettsiaceae family (Tamura et al., 1995; Perlman et al., 2006). The trombiculid mite vectors (*Leptotrombidium deliense*) feed on mice and humans in their chigger stage, or parasitic larval stage, which is responsible for the transmission of the bacterium. Vertical transmission is also possible (Traub & Wisseman, 1974). The disease is endemic in a region, known as the 'tsutsugamushi triangle', ranging from Afghanistan, China, Korea, the islands of the southwestern Pacific, and northern Australia (Kelly et al., 2009) and

Query fever (commonly referred to as Q Fever) is a worldwide zoonosis caused by *Coxiella burnetii*, an obligatory intracellular organism which is a member of the family Rickettsiaceae, though genetic comparison revealed it is closer homology to *Legionella pneumophila* (Vogel, 2004; Parker et al., 2006). It enters the phagolysosome and later develops into the parasitophorous vacuole (PV), characterized by low pH, acid hydrolases and cationic peptides (Voth & Heinzen, 2007). These strange optimal conditions for growth make the culturing of this bacterium difficult (Omsland et al., 2009). Meningoencephalitis, though rare, is a potential complication of infection (Sawyer et al., 1987; Raoult et al., 2000). The bacterium is shed in large volumes during the birthing process (Welsh et al., 1958) and through milk production (Fishbein & Raoult, 1992). Domesticated ruminants (cattle, sheep, goats) are the predominate bridge to human infection, making slaughterhouses workers, farmers and livestock researchers at the greatest risk for direct infection (McQuiston & Childs, 2002), though it has been detected in other domestic and wild animals (Marrie et al., 1988; Buhariwalla et al., 1996; Stein & Raoult, 1999). The bacterium can also be isolated from environmental samples where livestock reside (DeLay et al., 1950). Ticks are considered a reservoir, though not a disease vector (Mediannikov et al., 2010). There is also evidance of wind-blown induced infections of

*Ehrlichia chaffeensis* (Family Anaplasmataceae) is the causative agent for human monocytic ehrlichiosis (HME) (Dumler, Madigan et al. 2007). White tail deer (*Odocoileus virginianus*), rodents and other wildlife have been shown to harbor *E. chaffeensis*, which is transmitted to humans via *Ixodes* ticks (*Amblyomma americanum*) (Telford et al., 1996; Lockhart et al., 1997; Walls et al., 1998; A. A. Kocan, 2000; Varela-Stokes, 2007). Genera *Ehrlichia* does not undergo transovarial transmission, so the perpetuation of infected ticks is through horizontal transfer from mammals to ticks (Rikihisa, 2003). Encephalitis is a reported complication of the disease (Ratnasamy et al., 1996; Paddock & Childs, 2003; Stone et al., 2004), which is found

Despite the name, Rocky Mountain Spotted Fever (RMSF) has been reported in at least 42 states and the District of Columbia (Treadwell et al., 2000). The lifecycle and transmission of *R*. rickettsii is primarily through transoverial. Infected female ticks give rise to infected eggs, which develop into infected larva/nymphs, which feed on small rodents and adults infect humans, an incidental host. Uninfected ticks can also feed on infected rodents to acquire the bacterium. Close contact during mating is also able to pass the virus (Walker, 1996 ). The main vectors for RMSF are the *Dermacentor variabilis* (American dog tick); in the northwestern US and Canada, and *D. andersoni* (Rocky Mountain Wood Tick) and the Lone Star Tick,

in the Atlantic, southeastern, and south central states (Paddock & Childs, 2003).

**3.5** *Rickettsiaceae***: Scrub Typhus, Q Fever, Human Monocytic Ehrlichiosis, Rocky** 

**Mountain Spotted Fever and Colorado Tick Fever, and Epidemic Typhus** 

meningoencephalitis (Broderick et al., 1987; Oschmann et al., 1998).

encephalomyelitis was observed (Kim et al., 2000; Seong et al., 2001)

cites downwind of sheep farms (Tissot-Dupont et al., 1999).

dependent. Genome analysis between these two pathogenic strains showed that the host dependent strain had approximately 700 bp smaller genome and overall lower gene density than *L. interrogans*, and an obligate host to host transmission cycle (Bulach et al., 2006). Leptospires reproduce in the kidneys are shed through the urine of infected animals. Disease contraction occurs with exposure to urine and pathways to the body include skin abrasions, passage of the mucous membranes or consumption of contaminated water. Rodents are asymptomatic and are reservoirs for the bacterium, which facilitates and maintains infection in domesticated animals, as well as from passage to animal to animal in herds (Antony, 1996; Ko et al., 2009). A review of global occurrences of leptospirosis was done by Pappas et al. (2008), which showed the endemic areas of the world were mainly located in the Caribbean and Central and South America, as well as in Southeast Asia and Oceania, though the authors reported that it is probably an incomplete list due to lack of data from developing countries and unreliable reports from other parts of the world. The human leucocyte- like antigen DQ-6 (HLA-DQ6) polymorphism in has showed an increased risk of leptospirosis via consumption of contaminated water (Lingappa et al., 2004). Encephalitis onset has been reported (Dimopoulou et al., 2002).

#### **3.3 Listeriosis: Listeria monocytogenes**

Human *Listeria* infections most often occur because of consumption of contaminated food products, but *Listeria* is also shed in the feces of infected livestock. When the manure is spread on crop fields, food, soil and water contamination becomes an issue (Swaminathan & Gerner-Smidt, 2007). This pathogen is capable of living in a wide range conditions, tolerating in both an extensive temperature and pH range (0.5-45C, pH 4.3-9.8) (Gandhi & Chikindas, 2007). *L. monocytogenes* is capable of infecting a variety of hosts (Roberts & Wiedmann, 2003), but mainly reported in livestock (Low & Donachie, 1997). Human encephalitic cases have been reported (Johnson & Colley, 1969; Armstrong & Fung, 1993). The genetic changes seen in two lineages of *L. monocytogenes*, lineage II, the more environmentally resistant strain, and lineage I, the more host adapted lineage, was found to be in the cell wall and membrane biogenesis and motility-related genes (Orsi et al., 2008).

#### **3.4 Lyme's Disease: Borrelia** *burgdorferi*

The Lyme's disease (Lyme borreliosis) spirochete (*Borrelia burgdorferi*) is spread through ixodid ticks. Humans make up a small portion of bloodmeals, but can become infected through bites of *Ixodes dammini/scapularis* in the eastern U.S., *Ixodes pacificus* in the western United States and *Ixodes ricinus* in Europe. *Ixodes dammini*'s primary host is the white-footed mouse, *Peromyscus eucopus*, and the white-tailed deer, *Odocoileus virginianus*. In the western US, fence lizards (*Sceloporus occidentalis*) and Columbian black-tailed deer are reservoirs (as reviewed by Lane et al. (1991)). A study done in California found that woodrats serve as the reservoir hosts while *Ixodes neotomae* maintains the spirochete, though it does not facilitate human transfer (Brown & Lane, 1992). After the spirochete is ingested in the initial bloodmeal, protective outer surface proteins are produced as a buffer from digestion mechanisms in the tick's midgut. There it will stay until the tick molts and engages in its second bloodmeal. Feeding triggers spirochete reproduction, followed by migration to the salivary glands, allowing for host transfer (Spielman et al., 1987). The bacterium enter the host's skin and migrate out from the bite site and create the characteristic bull's eye mark of infection (Steere, 2001). A small portion of patients suffer from neurological complications

dependent. Genome analysis between these two pathogenic strains showed that the host dependent strain had approximately 700 bp smaller genome and overall lower gene density than *L. interrogans*, and an obligate host to host transmission cycle (Bulach et al., 2006). Leptospires reproduce in the kidneys are shed through the urine of infected animals. Disease contraction occurs with exposure to urine and pathways to the body include skin abrasions, passage of the mucous membranes or consumption of contaminated water. Rodents are asymptomatic and are reservoirs for the bacterium, which facilitates and maintains infection in domesticated animals, as well as from passage to animal to animal in herds (Antony, 1996; Ko et al., 2009). A review of global occurrences of leptospirosis was done by Pappas et al. (2008), which showed the endemic areas of the world were mainly located in the Caribbean and Central and South America, as well as in Southeast Asia and Oceania, though the authors reported that it is probably an incomplete list due to lack of data from developing countries and unreliable reports from other parts of the world. The human leucocyte- like antigen DQ-6 (HLA-DQ6) polymorphism in has showed an increased risk of leptospirosis via consumption of contaminated water (Lingappa et al., 2004).

Human *Listeria* infections most often occur because of consumption of contaminated food products, but *Listeria* is also shed in the feces of infected livestock. When the manure is spread on crop fields, food, soil and water contamination becomes an issue (Swaminathan & Gerner-Smidt, 2007). This pathogen is capable of living in a wide range conditions, tolerating in both an extensive temperature and pH range (0.5-45C, pH 4.3-9.8) (Gandhi & Chikindas, 2007). *L. monocytogenes* is capable of infecting a variety of hosts (Roberts & Wiedmann, 2003), but mainly reported in livestock (Low & Donachie, 1997). Human encephalitic cases have been reported (Johnson & Colley, 1969; Armstrong & Fung, 1993). The genetic changes seen in two lineages of *L. monocytogenes*, lineage II, the more environmentally resistant strain, and lineage I, the more host adapted lineage, was found to be in the cell wall and membrane biogenesis and motility-related genes (Orsi et al., 2008).

The Lyme's disease (Lyme borreliosis) spirochete (*Borrelia burgdorferi*) is spread through ixodid ticks. Humans make up a small portion of bloodmeals, but can become infected through bites of *Ixodes dammini/scapularis* in the eastern U.S., *Ixodes pacificus* in the western United States and *Ixodes ricinus* in Europe. *Ixodes dammini*'s primary host is the white-footed mouse, *Peromyscus eucopus*, and the white-tailed deer, *Odocoileus virginianus*. In the western US, fence lizards (*Sceloporus occidentalis*) and Columbian black-tailed deer are reservoirs (as reviewed by Lane et al. (1991)). A study done in California found that woodrats serve as the reservoir hosts while *Ixodes neotomae* maintains the spirochete, though it does not facilitate human transfer (Brown & Lane, 1992). After the spirochete is ingested in the initial bloodmeal, protective outer surface proteins are produced as a buffer from digestion mechanisms in the tick's midgut. There it will stay until the tick molts and engages in its second bloodmeal. Feeding triggers spirochete reproduction, followed by migration to the salivary glands, allowing for host transfer (Spielman et al., 1987). The bacterium enter the host's skin and migrate out from the bite site and create the characteristic bull's eye mark of infection (Steere, 2001). A small portion of patients suffer from neurological complications

Encephalitis onset has been reported (Dimopoulou et al., 2002).

**3.3 Listeriosis: Listeria monocytogenes**

**3.4 Lyme's Disease: Borrelia** *burgdorferi* 

(similar to neuroborreliosis in animal models (Steere, 2001)), which can result in meningoencephalitis (Broderick et al., 1987; Oschmann et al., 1998).

#### **3.5** *Rickettsiaceae***: Scrub Typhus, Q Fever, Human Monocytic Ehrlichiosis, Rocky Mountain Spotted Fever and Colorado Tick Fever, and Epidemic Typhus**

Scrub Typhus, or tsutsugamushi disease, is caused by *Orientia tsutsugamushi*, grouped into a separate genus in the Rickettsiaceae family (Tamura et al., 1995; Perlman et al., 2006). The trombiculid mite vectors (*Leptotrombidium deliense*) feed on mice and humans in their chigger stage, or parasitic larval stage, which is responsible for the transmission of the bacterium. Vertical transmission is also possible (Traub & Wisseman, 1974). The disease is endemic in a region, known as the 'tsutsugamushi triangle', ranging from Afghanistan, China, Korea, the islands of the southwestern Pacific, and northern Australia (Kelly et al., 2009) and encephalomyelitis was observed (Kim et al., 2000; Seong et al., 2001)

Query fever (commonly referred to as Q Fever) is a worldwide zoonosis caused by *Coxiella burnetii*, an obligatory intracellular organism which is a member of the family Rickettsiaceae, though genetic comparison revealed it is closer homology to *Legionella pneumophila* (Vogel, 2004; Parker et al., 2006). It enters the phagolysosome and later develops into the parasitophorous vacuole (PV), characterized by low pH, acid hydrolases and cationic peptides (Voth & Heinzen, 2007). These strange optimal conditions for growth make the culturing of this bacterium difficult (Omsland et al., 2009). Meningoencephalitis, though rare, is a potential complication of infection (Sawyer et al., 1987; Raoult et al., 2000). The bacterium is shed in large volumes during the birthing process (Welsh et al., 1958) and through milk production (Fishbein & Raoult, 1992). Domesticated ruminants (cattle, sheep, goats) are the predominate bridge to human infection, making slaughterhouses workers, farmers and livestock researchers at the greatest risk for direct infection (McQuiston & Childs, 2002), though it has been detected in other domestic and wild animals (Marrie et al., 1988; Buhariwalla et al., 1996; Stein & Raoult, 1999). The bacterium can also be isolated from environmental samples where livestock reside (DeLay et al., 1950). Ticks are considered a reservoir, though not a disease vector (Mediannikov et al., 2010). There is also evidance of wind-blown induced infections of cites downwind of sheep farms (Tissot-Dupont et al., 1999).

*Ehrlichia chaffeensis* (Family Anaplasmataceae) is the causative agent for human monocytic ehrlichiosis (HME) (Dumler, Madigan et al. 2007). White tail deer (*Odocoileus virginianus*), rodents and other wildlife have been shown to harbor *E. chaffeensis*, which is transmitted to humans via *Ixodes* ticks (*Amblyomma americanum*) (Telford et al., 1996; Lockhart et al., 1997; Walls et al., 1998; A. A. Kocan, 2000; Varela-Stokes, 2007). Genera *Ehrlichia* does not undergo transovarial transmission, so the perpetuation of infected ticks is through horizontal transfer from mammals to ticks (Rikihisa, 2003). Encephalitis is a reported complication of the disease (Ratnasamy et al., 1996; Paddock & Childs, 2003; Stone et al., 2004), which is found in the Atlantic, southeastern, and south central states (Paddock & Childs, 2003).

Despite the name, Rocky Mountain Spotted Fever (RMSF) has been reported in at least 42 states and the District of Columbia (Treadwell et al., 2000). The lifecycle and transmission of *R*. rickettsii is primarily through transoverial. Infected female ticks give rise to infected eggs, which develop into infected larva/nymphs, which feed on small rodents and adults infect humans, an incidental host. Uninfected ticks can also feed on infected rodents to acquire the bacterium. Close contact during mating is also able to pass the virus (Walker, 1996 ). The main vectors for RMSF are the *Dermacentor variabilis* (American dog tick); in the northwestern US and Canada, and *D. andersoni* (Rocky Mountain Wood Tick) and the Lone Star Tick,

Zoonotic and Animal Vector Mediated Encephalitides 13

eggs move to either the intestine or ureters and are then released in the feces or urine respectively, completing the cycle and the means of egg release is species dependent (Cox, 2002). The main schistosomes infecting human are *S. mansoni*, *S. haematobium*, and *S. japonicum* and their respective snail hosts, *Biomphalaria*, *Bulinus* and *Oncomelania*. *S. mansoni*  is found in Africa, the Arabian peninsula, and South America, with humans as its main host, but can also infect rodents and primates (as reviewed by (Gryseels et al., 2006; Brooker, 2010). The biodiversity of an area, as can the genetic diversity of a population, can play a role in the risk of human *S. mansoni* infection. Johnson et al. (2009) found when *Biomphalaria glabrata* was raised along with non-host snails, 60–80 per cent fewer cercariae were

*Toxoplasma gondii* is responsible for toxoplasmosis, and cases of severe encephalitis have been reported, especially in immnocompromised individuals (i.e., transplant, AIDS and lymphatic cancer patients) (Frenhel et al., 1975; Araujo & Remington, 1987; Luft & Remington, 1992; Touahri et al., 2002; Derouin et al., 2008). As an obligate intracellular parasite, producing many asymptomatic infections, this parasite has balanced host immune detection and successful infection and reproduction and passage through blood-brain, placenta and intestinal barriers (Lambert & Barragan, 2010). This phylum is named for the apical complex that assistants host cell infection (Lim & McFadden, 2010). Although Family Felidae are the sole definitive host (allowing for sexual reproduction) (Hutchison, 1965), wide range of warm-blooded animals (including livestock) and birds can act as a intermediate host (Jacobs et al., 1960; Work, 1967; Tenter et al., 2000; Innes, 2010). Initial infection is through ingestion of raw or undercooked meat containing oocysts or live organisms (Jacobs et al., 1960) or through fecal matter contact (Dubey et al., 1970). Cysts are also persistent in the environment through a wide range of conditions (Frenkel et al., 1975), and after exposure to sodium hypochlorite or ozone (Wainwright et al., 2007). Infection can occur in three forms of the parasite: tachyzoites, bradyzoites found in cysts of infected tissue or the oocysts that are released in feces. Ingestion of cysts leads to rapid infection through the release of the bradyzoite in the digestive tract followed by integration into epithelial cells of the small intestine (Dubey, 1996). There are three strains of *T. gondii.* Type I is virulent with low genetic diversity, while Type II and III are distinct lineages and are nonvirulent (Sibley & Boothroyd, 1992; Howe & Sibley, 1995; Ajzenberg et al., 2004). The epigenetic mechanisms of these parasites have been investigated as a means of parasite

The variety of encephalitic diseases mediated by arthropod and mammalian vectors, and requiring humans as a host in a parasitic lifestyle, is vast. With the advent of more sophisticated molecular technologies and a greater understanding of these diseases and their genetic codes, novel vaccines could be developed to help curb or prevent future infections (Seshadri et al., 2003; Diamond & Mehlhop, 2008; Ertl, 2009). As genomes become available, a further characterization of phylogenetic relationships can be made (Mavarez et al., 2002; Bourhy et al., 2005; Jackson et al., 2010). PCR applications, including multiplex PCR (Paris et al., 2008), nested PCR (James et al., 2011), heteroduplex PCR (Lee et al., 2002), reverse transcriptase PCR and direct sequencing (Telford et al., 1997), restriction fragment

produced, resulting in a decreased risk of human infection.

physiology and potential therapeutics (Dixon et al., 2010).

**5. Conclusion** 

**4.3 Toxoplasmosis: Toxoplasma gondii** 

*Amblyomma americanum*. In Latin America, *Amblyomma cajennense* (Cayenne Tick) is a human vector (Alderdice & Burgess, 1998; Thorner et al., 1998; Treadwell et al., 2000; Dumler & Walker, 2005). Meningoencephalitis can be a side effect of this disease (Horney & Walker, 1988; Sexton & Corey, 1992). To a smaller extent, Colorado Tick fever (CTF), transmitted by *D. andersoni,* manifested as meningoencephalitis in the past (Draughn et al., 1965).

Similar to RMSF and CTF, *Rickettsia prowazekii* is the causative agent of epidemic typhus, transmitted by the body louse (*Pediculus humanus corporis*). *R prowazekii* is not carried in the saliva, rather excreted in the feces and present in ruptured lice remains, so open bite wounds, conjunctivae, and mucous membranes are pathways into the body (Andersson & Andersson, 2000). Infection can still occur without a lice infestation through aerosols of fecal dust, which can maintain viable pathogens for several months (Raoult & Roux, 1999). The lice themselves also succumb to the *R. prowazekii* infection, suffering from rupture of the infected epithelial cells and subsequent loss of blood, which is witnessed by the red color shift of the infected louse, and death within a week of infection (Houhamdi et al., 2002).

#### **4. Parasitic Encephalitis: Human African Trypanosomiasis, Schistosomiasis and Toxoplasmosis**

#### **4.1 Human African Trypanosomiasis:** *Trypanosoma brucei*

In humans, a *Trypanosoma brucei infection results in* Human African Trypanosomiasis, or sleeping sickness, of which the central nervous system becomes involved later in the disease onset (Kennedy, 2004; Bentivoglio et al., 2011). The blood-sucking tsetse fly (genus *Glossina*) is insect vector of *Trypanosoma brucei gambiense,* of which, humans are the parasitic reservoir. *T.b. rhodesiense* is a subspecies, and whose main reservoir is game animals and cattle, and results in an acute form of the disease (Bentivoglio et al., 2011). A bloodmeal from an infected animal starts the lifecycle of the trypanosomes. Procyclic trypomastigotes are ingested and multiply via binary fission in the fly's midgut cells. From there they travel through to the salivary glands and transform into epimastigotes then metacyclic trypomastigotes, which are capable of being transferred to a human host. The metacyclic trypomastigotes transform into trypomastigotes, are carried throughout the body and allowed to multiply in blood, lymph and spinal fluid (reviewed by Kennedy (2004)). Infection is usually fatal, but rare cases of recovery have been documented without chemotherapy treatment (Deborggraeve et al., 2008). A study done by Courtin et al. (2006) suggests that host genetics, specifically, single nucleotide polymorphisms in the *IL10*−592 A allele is associated with a lower risk of disease. A review done by Solano et al. (2010) of both tsetse fly genetics and genetic susceptibility of the host highlights the complexity of this disease.

#### **4.2 Schistosomiasis:** *Schistosoma*

Schistosomiasis (also called bilharzias) is caused by schistosomes, blood-dwelling fluke worms of the genus *Schistosoma.* Encephalitic onset is observed as Neuroschistosomiasis (Devine et al., 2008; Carod-Artal, 2010). Infection is worldwide, but is limited to areas conducive to maintaining the complex life cycle of the fluke, which involves a snail and human host and an aquatic environment to as passage between hosts. Eggs are released into waterway and hatch to form miracidia. These then penetrate the snail intermediate host. Sporocysts are formed, followed by cercariae, which can penetrate the human host, turning into schistosomulae. Adult worms reside in mesenteric venules. Once reproduction occurs,

*Amblyomma americanum*. In Latin America, *Amblyomma cajennense* (Cayenne Tick) is a human vector (Alderdice & Burgess, 1998; Thorner et al., 1998; Treadwell et al., 2000; Dumler & Walker, 2005). Meningoencephalitis can be a side effect of this disease (Horney & Walker, 1988; Sexton & Corey, 1992). To a smaller extent, Colorado Tick fever (CTF), transmitted by *D.* 

Similar to RMSF and CTF, *Rickettsia prowazekii* is the causative agent of epidemic typhus, transmitted by the body louse (*Pediculus humanus corporis*). *R prowazekii* is not carried in the saliva, rather excreted in the feces and present in ruptured lice remains, so open bite wounds, conjunctivae, and mucous membranes are pathways into the body (Andersson & Andersson, 2000). Infection can still occur without a lice infestation through aerosols of fecal dust, which can maintain viable pathogens for several months (Raoult & Roux, 1999). The lice themselves also succumb to the *R. prowazekii* infection, suffering from rupture of the infected epithelial cells and subsequent loss of blood, which is witnessed by the red color shift of the infected louse, and death within a week of infection (Houhamdi et al., 2002).

**4. Parasitic Encephalitis: Human African Trypanosomiasis, Schistosomiasis** 

In humans, a *Trypanosoma brucei infection results in* Human African Trypanosomiasis, or sleeping sickness, of which the central nervous system becomes involved later in the disease onset (Kennedy, 2004; Bentivoglio et al., 2011). The blood-sucking tsetse fly (genus *Glossina*) is insect vector of *Trypanosoma brucei gambiense,* of which, humans are the parasitic reservoir. *T.b. rhodesiense* is a subspecies, and whose main reservoir is game animals and cattle, and results in an acute form of the disease (Bentivoglio et al., 2011). A bloodmeal from an infected animal starts the lifecycle of the trypanosomes. Procyclic trypomastigotes are ingested and multiply via binary fission in the fly's midgut cells. From there they travel through to the salivary glands and transform into epimastigotes then metacyclic trypomastigotes, which are capable of being transferred to a human host. The metacyclic trypomastigotes transform into trypomastigotes, are carried throughout the body and allowed to multiply in blood, lymph and spinal fluid (reviewed by Kennedy (2004)). Infection is usually fatal, but rare cases of recovery have been documented without chemotherapy treatment (Deborggraeve et al., 2008). A study done by Courtin et al. (2006) suggests that host genetics, specifically, single nucleotide polymorphisms in the *IL10*−592 A allele is associated with a lower risk of disease. A review done by Solano et al. (2010) of both tsetse fly genetics and genetic susceptibility of the host highlights the

Schistosomiasis (also called bilharzias) is caused by schistosomes, blood-dwelling fluke worms of the genus *Schistosoma.* Encephalitic onset is observed as Neuroschistosomiasis (Devine et al., 2008; Carod-Artal, 2010). Infection is worldwide, but is limited to areas conducive to maintaining the complex life cycle of the fluke, which involves a snail and human host and an aquatic environment to as passage between hosts. Eggs are released into waterway and hatch to form miracidia. These then penetrate the snail intermediate host. Sporocysts are formed, followed by cercariae, which can penetrate the human host, turning into schistosomulae. Adult worms reside in mesenteric venules. Once reproduction occurs,

*andersoni,* manifested as meningoencephalitis in the past (Draughn et al., 1965).

**4.1 Human African Trypanosomiasis:** *Trypanosoma brucei*

**and Toxoplasmosis** 

complexity of this disease.

**4.2 Schistosomiasis:** *Schistosoma*

eggs move to either the intestine or ureters and are then released in the feces or urine respectively, completing the cycle and the means of egg release is species dependent (Cox, 2002). The main schistosomes infecting human are *S. mansoni*, *S. haematobium*, and *S. japonicum* and their respective snail hosts, *Biomphalaria*, *Bulinus* and *Oncomelania*. *S. mansoni*  is found in Africa, the Arabian peninsula, and South America, with humans as its main host, but can also infect rodents and primates (as reviewed by (Gryseels et al., 2006; Brooker, 2010). The biodiversity of an area, as can the genetic diversity of a population, can play a role in the risk of human *S. mansoni* infection. Johnson et al. (2009) found when *Biomphalaria glabrata* was raised along with non-host snails, 60–80 per cent fewer cercariae were produced, resulting in a decreased risk of human infection.

#### **4.3 Toxoplasmosis: Toxoplasma gondii**

*Toxoplasma gondii* is responsible for toxoplasmosis, and cases of severe encephalitis have been reported, especially in immnocompromised individuals (i.e., transplant, AIDS and lymphatic cancer patients) (Frenhel et al., 1975; Araujo & Remington, 1987; Luft & Remington, 1992; Touahri et al., 2002; Derouin et al., 2008). As an obligate intracellular parasite, producing many asymptomatic infections, this parasite has balanced host immune detection and successful infection and reproduction and passage through blood-brain, placenta and intestinal barriers (Lambert & Barragan, 2010). This phylum is named for the apical complex that assistants host cell infection (Lim & McFadden, 2010). Although Family Felidae are the sole definitive host (allowing for sexual reproduction) (Hutchison, 1965), wide range of warm-blooded animals (including livestock) and birds can act as a intermediate host (Jacobs et al., 1960; Work, 1967; Tenter et al., 2000; Innes, 2010). Initial infection is through ingestion of raw or undercooked meat containing oocysts or live organisms (Jacobs et al., 1960) or through fecal matter contact (Dubey et al., 1970). Cysts are also persistent in the environment through a wide range of conditions (Frenkel et al., 1975), and after exposure to sodium hypochlorite or ozone (Wainwright et al., 2007). Infection can occur in three forms of the parasite: tachyzoites, bradyzoites found in cysts of infected tissue or the oocysts that are released in feces. Ingestion of cysts leads to rapid infection through the release of the bradyzoite in the digestive tract followed by integration into epithelial cells of the small intestine (Dubey, 1996). There are three strains of *T. gondii.* Type I is virulent with low genetic diversity, while Type II and III are distinct lineages and are nonvirulent (Sibley & Boothroyd, 1992; Howe & Sibley, 1995; Ajzenberg et al., 2004). The epigenetic mechanisms of these parasites have been investigated as a means of parasite physiology and potential therapeutics (Dixon et al., 2010).
