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Zoonotic Parasitic Diseases: Emerging issues and Problems Several hundred infectious diseases are classified as zoonotic diseases as they are caused by bacteria, virus, fungi or parasites that can be transmitted from animals to humans. These zoonotic diseases include many of the classic infectious diseases such as rabies and ricketsia (e.g. Rocky Mountain Spotted Fever), as well as most of the “new” emerging infectious diseases such as HIV, SARS. Zoonotic infections can be significant pathogens, with a more severe outcome, in patients with various forms of immune suppression due to infection, i.e. HIV, or immune suppressive drugs. A number of parasitic zoonoses such as cryptosporidiosis, toxoplasmosis and leishmaniasis have gained in importance as human pathogens due to their ability to cause disease in patients with immune suppression due to HIV. The majority of the classic parasitic diseases due to helminthes, trematodes, cestodes and protozoa are zoonotic. There are increasing numbers of cases of zoonotic infections being recognized. A number of factors underlie this emergence of zoonotic disease including overpopulation, disruptions due to military action, mass migrations of populations due to natural or man-made disasters, the migration of populations into large urban centers, and inadequate food and water supplies. The clearing of new areas for the cultivation of food and other land uses has resulted in human settlement in areas were animal populations and parasites were previously isolated from humans. In addition, displacement and stress of wildlife through development as well as global warming. can lead to epidemics of wildlife disease with resultant overflow infections into domestic animals and humans as well as bring additional zoonotic infections into contact with human hosts. The use of bushmeat as a food source has been linked to the emergence of several zoonotic diseases such as SARS and HIV. Worldwide tourism and adventure travel has resulted in the exposure of new groups to “exotic” zoonotic pathogens. The popularity of exotic pets has resulted in several reports of zoonotic infections, such as human Monkeypox transmission linked to Prairie dogs which were infected due to exposure to an exotic rodent while being housed at an animal dealer’s facility. Advances in medical progress such as xenotranplantation or the use of various animal cells in the production of therapeutic agents has the potential to result in the emergence of new zoonotic infections. Both organ transplantation and blood transfusion have been associated with the transmission of zoonotic infections such as Leishmaniasis and Trypanosoma cruzi due to these infections being present in donors. As pointed out in article on emerging parasitic zoonoses, emerging infectious diseases are dominated by zoonoses and the majority of these infections originate in wildlife. While protozoa are more likely to account for emerging parasitic infections, there are clear examples of metazoan infections as emerging or re-emerging diseases. Interactions of wildlife and human populations often drive this process as illustrated by the increase in Echinococus multilocularis in Europe as a consequence of control of rabies in the red fox population leading to an increase in these animals in urban centers. The fox population may also play a role in increased exposure to Toxocara canis and other parasites. Control and prevention of these zoonotic diseases is complex and requires an 1 integrative multidisciplinary approach grounded in careful epidemiological studies understanding the variables that influence disease emergence and transmission. For example, culling of infected dogs does not reduce the risk of human infection from Leishmania, but providing insecticide collars has been demonstrated to be an effective strategy. A comprehensive review of the phylogeny and biology of Babesia spp. These Ixodid tick-borne zoonotic infectious diseases associated with infection of erythrocytes resulting in cell lysis leading to anemia, hyperbillirubinuria, hemoglobinuria and other disease manifestations. There are over 100 Babesia spp. that have been recognized, infecting many mammalian and some avian species, of these the Babesia microti complex, Babesia divergens, Babesia bovis, Babesia canis, Babesia duncani, Babesia enatorum. Blood transfusion has been recognized as an increasing source of transmission and immune compromised patients have been demonstrated to have persistent infections with non-classical presentations. Increases in wildlife animal reservoirs and the expansion of urban environments into undeveloped areas have resulted in increases in these illnesses and the recognition of new species of Babesia that can infect humans. A comprehensive review of the species and genotypes ofCryptosporidium and Giardia as they relate to the zoonotic potential of these pathogenic protozoa.Cryptosporidium oocysts are often found in water supplies and molecular studies have been applied to allow species recognition, enabling studies of the zoonotic potential of the 18 Cryptosporidium spp. currently recognized. Host-adapted genotypes of various Cryptosporidium spp. have been described and characterized. Of these, Cryptosporidium parvum has a broad host range and molecular studies suggest zoonotic human transmission occurs. In contrast, studies on Giardia have suggested that zoonotic transmission is not as common as previously suggested. Overall, they point out the utility of molecular epidemiological tools in dissecting the presence of anthroponotic as well as zoonotic transmission of these parasites. The epidemiology of Toxoplasma gondii infection in animals and humans in the United States of America. It has been 100 years since the discovery of this pathogenic protozoan associated with infections in both immune competent and immune compromised hosts. It is one of the most ubiquitous zoonotic infections being transmitted through meat via tissue cysts containing bradyzoites and through the contamination of both food and water by oocysts shed by cats. Given the complex relationships between humans, domestic animals and wildlife, as well as the profound alternations in the environment due to human interventions, we can expect to see changes in the epidemiology of zoonotic parasitic infections with increasing importance being paid to the emergence of these zoonotic infections. Control strategies for these emerging infections will require the use of molecular techniques and traditional epidemiological investigations to define the problem, and management strategies that will be effective for these infections. 2 Tick paralysis Tick paralysis is the only tick-borne disease that is not caused by an infectious organism. The illness is caused by a neurotoxinproduced in the tick's salivary gland. After prolonged attachment, the engorged tick transmits the toxin to its host. The incidence of tick paralysis is unknown. Patients can experience severe respiratory distress (similar to anaphylaxis). Signs and symptoms Tick paralysis results from inoculation of a toxin from tick salivary glands during a blood meal. The toxin causes symptoms within 2–7 days, beginning with weakness in both legs that progresses to paralysis. The paralysis ascends to the trunk, arms, and head within hours and may lead to respiratory failure and death. The disease can present as acuteataxia without muscle weakness. Electromyographic (EMG) studies usually show a variable reduction in the amplitude of compound muscle action potentials, but no abnormalities of repetitive nerve stimulation studies. These appear to result from a failure of acetylcholine release at the motor nerve terminal level. Pathogenesis Tick paralysis is believed to be due to toxins found in the tick's saliva that enter the bloodstream while the tick is feeding. The two ticks most commonly associated with North American tick paralysis are the Rocky Mountain wood tick (Dermacentor andersoni) and the American dog tick (Dermacentor variabilis); however, 43 tick species have been implicated in human disease around the world. Most North American cases of tick paralysis occur from April to June, when adult Dermacentor ticks emerge from hibernation and actively seek hosts. In Australia, tick paralysis is caused by the tick Ixodes holocyclus. 20 fatal cases were reported in Australia. Although tick paralysis is of concern in domestic animals and livestock in the United States as well, human cases are rare and usually occur in children under the age of 10. Tick paralysis occurs when an engorged and gravid (egg-laden) female tick produces a neurotoxin in its salivary glands and transmits it to its host during feeding. Experiments have indicated that the greatest amount of toxin is produced between the fifth and seventh day of attachment (often initiating or increasing the severity of symptoms), although the timing may vary depending on the species of tick. Unlike babesiosis, which are caused by the systemic proliferation and expansion of parasites in their hosts long after the offending tick is gone, tick paralysis is chemically induced by the tick and therefore usually only continues in its presence. Once the tick is removed, symptoms usually diminish rapidly. However, in some cases, profound paralysis can develop and even become fatal before anyone becomes aware of a tick's presence. 3 Diagnostic tests Diagnosis is based on symptoms and upon finding an embedded tick, usually on the scalp. Treatment Removal of the embedded tick usually results in resolution of symptoms within several hours to days. If the tick is not removed, the toxin can be fatal, with reported mortality rates of 10–12 percent, usually due to respiratory paralysis. The tick is best removed by grasping the tick as close to the skin as possible and pulling in a firm steady manner. Unlike the other species of ticks, the toxin of Ixodes holocyclus (Australian Paralysis Tick) will not resolve itself and will be fatal if medical assistant is not immediately sought after pulling the tick off of the animal. Contrary to popular belief, if the head detaches from the body while being pulled off, leaving the head will not inject more venom. The head may cause a skin irritation but it will not inject any more venom. Once the tick is removed, place it in a clear bag, so the vet can identify it. Water and food can worsen the results of the animal as the venom can prevent the animal from swallowing properly. If you find an Australian Paralysis Tick on your animal, immediately remove the tick and seek veterinary assistance even if you do not think the tick has been on the animal long enough to inject venom. Prevention No human vaccine is currently available for any tick-borne disease, except for tick-borne encephalitis. Individuals should therefore take precautions when entering tick-infested areas, particularly in the spring and summer months. Preventive measures include avoiding trails that are overgrown with bushy vegetation, wearing light-coloured clothes that allow one to see the ticks more easily, and wearing long pants and closed-toe shoes. Young children may be especially vulnerable to these adverse effects. Permethrin, which can only be applied to clothing, is much more effective in preventing tick bites. Permethrin is not a repellent but rather an insecticide; it causes ticks to curl up and fall off the protected clothing. Toxoplasmosis Toxoplasmosis is a parasitic disease caused by Toxoplasma gondii. ] Infections with toxoplasmosis usually cause no symptoms in adult humans.[ ] Occasionally there may be a few weeks or months of mild flu-like illness such as muscle aches and tender lymph nodes.[ ] In a small number of people, eye problems may develop. In those with a weak immune system, severe symptoms such asseizures and poor coordination may occur. If infected during pregnancy, a condition known as congenital toxoplasmosis may affect the child.[ ] Toxoplasmosis is usually spread by eating poorly cooked food that contains cysts, exposure to infected cat feces, and from a mother to a child during pregnancy if the mother becomes infected. 4 Rarely the disease may be spread by a blood transfusion. It is not otherwise spread between people. ] The parasite is only known to reproduce sexually in the cat family. However, it can infect most types of warm-blooded animals, including humans. ] Diagnosis is typically by testing the blood for antibodies or by testing theamniotic fluid for the parasite's DNA.[ ] Prevention is by properly preparing and cooking food. It is also recommended that pregnant women not clean cat litter boxes. ]Treatment of otherwise healthy people is usually not needed. During pregnancy spiramycin or pyrimethamine/sulfadiazine and folinic acid may be used for treatment.[ ] Up to half of the world's population are infected by toxoplasmosis but have no symptoms.[ ] In the United States about 23% are affected ] and in some areas of the world this is up to 95%.[ ] About 200,000 cases of congenital toxoplasmosis occur a year.[ ]Charles Nicolle and Louis Manceaux first described the organism in 1908. In 1941 transmission during pregnancy from a mother to a child was confirmed.[ ] Signs and symptoms[ ] Infection has three stages: Acute toxoplasmosis[ ] Acute toxoplasmosis is often asymptomatic in healthy adults. However, symptoms may manifest and are often influenza-like: swollen lymph nodes, headaches, fever, and fatigue,[ ] or muscle aches and pains that last for a month or more. Rarely will a human with a fully functioning immune system develop severe symptoms following infection. People with weakened immune systems are likely to experience headache, confusion, poor coordination, seizures, lung problems that may resemble tuberculosis or Pneumocystis jiroveci pneumonia (a common opportunistic infection that occurs in people with AIDS), or blurred vision caused by severe inflammation of the retina (ocular toxoplasmosis)[ ] Young children and immunocompromised people, such as those with HIV/AIDS, those taking certain types of chemotherapy, or those who have recently received an organ transplant, may develop severe toxoplasmosis. This can cause damage to the brain (encephalitis) or the eyes (necrotizing retinochoroiditis).[ ] Infants infected via placental transmission may be born with either of these problems, or with nasal malformations, although these complications are rare in newborns. The toxoplasmictrophozoites causing acute toxoplasmosis are referred to as tachyzoites, and are typically found in bodily fluids. Swollen lymph nodes are commonly found in the neck or under the chin, followed by the armpits and the groin. Swelling may occur at different times after the initial infection, persist, and recur for various times independently of antiparasitic treatment.[ ] It is usually found at single sites in adults, but in children, multiple sites may be more common. Enlarged lymph nodes will resolve within one to two months in 60% of cases. However, a quarter of those affected take two to four months to return to normal, and 8% take four to six months. A substantial number (6%) do not return to normal until much later.[ ] 5 Latent toxoplasmosis[ ] Due to its asymptomatic nature, it is easy for a host to become infected with Toxoplasma gondii and develop toxoplasmosis without knowing it. Although mild, flu-like symptoms occasionally occur during the first few weeks following exposure, infection with T. gondii produces no readily observable symptoms in healthy human adults. In most immunocompetent people, the infection enters a latent phase, during which only bradyzoites (tissue cysts) are present;[ ] these tissue cysts and even lesions can occur in the retinas, alveolar lining of the lungs (where an acute infection may mimic a Pneumocystis jirovecii infection), heart, skeletal muscle, and the central nervous system (CNS), including the brain.[ ] Cysts form in the CNS (brain tissue) upon infection with T. gondii and persist for the lifetime of the host.[ ] Most infants who are infected while in the womb have no symptoms at birth, but may develop symptoms later in life.[ ] Reviews of serological studies have estimated that 30–50% of the global population has been exposed to and may be chronically infected with latent toxoplasmosis, although infection rates differ significantly from country to country. This latent state of infection has recently been associated with numerous disease burdens,[ ] neural alterations, and subtle gender-dependent behavioral changes in immunocompetent humans. Cutaneous toxoplasmosis[ ] While rare, skin lesions may occur in the acquired form of the disease, including roseola and erythema multiforme-like eruptions, prurigo-like nodules, urticaria, and maculopapular lesions. Newborns may have punctate macules, ecchymoses, or “blueberry muffin” lesions. Diagnosis of cutaneous toxoplasmosis is based on the tachyzoite form of T. gondii being found in the epidermis.[ ] It is found in all levels of the epidermis, is about 6 μm by 2 μm and bowshaped, with the nucleus being one-third of its size. It can be identified by electron microscopy or by Giemsa staining tissue where the cytoplasm shows blue, the nucleus red.[ ] life cycle In its life cycle, T. gondii adopts several forms.[ ] Tachyzoites are responsible for acute infection; they divide rapidly and spread through the tissues of the body. After proliferating, tachyzoites convert into bradyzoites, which take the form of latent intracellular tissue cysts that form mainly in the tissues of the muscles and brain. The transformation into cysts is in part triggered by the pressure of the host immune system.[ ] The bradyzoites are not responsive to antibiotics. The bradyzoites, once formed, can remain in the tissues for the lifespan of the host. In a healthy host, if some bradyzoites convert back into active tachyzoites, the immune system will quickly destroy them. However, in immunocompromised individuals, or in fetuses, which lack a developed immune system, the tachyzoites can run rampant and cause significant neurological damage.[ ] The parasite’s survival is dependent on a balance between host survival and parasite proliferation.[ ] T. gondii achieves this balance by manipulating the host’s immune response, reducing the host’s immune response and enhancing the parasite’s reproductive advantage. ] Once it infects a normal 6 host cell, it resists damage caused by the host’s immune system, and changes the host's immune processes. As it forces its way into the host cell, the parasite forms a parasitophorous vacuole (PV) membrane from the membrane of the host cell. The PV encapsulates the parasite, and is both resistant to the activity of the endolysosomal system, and can take control of the host’s mitochondria and endoplasmic reticulum. . T. gondii also has the ability to initiate autophagy of the host’s cells.[ ] This leads to a decrease in healthy, uninfected cells, and consequently fewer host cells to attack the infected cells. Research by Wang et al finds that infected cells lead to higher levels of autophagosomes in normal and infected cells.[ ] Their research reveals that T. gondiicauses host cell autophagy using a calcium-dependent pathway.[ ] Another study suggests that the parasite can directly affect calcium being released from calcium stores, which are important for the signalling processes of cells.[ ] The mechanisms above allow T. gondii to persist in a host. Some limiting factors for the toxoplasma is that its influence on the host cells is stronger in a weak immune system and is quantity-dependent, so a large number of T. gondii per host cell cause a more severe effect.[ ] The effect on the host also depends on the strength of the host immune system. Immunocompetent individuals do not normally show severe symptoms or any at all, while fatality or severe complications can result in immunocompromised individuals.[ ] It should be noted that since the parasite can change the host’s immune response, it may also have an effect, positive or negative, on the immune response to other pathogenic threats.[ ] This includes, but is not limited to, the responses to infections by Helicobacter felis, Leishmania major, or other parasites, such as Nippostrongylus brasiliensis.[ ] Transmission[ ] Toxoplasmosis is generally transmitted through an oral route, by accidentally ingesting toxoplama gondii cysts, but can be transmitted congenitally, passed from mother to fetus through the placenta.[ Oral transmission may occur through: Ingestion of raw or partly cooked meat, especially pork, lamb, or venison containing Toxoplasma cysts: Infection prevalence in countries where undercooked meat is traditionally eaten has been related to this transmission method. Tissue cysts may also be ingested during hand-to-mouth contact after handling undercooked meat, or from using knives, utensils, or cutting boards contaminated by raw meat.[ ] Ingestion of unwashed fruits or vegetables that have been in contact with contaminated soil containing infected cat feces.[ ] Ingestion of contaminated cat feces: This can occur through hand-to-mouth contact following gardening, cleaning a cat's litter box, contact with children's sandpits; the parasite can survive in the environment for over a year.[ ] 7 Cats excrete the pathogen in their feces for a number of weeks after contracting the disease, generally by eating an infected rodent. Even then, cat feces are not generally contagious for the first day or two after excretion, after which the cyst 'ripens' and becomes potentially pathogenic.[40] Pregnancy precautions[ ] Congenital toxoplasmosis is a specific form of toxoplasmosis in which an unborn fetus is infected via the placenta.[ ] Congenital toxoplasmosis is associated with fetal death and abortion, and in infants, it is associated with neurologic deficits, neurocognitive deficits, and chorioretinitis.[ ] A positive antibody titer indicates previous exposure and immunity, and largely ensures the unborn fetus' safety. A simple blood draw at the first prenatal doctor visit can determine whether or not a woman has had previous exposure and therefore whether or not she is at risk. If a woman receives her first exposure to T. gondii while pregnant, the fetus is at particular risk.[ ] For pregnant women with negative antibody titers, indicating no previous exposure to T. gondii, serology testing as frequent as monthly is advisable as treatment during pregnancy for those women exposed to T. gondii for the first time dramatically decreases the risk of passing the parasite to the fetus. Since a baby's immune system does not develop fully for the first year of life, and the resilient cysts that form throughout the body are very difficult to eradicate with antiprotozoans, an infection can be very serious in the young. Despite these risks, pregnant women are not routinely screened for toxoplasmosis in most countries, for reasons of cost-effectiveness and the high number of false positivesgenerated; Portugal, ] France, ] Austria, ] Uruguay, ] and Italy[ ] are notable exceptions, and some regional screening programmes operate in Germany, Switzerland andBelgium.[ ] As invasive prenatal testing incurs some risk to the fetus (18.5 pregnancy losses per toxoplasmosis case prevented),[ ] postnatal or neonatal screening is preferred. The exceptions are cases where fetal abnormalities are noted, and thus screening can be targeted.[ ] Pregnant women should avoid handling raw meat, drinking raw milk (especially goat milk) and be advised to not eat raw or undercooked meat regardless of type.[ ] Because of the obvious relationship between Toxoplasma and cats it is also often advised to avoid exposure to cat feces, and refrain from gardening (cat feces are common in garden soil) or at least wear gloves when so engaged. [ ] Most cats are not actively shedding oocysts, since they get infected in the first six months of their life, when they shed oocysts for a short period of time (1–2 weeks.)[ ] However, these oocysts get buried in the soil, sporulate and remain infectious for periods ranging from several months to more than a year.[ ] Numerous studies have shown living in a household with a cat is not a significant risk factor for T. gondii infection, though living with several kittens has some significance.[ ] In 2006, a Czech research team[ ] discovered women with high levels of toxoplasmosis antibodies were significantly more likely to have baby boys than baby girls. In most populations, the birth rate is around 51% boys, but women infected with T. gondii had up to a 72% chance of a boy. In mice, the sex ratio was higher in early latent toxoplasmosis and lower in later latent toxoplasmosis.[ ] 8 Rodent behavior[ ] Infection with T. gondii has been shown to alter the behavior of mice and rats in ways thought to increase the rodents’ chances of being preyed upon by cats. Infected rodents show a reduction in their innate aversion to cat odors; while uninfected mice and rats will generally avoid areas marked with cat urine or with cat body odor, this avoidance is reduced or eliminated in infected animals. Moreover, some evidence suggests this loss of aversion may be specific to feline odors: when given a choice between two predator odors (cat or mink), infected rodents show a significantly stronger preference to cat odors than do uninfected controls. In rodents, T. gondii–induced behavioral changes occur through epigenetic remodeling in neurons associated observed behaviors; for example, it modifies epigenetic methylation to induce hypomethylation of arginine vasopressin-related genes in the medial amygdala to greatly decrease predator aversion. Similar epigenetically-induced behavioral changes have also been observed in mouse models of addiction, where changes in the expression of histone-modifying enzymes via gene knockout or enzyme inhibition in specific neurons produced alterations in drug-related behaviors. Widespread histone-lysine acetylation in cortical astrocytes appears to be another epigenetic mechanism employed by T. gondii. T. gondii-infected rodents show a number of behavioral changes beyond altered responses to cat odors. Rats infected with the parasite show increased levels of activity and decreased neophobic behavior.[ ] Similarly, infected mice show alterations in patterns of locomotion and exploratory behavior during experimental tests. These patterns include traveling greater distances, moving at higher speeds, accelerating for longer periods of time, and showing a decreased pause-time when placed in new arenas.[ ] Infected rodents have also been shown to have lower anxiety, using traditional models such as elevated plus mazes, open field arenas, and social interaction tests. Diagnosis[ ] Diagnosis of toxoplasmosis in humans is made by biological, serological, histological, or molecular methods, or by some combination of the above.[ ] Toxoplasmosis can be difficult to distinguish from primary central nervous system lymphoma. It mimics several other infectious diseases so clinical signs are non-specific and are not sufficiently characteristic for a definite diagnosis. As a result, the diagnosis is made by a trial of therapy (pyrimethamine, sulfadiazine, and folinic acid (USAN: leucovorin)), if the drugs produce no effect clinically and no improvement on repeat imaging. T. gondii in may also be detected in blood, amniotic fluid, or cerebrospinal fluid by using polymerase chain reaction.[ ] T. gondii may exist in a host as an inactive cyst that would likely evade detection. Serological testing can detect T. gondii antibodies in the blood serum, using methods including the Sabin–Feldman dye test (DT), the indirect hemagglutination assay, the indirect fluorescent 9 antibody assay (IFA), the direct agglutination test, the latex agglutination test (LAT), the enzymelinked immunosorbent assay (ELISA), and the immunosorbent agglutination assay test (IAAT).[ ] The most commonly used tests to measure IgG antibody are the DT, the ELISA, the IFA, and the modified direct agglutination test.[ ] IgG antibodies usually appear within a week or two of infection, peak within one to two months, then decline at various rates.[ ] Toxoplasma IgG antibodies generally persist for life, and therefore may be present in the bloodstream as a result of either current or previous infection.[ ] To some extent, acute toxoplasmosis infections can be differentiated from chronic infections using an IgG avidity test, which is a variation on the ELISA. In the first response to infection, toxoplasmaspecific IgG has a low affinity for the toxoplasma antigen; in the following weeks and month, IgG affinity for the antigen increases. Based on the IgG avidity test, if the IgG in the infected individual has a high affinity, it means that the infection began three to five months before testing. This is particularly useful in congenital infection, where pregnancy status and gestational age at time of infection determines treatment.[ ] In contrast to IgG, IgM antibodies can be used to detect acute infection, but generally not chronic infection.[ ] The IgM antibodies appear sooner after infection than the IgG antibodies and disappear faster than IgG antibodies after recovery.[ ] In most cases, T. gondii-specific IgM antibodies can first be detected approximately a week after acquiring primary infection, and decrease within one to six months; 25% of those infected are negative for T. gondii-specific IgM within seven months.[ ] However, IgM may be detectable months or years after infection, during the chronic phase, and false positives for acute infection are possible.[ ] The most commonly used tests for the measurement of IgM antibody are double-sandwich IgM-ELISA, the IFA test, and the immunosorbent agglutination assay (IgM-ISAGA). Commercial test kits often have low specificity, and the reported results are frequently misinterpreted.[ ] Congenital toxoplasmosis[ ] Recommendations for the diagnosis of congenital toxoplasmosis include: prenatal diagnosis based on testing of amniotic fluid and ultrasound examinations; neonatal diagnosis based on molecular testing of placenta and cord blood and comparative mother-child serologic tests and a clinical examination at birth; and early childhood diagnosis based onneurologic and ophthalmologic examinations and a serologic survey during the first year of life.[ ] During pregnancy, serological testing is recommended at three week intervals.[ ] Even though diagnosis of toxoplasmosis heavily relies on serological detection of specific antiToxoplasma immunoglobulin, serological testing has limitations. For example, it may fail to detect the active phase of T. gondii infection because the specific anti-Toxoplasma IgG or IgM may not be produced until after several weeks of infection. As a result, a pregnant woman might test negative during the active phase of T. gondii infection leading to undetected and therefore untreated congenital toxoplasmosis.[ ] Also, the test may not detect T. gondii infections in 10 immunocompromised patients because the titers of specific anti-Toxoplasma IgG or IgM may not rise in this type of patient. Many PCR-based techniques have been developed to diagnose toxoplasmosis using clinical specimens that include amniotic fluid, blood, cerebrospinal fluid, and tissue biopsy. The most sensitive PCR-based technique is nested PCR, followed by hybridization of PCR products.[ ] The major downside to these techniques is that they are time consuming and do not provide quantitative data.[ ] Real-time PCR is useful in pathogen detection, gene expression and regulation, and allelic discrimination. This PCR technique utilizes the 5' nuclease activity of Taq DNA polymerase to cleave a nonextendible, fluorescence-labeled hybridization probe during the extension phase of PCR.[ ] A second fluorescent dye, e.g., 6-carboxy-tetramethyl-rhodamine, quenches the fluorescence of the intact probe. ] The nuclease cleavage of the hybridization probe during the PCR releases the effect of quenching resulting in an increase of fluorescence proportional to the amount of PCR product, which can be monitored by a sequence detector.[ ] Toxoplasmosis cannot be detected with immunostaining. Lymph nodes affected by Toxoplasma have characteristic changes, including poorly demarcated reactive germinal centers, clusters of monocytoid B cells, and scattered epithelioid histiocytes. Treatment[ ] Treatment is often only recommended for people with serious health problems, such as people with HIV whose CD4 counts are under 200 cells/mm3, because the disease is most serious when one's immune system is weak. Trimethoprim/sulfamethoxazole is the drug of choice to prevent toxoplasmosis, but not for treating active disease. A new study (May 2012) shows a promising new way to treat the active and latent form of this disease using two endochin-like quinolones.[ ] Cryptosporidiosis Cryptosporidiosis, also known as crypto, ] is a parasitic disease caused by Cryptosporidium, a genus of protozoan parasites in the phylum Apicomplexa. It affects the distal small intestine and can affect the respiratory tract in both immunocompetent (i.e., individuals with a normal functioning immune system) and immunocompromised (e.g., persons with HIV/AIDS) individuals, resulting in watery diarrhea with or without an unexplained cough.[ ] In immunocompromised individuals, the symptoms are particularly severe and can be fatal. It is primarily spread through the fecal-oral route, often through contaminated water; recent evidence suggests that it can also be transmitted via fomites in respiratory secretions.[ ] Cryptosporidium is the organism most commonly isolated in HIV-positive patients presenting with diarrhea.[ ]Despite not being identified until 1976, it is one of the most common waterborne diseases and is found worldwide. The parasite is transmitted by environmentally hardy microbial 11 cysts (oocysts) that, once ingested, exist in the small intestine and result in an infection of intestinal epithelial tissue. Signs and symptoms[ ] Cryptosporidiosis may occur as an asymptomatic infection, an acute infection (i.e., duration shorter than 2 weeks), recurrent acute infections in which symptoms reappear following a brief period of recovery for up to 30 days, and a chronic infection (i.e., duration longer than 2 weeks) in which symptoms are severe and persistent. It may be fatal in individuals with a severely compromised immune system. Symptoms usually appear 5–10 days after infection (range: 2–28 days) and normally last for up to 2 weeks in immunocompetent individuals (i.e., individuals with a normal functioning immune system); symptoms are usually more severe and persist longer in immunocompromisedindividuals . Following the resolution of diarrhea, symptoms can reoccur after several days or weeks due to reinfection. Based upon one clinical trial, the likelihood of reinfection is high in immunocompetent adults. In immunocompetent individuals, cryptosporidiosis is primarily localized to the distal small intestine and sometimes the respiratory tract as well. In immunocompromised persons, cryptosporidiosis may disseminate to other organs, including the hepatobiliary system, pancreas, upper gastrointestinal tract, and urinary bladder; pancreatic and biliary infection can involve acalculous cholecystitis, sclerosing cholangitis, papillary stenosis, or pancreatitis. Intestinal cryptosporidiosis[ ] Common signs and symptoms of intestinal cryptosporidiosis include: Moderate to severe watery diarrhea, sometimes contains mucus and rarely contains blood or leukocytes[ ] In very severe cases, diarrhea may be profuse and cholera-like with malabsorption and hypovolemia Low-grade fever Crampy abdominal pain Dehydration Weight loss Fatigue[ ] Nausea and vomiting – suggests upper GI tract involvement[ ] and may lead to respiratory cryptosporidiosis Epigastric or right upper quadrant tenderness ] Less common or rare signs and symptoms include: Reactive arthritis (may affect the hands, knees, ankles, and feet)[ ] Jaundice – suggests hepatobiliary involvement 12 Ascites – suggests pancreatic involvement[ Respiratory cryptosporidiosis[ ] Symptoms of upper respiratory cryptosporidiosis include: Inflammation of the nasal mucosa, sinuses, larynx, or trachea[ Nasal discharge[ ] Voice change[2] (e.g., hoarseness)[ ] Symptoms of lower respiratory cryptosporidiosis include: Cough Shortness of breath Fever[ ] Hypoxemia[ ] Cause[ ] Cryptosporidium is a genus of protozoan pathogens which is categorized under the phylum Apicomplexa. Other apicomplexan pathogens include the malaria parasite Plasmodium, and Toxoplasma, the causative agent of toxoplasmosis. A number of Cryptosporidium infect mammals. In humans, the main causes of disease are C. parvum and C. hominis(previously C. parvum genotype 1). C. canis, C. felis, C. meleagridis, and C. muris can also cause disease in humans.Cryptosporidium is capable of completing its life cycle within a single host, resulting in microbial cyst stages that are excreted in feces and are capable of transmission to a new host via the fecal-oral route. Other vectors of disease transmission also exist. The pattern of Cryptosporidium life cycle fits well with that of other intestinal homogeneous coccidian genera of the suborderEimeriina: macro- and microgamonts develop independently; a microgamont gives rise to numerous male gametes; and oocysts serving for parasites' spreading in the environment. Electron microscopic studies made from the 1970s have shown the intracellular, although extracytoplasmic localization of Cryptosporidium species. These species possess a number of unusual features: an endogenous phase of development in microvilli of epithelial surfaces two morphofunctional types of oocysts the smallest number of sporozoites per oocyst a multi-membraneous "feeder" organelle DNA studies suggest a relationship with the gregarines rather than the coccidia.[ ] The taxonomic position of this group has not yet been finally agreed upon. 13 The genome of Cryptosporidium parvum was sequenced in 2004 and was found to be unusual amongst Eukaryotes in that the mitochondria seem not to contain DNA.[ ] A closely related species, C. hominis, also has its genome sequence available.[ ] CryptoDB.org is a NIH-funded database that provides access to the Cryptosporidium genomics data sets. Transmission[ ] Infection is through contaminated material such as earth, water, uncooked or crosscontaminated food that has been in contact with the feces of an infected individual or animal. Contact must then be transferred to the mouth and swallowed. It is especially prevalent amongst those in regular contact with bodies of fresh water including recreational water such as swimming pools. Other potential sources include insufficiently treated water supplies, contaminated food, or exposure to feces.[ ] The high resistance of Cryptosporidiumoocysts to disinfectants such as chlorine bleach enables them to survive for long periods and still remain infective.[ ] Some outbreaks have happened in day care related to diaper changes.[ ] The following groups have an elevated risk of being exposed to Cryptosporidium:[ ] Child care workers Parents of infected children People who take care of other people with cryptosporidiosis International travelers Backpackers, hikers, and campers who drink unfiltered, untreated water People, including swimmers, who swallow water from contaminated sources People who handle infected cattle People exposed to human feces through sexual contact Cases of cryptosporidiosis can occur in a city that does not have a contaminated water supply. In a city with clean water, it may be that cases of cryptosporidiosis have different origins. Testing of water, as well as epidemiological study, are necessary to determine the sources of specific infections. Note that Cryptosporidium typically does not cause serious illness in healthy people. It may chronically sicken some children, as well as adults who are exposed and immunocompromised. A subset of the immunocompromised population is people with AIDS. Some sexual behaviours can transmit the parasite directly. Life cycle[ ] Cryptosporidium spp. exist as multiple cell types which correspond to different stages in an infection (e.g., a sexual and asexual stage).[ ] As an oocyst – a type of hardy, thick-walled spore – it can survive in the environment for months and is resistant to many common disinfectants, particularly chlorine-based disinfectants. After being ingested, the oocysts excyst in the small intestine. They release sporozoites that attach to the microvilli of the epithelial cells of the small intestine. From there they become trophozoites that reproduce asexually by multiple fission, a 14 process known as schizogony. The trophozoites develop into Type 1 meronts [ ] that contain 8 daughter cells.[ ] These daughter cells are Type 1 merozoites, which get released by the meronts. Some of these merozoites can cause autoinfection by attaching to epithelial cells. Others of these merozoites become Type II meronts,[18] which contain 4 Type II merozoites.[ ] These merozoites get released and they attach to the epithelial cells. From there they become either macrogamonts or microgamonts.[ ] These are the female and male sexual forms, respectively.[ ] This stage, when sexual forms arise, is called gametogony.[ ] Zygotes are formed by microgametes from the microgamont penetrating the macrogamonts. The zygotes develop into oocysts of two types.[ ] 20% of oocysts have thin walls and so can reinfect the host by rupturing and releasing sporozoites that start the process over again. ] The thick-walled oocysts are excreted into the environment.[18] The oocysts are mature and infective upon being excreted.[ ] Pathogenesis[ ] The oocysts are ovoid or spherical and measure 5 to 6 micrometers across. When in flotation preparations they appear highly refractile. The oocysts contains up to 4 sporozoites that are bowshaped.[ ] As few as 2 to 10 oocysts can initiate an infection.[ ] The parasite is located in the brush border of the epithelial cells of the small intestine.[ ] They are mainly located in the jejunum. When the sporozoites attach the epithelial cells’ membrane envelops them. Thus, they are “intracellular but extracytoplasmic”.[ ] The parasite can cause damage to the microvilli where it attaches.[ ] The infected human excretes the most oocysts during the first week.[ ] Oocysts can be excreted for weeks after the diarrhea subsides from infections by C. parvum or C. hominis;[ ] however, immunocompetent individuals with C. muris infections have been observed excreting oocysts for seven months The immune system reduces the formation of Type 1 merozoites as well as the number of thinwalled oocysts.[ ] This helps prevent autoinfection. B cells do not help with the initial response or the fight to eliminate the parasite.[ ] Diagnosis[ ] There are many diagnostic tests for Cryptosporidium. They include microscopy, staining, and detection of antibodies. Microscopy ] can help identify oocysts in fecal matter.[ ] To increase the chance of finding the oocysts, the diagnostician should inspect at least 3 stool samples.[ ] There are several techniques to concentrate either the stool sample or the oocysts. The modified formalin-ethyl acetate (FEA) concentration method concentrates the stool.[20] Both the modified zinc sulfate centrifugal flotation technique and the Sheather’s sugar flotation procedure can concentrate the 15 oocysts by causing them to float.[ ] Another form of microscopy is fluorescent microscopy done by staining withauramine.[ ] Other staining techniques include acid-fast staining,[ ] which will stain the oocysts red. ] One type of acid-fast stain is the Kinyoun stain.[ ] Giemsa staining can also be performed. ] Part of the small intestine can be stained with hematoxylin and eosin (H & E), which will show oocysts attached to the epithelial cells.[ ] Detecting antigens is yet another way to diagnose the disease. This can be done with direct fluorescent antibody (DFA) techniques.[ ] It can also be achieved through indirect immunofluorescence assay.[ ] Enzyme-linked immunosorbent assay (ELISA) also detects antigens.[ ] Polymerase chain reaction (PCR) is another way to diagnose cryptosporidiosis. It can even identify the specific species of Cryptosporidium.[ ] If the patient is thought to have biliary cryptosporidiosis, then an appropriate diagnostic technique is ultrasonography. If that returns normal results, the next step would be to perform endoscopic retrograde cholangiopancreatography.[ ] Prevention[ ] Many treatment plants that take raw water from rivers, lakes, and reservoirs for public drinking water production use conventional filtration technologies. This involves a series of processes, including coagulation, flocculation, sedimentation, and filtration. Direct filtration, which is typically used to treat water with low particulate levels, includes coagulation and filtration, but not sedimentation. Other common filtration processes, including slow sand filters, diatomaceous earth filters and membranes will remove 99% ofCryptosporidium.[ ] Membranes and bag and cartridge filters remove Cryptosporidium product-specifically. While Cryptosporidium is highly resistant to chlorine disinfection,[ ] with high enough concentrations and contact time, Cryptosporidium will be inactivated by chlorine dioxide and ozone treatment. The required levels of chlorine generally preclude the use of chlorine disinfection as a reliable method to control Cryptosporidium in drinking water. Ultraviolet light treatment at relatively low doses will inactivate Cryptosporidium. Water Research Foundation-funded research originally discovered UV's efficacy in inactivatingCryptosporidium. One of the largest challenges in identifying outbreaks is the ability to identify Cryptosporidium in the laboratory. Real-time monitoring technology is now able to detectCryptosporidium with online systems, unlike the spot and batch testing methods used in the past. The most reliable way to decontaminate drinking water that may be contaminated by Cryptosporidium is to boil it. In the US the law requires doctors and labs to report cases of cryptosporidiosis to local or state health departments. These departments then report to the Center for Disease Control and Prevention.[ ] The best way to prevent getting and spreading cryptosporidiosis is to have good hygiene and sanitation.[ ] An example would be hand-washing.[ ]Prevention is through washing 16 hands carefully after going to the bathroom or contacting stool, and before eating. People should avoid contact with animal feces.[ ] They should also avoid possibly contaminated food and water.[ ] In addition, people should refrain from engaging in sexual activities that can expose them to feces.[ Standard water filtration may not be enough to eliminate Cryptosporidium; boiling for at least 1 minute (3 minutes above 6,500 feet (2,000 m) of altitude) will decontaminate it. Heating milk at 71.7 °C (161 °F) for 15 seconds pasteurizes it and can destroy the oocysts' ability to infect. [ ] Water can also be made safe by filtering with a filter with pore size not greater than 1 micrometre, or by filters that have been approved for “cyst removal” by NSF International National Sanitation Foundation.[ ] Bottled drinking water is less likely to contain Cryptosporidium, especially if the water is from an underground source.[ ] People with cryptosporidiosis should not swim in communal areas because the pathogen can reside in the anal and genital areas and be washed off. They should wait until at least two weeks after diarrhea stops before entering public water sources, since oocysts can still be shed for a while. Also, they should stay away from immunosuppressed people. ] Immunocompromised people should take care to protect themselves from water in lakes and streams.[21] They should also stay away from animal stools and wash their hands after touching animals. To be safe, they should boil or filter their water. They should also wash and cook their vegetables.[ The US CDC notes the recommendation of many public health departments to soak contaminated surfaces for 20 minutes with a 3% hydrogen peroxide (99% kill rate) and then rinse them thoroughly, with the caveat that no disinfectant is guaranteed to be completely effective against Cryptosporidium. However, hydrogen peroxide is more effective than standard bleach solutions.[ ] Treatment[ ] Symptomatic treatment primarily involves fluid rehydration, electrolyte replacement (sodium, potassium, bicarbonate, and glucose), and antimotility agents (e.g.,loperamide). Supplemental zinc may improve symptoms,[ ] particularly in recurrent or persistent infections or in others at risk for zinc deficiency. Giardiasis Giardiasis (popularly known as beaver fever) ] is a zoonotic parasitic disease caused by the flagellate protozoan Giardia lamblia(also sometimes called Giardia intestinalis and Giardia duodenalis). ] The giardia organism inhabits the digestive tract of a wide variety of domestic and wild animal species, as well as humans. It is one of the most common pathogenic parasitic infections in humans worldwide; in 2013, there were about 280 million people worldwide with symptomatic giardiasis.[ ] 17 Signs and symptoms[ ] Symptoms vary from none to severe diarrhea with poor absorption of nutrients.[ ] It can result in weakness, loss of appetite, stomach cramps, vomiting (uncommon), bloating, excessive gas, and burping. Symptoms typically develop 9–15 days after exposure,[ ] but may occur as early as one day.[ ] Symptoms are caused by Giardia organisms infecting the cells of the duodenum and jejunum of the small intestine[ ] and blocking nutrient absorption. Most people are asymptomatic; only about a third of infected people exhibit symptoms. If the infection is not treated, these symptoms may last for six weeks or more. Symptomatic infections are well recognized as causing lactose intolerance, ] which, while usually temporary, may become permanent. Although hydrogen breath testsindicate poorer rates of carbohydrate absorption in those asymptomatically infected, such tests are not diagnostic of infection.[ ] It has been suggested that these observations are explained by symptomatic giardia infection allowing for the overgrowth of other bacteria. Some studies have shown giardiasis should be considered as a cause of vitamin B12 deficiency as a result of the problems caused within the intestinal absorption system.[ ] Cause[ ] Giardiasis is caused by the protozoan Giardia lamblia.[ ] The infection occurs in many animals including beavers hence its nickname, cows, rodents, and sheep.[ ] Animals are believed to play a role in keeping infections present in an environment.[ ] Risk factors[ ] Those at greatest risk are travelers to countries where giardiasis is common, people in child care settings, those who are in close contact with someone who has the disease, people who swallow contaminated drinking water, backpackers or campers who drink untreated water from lakes or rivers, people who have contact with animals who have the disease, and men who have sex with men."[ ] It occurs more often during the summer in the United States.[ ] This is believed to be due to a greater amount of time spent on outdoor activities.[ ] Wilderness travel within the United States is believed to be a risk factor with poorly treated or untreated water playing a role.[ ] Transmission[ ] Giardiasis is transmitted via the fecal-oral route with the ingestion of cysts.[ ] Primary routes are personal contact and contaminated water and food.[ ] The cysts can stay infectious for up to three months in cold water.[ ] 18 Not all Giardia infections are symptomatic, and many people can unknowingly serve as carriers of the parasite.[ ] Pathophysiology[ ] Giardia are flagellated protozoans that cause decreased expression of brush border enzymes, morphological changes to the microvillus, and programmed cell death of small intestinal epithelial cells. There is no invasion of giardia trophozoites, and small intestinal morphology may appear normal in light microscopy. The attachment of trophozoites causes villus flattening and inhibition of enzymes that break down disaccharide sugars in the intestines. Ultimately, the community of microorganisms that lives in the intestine may overgrow and may be the cause of further symptoms, though this idea has not been fully investigated. The alteration of the villi leads to an inability of nutrient and water absorption from the intestine, resulting in diarrhea, one of the predominant symptoms. In the case of asymptomatic giardiasis, there can be malabsorption with or without histological changes to the small intestine. The degree to which malabsorption occurs in symptomatic and asymptomatic cases is highly varied. The species Giardia intestinalis uses enzymes that break down proteins to attack the villi of the brush border and appears to increase crypt cell proliferation and crypt length of crypt cells existing on the sides of the villi. On an immunological level, activated host T lymphocytes attack endothelial cells that have been injured in order to remove the cell. This occurs after the disruption of proteins that connect brush border endothelial cells to one another. The result is heavily increased intestinal permeability. There appears to be a further increase in programmed cell death by Giardia intestinalis, which further damages the intestinal barrier and increases permeability. There is significant upregulation of the programmed cell death cascade by the parasite, and, furthermore, substantial downregulation of the anti-apoptotic protein Bcl-2 and upregulation of the proapoptotic protein Bax. These connections suggest a role of caspase-dependent apoptosis in the pathogenesis of giardiasis. Giardia protects its own growth by reducing the formation of the gas nitric oxide by consuming all local arginine, which is the amino acid necessary to make nitric oxide. Arginine starvation is known to be a cause of programmed cell death, and local removal is a strong apoptotic agent.[ ] Diagnosis[ ] According to the CDC, detection of antigens on the surface of organisms in stool specimens is the current test of choice for diagnosis of giardiasis and provides increased sensitivity over more common microscopy techniques.[ ] A trichrome stain of preserved stool is another method used to detect giardia.[ ] 19 Microscopic examination of the stool for motile trophozoites or for the distinctive oval G.lamblia cysts can be performed. The entero-test uses a gelatin capsule with an attached thread. One end is attached to the inner aspect of the patient's cheek, and the capsule is swallowed. Later, the thread is withdrawn and shaken in saline to release trophozoites which can be detected with a microscope. Immunologic enzyme-linked immunosorbent assay (ELISA) testing is now available. These tests are capable of a 90% detection rate or more.[ ] Because Giardia lamblia is difficult to detect, this often leads to a delay in diagnosis or misdiagnosis; several tests should be conducted over a one-week period.[ ] Prevention[ ] The CDC recommends hand-washing and avoiding potentially contaminated food and untreated water.[ ] Boiling suspect water for one minute is the surest method to make water safe to drink and kill disease-causing microorganisms such as Giardia lamblia if in doubt about whether water is infected.[20] Chemical disinfectants or filters may be used. According to a review of the literature from 2000, there is little evidence linking the drinking of water in the N. American wilderness and Giardia.[ ] The researcher notes that treatment of drinking water for Giardia may not be as important as recommended hand-washing in wilderness regions in North America.[ ] CDC surveillance data (for 2005 and 2006) reports one outbreak (6 cases) of waterborne giardiasis contracted from drinking wilderness river water in Colorado. However, less than 1% of reported giardiasis cases are associated with outbreaks.[ ] Treatment[ ] Treatment is not always necessary as the infection usually resolves on its own. However, if the illness is acute or symptoms persist and medications are needed to treat it, anitroimidazole medication is used such as metronidazole, tinidazole, secnidazole or ornidazole.[ ] The World Health Organization and Infectious Disease Society of America recommend metronidazole as first line therapy. The US CDC lists metronidazole, tinidazole, andnitazoxanide as effective first-line therapies;[ ] of these three, only nitazoxanide and tinidazole are approved for the treatment of giardiasis by the US FDA. A meta-analysis done by the Cochrane Collaboration found that compared to the standard of metronidazole, albendazole had equivalent efficacy while having fewer side effects, such as gastrointestinal or neurologic issues. ] Other meta-analyses have reached similar conclusions.[ ] Both medications need a five to 10 day long course; albendazole is taken once a day, while metronidazole needs to be taken three times a day. The evidence for comparing metronidazole to other alternatives such as mebendazole, tinidazole or nitazoxanide was felt to be of very low quality.[ ] While tinidazole has similar side effects and efficacy to metronidazole, it is administered with a single dose.[ ] 20 Resistance has been seen clinically to both nitroimidazoles and albendazole, but not nitazoxanide, though nitazoxanide resistance has been induced in research laboratories so is theoretically possible.[ ] The exact mechanism of resistance to all of these medications are not well understood.[ ] In the case of nitroimidazole-resistant strains of Giardia, other drugs are available which have showed efficacy in treatment including quinacrine, nitazoxanide, bacitracin zinc, furazolidone and paromomycin.[ ] During pregnancy, paromomycin is the preferred treatment drug because of its poor intestinal absorption, and thus less exposure to the fetus.[ ] Alternatively, metronidazole can be used after the first trimester as there has been wide experience in its use for trichomonas in pregnancy. Sarcocystis Sarcocystis is a genus of protozoa. Species in this infecting mammals, and some infectingreptiles and birds. genus are parasites, the majority The life-cycle of a typical member of this genus involves two host species, a definitive host and an intermediate host. Often the definitive host is a predator and the intermediate host is its prey. The parasite reproduces sexually in the gut of the definitive host, is passed with the feces and ingested by the intermediate host. There it eventually enters muscle tissue. When the intermediate host is eaten by the definitive host, the cycle is completed. The definitive host usually does not show any symptoms of infection, but the intermediate host does. There are about 130 recognized species in this genus. Revision of the taxonomy of the genus is ongoing, and it is possible that all the currently recognised species may in fact be a much smaller number of species that can infect multiple hosts. The name Sarcocystis is dervived from Greek: sarx = flesh and kystis = bladder. History[ ] The organism was first recognised in a mouse by Miescher in 1843.[ ] His findings were not recognised as a protist initially and the literature referred to the structures he described as "Miescher's Tubules". Incidentally Miescher's son — Johann Friedrich Miescher — discovered DNA. Similar structures were found in pig muscle in 1865 but these remained unnamed until 1899 when the name Sarcocystis meischeriana was proposed to identify them. Initially it was unclear whether these organisms were fungi or protozoa. This uncertainty was resolved in 1967 when electron microscopic studies showed that these organism were protozoa, related to Toxoplasma and Eimeria. The life cycle remained unknown until 1970 when bradyzoites from sarcocysts in bird muscles were inoculated into cultured mammalian cells and underwent development into sexual stages and oocysts. Transmission studies with the three morphotypes found in cattle then considered a single species - Sarcoplasma fusiformis - in dogs, cats and humans revealed that these were three different species now named Sarcoplasma bovicanis, Sarcoplasma bovifelis and Sarcoplasma bovihominis. 21 Life cycle[ ] The heteroxenous (more than one obligatory host in its life cycle) life cycle of these apicomplexan parasites remained obscure until 1972 when the prey-predator relationship of its definitive and intermediate hosts was recognised. The life cycles of about 60 of these species is now known. In outline gametogony and sporogony occur in the intestine of the definitive host while both schizogony which occurs in various tissues and the formation of sarcocysts (containing bradyzoites and metrocytes) occurs principally in the muscles of the intermediate host. In some cases a single species may act as both the definitive and intermediate host. Oocysts are passed in the feces of an infected definitive host. The oocyst undergoes sporogony creating two sporocysts. Once this is complete the oocyst itself undergoes lysis releasing the sporocysts into the environment. Sporocysts typically contain 4 sporozoites and measure 15-19 by 8-10 micrometres. An intermediate host such as a cow or pig then ingests a sporocyst. Sporozoites are then released in the body and migrate to vessels where they undergo the first two generation of asexual reproduction. These rounds result in the development ofmeronts. This stage lasts about 15 to 16 days after ingestion of sporocysts. Merozoites emerge from the second generation meronts and enter the mononucleate cells where they develop by endodyogeny. Subsequent generations of merozoites develop downstream in the direction of blood flow to arterioles, capillaries, venules, and veins throughout the body subsequently developing into the final asexual generation in muscles. Merozoites entering muscle cells round up to form metrocytes and initiate sarcocyst formation. Sarcocysts begin as unicellular bodies containing a single metrocyte and through asexual multiplication numerous metrocytes accumulate and the sarcocyst increases in size. As the sarcocyst matures, the small, rounded, noninfectious metrocytes give rise to crescent-shaped bodies called bradyzoites that are infections for the definitive host. Time required for maturation varies with the species and may take 2 months or more. In species in which symptoms develop these typically occur 20–40 days after ingestion of sporocysts and during the subsequent migration of sporozoites through the body vessels. Acute lesions (oedema, hemorrhages and necrosis) develop in the affected tissues. The parasite has a predilection for skeletal muscle (myositis), cardiac muscle (petechial hemorrhages of cardiac muscle and serosae), and lymph nodes (oedema, necrosis and hemorrhage). These lesions are associated with maturation of second generation of meronts within the endothelial and subendothelials cells. Occasionally mononuclear infiltration or hyperemia has been observed in the lamina propria of the small intestine. After the acute phase cysts may be found in various muscular tissues, generally without pathology. 22 Once the intermediate host is eaten by the definitive host such as a dog or human, the parasite undergoes sexual reproduction within the gut to create macrogamonts and microgamonts. Most definitive hosts do not show any clinical sign or symptoms. Fusion of a macrogamont and a microgamont creates a zygote which develops into an oocyst. The oocyst is passed through the faeces completing the life cycle. A second life cycle has more recently been described whereby carnivores and omnivores pass the infectious stages in their faeces. Ingestion of this material may lead to successful infection of the ingesting animal. Birds[ ] Although sarcocysts were first reported in the muscles of birds by Kuhn in 1865 not until 1977 was the first life cycle involving a bird (Gallus gallus) and a carnivore (Canis familiaris) described by Munday et al. In 1986 the first life cycle involving birds as both the definitive (Northern goshawk Accipiter gentilis) and intermediate (Atlantic canary - Serinus canaria) hosts was described by Cern and Kvasnovsk.[ ] Taxonomy[ ] The taxonomy of this genus and its relationship to other protozoal genera is currently under investigation. Related genera include: Besnoitia, Caryospora, Cystoisospora, Frenkelia, Isospora, Hammondia, Hyaloklossia, Lan kesterella,Neospora and Toxoplasma. Sarcocystis is the largest genus within the family Sarcocystidae and consists of species which infecting a range of animals including mammals, birds and reptiles. Frenkelia, another genus within this family, consists of parasites that use rodents as intermediate hosts and birds of prey as definitive hosts. It appears that Besnoitia, Hammondia, Neospora and Toxoplasma form a single clade. Within this clade Toxoplasma andNeospora appear to be sister clades. Isospora also appear to belong to this clade and this clade is a sister to Sarcocystis.Frenkelia appears to be very closely related to Sarcocystis. Several molecular studies have suggested that Frenkelia is actually a species of Sarcocystis. This genus was distinguished from Sarcocystis on the basis of its tendency to encyst within the brain rather than within muscle. This distinction may not be taxonomically valid. Within the genus a number of clades have been identified. These include one that contains S. dispersa, S. lacertae, S. mucosa, S. muris, S. neurona and S. rodentifelis.[4] Frenkelia also groups with this clade. 23 Evolution[ ] These protozoa are mostly found in mammals. They do not appear to infect mammals of the superorder Afrotheria and infect only two species of the Xenarthra. Because of this pattern the genus may have evolved in the Northern hemisphere from a preexisting protozoan species that infected mammals. Alternatively because a number of Australian marsupials are also infected by this genus, marsupials may have been the original hosts of this genus and the parasites were spread to the Northern hemisphere by birds. A third possibility is that the genus originally infected birds and was spread world wide by these hosts. A final possibility because of the existence of life cycles where both the intermediate and final hosts are reptiles, the genus may have originated in reptiles and spread from there to other genera. The resolution of this question awaits the outcome of further molecular studies. Clinical: Human[ ] Infection with this parasite is known as sarcosporidiosis. Because of initial confusion over the taxonomy of this parasite it was originally referred to as Isospora hominis. The older literature may refer to this organism. Epidemiology[ ] Human infection is considered rare with less than one hundred published cases of invasive disease (approximately 46 cases reported by 1990). These figures represent a gross underestimate of the human burden of disease. The extremes of age reported to date are a 26-day-old infant and a 75-year-old man. Infectons have been reported fromAfrica, Europe (Germany, Spain and Poland), the United States (California), Central and South America, China, India, Tibet,Malaysia and Southeast Asia. Stool examinations in Thai laborers showed that sarcocystis infection had a prevalence of ~23%. Virtually all cases appeared to be asymptomatic which probably explains the lack of recognition. A study of 100 human tongues obtained at post mortum in Malaya revealed an infection rate of 21%. There was no sex difference and the age range was 16 to 57 years (mean 37.7 years).[ ] Route of infection[ ] Infection occurs when undercooked meat is ingested. The incubation period is 9–39 days. Human outbreaks have occurred in Europe. Rats are a known carrier. It has been suggested that contaminated water may be able to cause infection but this presently remains a theoretical possibility. 24 Pathology[ ] The pathology is of two types: a rare invasive form with vasculitis and myositis and an intestinal form that presents withnausea, abdominal pain, and diarrhea. While normally mild and lasting under 48 hours, the intestinal form may occasionally be severe or even life-threatening. The invasive form may involve a wide variety of tissues including lymph nodes, muscles and the larynx. Clinical features[ ] In volunteer studies with infected beef symptoms appeared 3–6 hours after eating. These included anorexia, nausea, abdominal pain, distension, diarrhea, vomiting, dyspnoea and tachycardia. All symptoms were transient and lasted about 36 hours. In a second series symptoms - abdominal pain, distension, watery diarrhea and eosinophilia - appeared at 1 week and resolved after 3 weeks. Clinical cases have been associated with acute fever, myalgias, bronchospasm, pruritic rashes, lymphadenopathy, subcutaneous nodules associated with eosinophilia, elevated erythrocyte sedimentation rate and elevated creatinine kinase levels. Symptoms may last as long as five years. Segmental necrotizing enteritis has been reported on one occasion. Diagnosis[ ] Definitive diagnosis by biopsy of an infected muscle. Sarcocysts are identifiable with hematoxylin and eosin. The PAS stain may be helpful but variable uptake of stain is common. Along with the sarcocysts inflammatory cells may be found. Other findings include myositis, myonecrosis, perivascular and interstitial inflammation, vasculitis and eosinophilic myositis. Treatment[ ] Because infection is rarely symptomatic, treatment is rarely required. There have been no published trials so treatment remains empirical. Agents that have been used includealbendazole, metronidazole and cotrimoxazole for myositis. Corticosteroids have also been used for symptomatic relief. Amprolium and salinomycin was effective in preventing severe illness and death in experimentally infected calves and lambs. These agents have not been tried in humans to date. Prevention[ ] Infection can be prevented by cooking the meat before eating. Alternatively freezing the meat at -5C for several days before ingestion will kill the sporocysts. Fasciolosis Fasciolosis (also known as fascioliasis, distomatosis and liver rot) is a parasitic worm infection caused by the common liver fluke Fasciola hepatica as well as by Fasciola gigantica. The disease is a plant-borne trematode zoonosis, and is classified as a Neglected Tropical Disease (NTD). It affects humans, but its main host is ruminants such as cattle and sheep. The disease progresses 25 through four distinct phases; an initial incubation phase of between a few days up to three months with little or no symptoms; an invasive or acute phase which may manifest with: fever, malaise, abdominal pain, gastrointestinal symptoms, urticaria, anemia, jaundice, and respiratory symptoms. The disease later progresses to a latent phase with less symptoms and ultimately into a chronic or obstructive phase months to years later. In the chronic state the disease causes inflammation of the bile ducts, gall bladder and may cause gall stones as well as fibrosis. While chronic inflammation is connected to increased cancer rates it is unclear whether fasciolosis is associated with increased cancer risk. Up to half of those infected display no symptoms, and diagnosis is difficult because eggs are often missed in fecal examination. The methods of detection are through fecal examination, parasitespecific antibody detection, radiological diagnosis as well as laparotomy. In case of a suspected outbreak it may be useful to keep track of dietary history, which is also useful for exclusion of differential diagnoses. Fecal examination is generally not helpful because eggs can seldom be detected in the chronic phase of the infection. Eggs appear in the feces first between 9–11 weeks post-infection. The cause of this is unknown, and it is also difficult to distinguish between the different species of fasciola as well distinguishing them from Echinostomes and Fasciolopsis. Most immunodiagnostic tests detect infection with very high sensitivity and as concentration drops after treatment it is a very good diagnostic method. Clinically it is not possible to differentiate from other liver and bile diseases. Radiological methods can detect lesions in both acute and chronic infection, while laparotomy will detect lesions and also occasionally eggs and live worms. Because of the size of the parasite (adult F. hepatica: 20–30 × 13 mm, adult F. gigantica: 25–75×12 mm) fasciolosis is a big concern. The amount of symptoms depend on how many worms and what stage the infection is in. The death rate is significant in both sheep and cattle, but generally low among humans. Treatment with triclabendazole is highly effective against the adult worms as well as various developing stages. Praziquantel is not effective, and older drugs such as bithionol are moderately effective but also cause more side effects. Secondary bacterial infection causing cholangitis is also a concern and can be treated with antibiotics, and toxaemia may be treated with prednisolone. Humans are infected by eating water grown plants. Infection may also occur by drinking contaminated water with floating young fasciola. Human infection is rare even if the infection rate is high among animals. Especially high rates of human infection have been found in Bolivia, Peru and Egypt, and this may be due to consumption of certain foods. No vaccine is available to protect people against Fasciola infection. Preventative measures are primarily treating and immunization the livestock. Other methods include using molluscicides to decrease the amount of snails that act as vectors, but it is not practical. Educational methods to decrease consumption of wild watercress and other waterplants has been shown to work in areas with a high disease burden. Fascioliasis occurs in Europe, Africa, the Americas. 26 Signs and symptoms The course of fasciolosis in humans has 4 main phases: Incubation phase: from the ingestion of metacercariae to the appearance of the first symptoms; time period: few days to 3 months; depends on number of ingested metacercariae and immune status of host Invasive or acute phase: fluke migration up to the bile ducts. This phase is a result of mechanical destruction of the hepatic tissue and the peritoneum by migrating juvenile flukes causing localized and or generalized toxic and allergic reactions. The major symptoms of this phase are: Fever, Abdominal pain, loss of appetite, flatulence, nausea, diarrhoea, Urticaria, cough, dyspnoea, chest pain, hemoptysis, Hepatomegaly and splenomegaly, Ascites, Anaemia, Jaundice. Latent phase: This phase can last for months or years. The proportion of asymptomatic subjects in this phase is unknown. They are often discovered during family screening after a patient is diagnosed. Chronic or obstructive phase: This phase may develop months or years after initial infection. Adult flukes in the bile ducts cause inflammation and hyperplasia of the epithelium. The resulting cholangitis and cholecystitis, combined with the large body of the flukes, are sufficient to cause mechanical obstruction of the biliary duct. In this phase, biliary colic, epigastric pain, fatty food intolerance, nausea, jaundice, pruritus, right upper-quadrant abdominal tenderness, etc., are clinical manifestations indistinguishable from cholangitis, cholecystitis and cholelithiasis of other origins. Hepatic enlargement may be associated with an enlarged spleen or ascites. In case of obstruction, the gall bladder is usually enlarged and edematous with thickening of the wall. Fibrous adhesions of the gall bladder to adjacent organs are common. Lithiasis of the bile duct or gall bladder is frequent and the stones are usually small and multiple. Other animals Clinical signs of fasciolosis are always closely associated with infectious dose (amount of ingested metacercariae). In sheep, as the most common definitive host, clinical presentation is divided into 4 types: Acute Type I Fasciolosis: infectious dose is more than 5000 ingested metacercariae. Sheep suddenly die without any previous clinical signs. Ascites, abdominal haemorrhage, icterus, pallor of membranes, weakness may be observed in sheep. Acute Type II Fasciolosis: infectious dose is 1000-5000 ingested metacercariae. As above, sheep die but briefly show pallor, loss of condition and ascites. 27 Subacute Fasciolosis: infectious dose is 800-1000 ingested metacercariae. Sheep are lethargic, anemic and may die. Weight loss is dominant feature. Chronic Fasciolosis: infectious dose is 200-800 ingested metacercariae. Asymptomatic or gradual development of bottle jaw and ascites (ventral edema), emaciation, weight loss. In blood, anemia, hypoalbuminemia, and eosinophilia may be observed in all types of fasciolosis. Economical effect of fasciolosis in sheep consists in sudden deaths of animals as well as in reduction of weight gain and wool production. In goats and cattle, the clinical manifestation is similar to sheep. However, acquired resistance to F. hepatica infection is well known in adult cattle. Calves are susceptible to disease but in excess of 1000 metacercariae are usually required to cause clinical fasciolosis. In this case the disease is similar to sheep and is characterized by weight loss, anemia, hypoalbuminemia and (after infection with 10,000 metacercariae) death. Importance of cattle fasciolosis consist in economic losses caused by condemnation of livers at slaughter and production losses especially due to reduced weight gain. In sheep and sometimes cattle, the damaged liver tissue may become infected by the Clostridium bacteria C. novyi type B. The bacteria will release toxins into the bloodstream resulting in what is known as black disease. There is no cure and death follows quickly. As C. novyi is common in the environment, black disease is found wherever populations of liver flukes and sheep overlap. Intermediate hosts Intermediate hosts of F. hepatica are freshwater snails from family Lymnaeidae. Snails from family Planorbidaeact as an intermediate host of F. hepatica very occasionally. Mechanism The development of infection in definitive host is divided into two phases: the parenchymal (migratory) phase and the biliary phase. The parenchymal phase begins when excysted juvenile flukes penetrate the intestinal wall. After the penetration of the intestine, flukes migrate within the abdominal cavity and penetrate the liver or other organs. F. hepatica has a strong predilection for the tissues of the liver. Occasionally, ectopic locations of flukes such as the lungs, diaphragm, intestinal wall, kidneys, and subcutaneous tissue can occur. During the migration of flukes, tissues are mechanically destroyed and inflammation appears around migratory tracks of flukes. The second phase (the biliary phase) begins when parasites enter the biliary ducts of the liver. In biliary ducts, flukes mature, feed on blood, and produce eggs. Hypertrophy of biliar ducts associated with obstruction of the lumen occurs as a result of tissue damage. Diagnosis Most immunodiagnostic tests will detect infection and have a sensitivity above 90% during all stages of the diseases. In addition antibody concentration quickly drops post treatment and no 28 antibodies are present one year after treatment, which makes it a very good diagnostic method. In humans, diagnosis of fasciolosis is usually achieved parasitologically by findings the fluke eggs in stool, and immunologically by ELISA . Coprological examinations of stool alone are generally not adequate because infected humans have important clinical presentations long before eggs are found in the stools. Moreover, in many human infections, the fluke eggs are often not found in the faeces, even after multiple faecal examinations. Furthermore, eggs of F. hepatica, F. gigantica and Fasciolopsis buski are morphologically indistinguishable. Therefore, immunonological methods such ELISA and enzyme-linked immunoelectrotransfer blot, also called Western blot, are the most important methods in diagnosis of F. hepatica infection. These immunological tests are based on detection of species-specific antibodies from sera. The antigenic preparations used have been primarily derived from extracts of excretory/secretory products from adult worms, or with partially purified fractions. In addition, biochemical and haematological examinations of human sera support the exact diagnosis (eosinophilia, elevation of liver enzymes). Ultrasonography and xray of the abdominal cavity, biopsy of liver, and gallbladder punctuate can also be used. False fasciolosis (pseudofasciolosis) refers to the presence of eggs in the stool resulting not from an actual infection but from recent ingestion of infected livers containing eggs. This situation (with its potential for misdiagnosis) can be avoided by having the patient follow a liver-free diet several days before a repeat stool examination. Treatment and prevention Several drugs are effective for fascioliasis, both in humans and in domestic animals. The drug of choice in the treatment of fasciolosis is triclabendazole, a member of thebenzimidazole family of anthelmintics. The drug works by preventing the polymerization of the molecule tubulin into the cytoskeletal structures, microtubules. Nitazoxanide has been found effective in trails, but is currently not recommended. The life cycle includes freshwater snails as an intermediate host of the parasite. 29 Babesiosis Babesiosis is a malaria-like parasitic disease caused by infection with Babesia, [ ] a genus of Apicomplexa. Human babesiosis is an uncommon but emerging disease in the Northeastern and Midwestern United States and parts of Europe, and sporadic throughout the rest of the world. It occurs in warm months. ] Ticks transmit the human strain of babesiosis, so it often presents with other tick-borne illnesses such as Lyme disease.[ ] After trypanosomes, Babesia is thought to be the second-most common blood parasite of mammals, and they can have a major impact on health of domestic animals in areas without severe winters. In cattle, a major host, the disease is known as Texas cattle fever, redwater, or piroplasmosis Classification Babesia species are in the phylum Apicomplexa, which also has the protozoan parasites that cause malaria, toxoplasmosis, and cryptosporidiosis.[3] Four clades of Babesiaspecies infect humans. The main species in each clade are: 1. B. microti (<3 µm) 2. B. duncani, related to babesia of dogs 3. B. divergens (cattle parasite seen mostly in Europe) and B. venatorum (roe deer parasite, formerly called EU1), most closely related to the large babesia clade 4. Large Babesia (>3 µm) mostly infects ungulates, but also includes K01 strain (an isolated case observed in South Korea, see isolated cases) Signs and symptoms Half of all children and a quarter of previously healthy adults are asymptomatic with Babesia infection. For those who develop symptoms, they are similar to malaria, because both cause fever and hemolytic anemia. People with symptoms usually become ill 1 to 4 weeks after the bite, or 1 to 9 weeks after transfusion of contaminated blood products. A person infected with babesiosis gradually develops malaise and fatigue, followed by a fever. Hemolytic anemia, in which red blood cells are destroyed and removed, also develops. Chills, sweats, and thrombocytopenia (a low number of platelets in the blood) are also common symptoms. Less common symptoms and physical exam findings of mild-to-moderate babesiosis:[ ] Headache Muscle pain Anorexia Nonproductive cough (mucus is not coughed up) Arthralgias (noninflammatory joint pain, unlike arthritis, which is inflammatory) Nausea Vomiting 30 Sore throat Abdominal pain Pink eye Photophobia Weight loss Emotional lability Depression Hyperesthesia (more sensitive to stimuli) Enlarged spleen Pharyngeal erythema Enlarged liver Jaundice (yellowing of the skin and of the sclera) Retinopathy with splinter hemorrhages Retinal infarcts Neutropenia] In more severe cases, symptoms similar to malaria occur, with fevers up to 40.5 °C (105 °F), shaking chills, and severe anemia (hemolytic anemia). Organ failure may follow, including adult respiratory distress syndrome. Severe cases occur mostly in people who have had a splenectomy. Severe cases are also more likely to occur in the very young, very old, and persons with immunodeficiency, such as HIV/AIDS patients. A reported increase in human babesiosis diagnoses in the 2000s is thought to be caused by more widespread testing and higher numbers of people with immunodeficiencies coming in contact with ticks, the disease vector.[ ] Little is known about the occurrence of Babesia species in malariaendemic areas, where Babesia can easily be misdiagnosed as Plasmodium. Human patients with babesiosis may exhibit premunity Pathophysiology Babesia parasites reproduce in red blood cells, where they can be seen as cross-shaped inclusions (four merozoites asexually budding, but attached together forming a structure looking like a "Maltese cross")[ ] and cause hemolytic anemia, quite similar to malaria. Unlike the Plasmodium parasites that cause malaria, Babesia species lack an exoerythrocytic phase, so the liver is usually not affected. In nonhuman animals, Babesia canis rossi, Babesia bigemina, and Babesia bovis cause particularly severe forms of the disease, including a severe haemolytic anaemia, with positive erythrocyte-insaline-agglutination test indicating an immune-mediated component to the haemolysis. Common sequelae include haemoglobinuria "red-water", disseminated intravascular coagulation, and "cerebral babesiosis" caused by sludging of erythrocytes in cerebral capillaries. 31 In bovine species, the organism causes hemolytic anemia, so an infected animal shows pale mucous membranes initially. As the levels of bilirubin (a byproduct of red blood cell lysis) continue to increase, the visible mucous membranes become yellow in color (icterus) due to the failure of the liver to metabolise the excess bilirubin. Hemoglobinuria is seen due to excretion of red-blood-cell lysis byproducts via the kidneys. Fever of 40.5 °C (105 °F) develops due to release of inflammatory byproducts. Diagnosis Only specialized laboratories can adequately diagnose Babesia infection in humans, and as a result,Babesia infections are considered highly under-reported. It develops in patients who live in or travel to an endemic area or receive a contaminated blood transfusion within the preceding 9 weeks, so this aspect of the medical history is vital.[8] Babesiosis may be suspected when a person with such an exposure history develops persistent fevers and hemolytic anemia. The definitive diagnostic test is the identification of parasites on a Giemsa-stained thin blood smear.[ ] So-called "Maltese cross formations" on the blood film are essentially diagnostic of babesiosis, since they are not seen in malaria, the primary differential diagnosis.[7] Careful examination of multiple smears may be necessary, since Babesia may infect less than 1% of circulating red blood cells, thus be easily overlooked.[ ] Serologic testing for antibodies against Babesia (both IgG and IgM) can detect low-level infection in cases with a high clinical suspicion, but negative blood film examinations. Serology is also useful for differentiating babesiosis from malaria in cases where people are at risk for both infections. Since detectable antibody responses require about a week after infection to develop, serologic testing may be falsely negative early in the disease course.[ ] A polymerase chain reaction (PCR) test has been developed for the detection of Babesia from the peripheral blood.[ ] PCR may be at least as sensitive and specific as blood film examination in diagnosing babesiosis, though it is also significantly more expensive.[ ] Most often, PCR testing is used in conjunction with blood film examination and possiblyserologic testing.[ ] Other laboratory findings include decreased numbers of red blood cells and platelets on complete blood count. In animals, babesiosis is suspected by observation of clinical signs (haemoglobinuria and anaemia) in animals in endemic areas. Diagnosis is confirmed by observation of merozoites on thin film blood smear examined at maximum magnification under oil using Romonovski stains (methylene blue and eosin). This is a routine part of the veterinary examination of dogs and ruminants in regions where babesiosis is endemic. Babesia canis and B. bigemina are "large Babesias" that form paired merozoites in the erythrocytes, commonly described as resembling "two pears hanging together", rather than the "Maltese cross" of the "small Babesias". Their merozoites are around twice the size of small Babesias. 32 Cerebral babesiosis is suspected in vivo when neurological signs (often severe) are seen in cattle that are positive for B. bovis on blood smear, but this has yet to be proven scientifically. Outspoken red discolouration of the grey matter post mortem further strengthens suspicion of cerebral babesiosis. Diagnosis is confirmed post mortem by observation of Babesia-infected erythrocytes sludged in the cerebral cortical capillaries in a brain smear. Treatment[ ] In mild-to-moderate babesiosis, the treatment of choice is a combination of atovaquone and azithromycin. This regimen is preferred to clindamycin and quinine because side effects are fewer. The standard course is 7 to 10 days, but this is extended to at least 6 weeks in people with relapsing disease. It is recommended that even mild cases are treated to decrease the chance of inadvertently transmitting the infection by donating blood.[ ] In life-threatening cases, exchange transfusion is performed.[ ] In this procedure, the infected red blood cells are removed and replaced with uninfected ones. Imizol is a drug used for treatment of babesiosis in dogs.[ ] Extracts of the poisonous, bulbous plantBoophone disticha are used in the folk medicine of South Africa to treat equine babesiosis. B. disticha is a member of the daffodil family Amaryllidaceae and has also been used in preparations employed as arrow poisons, hallucinogens, and in embalming. The plant is rich in alkaloids, some of which display an action similar to that of scopolamine.[ ] Epidemiology[ ] Babesiosis is a vector-borne illness usually transmitted by Ixodes scapularis ticks. Babesia microti uses the same tick vector as Lyme disease and ehrlichiosis, and may occur in conjunction with these other diseases.[ ] The organism can also be transmitted by blood transfusion. Ticks of domestic animals, especially Rhipicephalus (Boophilus) microplus and R. (B.) decoloratus transmit several species of Babesia to livestock, causing considerable economic losses to farmers in tropical and subtropical regions. In the United States, the majority of babesiosis cases are caused by B. microti, and occur in the Northeast and northern Midwest from May through October.[ ] Areas with especially high rates include eastern Long Island, Fire Island, Nantucket Island, and Martha's Vineyard. In Europe, B. divergens is the primary cause of infectious babesiosis and is transmitted by I. ricinus. Babesiosis has emerged in Lower Hudson Valley, New York since 2001.[ ] In Australia, babesiosis of types B. duncani and B. microti has recently been found in symptomatic patients along the eastern coastline of the continent.[ ] A similar disease in cattle, commonly known as tick fever, is spread by Babesia bovis and B. bigemina in the introduced cattle tick Rhipicephalus microplus. This disease is found in eastern and northern Australia.[ 33 Balantidiasis Balantidiasis is a protozoan infection caused by infection with Balantidium coli.[ Symptoms[ ] Symptoms can be local due to involvement of the intestinal mucosa, or systemic in nature and include either diarrhea or constipation. Transmission[ ] Balantidium is the only ciliated protozoan known to infect humans. Balantidiasis is a zoonotic disease and is acquired by humans via the feco-oral route from the normal host, the pig, where it is asymptomatic. Contaminated water is the most common mechanism of transmission.[ ] Treatment[ ] Balantidiasis can be treated with tetracycline,[ ] carbarsone, metronidazole, or diiodohydroxyquin. History and epidemiology The first study to generate Balantidiasis in humans was undertaken by Cassagrandi and Barnagallo in 1896. ] However, this experiment was not successful in creating an infection and it was unclear whether Balantidium coli was the actual parasite used.[ ] The first case of Balantidiasis in the Philippines, where it is the most common, was reported in 1904. Currently, Balantidium coli is distributed worldwide but less than 1% of the human population is infected. Pigs are a major reservoir of the parasite, and infection of humans occurs more frequently in areas where pigs comingle with people.[ ] This includes places like the Philippines, as previously mentioned, but also includes countries such as Bolivia and Papua New Guinea. But pigs are not the only animal where the parasite is found. In a Japanese study that analyzed the fecal samples in 56 mammalian species, Balantidium coli was found to be present not just in all the wild boars tested (with wild boars and pigs being considered the same species), it was also found in five species of non human primate: Chimpanzee (Pan troglodytes), White-handed gibbon (Hylobates lar), Squirrelmonkey (Saimiri sciurea), Sacred baboon (Comopithecus hamadryas), and Japanese macaque (Macaca fuscata).[ ] In other studies, Balantidium coli was also found in species from the orders Rodentia and Carnivora.[ ] Morphology Balantidium coli exists in either of two developmental stages: Trophozoites and Cysts.[ ] In the trophozoite form, they can be oblong or spherical, and are typically 30 to 150 µm in length and 25 to 120 µm in width.[ ] It is its size at this stage that allows Balantidium coli to be characterized as the largest protozoan parasite of humans.[ ] Trophozoites possess both a macronucleus and a 34 micronucleus, and both are usually visible. The macronucleus is large and sausage-shaped while the micronucleus is less prominent. At this stage, the organism is not infective but it can replicate by transverse binary fission. In its cyst stage, the parasite takes on a smaller, more spherical shape, with a diameter of around 40 to 60 µm.[ ] Unlike the trophozoite, whose surface is covered only with cilia, the cyst form has a tough wall made of one or more layers.[ ] The cyst form also differs from the trophozoite form because it is non-motile and does not undergo reproduction. ] Instead, the cyst is the form that the parasite takes when it causes infection.[ ] Disease diagnosis The diagnosis of Balantidiasis can be an intricate process, partly because the related symptoms may or may not be present. However, the diagnosis of Balantidiasis can be considered when a patient has diarrhea combined with a probable history of current exposure to amebiasis through travel, contact with infected persons, or anal intercourse.]In addition, the diagnosis of Balantidiasis can be made by microscopic examination of stool or tissue samples.[ ] Prevention[ Preventative measures require effective personal and community hygiene. Some specific safeguards include the following: Purification of drinking water. Proper handling of food. Careful disposal of human feces. Monitoring the contacts of balantidiasis patients. Leishmaniasis Leishmaniasis, also spelled leishmaniosis, is a disease caused by protozoan parasites of the genus Leishmania and spread by the bite of certain types of sandflies.[ ] The disease can present in three main ways: cutaneous, mucocutaneous, or visceral leishmaniasis.[ ] The cutaneous form presents with skin ulcers, while the mucocutaneous form presents with ulcers of the skin, mouth, and nose, and the visceral form starts with skin ulcers and then later presents with fever, low red blood cells, and enlarged spleen and liver. Infections in humans are caused by more than 20 species of Leishmania. Risk factors include poverty, malnutrition, deforestation, and urbanization. All three types can be diagnosed by seeing the parasites under the microscope. Additionally, visceral disease can be diagnosed by blood tests. 35 Leishmaniasis can be partly prevented by sleeping under nets treated with insecticide. Other measures include spraying insecticides to kill sandflies and treating people with the disease early to prevent further spread.[ ] The treatment needed is determined by where the disease is acquired, the species of Leishmania, and the type of infection.[ ] Some possible medications used for visceral ] disease include liposomal amphotericin B, a combination of pentavalent [ ] [ ] antimonials and paromomycin, andmiltefosine. For cutaneous disease, [] paromomycin, fluconazole, or pentamidine may be effective. About 12 million people are currently infected[ ] in some 98 countries.[ ] About 2 million new cases[ ] and between 20 and 50 thousand deaths occur each year. About 200 million people in Asia, Africa, South and Central America, and southern Europe live in areas where the disease is common. The World Health Organization has obtained discounts on some medications to treat the disease.[ ] The disease may occur in a number of other animals, including dogs and rodents.[ ] Signs and symptoms The symptoms of leishmaniasis are skin sores which erupt weeks to months after the person is bitten by infected sand flies. Leishmaniasis may be divided into the following types:[ ] Cutaneous leishmaniasis is the most common form, which causes an open sore at the bite sites, which heals in a few months to a year and half, leaving an unpleasant-looking scar. Diffuse cutaneous leishmaniasis produces widespread skin lesions which resembleleprosy, and may not heal on its own.[ ] Mucocutaneous leishmaniasis causes both skin and mucosal ulcers with damage primarily of the nose and mouth. Visceral leishmaniasis or kala-azar ('black fever') is the most serious form, and is potentially fatal if untreated.[ ] Other consequences, which can occur a few months to years after infection, include fever, damage to the spleen and liver, and anemia.[ ] Leishmaniasis is considered one of the classic causes of a markedly enlarged (and therefore palpable) spleen; the organ, which is not normally felt during examination of the abdomen, may even become larger than the liver in severe cases. Cause[ Leishmaniasis is transmitted by the bite of infected female phlebotomine sandflies[ ] which can transmit the protozoa Leishmania.[ ] The sandflies inject the infective stage, metacyclicpromastigotes, during blood meals (). Metacyclic promastigotes that reach the puncture wound are phagocytized by macrophages () and transform into amastigotes (). Amastigotes multiply in infected cells and affect different tissues, depending in part on whichLeishmania species is involved (. These differing tissue specificities cause the differing clinical manifestations of the 36 various forms of leishmaniasis. Sandflies become infected during blood meals on infected hosts when they ingest macrophages infected with amastigotes ). In the sandfly's midgut, the parasites differentiate into promastigotes (), which multiply, differentiate into metacyclic promastigotes, and migrate to the proboscis (). The genomes of three Leishmania species (L. major, L. infantum, and L. braziliensis) have been sequenced, and this has provided much information about the biology of the parasite. For example, in Leishmania, protein-coding genes are understood to be organized as largepolycistronic units in a head-to-head or tail-to-tail manner; RNA polymerase II transcribes long polycistronic messages in the absence of defined RNA pol II promoters, and Leishmania has unique features with respect to the regulation of gene expression in response to changes in the environment. The new knowledge from these studies may help identify new targets for urgently needed drugs and aid the development of vaccines.[ ] Vector[ ] Although most of the literature mentions only one genus transmitting Leishmania to humans (Lutzomyia) in the New World, a 2003 study by Galati suggested a new classification for New World sand flies, elevating several subgenera to the genus level. Elsewhere in the world, the genus Phlebotomus is considered the vector of leishmaniasis.[ ] Organisms[ ] Visceral disease is usually caused by Leishmania donovani, L. infantum, or L. chagasi,[ ] but occasionally these species may cause other forms of disease.[ ] The cutaneous form of the disease is caused by more than 15 species of Leishmania. Risk factors[ ] Risk factors include poverty, malnutrition, deforestation,lack of sanitation and urbanization. Diagnosis[ ] Leishmaniasis is diagnosed in the hematology laboratory by direct visualization of the amastigotes (Leishman-Donovan bodies). Buffy-coat preparations of peripheral blood or aspirates from marrow, spleen, lymph nodes, or skin lesions should be spread on a slide to make a thin smear and stained with Leishman stain or Giemsa stain (pH 7.2) for 20 minutes. Amastigotes are seen within blood and spleen monocytes or, less commonly, in circulating neutrophils and in aspirated tissue macrophages. They are small, round bodies 2–4 μm in diameter with indistinct cytoplasm, a nucleus, and a small, rod-shaped kinetoplast. Occasionally, amastigotes may be seen lying free between cells.[ ] However, the retrieval of tissue samples is often painful for the patient and identification of the infected cells can be difficult. So, other indirect immunological methods of diagnosis are developed, including enzyme-linked immunosorbent assay, antigen-coated dipsticks, and direct agglutination test. Although these tests are readily available, they are not the standard diagnostic tests due to their insufficient sensitivity and specificity. 37 Several different polymerase chain reaction tests are available for the detection of Leishmania DNA. With this assay, a specific and sensitive diagnostic procedure is finally possible. Prevention Leishmaniasis can be partly prevented by using nets treated with insecticide while sleeping. Stray dog removal Treatment[edit] The treatment is determined by where the disease is acquired, the species of Leishmania, and the type of infection. For visceral leishmaniasis in India, South America, and the Mediterranean, liposomal amphotericin B is the recommended treatment and is often used as a single dose. Rates of cure with a single dose of amphotericin have been reported as 95%. In India, almost all infections are resistant to pentavalent antimonials. In Africa, a combination of pentavalent antimonials and paromomycin is recommended. These, however, can have significant side effects. Miltefosine, an oral medication, is effective against both visceral and cutaneous leishmaniasis. Side effects are generally mild, though it can cause birth defects if taken within 3 months of getting pregnant. It does not appear to work for L. major or L. braziliensis. The evidence around the treatment of cutaneous leishmaniasis is poor. A number of topical treatments may be used for cutaneous leishmaniasis. Which treatments are effective depends on the strain, with topical paromomycin effective for L. major, L. tropica, L. mexicana, L. panamensis, and L. braziliensis. Pentamidine is effective for L. guyanensis. Oral fluconazole or itraconazole appears effective in L. major and L. tropica. Epidemiology Leishmaniasis occurs in 88 tropical and subtropical countries. About 350 million people live in these areas. The settings in which leishmaniasis is found range from rainforests in Central and South America to deserts in western Asia and the Middle East. It affects as many as 12 million people worldwide, with 1.5–2.0 million new cases each year. The visceral form of leishmaniasis has an estimated incidence of 500,000 new cases. More than 90% of the world's cases of visceral leishmaniasis are in India, Bangladesh, Nepal, Sudan, and Brazil.[16]As of 2010, it caused about 52,000 deaths, down from 87,000 in 1990. Different types of the disease occur in different regions of the world.[2] Cutaneous disease is most common in Afghanistan, Algeria, Brazil, Colombia, and Iran, while mucocutaneous disease is most common in Bolivia, Brazil, and Peru, and visceral disease is most common in Bangladesh, Brazil, Ethiopia, India, and Sudan. Leishmaniasis is found through much of the Americas from northern Argentina to South Texas, though not in Uruguay or Chile, and has recently been shown to be spreading to North Texas.[17] Leishmaniasis is also known as papalomoyo, papa lo moyo, ulcero de los chicleros, 38 and chiclera in Latin America.[18] During 2004, an estimated 3,400 troops from the Colombian army, operating in the jungles near the south of the country (in particular around the Meta and Guaviare departments), were infected with leishmaniasis. Allegedly, a contributing factor was that many of the affected soldiers did not use the officially provided insect repellent because of its disturbing odor. Nearly 13,000 cases of the disease were recorded in all of Colombia throughout 2004, and about 360 new instances of the disease among soldiers had been reported in February 2005. The disease is found across much of Asia, and in the Middle East. Within Afghanistan, leishmaniasis occurs commonly in Kabul, partly due to bad sanitation and waste left uncollected in streets, allowing parasite-spreading sand flies an environment they find favorable. In Kabul, the number of people infected was estimated to be at least 200,000, and in three other towns (Herat, Kandahar, and Mazar-i-Sharif) about 70,000 more occurred, according to WHO figures from 2002.[][verification needed] Kabul is estimated as the largest center of cutaneous leishmaniasis in the world, with around 67,500 cases as of 2004. Africa, in particular the East and North, is also home to cases of leishmaniasis. Leishmaniasis is mostly a disease of the developing world, and is rarely known in the developed world outside a small number of cases, mostly in instances where troops are stationed away from their home countries. Leishmaniasis has been reported by U.S. troops stationed in Saudi Arabia and Iraq since the Gulf War of 1990, including visceral leishmaniasis. In September 2005, the disease was contracted by at least four Dutch marines who were stationed in Mazari Sharif, Afghanistan, and subsequently repatriated for treatment.[citation needed] Trypanosomiasis Trypanosomiasis or trypanosomosis is the name of several by parasitic protozoan trypanosomesof the genus Trypanosoma. diseases in vertebrates caused In humans this includes African trypanosomiasis and Chagas disease. A number of other diseases occur in other animals. Approximately 30,000 people in 36 countries of sub-Saharan Africa have African trypanosomiasis, which is caused by eitherTrypanosoma brucei gambiense or Trypanosoma brucei rhodesiense. Chagas disease causes 21,000 deaths per year mainly inLatin America Signs and symptoms The tsetse fly bite erupts into a red chancre sore and within a few weeks, the person can experience fever, swollen lymph glands, blood in urine, aching muscles and joints, headaches and irritability. In the first phase, the patient has only intermittent bouts of fever with lymphadenopathy together with 39 other non-specific signs and symptoms. The second stage of the disease is marked by involvement of the central nervous system with extensive neurological effects like changes in personality, alteration of the biological clock (the circadian rhythm), confusion, slurred speech, seizures and difficulty in walking and talking. These problems can develop over many years and if not treated, the person dies. It is common to the African continent. Treatment Diagnosis is often missed in the first phase of the disease due to non-specific nature of symptoms. Pentamidine and Suramin are used for treatment in the first phase.Melarsoprol, nifurtimox and eflornithine are drugs used in second phase of the disease. However none of the therapies available are optimal in terms of adverse events and ease of administration. Other animals Nagana, or animal African trypanosomiasis, also called 'Souma' or 'Soumaya' in Sudan. Surra Mal de caderas (of central South America) Murrina de caderas (of Panama; Derrengadera de caderas) Dourine Cachexial fevers (various) Gambian horse sickness (of central Africa) Baleri (of Sudan) Kaodzera (Rhodesian trypanosomiasis) Tahaga (a disease of camels in Algeria) Galziekte, galzietzke (bilious fever of cattle; gall sickness of South Africa) Peste-boba (of Venezuela; Derrengadera) Some species of cattle such as the African buffalo, N'dama, and Keteku appear trypanotolerant and do not develop symptoms. Calves are more resistant than adults. Clinical signs and diagnosis[edit] Cattle may show enlarged lymph nodes and internal organs. Haemolytic anaemia is a characteristic sign. Systemic disease and reproductie are common, and cattle appear to waste away. Horses with dourine show signs of ventral and genital edema and urticaria. Infected dogs and cats may show severe systemic signs. Diagnosis relies on recognition of the flagellate on a blood smear. Motile organisms may be visible in the buffy coat when a blood sample is spun down. Serological testing is also common. 40 Prevention. Diminazene, homidium, isometadium, suramin, and melarsomine can all be used to treat infections. Resistance is increasing in endemic areas and recurrent treatments may be necessary. The use of trypanotolerant breeds for livestock farming should be considered if the disease is widespread. Fly control is another option but is difficult to implement. [[The main approaches to controlling African trypanosomiasis are to reduce the reservoirs of infection and the presence of the tsetse fly. Screening of people at risk helps identify patients at an early stage. Diagnosis should be made as early as possible and before the advanced stage to avoid complicated, difficult and risky treatment procedures. Coenurosis in humans Coenurosis is a parasitic infection that results dog tapeworm species Taenia multiceps, T. serialis. when humans ingest the eggs of It is important to distinguish that there is a very significant difference between intestinal human tapeworm infection and human coenurosis. Humans are the definitive hosts for some tapeworm species, the most common being T. saginata and T. solium (pork and beef tapeworms). This means that these species can develop into full grown, reproductively capable adult worms within the human body. People infected with these species have a tapeworm infection. In contrast, the four species that cause human coenurosis can only grow into mature, reproductively capable worms inside their definitive hosts, canids such as dogs, wolves, foxes and coyotes. Humans who ingest eggs from any of these four species of Taenia become intermediate hosts, or places where the eggs can mature into larvae but not into adult worms. When humans ingest these eggs, the eggs develop into tapeworm larvae that group within cysts known as coenuri, which can be seen in the central nervous system, muscles, and subcutaneous tissues of infected humans. People with coenurosis do not develop a tapeworm infection because the larvae of coenurosis-causing parasites cannot develop into worms inside of humans. Clinical signs in Humans In humans, this parasitic infection causes a variety of symptoms, depending on where the cyst occurs. The tapeworm larvae group together to form fluid filled cysts in various body tissues. These cysts start out small, but as the larvae grow, the cyst can reach the size of an egg. The cysts of T. multiceps are usually between 2 and 6 cm in diameter and are most commonly found in the CNS and can contain anywhere from a few to over a hundred worm larvae within them. T serialis and T. glomerata cysts present in the CNS, muscles, or subcutaneous tissue, and T. brauni cysts occupy these same areas but occur in the eye more frequently than the other three species. 41 When the cyst occurs in the brain, as it often does, the infected individual may experience headaches, seizures, vomiting, paralysis affecting one side of the body (hemiplegia), paralysis involving one limb (monoplegia), and loss of ability to coordinate muscles and muscle movements. Many of these symptoms are due to the buildup of inter-cranial pressure from the growing cyst or from the cyst pressing on other parts of brain. When the cyst occurs in the spinal cord, it can cause severe pain and inflammation, and loss of feeling in some nerves. When the cyst occurs in the eyes, it causes decreased vision and headaches. In the muscular and subcutaneous tissues, the cyst causes disfiguring nodules that can protrude out of the body. These nodules can be painful, uncomfortable, and can cause loss of muscle function. Transmission The definitive hosts for these Taenia species are canids. The adult tapeworms live in the intestines of animals like dogs, foxes, and coyotes. Intermediate hosts such as rabbits, goats, sheep, horses, cattle and sometimes humans get the disease by inadvertently ingesting tapeworm eggs (gravid proglottids) that have been passed in the feces of an infected canid. This can happen from ingesting food, water or soil that has been contaminated by dog feces. The disease cannot be transmitted from one intermediate host to another, but it is still not a good idea to eat meat that presents with cystic nodules from coenurosis. Taeniasis Taeniasis is a parasitic disease due to infection with tapeworms belonging to the genus Taenia. The two most important humanpathogens in the genus are Taenia solium (the pork tapeworm) and Taenia saginata (the beef tapeworm). Taeniasis is generally asymptomatic, but severe infection causes weight loss, dizziness,abdominal pain, diarrhea, headaches, nausea, constipation, chronic indigestion, and loss of appetite. A type of taeniasis called cysticercosis is caused by accidental infection with the eggs of T. solium from contaminated food and water. It is known as the most pathogenic form caused by tapeworms. A specific form of cysticercosis called neurocysticercosis is said to be the most common infection of the central nervous system. Signs and symptoms Taeniasis is generally asymptomatic and is diagnosed when a portion of the worm is passed in the stool. It is not fatal, although cysticercosis can cause epilepsy and neurocystocercosis can be fatal. 42 Taenia solium Infection by T. solium is normally asymptomatic. Heavy infection is indicated by intestinal irritation, anaemia, and indigestion. Cysticercosis There are accidental consumptions of eggs of T. solium from contaminated vegetables or water. The eggs enter the intestine where they develop into larvae. The larvae enterbloodstream and invade host tissues. This clinical condition, called cysticercosis, is the most frequent and severe disease caused by any tapeworm. It can lead to severe headaches, dizziness, occasional seizures, dementia, hypertension, lesions in the brain, blindness, tumor-like growths, and low eosinophil levels. It is the cause of major neurological problems, such as hydrocephalus, paraplegy, meningitis, convulsions, and even death. Taenia saginata Taenia saginata infection is asymptomatic, but heavy infection causes weight loss, dizziness, abdominal pain, diarrhea, headaches, nausea, constipation, chronic indigestion, and loss of appetite. It can cause antigen reaction that induce allergic reaction. It is an also rare cause of pancreatitis, cholecystitis, and cholangitis. Transmission Taeniasis is contracted after eating undercooked or raw pork and beef that contain the larvae. Cysticercosis occurs after ingestion of contaminated food, water, or soil that contain T. solium eggs. Infection is acquired by eating undercooked beef and pork that contain the fluidfilled cysticerci of the tapeworms. The adult worms live in the lumen of the intestine where they cause the symptoms. They acquire nutrients from the intestine, leading to malnutrition of the host. The gravid proglottids, body segments containing fertilised eggs, are released in the faeces of the host. Then they are consumed by an intermediate host such as a cow or pig, where they hatch within the duodenum to become larvae, penetrate through the intestinal wall into nearby blood vessels, and enter the bloodstream. Once they reach organs such as the skeletal muscles, liver or lungs, the larvae then develop into a cyst, which then becomes a fluid-filled cysticercus. These contaminated tissues are then consumed through raw or undercooked meat. Diagnosis Diagnosis of taeniasis is mainly using stool sample, particularly by identifying the eggs. However, this has limitation at the species level because tapeworms basically have similar eggs. Examination of the scolex or the gravid proglottids can resolve the exact species. But body segments are not often available, therefore, laborious histological observation of the uterine branches. 43 Prevention The fundamental prevention strategy is hygiene and sanitation. Secondary measures include stricter meat-inspection standards, livestock confinement, health education, safe meat preparation, mass drug therapy, and identifying and treating human and pig carriers. Moreover, a high level of sanitation and prevention of human faecal contamination of pig feeds also plays a major role in prevention. Infection can be prevented with proper disposal of human faeces around pigs, cooking meat thoroughly and/or freezing the meat at −10 °C for 5 days. For human cysticercosis, dirty hands are attributed to be the primary cause. Proper cooking of meat is an effective prevention Treatment Oral anti-parasitic drugs such as praziquantel are the treatment of choice. (5–10 mg/kg, singleadministration) or niclosamide (adults and children over 6 years: 2 g, single-administration after a light breakfast, Albendazole is also highly effective. Echinococcus The genus Echinococcus includes six parasite species of cyclophyllid tapeworms to date, of the family Taeniidae. Infection with Echinococcus results in hydatid disease, also known as echinococcosis. Echinococcus is triploblastic - it has three layers- outermost ectoderm, middle mesoderm, and inner endoderm. An anus is absent, and it has no digestive system. Its body is covered by tegument and the worm is divided into a scolex, a short neck, and three to six proglottids. Its body shape is ribbonlike. In humans, this causes a disease called echinococcosis. The three types of echinococcosis are cystic echinococcosis caused by E. granulosus, alveolar echinococcosis caused by E. multilocularis, and polycystic echinococcosis caused by E. vogeli or E. oligarthrus. A worm's incubation period is usually long and can be up to 50 years. Cystic echinococcosis is mostly found in South and Central America,Africa, the Middle East, China, Italy, Spain, Greece, Russia, and the western United States (Arizona, New Mexico, and California). Echinococcosis is a zoonosis; humans are dead-end hosts. The definitive hosts are carnivorous predators - dogs, wolves, foxes, and lions. The adult tapeworm lives in their small intestines and delivers eggs to be excreted with the stool. The intermediate hosts are infected by ingesting eggs. Sheep, goats, cattle, camels, pigs, wild herbivores, and rodents are the usual intermediate hosts, but humans can also be infected. The egg hatches in the digestive system of the intermediate host, producing an onchospher. It penetrates the intestinal wall and is carried by bloodstream to liver, lung, brain, or another organ. It settles there and turns into a bladder-like structure called hydatid cyst. From the inner lining of its 44 wall, protoscoleces (i.e. scoleces with invaginated tissue layers) bud and protrude into the fluid filling the cyst. After the death of the normal intermediate host, its body can be eaten by carnivores suitable as definitive hosts. In their small intestines, protoscoleces turn inside out, attach, and give rise to adult tapeworms, completing the lifecycle. In humans, the cysts persist and grow for years. They are regularly found in the liver (and every possible organ: spleen, kidney, bone, brain, tongue and skin) and are asymptomatic until their growing size produces symptoms or are accidentally discovered. Cysts are detected with ultrasound, X-ray computed tomography, or other imaging techniques. Antiechinococcus antibodies can be detected with serodiagnostic tests - indirect fluorescent antibody, complement fixation, ELISA. Diphyllobothriasis Diphyllobothriasis is the infection caused by tapeworms of the Diphyllobothrium genus, commonly Diphyllobothrium latum. Geographic distribution Diphyllobothriasis occurs in areas where lakes and rivers coexist with human consumption of raw or undercooked freshwater fish. Such areas are found in Europe, newly independent states of the former Soviet Union, North America, Asia, Uganda, Peru and Chile. It is particularly common in Japan, because of sushi. Around the middle of the 20th century in Japan, before advancements in refrigeration, many sushi/sashimi connoisseurs suffered great morbidity and mortality from Diphyllobothrium after eating unrefrigerated sashimi. Through research in parasitology, scientists came to realize that the primary cause was the relatively favorable parasite-breeding conditions that raw fish offered. The disease is rare in the United States. It was, however, once more common and was referred to as "Jewish housewife's disease" because Jewish housewives preparing the traditional "gefilte fish" frequently tasted the fish before it was cooked. Clinical features Diphyllobothriasis can last for decades if untreated. Most infections are asymptomatic. Manifestations may include abdominal discomfort, diarrhea, vomiting and weight loss. Vitamin B12 deficiency with subsequent megaloblastic anemia may occur, but has not for several decades in D. latum infections, possibly because of improved nutrition. In one test, nearly half of the ingested vitamin was absorbed by D. latum in otherwise healthy patients, while 80-100% was absorbed by 45 the worm in patients with anemia. It is not known why anemia occurs in some cases but not others. Massive infections may result in intestinal obstruction. Migration of proglottids can cause cholecystitis or cholangitis. Females cases are disproportionately reported, most likely due to the higher likelihood for them to be involved in meal preparation, rather than any morphological differences. Diagnosis Microscopic identification of eggs in the stool is the basis of specific diagnosis. Eggs are usually numerous and can be demonstrated without concentration techniques. Examination of proglottids passed in the stool is also of diagnostic value. Though it is difficult to identify the eggs or proglottids to the species level, the distinction is of little medical importance because, like most adult tapeworms in the intestine, all members of this genus respond to the same drugs. Treatment Upon diagnosis, treatment is quite simple and effective. The standard treatment for diphyllobothriasis, as well as many other tapeworm infections is a single dose of praziquantel, 5–10 mg/kg orally once for both adults and children. An alternative treatment is niclosamide, 2 g orally once for adults or 50 mg/kg (max 2 g) for children. Albendazole can also be effective. Prevention Avoid ingestion of raw freshwater fish. Adequate cooking or freezing of freshwater fish will kill the encysted fish tapeworm larvae. Also, because human feces is an important mechanism for spreading eggs, proper disposal of sewage can cut down on infection of fish and thus of humans. 46