{"id":1141,"date":"2016-11-04T03:36:24","date_gmt":"2016-11-04T03:36:24","guid":{"rendered":"https:\/\/courses.lumenlearning.com\/microbiology\/?post_type=chapter&#038;p=1141"},"modified":"2017-03-30T23:08:59","modified_gmt":"2017-03-30T23:08:59","slug":"fungal-and-parasitic-diseases-of-the-nervous-system","status":"publish","type":"chapter","link":"https:\/\/courses.lumenlearning.com\/suny-microbiology\/chapter\/fungal-and-parasitic-diseases-of-the-nervous-system\/","title":{"raw":"Fungal and Parasitic Diseases of the Nervous System","rendered":"Fungal and Parasitic Diseases of the Nervous System"},"content":{"raw":"<div class=\"textbox learning-objectives\">\r\n<h3>Learning Objectives<\/h3>\r\n<ul>\r\n \t<li>Identify the most common fungi that can cause infections of the nervous system<\/li>\r\n \t<li>Compare the major characteristics of specific fungal diseases affecting the nervous system<\/li>\r\n<\/ul>\r\n<\/div>\r\nFungal infections of the nervous system, called <strong>neuromycoses<\/strong>, are rare in healthy individuals. However, neuromycoses can be devastating in immunocompromised or elderly patients. Several eukaryotic parasites are also capable of infecting the nervous system of human hosts. Although relatively uncommon, these infections can also be life-threatening in immunocompromised individuals. In this section, we will first discuss neuromycoses, followed by parasitic infections of the nervous system.\r\n<h2>Cryptococcocal Meningitis<\/h2>\r\n<strong><em>Cryptococcus neoformans<\/em><\/strong> is a fungal pathogen that can cause meningitis. This yeast is commonly found in soils and is particularly associated with pigeon droppings. It has a thick capsule that serves as an important <strong>virulence factor<\/strong>, inhibiting clearance by phagocytosis. Most <em>C. neoformans<\/em> cases result in subclinical respiratory infections that, in healthy individuals, generally resolve spontaneously with no long-term consequences (see <a href=\".\/chapter\/respiratory-mycoses\/\" target=\"_blank\">Respiratory Mycoses<\/a>). In immunocompromised patients or those with other underlying illnesses, the infection can progress to cause <strong>meningitis<\/strong> and granuloma formation in brain tissues. <em>Cryptococcus<\/em> antigens can also serve to inhibit cell-mediated immunity and delayed-type hypersensitivity.\r\n\r\n[caption id=\"\" align=\"alignright\" width=\"400\"]<img class=\"\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03180006\/OSC_Microbio_26_04_Cryptococc.jpg\" alt=\"Micrograph of circles with rings around them.\" width=\"400\" height=\"220\" data-media-type=\"image\/jpeg\" \/> Figure\u00a01. An India ink-negative stain of <em>C. neoformans<\/em> showing the thick capsules around the spherical yeast cells. (credit: modification of work by Centers for Disease Control and Prevention)[\/caption]\r\n\r\n<em>Cryptococcus<\/em> can be easily cultured in the laboratory and identified based on its extensive capsule (Figure\u00a01). <em>C. neoformans<\/em> is frequently cultured from urine samples of patients with disseminated infections.\r\n\r\nProlonged treatment with antifungal drugs is required to treat cryptococcal infections. Combined therapy is required with <strong>amphotericin B<\/strong> plus <strong>flucytosine<\/strong> for at least 10 weeks. Many antifungal drugs have difficulty crossing the <strong>blood-brain barrier<\/strong> and have strong side effects that necessitate low doses; these factors contribute to the lengthy time of treatment. Patients with AIDS are particularly susceptible to <em>Cryptococcus<\/em> infections because of their compromised immune state. <strong>AIDS<\/strong> patients with cryptococcosis can also be treated with antifungal drugs, but they often have relapses; lifelong doses of fluconazole may be necessary to prevent reinfection.\r\n<div class=\"textbox key-takeaways\">\r\n<h3>Think about It<\/h3>\r\n<ul>\r\n \t<li>Why are neuromycoses infections rare in the general population?<\/li>\r\n \t<li>How is a cryptococcal infection acquired?<\/li>\r\n<\/ul>\r\n<\/div>\r\n<div class=\"textbox shaded\">\r\n<h3>Neuromycoses<\/h3>\r\nNeuromycoses typically occur only in immunocompromised individuals and usually only invade the nervous system after first infecting a different body system. As such, many diseases that sometimes affect the nervous system have already been discussed in previous chapters. Table 1\u00a0presents some of the most common fungal infections associated with neurological disease. This table includes only the neurological aspects associated with these diseases; it does not include characteristics associated with other body systems.\r\n<table>\r\n<thead>\r\n<tr>\r\n<th colspan=\"6\">Table 1.\u00a0Neuromycoses<\/th>\r\n<\/tr>\r\n<tr>\r\n<th>Disease<\/th>\r\n<th>Pathogen<\/th>\r\n<th>Signs and Symptoms<\/th>\r\n<th>Transmission<\/th>\r\n<th>Diagnostic Tests<\/th>\r\n<th>Antimicrobial Drugs<\/th>\r\n<\/tr>\r\n<\/thead>\r\n<tbody>\r\n<tr>\r\n<td>Aspergillosis<\/td>\r\n<td><em>Aspergillus fumigatus<\/em><\/td>\r\n<td>Meningitis, brain abscesses<\/td>\r\n<td>Dissemination from respiratory infection<\/td>\r\n<td>CSF, routine culture<\/td>\r\n<td>Amphotericin\u00a0B, voriconazole<\/td>\r\n<\/tr>\r\n<tr>\r\n<td>Candidiasis<\/td>\r\n<td><em>Candida albicans<\/em><\/td>\r\n<td>Meningitis<\/td>\r\n<td>Oropharynx or urogenital<\/td>\r\n<td>CSF, routine culture<\/td>\r\n<td>Amphotericin\u00a0B, flucytosine<\/td>\r\n<\/tr>\r\n<tr>\r\n<td>Coccidioidomycosis (Valley fever)<\/td>\r\n<td><em>Coccidioides immitis<\/em><\/td>\r\n<td>Meningitis (in about 1% of infections)<\/td>\r\n<td>Dissemination from respiratory infection<\/td>\r\n<td>CSF, routine culture<\/td>\r\n<td>Amphotericin\u00a0B, azoles<\/td>\r\n<\/tr>\r\n<tr>\r\n<td>Cryptococcosis<\/td>\r\n<td><em>Cryptococcus neoformans<\/em><\/td>\r\n<td>Meningitis, granuloma formation in brain<\/td>\r\n<td>Inhalation<\/td>\r\n<td>Negative stain of CSF, routine culture<\/td>\r\n<td>Amphotericin\u00a0B, flucytosine<\/td>\r\n<\/tr>\r\n<tr>\r\n<td>Histoplasmosis<\/td>\r\n<td><em>Histoplasma capsulatum<\/em><\/td>\r\n<td>Meningitis, granulomas in the brain<\/td>\r\n<td>Dissemination from respiratory infection<\/td>\r\n<td>CSF, routine culture<\/td>\r\n<td>Amphotericin\u00a0B, itraconazole<\/td>\r\n<\/tr>\r\n<tr>\r\n<td>Mucormycosis<\/td>\r\n<td><em>Rhizopus arrhizus<\/em><\/td>\r\n<td>Brain abscess<\/td>\r\n<td>Nasopharynx<\/td>\r\n<td>CSF, routine culture<\/td>\r\n<td>Amphotericin\u00a0B, azoles<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n<\/div>\r\n<div class=\"textbox examples\">\r\n<h3>Clinical Focus: Mustafa, Resolution<\/h3>\r\nThis example concludes\u00a0Mustafa\u2019s story that started in <a href=\"https:\/\/courses.lumenlearning.com\/microbiology\/chapter\/acellular-diseases-of-the-nervous-system\/chapter\/anatomy-of-the-nervous-system\/\" target=\"_blank\">Anatomy of the Nervous System<\/a>\u00a0and <a href=\".\/chapter\/acellular-diseases-of-the-nervous-system\/\" target=\"_blank\">Acellular Diseases of the Nervous System<\/a>.\r\n\r\nThis example continues Mustafa\u2019s story that started in Anatomy of the Nervous System.\u2019s new prescription for two antifungal drugs, amphotericin B and flucytosine, proved effective, and his condition began to improve. Culture results from Mustafa\u2019s sputum, skin, and CSF samples confirmed a fungal infection. All were positive for <em>C. neoformans<\/em>. Serological tests of his tissues were also positive for the <em>C. neoformans<\/em> capsular polysaccharide antigen.\r\n\r\nSince <em>C. neoformans<\/em> is known to occur in bird droppings, it is likely that Mustafa had been exposed to the fungus while working on the barn. Despite this exposure, Mustafa\u2019s doctor explained to him that immunocompetent people rarely contract cryptococcal meningitis and that his immune system had likely been compromised by the anti-inflammatory medication he was taking to treat his Crohn\u2019s disease. However, to rule out other possible causes of immunodeficiency, Mustafa\u2019s doctor recommended that he be tested for HIV.\r\n\r\nAfter Mustafa tested negative for HIV, his doctor took him off the corticosteroid he was using to manage his Crohn\u2019s disease, replacing it with a different class of drug. After several weeks of antifungal treatments, Mustafa managed a full recovery.\r\n\r\n<\/div>\r\n<h2>Amoebic Meningitis<\/h2>\r\n[caption id=\"\" align=\"alignright\" width=\"450\"]<img class=\"\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03180013\/OSC_Microbio_26_04_Naegleria.jpg\" alt=\"Micrograph of white blood cells and a large cell with a small circle in the center labeled N. fowlerii.\" width=\"450\" height=\"228\" data-media-type=\"image\/jpeg\" \/> Figure\u00a02. Free-living amoeba in human brain tissue from a patient suffering from PAM. (credit: modification of work by the Centers for Disease Control and Prevention)[\/caption]\r\n\r\n<strong>Primary amoebic meningoencephalitis (PAM)<\/strong> is caused by <strong><em>Naegleria fowleri<\/em><\/strong>. This amoeboflagellate is commonly found free-living in soils and water. It can exist in one of three forms\u2014the infective amoebic trophozoite form, a motile flagellate form, and a resting cyst form. PAM is a rare disease that has been associated with young and otherwise healthy individuals. Individuals are typically infected by the <strong>amoeba<\/strong> while swimming in warm bodies of freshwater such as rivers, lakes, and hot springs. The pathogenic trophozoite infects the brain by initially entering through nasal passages to the sinuses; it then moves down olfactory nerve fibers to penetrate the submucosal nervous plexus, invades the cribriform plate, and reaches the subarachnoid space. The subarachnoid space is highly vascularized and is a route of dissemination of trophozoites to other areas of the CNS, including the brain (Figure\u00a02). Inflammation and destruction of gray matter leads to severe headaches and fever. Within days, confusion and convulsions occur and quickly progress to seizures, coma, and death. The progression can be very rapid, and the disease is often not diagnosed until autopsy.\r\n\r\n<em>N. fowleri<\/em> infections can be confirmed by direct observation of CSF; the amoebae can often be seen moving while viewing a fresh <strong>CSF<\/strong> wet mount through a microscope. Flagellated forms can occasionally also be found in CSF. The amoebae can be stained with several stains for identification, including Giemsa-Wright or a modified trichrome stain. Detection of antigens with indirect immunofluorescence, or genetic analysis with PCR, can be used to confirm an initial diagnosis. <em>N. fowleri<\/em> infections are nearly always fatal; only 3 of 138 patients with PAM in the United States have survived.[footnote]US Centers for Disease Control and Prevention, \"<em>Naegleria fowleri<\/em>\u2014Primary Amoebic Meningoencephalitis (PAM)\u2014Amebic Encephalitis,\" 2016. Accessed June 30, 2016. http:\/\/www.cdc.gov\/parasites\/naegleria\/treatment.html.[\/footnote] A new experimental drug called <strong>miltefosine<\/strong> shows some promise for treating these infections. This drug is a phosphotidylcholine derivative that is thought to inhibit membrane function in <em>N. fowleri<\/em>, triggering apoptosis and disturbance of lipid-dependent cell signaling pathways.[footnote]Dorlo, Thomas PC, Manica Balasegaram, Jos H. Beijnen, and Peter J. de Vries, \"Miltefosine: A Review of Its Pharmacology and Therapeutic Efficacy in the Treatment of Leishmaniasis,\" <em>Journal of Antimicrobial Chemotherapy<\/em> 67, no. 11 (2012): 2576-97.[\/footnote] When administered early in infection and coupled with therapeutic hypothermia (lowering the body\u2019s core temperature to reduce the cerebral edema associated with infection), this drug has been successfully used to treat primary amoebic encephalitis.\r\n<h2>Granulomatous Amoebic Encephalitis<\/h2>\r\n<strong><em>Acanthamoeba<\/em><\/strong> and <strong><em>Balamuthia<\/em><\/strong> species are free-living amoebae found in many bodies of fresh water. Human infections by these amoebae are rare. However, they can cause <strong>amoebic keratitis<\/strong> in contact lens wearers (see <a href=\".\/chapter\/protozoan-and-helminthic-infections-of-the-skin-and-eyes\/\" target=\"_blank\">Protozoan and Helminthic Infections of the Eyes<\/a>), disseminated infections in immunocompromised patients, and <strong>granulomatous amoebic encephalitis (GAE)<\/strong> in severe cases. Compared to PAM, GAE tend to be subacute infections. The microbe is thought to enter through either the nasal sinuses or breaks in the skin. It is disseminated hematogenously and can invade the CNS. There, the infections lead to inflammation, formation of lesions, and development of typical neurological symptoms of encephalitis (Figure\u00a03). GAE is nearly always fatal.\r\n\r\nGAE is often not diagnosed until late in the infection. Lesions caused by the infection can be detected using CT or MRI. The live amoebae can be directly detected in CSF or tissue biopsies. Serological tests are available but generally are not necessary to make a correct diagnosis, since the presence of the organism in <strong>CSF<\/strong> is definitive. Some antifungal drugs, like <strong>fluconazole<\/strong>, have been used to treat acanthamoebal infections. In addition, a combination of <strong>miltefosine<\/strong> and <strong>voriconazole<\/strong> (an inhibitor of ergosterol biosynthesis) has recently been used to successfully treat GAE. Even with treatment, however, the mortality rate for patients with these infections is high.\r\n\r\n[caption id=\"\" align=\"aligncenter\" width=\"900\"]<img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03180016\/OSC_Microbio_26_04_AmoeEnceph.jpg\" alt=\"a) Photo of brain section with red granules in the center. b) close-up of granules.\" width=\"900\" height=\"465\" data-media-type=\"image\/jpeg\" \/> Figure\u00a03. (a) Brain tissue from a patient who died of granulomatous amebic encephalitis (GAE) caused by Balamuthia mandrillaris. (b) A close-up of the necrosis in the center of the brain section. (credit a, b: modifications of work by the Centers for Disease Control and Prevention)[\/caption]\r\n\r\n<div class=\"textbox key-takeaways\">\r\n<h3>Think about It<\/h3>\r\n<ul>\r\n \t<li>How is granulomatous amoebic encephalitis diagnosed?<\/li>\r\n<\/ul>\r\n<\/div>\r\n<h2>Human African Trypanosomiasis<\/h2>\r\n<strong>Human African trypanosomiasis<\/strong> (also known as <strong>African sleeping sickness<\/strong>) is a serious disease endemic to two distinct regions in sub-Saharan Africa. It is caused by the insect-borne hemoflagellate <strong><em>Trypanosoma brucei<\/em><\/strong>. The subspecies <em>Trypanosoma brucei rhodesiense<\/em> causes <strong>East African trypanosomiasis<\/strong> (EAT), and another subspecies, <em>Trypanosoma brucei gambiense<\/em> causes <strong>West African trypanosomiasis<\/strong> (WAT). A few hundred cases of EAT are currently reported each year.[footnote]US Centers for Disease Control and Prevention, \"Parasites \u2013 African Trypanosomiasis (also known as Sleeping Sickness), East African Trypanosomiasis FAQs,\" 2012. Accessed June 30, 2016. http:\/\/www.cdc.gov\/parasites\/sleepingsickness\/gen_info\/faqs-east.html.[\/footnote] WAT is more commonly reported and tends to be a more chronic disease. Around 7000 to 10,000 new cases of WAT are identified each year.[footnote]US Centers for Disease Control and Prevention, \"Parasites \u2013 African Trypanosomiasis (also known as Sleeping Sickness), Epidemiology &amp; Risk Factors,\" 2012. Accessed June 30, 2016. http:\/\/www.cdc.gov\/parasites\/sleepingsickness\/epi.html.[\/footnote]\r\n\r\n[caption id=\"\" align=\"alignright\" width=\"399\"]<img class=\"\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03180022\/OSC_Microbio_26_04_Trypanosom.jpg\" alt=\"Micrograph of red circles labeled red blood cells and worm-shaped cells labeled Trypanosoma brucei.\" width=\"399\" height=\"268\" data-media-type=\"image\/jpeg\" \/> Figure\u00a04. Trypanosoma brucei, the causative agent of African sleeping sickness, in a human blood smear. (credit: modification of work by the Centers for Disease Control and Prevention)[\/caption]\r\n\r\n<em>T. brucei<\/em> is primarily transmitted to humans by the bite of the <strong>tsetse fly<\/strong> (<em>Glossina<\/em> spp.). Soon after the bite of a tsetse fly, a chancre forms at the site of infection. The flagellates then spread, moving into the circulatory system (Figure\u00a04). These systemic infections result in an <strong>undulating fever<\/strong>, during which symptoms persist for two or three days with remissions of about a week between bouts. As the disease enters its final phase, the pathogens move from the lymphatics into the CNS. Neurological symptoms include daytime sleepiness, insomnia, and mental deterioration. In EAT, the disease runs its course over a span of weeks to months. In contrast, WAT often occurs over a span of months to years.\r\n\r\nAlthough a strong immune response is mounted against the trypanosome, it is not sufficient to eliminate the pathogen. Through <strong>antigenic variation<\/strong>, <em>Trypanosoma<\/em> can change their surface proteins into over 100 serological types. This variation leads to the undulating form of the initial disease. The initial septicemia caused by the infection leads to high fevers. As the immune system responds to the infection, the number of organisms decrease, and the clinical symptoms abate. However, a subpopulation of the pathogen then alters its surface coat antigens by antigenic variation and evades the immune response. These flagellates rapidly proliferate and cause another bout of disease. If untreated, these infections are usually fatal.\r\n\r\nClinical symptoms can be used to recognize the early signs of African trypanosomiasis. These include the formation of a chancre at the site of infection and <strong>Winterbottom\u2019s sign<\/strong>. Winterbottom\u2019s sign refers to the enlargement of lymph nodes on the back of the neck\u2014often indicative of cerebral infections. <em>Trypanosoma<\/em> can be directly observed in stained samples including blood, lymph, CSF, and skin biopsies of chancres from patients. Antibodies against the parasite are found in most patients with acute or chronic disease. Serologic testing is generally not used for diagnosis, however, since the microscopic detection of the parasite is sufficient. Early diagnosis is important for treatment. Before the nervous system is involved, drugs like <strong>pentamidine<\/strong> (an inhibitor of nuclear metabolism) and <strong>suramin<\/strong> (mechanism unclear) can be used. These drugs have fewer side effects than the drugs needed to treat the second stage of the disease. Once the sleeping sickness phase has begun, harsher drugs including <strong>melarsoprol<\/strong> (an arsenic derivative) and <strong>eflornithine<\/strong> can be effective. Following successful treatment, patients still need to have follow-up examinations of their CSF for two years to detect possible relapses of the disease. The most effective means of preventing these diseases is to control the insect vector populations.\r\n<div class=\"textbox key-takeaways\">\r\n<h3>Think about It<\/h3>\r\n<ul>\r\n \t<li>What is the symptom of a systemic <em>Trypanosoma<\/em> infection?<\/li>\r\n \t<li>What are the symptoms of a neurological <em>Trypanosoma<\/em> infection<em>?<\/em><\/li>\r\n \t<li>Why are trypanosome infections so difficult to eradicate?<\/li>\r\n<\/ul>\r\n<\/div>\r\n<h2>Neurotoxoplasmosis<\/h2>\r\n<strong><em>Toxoplasma gondii<\/em><\/strong> is an ubiquitous intracellular parasite that can cause neonatal infections. Cats are the definitive host, and humans can become infected after eating infected meat or, more commonly, by ingesting oocysts shed in the feces of cats (see <a href=\".\/chapter\/parasitic-infections-of-the-circulatory-and-lymphatic-systems\/\" target=\"_blank\">Parasitic Infections of the Circulatory and Lymphatic Systems<\/a>). <em>T. gondii<\/em> enters the circulatory system by passing between the endothelial cells of blood vessels.[footnote]Carruthers, Vern B., and Yasuhiro Suzuki, \"Effects of <em>Toxoplasma gondii<\/em> Infection on the Brain,\" <em>Schizophrenia Bulletin<\/em> 33, no. 3 (2007): 745-51.[\/footnote] Most cases of toxoplasmosis are asymptomatic. However, in immunocompromised patients, <strong>neurotoxoplasmosis<\/strong> caused by <em>T. gondii<\/em> infections are one of the most common causes of brain abscesses.[footnote]Uppal, Gulshan, \"CNS Toxoplasmosis in HIV,\" 2015. Accessed June 30, 2016. http:\/\/emedicine.medscape.com\/article\/1167298-overview#a3.[\/footnote] The organism is able to cross the <strong>blood-brain barrier<\/strong> by infecting the endothelial cells of capillaries in the brain. The parasite reproduces within these cells, a step that appears to be necessary for entry to the brain, and then causes the endothelial cell to lyse, releasing the progeny into brain tissues. This mechanism is quite different than the method it uses to enter the bloodstream in the first place.[footnote]Konradt, Christoph, Norikiyo Ueno, David A. Christian, Jonathan H. Delong, Gretchen Harms Pritchard, Jasmin Herz, David J. Bzik et al., \"Endothelial Cells Are a Replicative Niche for Entry of <em>Toxoplasma gondii<\/em> to the Central Nervous System,\" <em>Nature Microbiology<\/em> 1 (2016): 16001.[\/footnote]\r\n\r\nThe brain lesions associated with neurotoxoplasmosis can be detected radiographically using MRI or CAT scans (Figure\u00a05). Diagnosis can be confirmed by direct observation of the organism in CSF. RT-PCR assays can also be used to detect <em>T. gondii<\/em> through genetic markers.\r\n\r\n[caption id=\"\" align=\"aligncenter\" width=\"550\"]<img class=\"\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03180024\/OSC_Microbio_26_04_Neurotoxpl.jpg\" alt=\"Micrograph of sphere wit red dots.\" width=\"550\" height=\"369\" data-media-type=\"image\/jpeg\" \/> Figure\u00a05. <em>This Toxoplasma<\/em> gondii cyst, observed in mouse brain tissue, contains thousands of inactive parasites. (credit: modification of work by USDA)[\/caption]\r\n\r\nTreatment of neurotoxoplasmosis caused by <em>T. gondii<\/em> infections requires six weeks of multi-drug therapy with <strong>pyrimethamine<\/strong>, <strong>sulfadiazine<\/strong>, and <strong>folinic acid<\/strong>. Long-term maintenance doses are often required to prevent recurrence.\r\n<div class=\"textbox key-takeaways\">\r\n<h3>Think about It<\/h3>\r\n<ul>\r\n \t<li>Under what conditions is <em>Toxoplasma<\/em> infection serious?<\/li>\r\n \t<li>How does <em>Toxoplasma<\/em> circumvent the blood-brain barrier<em>?<\/em><\/li>\r\n<\/ul>\r\n<\/div>\r\n<h2>Neurocysticercosis<\/h2>\r\nCysticercosis is a parasitic infection caused by the larval form of the <strong>pork tapeworm<\/strong>, <strong><em>Taenia solium<\/em><\/strong>. When the larvae invade the brain and spinal cord, the condition is referred to as <strong>neurocysticercosis<\/strong>. This condition affects millions of people worldwide and is the leading cause of adult onset <strong>epilepsy<\/strong> in the developing world.[footnote]DeGiorgio, Christopher M., Marco T. Medina, Reyna Dur\u00f3n, Chi Zee, and Susan Pietsch Escueta, \"Neurocysticercosis,\" <em>Epilepsy Currents<\/em> 4, no. 3 (2004): 107-11.[\/footnote]\r\n\r\nThe life cycle of <em>T. solium<\/em> is discussed in <a href=\".\/chapter\/helminthic-infections-of-the-gastrointestinal-tract\/\" target=\"_blank\">Helminthic Infections of the Gastrointestinal Tract<\/a>. Following ingestion, the eggs hatch in the intestine to form larvae called <strong>cysticerci<\/strong>. Adult tapeworms form in the small intestine and produce eggs that are shed in the feces. These eggs can infect other individuals through fecal contamination of food or other surfaces. Eggs can also hatch within the intestine of the original patient and lead to an ongoing autoinfection. The cystercerci, can migrate to the blood and invade many tissues in the body, including the CNS.\r\n\r\nNeurocysticercosis is usually diagnosed through noninvasive techniques. Epidemiological information can be used as an initial screen; cysticercosis is endemic in Central and South America, Africa, and Asia. Radiological imaging (MRI and CT scans) is the primary method used to diagnose neurocysticercosis; imaging can be used to detect the one- to two-centimeter cysts that form around the parasites (Figure\u00a06). Elevated levels of eosinophils in the blood can also indicate a parasitic infection. EIA and ELISA are also used to detect antigens associated with the pathogen.\r\n\r\n[caption id=\"\" align=\"aligncenter\" width=\"700\"]<img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03180027\/OSC_Microbio_26_04_Neurocyst.jpg\" alt=\"Brain scans with small lumps (look like pimples) indicated by arrows.\" width=\"700\" height=\"323\" data-media-type=\"image\/jpeg\" \/> Figure\u00a06. Brain CT scans of sagittal (left) and axial (right) sections of a brain with neurocysticercosis. Numerous cysts are visible in both images, as indicated by the arrows. (credit: modification of work by Segamwenge IL, Kioko NP)[\/caption]\r\n\r\nThe treatment for neurocysticercosis depends on the location, number, size, and stage of cysticerci present. Antihelminthic chemotherapy includes <strong>albendazole<\/strong> and <strong>praziquantel<\/strong>. Because these drugs kill viable cysts, they may acutely increase symptoms by provoking an inflammatory response caused by the release of <em>Taenia<\/em> cysticerci antigens, as the cysts are destroyed by the drugs. To alleviate this response, corticosteroids that cross the <strong>blood-brain barrier<\/strong> (e.g., <strong>dexamethasone<\/strong>) can be used to mitigate these effects. Surgical intervention may be required to remove intraventricular cysts.\r\n<div class=\"textbox shaded\">\r\n<h3>Parasitic Diseases of the Nervous System<\/h3>\r\nParasites that successfully invade the nervous system can cause a wide range of neurological signs and symptoms. Often, they inflict lesions that can be visualized through radiologic imaging. A number of these infections are fatal, but some can be treated (with varying levels of success) by antimicrobial drugs (Table 2).\r\n<table>\r\n<thead>\r\n<tr>\r\n<th colspan=\"6\">Table 2.\u00a0Parasitic Diseases of the Nervous System<\/th>\r\n<\/tr>\r\n<tr>\r\n<th>Disease<\/th>\r\n<th>Pathogen<\/th>\r\n<th>Signs and Symptoms<\/th>\r\n<th>Transmission<\/th>\r\n<th>Diagnostic Tests<\/th>\r\n<th>Antimicrobial Drugs<\/th>\r\n<\/tr>\r\n<\/thead>\r\n<tbody>\r\n<tr>\r\n<td>Granulomatous amoebic encephalitis (GAE)<\/td>\r\n<td><em>Acanthamoeba<\/em>\u00a0spp., <em>Balamuthia mandrillaris<\/em><\/td>\r\n<td>Inflammation, lesions in CNS, almost always fatal<\/td>\r\n<td>Freshwater ameobae invade CNS via breaks in skin or sinuses<\/td>\r\n<td>CT scan, MRI, CSF<\/td>\r\n<td>Fluconazole, miltefosine, voriconazole<\/td>\r\n<\/tr>\r\n<tr>\r\n<td>Human African trypanosomiasis<\/td>\r\n<td><em>Trypanosoma brucei gambiense<\/em>, <em>T.\u00a0brucei rhodesiense<\/em><\/td>\r\n<td>Chancre, Winterbottom\u2019s sign, undulating fever, lethargy, insomnia, usually fatal if untreated<\/td>\r\n<td>Protozoan transmitted via bite of tsetse fly<\/td>\r\n<td>Blood smear<\/td>\r\n<td>Pentamidine and suramine (initial phase); melarsoprol and eflornithine (final phase)<\/td>\r\n<\/tr>\r\n<tr>\r\n<td>Neurocysticercosis<\/td>\r\n<td><em>Taenia solium<\/em><\/td>\r\n<td>Brain cysts, epilepsy<\/td>\r\n<td>Ingestion of tapeworm eggs in fecally contaminated food or surfaces<\/td>\r\n<td>CT scan, MRI<\/td>\r\n<td>Albendazole, praziquantel, dexamethasone<\/td>\r\n<\/tr>\r\n<tr>\r\n<td>Neurotoxoplasmosis<\/td>\r\n<td><em>Toxoplasma gondii<\/em><\/td>\r\n<td>Brain abscesses, chronic encephalitis<\/td>\r\n<td>Protozoan transmitted via contact with oocytes in cat feces<\/td>\r\n<td>CT scan, MRI, CSF<\/td>\r\n<td>Pyrimethamine, sulfadiazine, folinic acid<\/td>\r\n<\/tr>\r\n<tr>\r\n<td>Primary amoebic meningoencephalitis (PAM)<\/td>\r\n<td><em>Naegleria fowleri<\/em><\/td>\r\n<td>Headache, seizures, coma, almost always fatal<\/td>\r\n<td>Freshwater ameobae invade brain via nasal passages<\/td>\r\n<td>CSF, IFA, PCR<\/td>\r\n<td>Miltefosine (experimental)<\/td>\r\n<\/tr>\r\n<\/tbody>\r\n<\/table>\r\n<\/div>\r\n<div class=\"textbox key-takeaways\">\r\n<h3>Think about It<\/h3>\r\n<ul>\r\n \t<li>What neurological condition is associated with neurocysticercosis?<\/li>\r\n \t<li>How is neurocysticercosis diagnosed?<\/li>\r\n<\/ul>\r\n<\/div>\r\n<div class=\"textbox key-takeaways\">\r\n<h3>Key Concepts and Summary<\/h3>\r\n<ul>\r\n \t<li><strong>Neuromycoses<\/strong> are uncommon in immunocompetent people, but immunocompromised individuals with fungal infections have high mortality rates. Treatment of neuromycoses require prolonged therapy with antifungal drugs at low doses to avoid side effects and overcome the effect of the blood-brain barrier.<\/li>\r\n \t<li>Some protist infections of the nervous systems are fatal if not treated, including <strong>primary amoebic meningitis<\/strong>, <strong>granulomatous amoebic encephalitis<\/strong>, <strong>human African trypanosomiasis<\/strong>, and <strong>neurotoxoplasmosis<\/strong>.<\/li>\r\n \t<li>The various forms of ameobic encephalitis caused by the different amoebic infections are typically fatal even with treatment, but they are rare.<\/li>\r\n \t<li><strong>African trypanosomiasis<\/strong> is a serious but treatable disease endemic to two distinct regions in sub-Saharan Africa caused by the insect-borne hemoflagellate <em>Trypanosoma brucei<\/em>.<\/li>\r\n \t<li><strong>Neurocysticercosis<\/strong> is treated using antihelminthic drugs or surgery to remove the large cysts from the CNS.<\/li>\r\n<\/ul>\r\n<\/div>\r\n<div class=\"textbox exercises\">\r\n<h3>Multiple Choice<\/h3>\r\nWhich of these diseases results in meningitis caused by an encapsulated yeast?\r\n<ol style=\"list-style-type: lower-alpha;\">\r\n \t<li>cryptococcosis<\/li>\r\n \t<li>histoplasmosis<\/li>\r\n \t<li>candidiasis<\/li>\r\n \t<li>coccidiomycosis<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"510178\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"510178\"]Answer a. Cryptococcosis\u00a0results in meningitis caused by an encapsulated yeast.[\/hidden-answer]\r\n\r\nWhat kind of stain is most commonly used to visualize the capsule of cryptococcus?\r\n<ol style=\"list-style-type: lower-alpha;\">\r\n \t<li>Gram stain<\/li>\r\n \t<li>simple stain<\/li>\r\n \t<li>negative stain<\/li>\r\n \t<li>fluorescent stain<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"451516\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"451516\"]Answer c. A\u00a0negative stain\u00a0is most commonly used to visualize the capsule of cryptococcus.[\/hidden-answer]\r\n\r\nWhich of the following is the causative agent of East African trypanosomiasis?\r\n<ol style=\"list-style-type: lower-alpha;\">\r\n \t<li><em>Trypanosoma cruzi<\/em><\/li>\r\n \t<li><em>Trypanosoma vivax<\/em><\/li>\r\n \t<li><em>Trypanosoma brucei rhodanese<\/em><\/li>\r\n \t<li><em>Trypanosoma brucei gambiense<\/em><\/li>\r\n<\/ol>\r\n[reveal-answer q=\"560815\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"560815\"]Answer c.\u00a0<em>Trypanosoma brucei rhodanese<\/em>\u00a0is the causative agent of East African trypanosomiasis.[\/hidden-answer]\r\n\r\nWhich of the following is the causative agent of primary amoebic meningoencephalitis?\r\n<ol style=\"list-style-type: lower-alpha;\">\r\n \t<li><em>Naegleria fowleri<\/em><\/li>\r\n \t<li><em>Entameba histolyticum<\/em><\/li>\r\n \t<li><em>Amoeba proteus<\/em><\/li>\r\n \t<li><em>Acanthamoeba polyphaga<\/em><\/li>\r\n<\/ol>\r\n[reveal-answer q=\"718879\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"718879\"]Answer a.\u00a0<em>Naegleria fowleri<\/em>\u00a0is the causative agent of primary amoebic meningoencephalitis.[\/hidden-answer]\r\n\r\nWhat is the biological vector for African sleeping sickness?\r\n<ol style=\"list-style-type: lower-alpha;\">\r\n \t<li>mosquito<\/li>\r\n \t<li>tsetse fly<\/li>\r\n \t<li>deer tick<\/li>\r\n \t<li>sand fly<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"740482\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"740482\"]Answer b. The\u00a0tsetse fly\u00a0is the biological vector for African sleeping sickness.[\/hidden-answer]\r\n\r\nHow do humans usually contract neurocysticercosis?\r\n<ol style=\"list-style-type: lower-alpha;\">\r\n \t<li>the bite of an infected arthropod<\/li>\r\n \t<li>exposure to contaminated cat feces<\/li>\r\n \t<li>swimming in contaminated water<\/li>\r\n \t<li>ingestion of undercooked pork<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"525465\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"525465\"]Answer d. Humans usually contract neurocysticercosis by\u00a0ingesting undercooked pork.[\/hidden-answer]\r\n\r\nWhich of these is the most important cause of adult onset epilepsy?\r\n<ol style=\"list-style-type: lower-alpha;\">\r\n \t<li>neurocysticercosis<\/li>\r\n \t<li>neurotoxoplasmosis<\/li>\r\n \t<li>primary amoebic meningoencephalitis<\/li>\r\n \t<li>African trypanosomiasis<\/li>\r\n<\/ol>\r\n[reveal-answer q=\"349477\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"349477\"]Answer a. Neurocysticercosis\u00a0is the most important cause of adult onset epilepsy.[\/hidden-answer]\r\n\r\n<\/div>\r\n<div class=\"textbox exercises\">\r\n<h3>Fill in the Blank<\/h3>\r\nThe __________ is the main virulence factor of <em>Cryptococcus neoformans<\/em>.\r\n\r\n[reveal-answer q=\"11050\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"11050\"]The <strong>capsule<\/strong> is the main virulence factor of <em>Cryptococcus neoformans<\/em>.[\/hidden-answer]\r\n\r\nThe drug of choice for fungal infections of the nervous system is __________.\r\n\r\n[reveal-answer q=\"356241\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"356241\"]The drug of choice for fungal infections of the nervous system is <strong>Amphotericin B<\/strong>.[\/hidden-answer]\r\n\r\nThe larval forms of a tapeworm are known as __________.\r\n\r\n[reveal-answer q=\"478329\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"478329\"]The larval forms of a tapeworm are known as <strong>cysticerci<\/strong>.[\/hidden-answer]\r\n\r\n__________ sign appears as swollen lymph nodes at the back of the neck in early African trypanosomiasis.\r\n\r\n[reveal-answer q=\"288854\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"288854\"]<strong>Winterbottom\u2019s<\/strong> sign appears as swollen lymph nodes at the back of the neck in early African trypanosomiasis.[\/hidden-answer]\r\n\r\n__________ African trypanosomiasis causes a chronic form of sleeping sickness.\r\n\r\n[reveal-answer q=\"528329\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"528329\"]<strong>West<\/strong> African trypanosomiasis causes a chronic form of sleeping sickness.[\/hidden-answer]\r\n\r\nThe definitive host for <em>Toxoplasma gondii<\/em> is __________.\r\n\r\n[reveal-answer q=\"221088\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"221088\"]The definitive host for <em>Toxoplasma gondii<\/em> is <strong>cats<\/strong>.[\/hidden-answer]\r\n\r\nTrypanosomes can evade the immune response through __________ variation.\r\n\r\n[reveal-answer q=\"417069\"]Show Answer[\/reveal-answer]\r\n[hidden-answer a=\"417069\"]Trypanosomes can evade the immune response through <strong>antigenic<\/strong> variation.[\/hidden-answer]\r\n\r\n<\/div>\r\n<div class=\"textbox key-takeaways\">\r\n<h3>Think about It<\/h3>\r\n<ol>\r\n \t<li>Why do nervous system infections by fungi require such long treatment times?<\/li>\r\n \t<li>Briefly describe how humans are infected by <em>Naegleria fowleri<\/em>.<\/li>\r\n \t<li>Briefly describe how humans can develop neurocysticercosis.<\/li>\r\n \t<li>Fungal meningoencephalitis is often the ultimate cause of death for AIDS patients. What factors make these infections more problematic than those of bacterial origin?<\/li>\r\n \t<li>Compare East African trypanosomiasis with West African trypanosomiasis.<\/li>\r\n \t<li>The graph shown tracks the body temperature of a patient infected with <em>Trypanosoma brucei<\/em>. How would you describe this pattern, and why does it occur?<\/li>\r\n<\/ol>\r\n[caption id=\"\" align=\"aligncenter\" width=\"870\"]<img src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03180035\/OSC_Microbio_26_04_ArtConnect_img.jpg\" alt=\"Graph with Days on the X axis and Temperature on the Y axis. There is a peak to 40 degrees C early on then a drop back to normal temperatures (37 degree C) for 7 days. Then another peak, then another drop to normal for 9 days, then another peak and then another drop to normal for 9 days.\" width=\"870\" height=\"482\" data-media-type=\"image\/jpeg\" \/> (credit: modification of work by Wellcome Images)[\/caption]\r\n\r\n<\/div>","rendered":"<div class=\"textbox learning-objectives\">\n<h3>Learning Objectives<\/h3>\n<ul>\n<li>Identify the most common fungi that can cause infections of the nervous system<\/li>\n<li>Compare the major characteristics of specific fungal diseases affecting the nervous system<\/li>\n<\/ul>\n<\/div>\n<p>Fungal infections of the nervous system, called <strong>neuromycoses<\/strong>, are rare in healthy individuals. However, neuromycoses can be devastating in immunocompromised or elderly patients. Several eukaryotic parasites are also capable of infecting the nervous system of human hosts. Although relatively uncommon, these infections can also be life-threatening in immunocompromised individuals. In this section, we will first discuss neuromycoses, followed by parasitic infections of the nervous system.<\/p>\n<h2>Cryptococcocal Meningitis<\/h2>\n<p><strong><em>Cryptococcus neoformans<\/em><\/strong> is a fungal pathogen that can cause meningitis. This yeast is commonly found in soils and is particularly associated with pigeon droppings. It has a thick capsule that serves as an important <strong>virulence factor<\/strong>, inhibiting clearance by phagocytosis. Most <em>C. neoformans<\/em> cases result in subclinical respiratory infections that, in healthy individuals, generally resolve spontaneously with no long-term consequences (see <a href=\".\/chapter\/respiratory-mycoses\/\" target=\"_blank\">Respiratory Mycoses<\/a>). In immunocompromised patients or those with other underlying illnesses, the infection can progress to cause <strong>meningitis<\/strong> and granuloma formation in brain tissues. <em>Cryptococcus<\/em> antigens can also serve to inhibit cell-mediated immunity and delayed-type hypersensitivity.<\/p>\n<div style=\"width: 410px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" class=\"\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03180006\/OSC_Microbio_26_04_Cryptococc.jpg\" alt=\"Micrograph of circles with rings around them.\" width=\"400\" height=\"220\" data-media-type=\"image\/jpeg\" \/><\/p>\n<p class=\"wp-caption-text\">Figure\u00a01. An India ink-negative stain of <em>C. neoformans<\/em> showing the thick capsules around the spherical yeast cells. (credit: modification of work by Centers for Disease Control and Prevention)<\/p>\n<\/div>\n<p><em>Cryptococcus<\/em> can be easily cultured in the laboratory and identified based on its extensive capsule (Figure\u00a01). <em>C. neoformans<\/em> is frequently cultured from urine samples of patients with disseminated infections.<\/p>\n<p>Prolonged treatment with antifungal drugs is required to treat cryptococcal infections. Combined therapy is required with <strong>amphotericin B<\/strong> plus <strong>flucytosine<\/strong> for at least 10 weeks. Many antifungal drugs have difficulty crossing the <strong>blood-brain barrier<\/strong> and have strong side effects that necessitate low doses; these factors contribute to the lengthy time of treatment. Patients with AIDS are particularly susceptible to <em>Cryptococcus<\/em> infections because of their compromised immune state. <strong>AIDS<\/strong> patients with cryptococcosis can also be treated with antifungal drugs, but they often have relapses; lifelong doses of fluconazole may be necessary to prevent reinfection.<\/p>\n<div class=\"textbox key-takeaways\">\n<h3>Think about It<\/h3>\n<ul>\n<li>Why are neuromycoses infections rare in the general population?<\/li>\n<li>How is a cryptococcal infection acquired?<\/li>\n<\/ul>\n<\/div>\n<div class=\"textbox shaded\">\n<h3>Neuromycoses<\/h3>\n<p>Neuromycoses typically occur only in immunocompromised individuals and usually only invade the nervous system after first infecting a different body system. As such, many diseases that sometimes affect the nervous system have already been discussed in previous chapters. Table 1\u00a0presents some of the most common fungal infections associated with neurological disease. This table includes only the neurological aspects associated with these diseases; it does not include characteristics associated with other body systems.<\/p>\n<table>\n<thead>\n<tr>\n<th colspan=\"6\">Table 1.\u00a0Neuromycoses<\/th>\n<\/tr>\n<tr>\n<th>Disease<\/th>\n<th>Pathogen<\/th>\n<th>Signs and Symptoms<\/th>\n<th>Transmission<\/th>\n<th>Diagnostic Tests<\/th>\n<th>Antimicrobial Drugs<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr>\n<td>Aspergillosis<\/td>\n<td><em>Aspergillus fumigatus<\/em><\/td>\n<td>Meningitis, brain abscesses<\/td>\n<td>Dissemination from respiratory infection<\/td>\n<td>CSF, routine culture<\/td>\n<td>Amphotericin\u00a0B, voriconazole<\/td>\n<\/tr>\n<tr>\n<td>Candidiasis<\/td>\n<td><em>Candida albicans<\/em><\/td>\n<td>Meningitis<\/td>\n<td>Oropharynx or urogenital<\/td>\n<td>CSF, routine culture<\/td>\n<td>Amphotericin\u00a0B, flucytosine<\/td>\n<\/tr>\n<tr>\n<td>Coccidioidomycosis (Valley fever)<\/td>\n<td><em>Coccidioides immitis<\/em><\/td>\n<td>Meningitis (in about 1% of infections)<\/td>\n<td>Dissemination from respiratory infection<\/td>\n<td>CSF, routine culture<\/td>\n<td>Amphotericin\u00a0B, azoles<\/td>\n<\/tr>\n<tr>\n<td>Cryptococcosis<\/td>\n<td><em>Cryptococcus neoformans<\/em><\/td>\n<td>Meningitis, granuloma formation in brain<\/td>\n<td>Inhalation<\/td>\n<td>Negative stain of CSF, routine culture<\/td>\n<td>Amphotericin\u00a0B, flucytosine<\/td>\n<\/tr>\n<tr>\n<td>Histoplasmosis<\/td>\n<td><em>Histoplasma capsulatum<\/em><\/td>\n<td>Meningitis, granulomas in the brain<\/td>\n<td>Dissemination from respiratory infection<\/td>\n<td>CSF, routine culture<\/td>\n<td>Amphotericin\u00a0B, itraconazole<\/td>\n<\/tr>\n<tr>\n<td>Mucormycosis<\/td>\n<td><em>Rhizopus arrhizus<\/em><\/td>\n<td>Brain abscess<\/td>\n<td>Nasopharynx<\/td>\n<td>CSF, routine culture<\/td>\n<td>Amphotericin\u00a0B, azoles<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<div class=\"textbox examples\">\n<h3>Clinical Focus: Mustafa, Resolution<\/h3>\n<p>This example concludes\u00a0Mustafa\u2019s story that started in <a href=\"https:\/\/courses.lumenlearning.com\/microbiology\/chapter\/acellular-diseases-of-the-nervous-system\/chapter\/anatomy-of-the-nervous-system\/\" target=\"_blank\">Anatomy of the Nervous System<\/a>\u00a0and <a href=\".\/chapter\/acellular-diseases-of-the-nervous-system\/\" target=\"_blank\">Acellular Diseases of the Nervous System<\/a>.<\/p>\n<p>This example continues Mustafa\u2019s story that started in Anatomy of the Nervous System.\u2019s new prescription for two antifungal drugs, amphotericin B and flucytosine, proved effective, and his condition began to improve. Culture results from Mustafa\u2019s sputum, skin, and CSF samples confirmed a fungal infection. All were positive for <em>C. neoformans<\/em>. Serological tests of his tissues were also positive for the <em>C. neoformans<\/em> capsular polysaccharide antigen.<\/p>\n<p>Since <em>C. neoformans<\/em> is known to occur in bird droppings, it is likely that Mustafa had been exposed to the fungus while working on the barn. Despite this exposure, Mustafa\u2019s doctor explained to him that immunocompetent people rarely contract cryptococcal meningitis and that his immune system had likely been compromised by the anti-inflammatory medication he was taking to treat his Crohn\u2019s disease. However, to rule out other possible causes of immunodeficiency, Mustafa\u2019s doctor recommended that he be tested for HIV.<\/p>\n<p>After Mustafa tested negative for HIV, his doctor took him off the corticosteroid he was using to manage his Crohn\u2019s disease, replacing it with a different class of drug. After several weeks of antifungal treatments, Mustafa managed a full recovery.<\/p>\n<\/div>\n<h2>Amoebic Meningitis<\/h2>\n<div style=\"width: 460px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" class=\"\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03180013\/OSC_Microbio_26_04_Naegleria.jpg\" alt=\"Micrograph of white blood cells and a large cell with a small circle in the center labeled N. fowlerii.\" width=\"450\" height=\"228\" data-media-type=\"image\/jpeg\" \/><\/p>\n<p class=\"wp-caption-text\">Figure\u00a02. Free-living amoeba in human brain tissue from a patient suffering from PAM. (credit: modification of work by the Centers for Disease Control and Prevention)<\/p>\n<\/div>\n<p><strong>Primary amoebic meningoencephalitis (PAM)<\/strong> is caused by <strong><em>Naegleria fowleri<\/em><\/strong>. This amoeboflagellate is commonly found free-living in soils and water. It can exist in one of three forms\u2014the infective amoebic trophozoite form, a motile flagellate form, and a resting cyst form. PAM is a rare disease that has been associated with young and otherwise healthy individuals. Individuals are typically infected by the <strong>amoeba<\/strong> while swimming in warm bodies of freshwater such as rivers, lakes, and hot springs. The pathogenic trophozoite infects the brain by initially entering through nasal passages to the sinuses; it then moves down olfactory nerve fibers to penetrate the submucosal nervous plexus, invades the cribriform plate, and reaches the subarachnoid space. The subarachnoid space is highly vascularized and is a route of dissemination of trophozoites to other areas of the CNS, including the brain (Figure\u00a02). Inflammation and destruction of gray matter leads to severe headaches and fever. Within days, confusion and convulsions occur and quickly progress to seizures, coma, and death. The progression can be very rapid, and the disease is often not diagnosed until autopsy.<\/p>\n<p><em>N. fowleri<\/em> infections can be confirmed by direct observation of CSF; the amoebae can often be seen moving while viewing a fresh <strong>CSF<\/strong> wet mount through a microscope. Flagellated forms can occasionally also be found in CSF. The amoebae can be stained with several stains for identification, including Giemsa-Wright or a modified trichrome stain. Detection of antigens with indirect immunofluorescence, or genetic analysis with PCR, can be used to confirm an initial diagnosis. <em>N. fowleri<\/em> infections are nearly always fatal; only 3 of 138 patients with PAM in the United States have survived.<a class=\"footnote\" title=\"US Centers for Disease Control and Prevention, &quot;Naegleria fowleri\u2014Primary Amoebic Meningoencephalitis (PAM)\u2014Amebic Encephalitis,&quot; 2016. Accessed June 30, 2016. http:\/\/www.cdc.gov\/parasites\/naegleria\/treatment.html.\" id=\"return-footnote-1141-1\" href=\"#footnote-1141-1\" aria-label=\"Footnote 1\"><sup class=\"footnote\">[1]<\/sup><\/a> A new experimental drug called <strong>miltefosine<\/strong> shows some promise for treating these infections. This drug is a phosphotidylcholine derivative that is thought to inhibit membrane function in <em>N. fowleri<\/em>, triggering apoptosis and disturbance of lipid-dependent cell signaling pathways.<a class=\"footnote\" title=\"Dorlo, Thomas PC, Manica Balasegaram, Jos H. Beijnen, and Peter J. de Vries, &quot;Miltefosine: A Review of Its Pharmacology and Therapeutic Efficacy in the Treatment of Leishmaniasis,&quot; Journal of Antimicrobial Chemotherapy 67, no. 11 (2012): 2576-97.\" id=\"return-footnote-1141-2\" href=\"#footnote-1141-2\" aria-label=\"Footnote 2\"><sup class=\"footnote\">[2]<\/sup><\/a> When administered early in infection and coupled with therapeutic hypothermia (lowering the body\u2019s core temperature to reduce the cerebral edema associated with infection), this drug has been successfully used to treat primary amoebic encephalitis.<\/p>\n<h2>Granulomatous Amoebic Encephalitis<\/h2>\n<p><strong><em>Acanthamoeba<\/em><\/strong> and <strong><em>Balamuthia<\/em><\/strong> species are free-living amoebae found in many bodies of fresh water. Human infections by these amoebae are rare. However, they can cause <strong>amoebic keratitis<\/strong> in contact lens wearers (see <a href=\".\/chapter\/protozoan-and-helminthic-infections-of-the-skin-and-eyes\/\" target=\"_blank\">Protozoan and Helminthic Infections of the Eyes<\/a>), disseminated infections in immunocompromised patients, and <strong>granulomatous amoebic encephalitis (GAE)<\/strong> in severe cases. Compared to PAM, GAE tend to be subacute infections. The microbe is thought to enter through either the nasal sinuses or breaks in the skin. It is disseminated hematogenously and can invade the CNS. There, the infections lead to inflammation, formation of lesions, and development of typical neurological symptoms of encephalitis (Figure\u00a03). GAE is nearly always fatal.<\/p>\n<p>GAE is often not diagnosed until late in the infection. Lesions caused by the infection can be detected using CT or MRI. The live amoebae can be directly detected in CSF or tissue biopsies. Serological tests are available but generally are not necessary to make a correct diagnosis, since the presence of the organism in <strong>CSF<\/strong> is definitive. Some antifungal drugs, like <strong>fluconazole<\/strong>, have been used to treat acanthamoebal infections. In addition, a combination of <strong>miltefosine<\/strong> and <strong>voriconazole<\/strong> (an inhibitor of ergosterol biosynthesis) has recently been used to successfully treat GAE. Even with treatment, however, the mortality rate for patients with these infections is high.<\/p>\n<div style=\"width: 910px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03180016\/OSC_Microbio_26_04_AmoeEnceph.jpg\" alt=\"a) Photo of brain section with red granules in the center. b) close-up of granules.\" width=\"900\" height=\"465\" data-media-type=\"image\/jpeg\" \/><\/p>\n<p class=\"wp-caption-text\">Figure\u00a03. (a) Brain tissue from a patient who died of granulomatous amebic encephalitis (GAE) caused by Balamuthia mandrillaris. (b) A close-up of the necrosis in the center of the brain section. (credit a, b: modifications of work by the Centers for Disease Control and Prevention)<\/p>\n<\/div>\n<div class=\"textbox key-takeaways\">\n<h3>Think about It<\/h3>\n<ul>\n<li>How is granulomatous amoebic encephalitis diagnosed?<\/li>\n<\/ul>\n<\/div>\n<h2>Human African Trypanosomiasis<\/h2>\n<p><strong>Human African trypanosomiasis<\/strong> (also known as <strong>African sleeping sickness<\/strong>) is a serious disease endemic to two distinct regions in sub-Saharan Africa. It is caused by the insect-borne hemoflagellate <strong><em>Trypanosoma brucei<\/em><\/strong>. The subspecies <em>Trypanosoma brucei rhodesiense<\/em> causes <strong>East African trypanosomiasis<\/strong> (EAT), and another subspecies, <em>Trypanosoma brucei gambiense<\/em> causes <strong>West African trypanosomiasis<\/strong> (WAT). A few hundred cases of EAT are currently reported each year.<a class=\"footnote\" title=\"US Centers for Disease Control and Prevention, &quot;Parasites \u2013 African Trypanosomiasis (also known as Sleeping Sickness), East African Trypanosomiasis FAQs,&quot; 2012. Accessed June 30, 2016. http:\/\/www.cdc.gov\/parasites\/sleepingsickness\/gen_info\/faqs-east.html.\" id=\"return-footnote-1141-3\" href=\"#footnote-1141-3\" aria-label=\"Footnote 3\"><sup class=\"footnote\">[3]<\/sup><\/a> WAT is more commonly reported and tends to be a more chronic disease. Around 7000 to 10,000 new cases of WAT are identified each year.<a class=\"footnote\" title=\"US Centers for Disease Control and Prevention, &quot;Parasites \u2013 African Trypanosomiasis (also known as Sleeping Sickness), Epidemiology &amp; Risk Factors,&quot; 2012. Accessed June 30, 2016. http:\/\/www.cdc.gov\/parasites\/sleepingsickness\/epi.html.\" id=\"return-footnote-1141-4\" href=\"#footnote-1141-4\" aria-label=\"Footnote 4\"><sup class=\"footnote\">[4]<\/sup><\/a><\/p>\n<div style=\"width: 409px\" class=\"wp-caption alignright\"><img loading=\"lazy\" decoding=\"async\" class=\"\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03180022\/OSC_Microbio_26_04_Trypanosom.jpg\" alt=\"Micrograph of red circles labeled red blood cells and worm-shaped cells labeled Trypanosoma brucei.\" width=\"399\" height=\"268\" data-media-type=\"image\/jpeg\" \/><\/p>\n<p class=\"wp-caption-text\">Figure\u00a04. Trypanosoma brucei, the causative agent of African sleeping sickness, in a human blood smear. (credit: modification of work by the Centers for Disease Control and Prevention)<\/p>\n<\/div>\n<p><em>T. brucei<\/em> is primarily transmitted to humans by the bite of the <strong>tsetse fly<\/strong> (<em>Glossina<\/em> spp.). Soon after the bite of a tsetse fly, a chancre forms at the site of infection. The flagellates then spread, moving into the circulatory system (Figure\u00a04). These systemic infections result in an <strong>undulating fever<\/strong>, during which symptoms persist for two or three days with remissions of about a week between bouts. As the disease enters its final phase, the pathogens move from the lymphatics into the CNS. Neurological symptoms include daytime sleepiness, insomnia, and mental deterioration. In EAT, the disease runs its course over a span of weeks to months. In contrast, WAT often occurs over a span of months to years.<\/p>\n<p>Although a strong immune response is mounted against the trypanosome, it is not sufficient to eliminate the pathogen. Through <strong>antigenic variation<\/strong>, <em>Trypanosoma<\/em> can change their surface proteins into over 100 serological types. This variation leads to the undulating form of the initial disease. The initial septicemia caused by the infection leads to high fevers. As the immune system responds to the infection, the number of organisms decrease, and the clinical symptoms abate. However, a subpopulation of the pathogen then alters its surface coat antigens by antigenic variation and evades the immune response. These flagellates rapidly proliferate and cause another bout of disease. If untreated, these infections are usually fatal.<\/p>\n<p>Clinical symptoms can be used to recognize the early signs of African trypanosomiasis. These include the formation of a chancre at the site of infection and <strong>Winterbottom\u2019s sign<\/strong>. Winterbottom\u2019s sign refers to the enlargement of lymph nodes on the back of the neck\u2014often indicative of cerebral infections. <em>Trypanosoma<\/em> can be directly observed in stained samples including blood, lymph, CSF, and skin biopsies of chancres from patients. Antibodies against the parasite are found in most patients with acute or chronic disease. Serologic testing is generally not used for diagnosis, however, since the microscopic detection of the parasite is sufficient. Early diagnosis is important for treatment. Before the nervous system is involved, drugs like <strong>pentamidine<\/strong> (an inhibitor of nuclear metabolism) and <strong>suramin<\/strong> (mechanism unclear) can be used. These drugs have fewer side effects than the drugs needed to treat the second stage of the disease. Once the sleeping sickness phase has begun, harsher drugs including <strong>melarsoprol<\/strong> (an arsenic derivative) and <strong>eflornithine<\/strong> can be effective. Following successful treatment, patients still need to have follow-up examinations of their CSF for two years to detect possible relapses of the disease. The most effective means of preventing these diseases is to control the insect vector populations.<\/p>\n<div class=\"textbox key-takeaways\">\n<h3>Think about It<\/h3>\n<ul>\n<li>What is the symptom of a systemic <em>Trypanosoma<\/em> infection?<\/li>\n<li>What are the symptoms of a neurological <em>Trypanosoma<\/em> infection<em>?<\/em><\/li>\n<li>Why are trypanosome infections so difficult to eradicate?<\/li>\n<\/ul>\n<\/div>\n<h2>Neurotoxoplasmosis<\/h2>\n<p><strong><em>Toxoplasma gondii<\/em><\/strong> is an ubiquitous intracellular parasite that can cause neonatal infections. Cats are the definitive host, and humans can become infected after eating infected meat or, more commonly, by ingesting oocysts shed in the feces of cats (see <a href=\".\/chapter\/parasitic-infections-of-the-circulatory-and-lymphatic-systems\/\" target=\"_blank\">Parasitic Infections of the Circulatory and Lymphatic Systems<\/a>). <em>T. gondii<\/em> enters the circulatory system by passing between the endothelial cells of blood vessels.<a class=\"footnote\" title=\"Carruthers, Vern B., and Yasuhiro Suzuki, &quot;Effects of Toxoplasma gondii Infection on the Brain,&quot; Schizophrenia Bulletin 33, no. 3 (2007): 745-51.\" id=\"return-footnote-1141-5\" href=\"#footnote-1141-5\" aria-label=\"Footnote 5\"><sup class=\"footnote\">[5]<\/sup><\/a> Most cases of toxoplasmosis are asymptomatic. However, in immunocompromised patients, <strong>neurotoxoplasmosis<\/strong> caused by <em>T. gondii<\/em> infections are one of the most common causes of brain abscesses.<a class=\"footnote\" title=\"Uppal, Gulshan, &quot;CNS Toxoplasmosis in HIV,&quot; 2015. Accessed June 30, 2016. http:\/\/emedicine.medscape.com\/article\/1167298-overview#a3.\" id=\"return-footnote-1141-6\" href=\"#footnote-1141-6\" aria-label=\"Footnote 6\"><sup class=\"footnote\">[6]<\/sup><\/a> The organism is able to cross the <strong>blood-brain barrier<\/strong> by infecting the endothelial cells of capillaries in the brain. The parasite reproduces within these cells, a step that appears to be necessary for entry to the brain, and then causes the endothelial cell to lyse, releasing the progeny into brain tissues. This mechanism is quite different than the method it uses to enter the bloodstream in the first place.<a class=\"footnote\" title=\"Konradt, Christoph, Norikiyo Ueno, David A. Christian, Jonathan H. Delong, Gretchen Harms Pritchard, Jasmin Herz, David J. Bzik et al., &quot;Endothelial Cells Are a Replicative Niche for Entry of Toxoplasma gondii to the Central Nervous System,&quot; Nature Microbiology 1 (2016): 16001.\" id=\"return-footnote-1141-7\" href=\"#footnote-1141-7\" aria-label=\"Footnote 7\"><sup class=\"footnote\">[7]<\/sup><\/a><\/p>\n<p>The brain lesions associated with neurotoxoplasmosis can be detected radiographically using MRI or CAT scans (Figure\u00a05). Diagnosis can be confirmed by direct observation of the organism in CSF. RT-PCR assays can also be used to detect <em>T. gondii<\/em> through genetic markers.<\/p>\n<div style=\"width: 560px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" class=\"\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03180024\/OSC_Microbio_26_04_Neurotoxpl.jpg\" alt=\"Micrograph of sphere wit red dots.\" width=\"550\" height=\"369\" data-media-type=\"image\/jpeg\" \/><\/p>\n<p class=\"wp-caption-text\">Figure\u00a05. <em>This Toxoplasma<\/em> gondii cyst, observed in mouse brain tissue, contains thousands of inactive parasites. (credit: modification of work by USDA)<\/p>\n<\/div>\n<p>Treatment of neurotoxoplasmosis caused by <em>T. gondii<\/em> infections requires six weeks of multi-drug therapy with <strong>pyrimethamine<\/strong>, <strong>sulfadiazine<\/strong>, and <strong>folinic acid<\/strong>. Long-term maintenance doses are often required to prevent recurrence.<\/p>\n<div class=\"textbox key-takeaways\">\n<h3>Think about It<\/h3>\n<ul>\n<li>Under what conditions is <em>Toxoplasma<\/em> infection serious?<\/li>\n<li>How does <em>Toxoplasma<\/em> circumvent the blood-brain barrier<em>?<\/em><\/li>\n<\/ul>\n<\/div>\n<h2>Neurocysticercosis<\/h2>\n<p>Cysticercosis is a parasitic infection caused by the larval form of the <strong>pork tapeworm<\/strong>, <strong><em>Taenia solium<\/em><\/strong>. When the larvae invade the brain and spinal cord, the condition is referred to as <strong>neurocysticercosis<\/strong>. This condition affects millions of people worldwide and is the leading cause of adult onset <strong>epilepsy<\/strong> in the developing world.<a class=\"footnote\" title=\"DeGiorgio, Christopher M., Marco T. Medina, Reyna Dur\u00f3n, Chi Zee, and Susan Pietsch Escueta, &quot;Neurocysticercosis,&quot; Epilepsy Currents 4, no. 3 (2004): 107-11.\" id=\"return-footnote-1141-8\" href=\"#footnote-1141-8\" aria-label=\"Footnote 8\"><sup class=\"footnote\">[8]<\/sup><\/a><\/p>\n<p>The life cycle of <em>T. solium<\/em> is discussed in <a href=\".\/chapter\/helminthic-infections-of-the-gastrointestinal-tract\/\" target=\"_blank\">Helminthic Infections of the Gastrointestinal Tract<\/a>. Following ingestion, the eggs hatch in the intestine to form larvae called <strong>cysticerci<\/strong>. Adult tapeworms form in the small intestine and produce eggs that are shed in the feces. These eggs can infect other individuals through fecal contamination of food or other surfaces. Eggs can also hatch within the intestine of the original patient and lead to an ongoing autoinfection. The cystercerci, can migrate to the blood and invade many tissues in the body, including the CNS.<\/p>\n<p>Neurocysticercosis is usually diagnosed through noninvasive techniques. Epidemiological information can be used as an initial screen; cysticercosis is endemic in Central and South America, Africa, and Asia. Radiological imaging (MRI and CT scans) is the primary method used to diagnose neurocysticercosis; imaging can be used to detect the one- to two-centimeter cysts that form around the parasites (Figure\u00a06). Elevated levels of eosinophils in the blood can also indicate a parasitic infection. EIA and ELISA are also used to detect antigens associated with the pathogen.<\/p>\n<div style=\"width: 710px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03180027\/OSC_Microbio_26_04_Neurocyst.jpg\" alt=\"Brain scans with small lumps (look like pimples) indicated by arrows.\" width=\"700\" height=\"323\" data-media-type=\"image\/jpeg\" \/><\/p>\n<p class=\"wp-caption-text\">Figure\u00a06. Brain CT scans of sagittal (left) and axial (right) sections of a brain with neurocysticercosis. Numerous cysts are visible in both images, as indicated by the arrows. (credit: modification of work by Segamwenge IL, Kioko NP)<\/p>\n<\/div>\n<p>The treatment for neurocysticercosis depends on the location, number, size, and stage of cysticerci present. Antihelminthic chemotherapy includes <strong>albendazole<\/strong> and <strong>praziquantel<\/strong>. Because these drugs kill viable cysts, they may acutely increase symptoms by provoking an inflammatory response caused by the release of <em>Taenia<\/em> cysticerci antigens, as the cysts are destroyed by the drugs. To alleviate this response, corticosteroids that cross the <strong>blood-brain barrier<\/strong> (e.g., <strong>dexamethasone<\/strong>) can be used to mitigate these effects. Surgical intervention may be required to remove intraventricular cysts.<\/p>\n<div class=\"textbox shaded\">\n<h3>Parasitic Diseases of the Nervous System<\/h3>\n<p>Parasites that successfully invade the nervous system can cause a wide range of neurological signs and symptoms. Often, they inflict lesions that can be visualized through radiologic imaging. A number of these infections are fatal, but some can be treated (with varying levels of success) by antimicrobial drugs (Table 2).<\/p>\n<table>\n<thead>\n<tr>\n<th colspan=\"6\">Table 2.\u00a0Parasitic Diseases of the Nervous System<\/th>\n<\/tr>\n<tr>\n<th>Disease<\/th>\n<th>Pathogen<\/th>\n<th>Signs and Symptoms<\/th>\n<th>Transmission<\/th>\n<th>Diagnostic Tests<\/th>\n<th>Antimicrobial Drugs<\/th>\n<\/tr>\n<\/thead>\n<tbody>\n<tr>\n<td>Granulomatous amoebic encephalitis (GAE)<\/td>\n<td><em>Acanthamoeba<\/em>\u00a0spp., <em>Balamuthia mandrillaris<\/em><\/td>\n<td>Inflammation, lesions in CNS, almost always fatal<\/td>\n<td>Freshwater ameobae invade CNS via breaks in skin or sinuses<\/td>\n<td>CT scan, MRI, CSF<\/td>\n<td>Fluconazole, miltefosine, voriconazole<\/td>\n<\/tr>\n<tr>\n<td>Human African trypanosomiasis<\/td>\n<td><em>Trypanosoma brucei gambiense<\/em>, <em>T.\u00a0brucei rhodesiense<\/em><\/td>\n<td>Chancre, Winterbottom\u2019s sign, undulating fever, lethargy, insomnia, usually fatal if untreated<\/td>\n<td>Protozoan transmitted via bite of tsetse fly<\/td>\n<td>Blood smear<\/td>\n<td>Pentamidine and suramine (initial phase); melarsoprol and eflornithine (final phase)<\/td>\n<\/tr>\n<tr>\n<td>Neurocysticercosis<\/td>\n<td><em>Taenia solium<\/em><\/td>\n<td>Brain cysts, epilepsy<\/td>\n<td>Ingestion of tapeworm eggs in fecally contaminated food or surfaces<\/td>\n<td>CT scan, MRI<\/td>\n<td>Albendazole, praziquantel, dexamethasone<\/td>\n<\/tr>\n<tr>\n<td>Neurotoxoplasmosis<\/td>\n<td><em>Toxoplasma gondii<\/em><\/td>\n<td>Brain abscesses, chronic encephalitis<\/td>\n<td>Protozoan transmitted via contact with oocytes in cat feces<\/td>\n<td>CT scan, MRI, CSF<\/td>\n<td>Pyrimethamine, sulfadiazine, folinic acid<\/td>\n<\/tr>\n<tr>\n<td>Primary amoebic meningoencephalitis (PAM)<\/td>\n<td><em>Naegleria fowleri<\/em><\/td>\n<td>Headache, seizures, coma, almost always fatal<\/td>\n<td>Freshwater ameobae invade brain via nasal passages<\/td>\n<td>CSF, IFA, PCR<\/td>\n<td>Miltefosine (experimental)<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n<\/div>\n<div class=\"textbox key-takeaways\">\n<h3>Think about It<\/h3>\n<ul>\n<li>What neurological condition is associated with neurocysticercosis?<\/li>\n<li>How is neurocysticercosis diagnosed?<\/li>\n<\/ul>\n<\/div>\n<div class=\"textbox key-takeaways\">\n<h3>Key Concepts and Summary<\/h3>\n<ul>\n<li><strong>Neuromycoses<\/strong> are uncommon in immunocompetent people, but immunocompromised individuals with fungal infections have high mortality rates. Treatment of neuromycoses require prolonged therapy with antifungal drugs at low doses to avoid side effects and overcome the effect of the blood-brain barrier.<\/li>\n<li>Some protist infections of the nervous systems are fatal if not treated, including <strong>primary amoebic meningitis<\/strong>, <strong>granulomatous amoebic encephalitis<\/strong>, <strong>human African trypanosomiasis<\/strong>, and <strong>neurotoxoplasmosis<\/strong>.<\/li>\n<li>The various forms of ameobic encephalitis caused by the different amoebic infections are typically fatal even with treatment, but they are rare.<\/li>\n<li><strong>African trypanosomiasis<\/strong> is a serious but treatable disease endemic to two distinct regions in sub-Saharan Africa caused by the insect-borne hemoflagellate <em>Trypanosoma brucei<\/em>.<\/li>\n<li><strong>Neurocysticercosis<\/strong> is treated using antihelminthic drugs or surgery to remove the large cysts from the CNS.<\/li>\n<\/ul>\n<\/div>\n<div class=\"textbox exercises\">\n<h3>Multiple Choice<\/h3>\n<p>Which of these diseases results in meningitis caused by an encapsulated yeast?<\/p>\n<ol style=\"list-style-type: lower-alpha;\">\n<li>cryptococcosis<\/li>\n<li>histoplasmosis<\/li>\n<li>candidiasis<\/li>\n<li>coccidiomycosis<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q510178\">Show Answer<\/span><\/p>\n<div id=\"q510178\" class=\"hidden-answer\" style=\"display: none\">Answer a. Cryptococcosis\u00a0results in meningitis caused by an encapsulated yeast.<\/div>\n<\/div>\n<p>What kind of stain is most commonly used to visualize the capsule of cryptococcus?<\/p>\n<ol style=\"list-style-type: lower-alpha;\">\n<li>Gram stain<\/li>\n<li>simple stain<\/li>\n<li>negative stain<\/li>\n<li>fluorescent stain<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q451516\">Show Answer<\/span><\/p>\n<div id=\"q451516\" class=\"hidden-answer\" style=\"display: none\">Answer c. A\u00a0negative stain\u00a0is most commonly used to visualize the capsule of cryptococcus.<\/div>\n<\/div>\n<p>Which of the following is the causative agent of East African trypanosomiasis?<\/p>\n<ol style=\"list-style-type: lower-alpha;\">\n<li><em>Trypanosoma cruzi<\/em><\/li>\n<li><em>Trypanosoma vivax<\/em><\/li>\n<li><em>Trypanosoma brucei rhodanese<\/em><\/li>\n<li><em>Trypanosoma brucei gambiense<\/em><\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q560815\">Show Answer<\/span><\/p>\n<div id=\"q560815\" class=\"hidden-answer\" style=\"display: none\">Answer c.\u00a0<em>Trypanosoma brucei rhodanese<\/em>\u00a0is the causative agent of East African trypanosomiasis.<\/div>\n<\/div>\n<p>Which of the following is the causative agent of primary amoebic meningoencephalitis?<\/p>\n<ol style=\"list-style-type: lower-alpha;\">\n<li><em>Naegleria fowleri<\/em><\/li>\n<li><em>Entameba histolyticum<\/em><\/li>\n<li><em>Amoeba proteus<\/em><\/li>\n<li><em>Acanthamoeba polyphaga<\/em><\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q718879\">Show Answer<\/span><\/p>\n<div id=\"q718879\" class=\"hidden-answer\" style=\"display: none\">Answer a.\u00a0<em>Naegleria fowleri<\/em>\u00a0is the causative agent of primary amoebic meningoencephalitis.<\/div>\n<\/div>\n<p>What is the biological vector for African sleeping sickness?<\/p>\n<ol style=\"list-style-type: lower-alpha;\">\n<li>mosquito<\/li>\n<li>tsetse fly<\/li>\n<li>deer tick<\/li>\n<li>sand fly<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q740482\">Show Answer<\/span><\/p>\n<div id=\"q740482\" class=\"hidden-answer\" style=\"display: none\">Answer b. The\u00a0tsetse fly\u00a0is the biological vector for African sleeping sickness.<\/div>\n<\/div>\n<p>How do humans usually contract neurocysticercosis?<\/p>\n<ol style=\"list-style-type: lower-alpha;\">\n<li>the bite of an infected arthropod<\/li>\n<li>exposure to contaminated cat feces<\/li>\n<li>swimming in contaminated water<\/li>\n<li>ingestion of undercooked pork<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q525465\">Show Answer<\/span><\/p>\n<div id=\"q525465\" class=\"hidden-answer\" style=\"display: none\">Answer d. Humans usually contract neurocysticercosis by\u00a0ingesting undercooked pork.<\/div>\n<\/div>\n<p>Which of these is the most important cause of adult onset epilepsy?<\/p>\n<ol style=\"list-style-type: lower-alpha;\">\n<li>neurocysticercosis<\/li>\n<li>neurotoxoplasmosis<\/li>\n<li>primary amoebic meningoencephalitis<\/li>\n<li>African trypanosomiasis<\/li>\n<\/ol>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q349477\">Show Answer<\/span><\/p>\n<div id=\"q349477\" class=\"hidden-answer\" style=\"display: none\">Answer a. Neurocysticercosis\u00a0is the most important cause of adult onset epilepsy.<\/div>\n<\/div>\n<\/div>\n<div class=\"textbox exercises\">\n<h3>Fill in the Blank<\/h3>\n<p>The __________ is the main virulence factor of <em>Cryptococcus neoformans<\/em>.<\/p>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q11050\">Show Answer<\/span><\/p>\n<div id=\"q11050\" class=\"hidden-answer\" style=\"display: none\">The <strong>capsule<\/strong> is the main virulence factor of <em>Cryptococcus neoformans<\/em>.<\/div>\n<\/div>\n<p>The drug of choice for fungal infections of the nervous system is __________.<\/p>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q356241\">Show Answer<\/span><\/p>\n<div id=\"q356241\" class=\"hidden-answer\" style=\"display: none\">The drug of choice for fungal infections of the nervous system is <strong>Amphotericin B<\/strong>.<\/div>\n<\/div>\n<p>The larval forms of a tapeworm are known as __________.<\/p>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q478329\">Show Answer<\/span><\/p>\n<div id=\"q478329\" class=\"hidden-answer\" style=\"display: none\">The larval forms of a tapeworm are known as <strong>cysticerci<\/strong>.<\/div>\n<\/div>\n<p>__________ sign appears as swollen lymph nodes at the back of the neck in early African trypanosomiasis.<\/p>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q288854\">Show Answer<\/span><\/p>\n<div id=\"q288854\" class=\"hidden-answer\" style=\"display: none\"><strong>Winterbottom\u2019s<\/strong> sign appears as swollen lymph nodes at the back of the neck in early African trypanosomiasis.<\/div>\n<\/div>\n<p>__________ African trypanosomiasis causes a chronic form of sleeping sickness.<\/p>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q528329\">Show Answer<\/span><\/p>\n<div id=\"q528329\" class=\"hidden-answer\" style=\"display: none\"><strong>West<\/strong> African trypanosomiasis causes a chronic form of sleeping sickness.<\/div>\n<\/div>\n<p>The definitive host for <em>Toxoplasma gondii<\/em> is __________.<\/p>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q221088\">Show Answer<\/span><\/p>\n<div id=\"q221088\" class=\"hidden-answer\" style=\"display: none\">The definitive host for <em>Toxoplasma gondii<\/em> is <strong>cats<\/strong>.<\/div>\n<\/div>\n<p>Trypanosomes can evade the immune response through __________ variation.<\/p>\n<div class=\"qa-wrapper\" style=\"display: block\"><span class=\"show-answer collapsed\" style=\"cursor: pointer\" data-target=\"q417069\">Show Answer<\/span><\/p>\n<div id=\"q417069\" class=\"hidden-answer\" style=\"display: none\">Trypanosomes can evade the immune response through <strong>antigenic<\/strong> variation.<\/div>\n<\/div>\n<\/div>\n<div class=\"textbox key-takeaways\">\n<h3>Think about It<\/h3>\n<ol>\n<li>Why do nervous system infections by fungi require such long treatment times?<\/li>\n<li>Briefly describe how humans are infected by <em>Naegleria fowleri<\/em>.<\/li>\n<li>Briefly describe how humans can develop neurocysticercosis.<\/li>\n<li>Fungal meningoencephalitis is often the ultimate cause of death for AIDS patients. What factors make these infections more problematic than those of bacterial origin?<\/li>\n<li>Compare East African trypanosomiasis with West African trypanosomiasis.<\/li>\n<li>The graph shown tracks the body temperature of a patient infected with <em>Trypanosoma brucei<\/em>. How would you describe this pattern, and why does it occur?<\/li>\n<\/ol>\n<div style=\"width: 880px\" class=\"wp-caption aligncenter\"><img loading=\"lazy\" decoding=\"async\" src=\"https:\/\/s3-us-west-2.amazonaws.com\/courses-images\/wp-content\/uploads\/sites\/1094\/2016\/11\/03180035\/OSC_Microbio_26_04_ArtConnect_img.jpg\" alt=\"Graph with Days on the X axis and Temperature on the Y axis. There is a peak to 40 degrees C early on then a drop back to normal temperatures (37 degree C) for 7 days. Then another peak, then another drop to normal for 9 days, then another peak and then another drop to normal for 9 days.\" width=\"870\" height=\"482\" data-media-type=\"image\/jpeg\" \/><\/p>\n<p class=\"wp-caption-text\">(credit: modification of work by Wellcome Images)<\/p>\n<\/div>\n<\/div>\n\n\t\t\t <section class=\"citations-section\" role=\"contentinfo\">\n\t\t\t <h3>Candela Citations<\/h3>\n\t\t\t\t\t <div>\n\t\t\t\t\t\t <div id=\"citation-list-1141\">\n\t\t\t\t\t\t\t <div class=\"licensing\"><div class=\"license-attribution-dropdown-subheading\">CC licensed content, Shared previously<\/div><ul class=\"citation-list\"><li>OpenStax Microbiology. <strong>Provided by<\/strong>: OpenStax CNX. <strong>Located at<\/strong>: <a target=\"_blank\" href=\"http:\/\/cnx.org\/contents\/e42bd376-624b-4c0f-972f-e0c57998e765@4.2\">http:\/\/cnx.org\/contents\/e42bd376-624b-4c0f-972f-e0c57998e765@4.2<\/a>. <strong>License<\/strong>: <em><a target=\"_blank\" rel=\"license\" href=\"https:\/\/creativecommons.org\/licenses\/by\/4.0\/\">CC BY: Attribution<\/a><\/em>. <strong>License Terms<\/strong>: Download for free at http:\/\/cnx.org\/contents\/e42bd376-624b-4c0f-972f-e0c57998e765@4.2<\/li><\/ul><\/div>\n\t\t\t\t\t\t <\/div>\n\t\t\t\t\t <\/div>\n\t\t\t <\/section><hr class=\"before-footnotes clear\" \/><div class=\"footnotes\"><ol><li id=\"footnote-1141-1\">US Centers for Disease Control and Prevention, \"<em>Naegleria fowleri<\/em>\u2014Primary Amoebic Meningoencephalitis (PAM)\u2014Amebic Encephalitis,\" 2016. Accessed June 30, 2016. http:\/\/www.cdc.gov\/parasites\/naegleria\/treatment.html. <a href=\"#return-footnote-1141-1\" class=\"return-footnote\" aria-label=\"Return to footnote 1\">&crarr;<\/a><\/li><li id=\"footnote-1141-2\">Dorlo, Thomas PC, Manica Balasegaram, Jos H. Beijnen, and Peter J. de Vries, \"Miltefosine: A Review of Its Pharmacology and Therapeutic Efficacy in the Treatment of Leishmaniasis,\" <em>Journal of Antimicrobial Chemotherapy<\/em> 67, no. 11 (2012): 2576-97. <a href=\"#return-footnote-1141-2\" class=\"return-footnote\" aria-label=\"Return to footnote 2\">&crarr;<\/a><\/li><li id=\"footnote-1141-3\">US Centers for Disease Control and Prevention, \"Parasites \u2013 African Trypanosomiasis (also known as Sleeping Sickness), East African Trypanosomiasis FAQs,\" 2012. Accessed June 30, 2016. http:\/\/www.cdc.gov\/parasites\/sleepingsickness\/gen_info\/faqs-east.html. <a href=\"#return-footnote-1141-3\" class=\"return-footnote\" aria-label=\"Return to footnote 3\">&crarr;<\/a><\/li><li id=\"footnote-1141-4\">US Centers for Disease Control and Prevention, \"Parasites \u2013 African Trypanosomiasis (also known as Sleeping Sickness), Epidemiology &amp; Risk Factors,\" 2012. Accessed June 30, 2016. http:\/\/www.cdc.gov\/parasites\/sleepingsickness\/epi.html. <a href=\"#return-footnote-1141-4\" class=\"return-footnote\" aria-label=\"Return to footnote 4\">&crarr;<\/a><\/li><li id=\"footnote-1141-5\">Carruthers, Vern B., and Yasuhiro Suzuki, \"Effects of <em>Toxoplasma gondii<\/em> Infection on the Brain,\" <em>Schizophrenia Bulletin<\/em> 33, no. 3 (2007): 745-51. <a href=\"#return-footnote-1141-5\" class=\"return-footnote\" aria-label=\"Return to footnote 5\">&crarr;<\/a><\/li><li id=\"footnote-1141-6\">Uppal, Gulshan, \"CNS Toxoplasmosis in HIV,\" 2015. Accessed June 30, 2016. http:\/\/emedicine.medscape.com\/article\/1167298-overview#a3. <a href=\"#return-footnote-1141-6\" class=\"return-footnote\" aria-label=\"Return to footnote 6\">&crarr;<\/a><\/li><li id=\"footnote-1141-7\">Konradt, Christoph, Norikiyo Ueno, David A. Christian, Jonathan H. Delong, Gretchen Harms Pritchard, Jasmin Herz, David J. Bzik et al., \"Endothelial Cells Are a Replicative Niche for Entry of <em>Toxoplasma gondii<\/em> to the Central Nervous System,\" <em>Nature Microbiology<\/em> 1 (2016): 16001. <a href=\"#return-footnote-1141-7\" class=\"return-footnote\" aria-label=\"Return to footnote 7\">&crarr;<\/a><\/li><li id=\"footnote-1141-8\">DeGiorgio, Christopher M., Marco T. Medina, Reyna Dur\u00f3n, Chi Zee, and Susan Pietsch Escueta, \"Neurocysticercosis,\" <em>Epilepsy Currents<\/em> 4, no. 3 (2004): 107-11. <a href=\"#return-footnote-1141-8\" class=\"return-footnote\" aria-label=\"Return to footnote 8\">&crarr;<\/a><\/li><\/ol><\/div>","protected":false},"author":17,"menu_order":5,"template":"","meta":{"_candela_citation":"[{\"type\":\"cc\",\"description\":\"OpenStax Microbiology\",\"author\":\"\",\"organization\":\"OpenStax CNX\",\"url\":\"http:\/\/cnx.org\/contents\/e42bd376-624b-4c0f-972f-e0c57998e765@4.2\",\"project\":\"\",\"license\":\"cc-by\",\"license_terms\":\"Download for free at http:\/\/cnx.org\/contents\/e42bd376-624b-4c0f-972f-e0c57998e765@4.2\"}]","CANDELA_OUTCOMES_GUID":"","pb_show_title":"on","pb_short_title":"","pb_subtitle":"","pb_authors":[],"pb_section_license":""},"chapter-type":[],"contributor":[],"license":[],"class_list":["post-1141","chapter","type-chapter","status-publish","hentry"],"part":1102,"_links":{"self":[{"href":"https:\/\/courses.lumenlearning.com\/suny-microbiology\/wp-json\/pressbooks\/v2\/chapters\/1141","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/courses.lumenlearning.com\/suny-microbiology\/wp-json\/pressbooks\/v2\/chapters"}],"about":[{"href":"https:\/\/courses.lumenlearning.com\/suny-microbiology\/wp-json\/wp\/v2\/types\/chapter"}],"author":[{"embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-microbiology\/wp-json\/wp\/v2\/users\/17"}],"version-history":[{"count":4,"href":"https:\/\/courses.lumenlearning.com\/suny-microbiology\/wp-json\/pressbooks\/v2\/chapters\/1141\/revisions"}],"predecessor-version":[{"id":2002,"href":"https:\/\/courses.lumenlearning.com\/suny-microbiology\/wp-json\/pressbooks\/v2\/chapters\/1141\/revisions\/2002"}],"part":[{"href":"https:\/\/courses.lumenlearning.com\/suny-microbiology\/wp-json\/pressbooks\/v2\/parts\/1102"}],"metadata":[{"href":"https:\/\/courses.lumenlearning.com\/suny-microbiology\/wp-json\/pressbooks\/v2\/chapters\/1141\/metadata\/"}],"wp:attachment":[{"href":"https:\/\/courses.lumenlearning.com\/suny-microbiology\/wp-json\/wp\/v2\/media?parent=1141"}],"wp:term":[{"taxonomy":"chapter-type","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-microbiology\/wp-json\/pressbooks\/v2\/chapter-type?post=1141"},{"taxonomy":"contributor","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-microbiology\/wp-json\/wp\/v2\/contributor?post=1141"},{"taxonomy":"license","embeddable":true,"href":"https:\/\/courses.lumenlearning.com\/suny-microbiology\/wp-json\/wp\/v2\/license?post=1141"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}