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26.4: Neuromycoses and Parasitic Diseases of the Nervous System - Biology

26.4: Neuromycoses and Parasitic Diseases of the Nervous System - Biology


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Learning Objectives

  • Identify the most common fungi that can cause infections of the nervous system
  • Compare the major characteristics of specific fungal diseases affecting the nervous system

Fungal infections of the nervous system, called neuromycoses, are rare in healthy individuals. 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.

Cryptococcocal Meningitis

Cryptococcus neoformans 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 virulence factor, inhibiting clearance by phagocytosis. Most C. neoformans cases result in subclinical respiratory infections that, in healthy individuals, generally resolve spontaneously with no long-term consequences (see Respiratory Mycoses). In immunocompromised patients or those with other underlying illnesses, the infection can progress to cause meningitisand granuloma formation in brain tissues. Cryptococcus antigens can also serve to inhibit cell-mediated immunity and delayed-type hypersensitivity.

Cryptococcus can be easily cultured in the laboratory and identified based on its extensive capsule (Figure (PageIndex{1})). C. neoformans is frequently cultured from urine samples of patients with disseminated infections.

Prolonged treatment with antifungal drugs is required to treat cryptococcal infections. Combined therapy is required with amphotericin B plus flucytosine for at least 10 weeks. Many antifungal drugs have difficulty crossing the blood-brain barrier 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 Cryptococcus infections because of their compromised immune state. AIDS 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.

Exercise (PageIndex{1})

  1. Why are neuromycoses infections rare in the general population?
  2. How is a cryptococcal infection acquired?

Neuromycoses

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. Figure (PageIndex{2}) presents 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.

Clinical Focus: Resolution

David’s new prescription for two antifungal drugs, amphotericin B and flucytosine, proved effective, and his condition began to improve. Culture results from David’s sputum, skin, and CSF samples confirmed a fungal infection. All were positive for C. neoformans. Serological tests of his tissues were also positive for the C. neoformans capsular polysaccharide antigen.

Since C. neoformans is known to occur in bird droppings, it is likely that David had been exposed to the fungus while working on the barn. Despite this exposure, David’s 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’s disease. However, to rule out other possible causes of immunodeficiency, David’s doctor recommended that he be tested for HIV.

After David tested negative for HIV, his doctor took him off the corticosteroid he was using to manage his Crohn’s disease, replacing it with a different class of drug. After several weeks of antifungal treatments, David managed a full recovery.

Amoebic Meningitis

Primary amoebic meningoencephalitis (PAM) is caused by Naegleria fowleri. This amoeboflagellate is commonly found free-living in soils and water. It can exist in one of three forms—the 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 amoeba 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 (PageIndex{3})). 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.

N. fowleri infections can be confirmed by direct observation of CSF; the amoebae can often be seen moving while viewing a fresh CSF 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. N. fowleri infections are nearly always fatal; only 3 of 138 patients with PAM in the United States have survived.1 A new experimental drug called miltefosine shows some promise for treating these infections. This drug is a phosphotidylcholine derivative that is thought to inhibit membrane function in N. fowleri, triggering apoptosis and disturbance of lipid-dependent cell signaling pathways.2 When administered early in infection and coupled with therapeutic hypothermia (lowering the body’s core temperature to reduce the cerebral edema associated with infection), this drug has been successfully used to treat primary amoebic encephalitis.

Granulomatous Amoebic Encephalitis

Acanthamoeba and Balamuthia species are free-living amoebae found in many bodies of fresh water. Human infections by these amoebae are rare. However, they can cause amoebic keratitis in contact lens wearers (see Protozoan and Helminthic Infections of the Eyes), disseminated infections in immunocompromised patients, and granulomatous amoebic encephalitis (GAE) 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 (PageIndex{4})). GAE is nearly always fatal.

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 CSF is definitive. Some antifungal drugs, like fluconazole, have been used to treat acanthamoebal infections. In addition, a combination of miltefosine and voriconazole (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.

Exercise (PageIndex{2})

How is granulomatous amoebic encephalitis diagnosed?

Human African Trypanosomiasis

Human African trypanosomiasis (also known as African sleeping sickness) is a serious disease endemic to two distinct regions in sub-Saharan Africa. It is caused by the insect-borne hemoflagellate Trypanosoma brucei. The subspecies Trypanosoma brucei rhodesiense causes East African trypanosomiasis (EAT), and another subspecies, Trypanosoma brucei gambiense causes West African trypanosomiasis (WAT). A few hundred cases of EAT are currently reported each year.3 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.4

T. brucei is primarily transmitted to humans by the bite of the tsetse fly (Glossina 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 (PageIndex{5})). These systemic infections result in an undulating fever, 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.

Although a strong immune response is mounted against the trypanosome, it is not sufficient to eliminate the pathogen. Through antigenic variation, Trypanosoma 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.

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 Winterbottom’s sign. Winterbottom’s sign refers to the enlargement of lymph nodes on the back of the neck—often indicative of cerebral infections. Trypanosoma 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 pentamidine (an inhibitor of nuclear metabolism) and suramin (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 melarsoprol (an arsenic derivative) and eflornithine 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.

Exercise (PageIndex{3})

  1. What is the symptom of a systemic Trypanosoma infection?
  2. What are the symptoms of a neurological Trypanosoma infection?
  3. Why are trypanosome infections so difficult to eradicate?

Neurotoxoplasmosis

Toxoplasma gondii 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 Parasitic Infections of the Circulatory and Lymphatic Systems). T. gondii enters the circulatory system by passing between the endothelial cells of blood vessels.5 Most cases of toxoplasmosis are asymptomatic. However, in immunocompromised patients, neurotoxoplasmosis caused by T. gondii infections are one of the most common causes of brain abscesses.6 The organism is able to cross the blood-brain barrier 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.7

The brain lesions associated with neurotoxoplasmosis can be detected radiographically using MRI or CAT scans (Figure (PageIndex{6})). Diagnosis can be confirmed by direct observation of the organism in CSF. RT-PCR assays can also be used to detect T. gondii through genetic markers.

Treatment of neurotoxoplasmosis caused by T. gondii infections requires six weeks of multi-drug therapy with pyrimethamine, sulfadiazine, and folinic acid. Long-term maintenance doses are often required to prevent recurrence.

Exercise (PageIndex{4})

  1. Under what conditions is Toxoplasma infection serious?
  2. How does Toxoplasma circumvent the blood-brain barrier?

Neurocysticercosis

Cysticercosis is a parasitic infection caused by the larval form of the pork tapeworm, Taenia solium. When the larvae invade the brain and spinal cord, the condition is referred to as neurocysticercosis. This condition affects millions of people worldwide and is the leading cause of adult onset epilepsy in the developing world.8

The life cycle of T. solium is discussed in Helminthic Infections of the Gastrointestinal Tract. Following ingestion, the eggs hatch in the intestine to form larvae called cysticerci. 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.

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 (PageIndex{7})). 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.

The treatment for neurocysticercosis depends on the location, number, size, and stage of cysticerci present. Antihelminthic chemotherapy includes albendazole and praziquantel. Because these drugs kill viable cysts, they may acutely increase symptoms by provoking an inflammatory response caused by the release of Taenia cysticerci antigens, as the cysts are destroyed by the drugs. To alleviate this response, corticosteroids that cross the blood-brain barrier(e.g., dexamethasone) can be used to mitigate these effects. Surgical intervention may be required to remove intraventricular cysts.

PARASITIC DISEASES OF THE NERVOUS SYSTEM

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 (Figure (PageIndex{8})).

Exercise (PageIndex{5})

  1. What neurological condition is associated with neurocysticercosis?
  2. How is neurocysticercosis diagnosed?

Key Concepts and Summary

  • Neuromycoses 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.
  • Some protist infections of the nervous systems are fatal if not treated, including primary amoebic meningitis, granulomatous amoebic encephalitis, human African trypanosomiasis, and neurotoxoplasmosis.
  • The various forms of ameobic encephalitis caused by the different amoebic infections are typically fatal even with treatment, but they are rare.
  • African trypanosomiasis is a serious but treatable disease endemic to two distinct regions in sub-Saharan Africa caused by the insect-borne hemoflagellate Trypanosoma brucei.
  • Neurocysticercosis is treated using antihelminthic drugs or surgery to remove the large cysts from the CNS.

Footnotes

  1. 1 US Centers for Disease Control and Prevention, “Naegleria fowleri—Primary Amoebic Meningoencephalitis (PAM)—Amebic Encephalitis,” 2016. Accessed June 30, 2016. http://www.cdc.gov/parasites/naegleria/treatment.html.
  2. 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,” Journal of Antimicrobial Chemotherapy 67, no. 11 (2012): 2576-97.
  3. 3 US Centers for Disease Control and Prevention, “Parasites – African Trypanosomiasis (also known as Sleeping Sickness), East African Trypanosomiasis FAQs,” 2012. www.cdc.gov/parasites/sleepin...faqs-east.html.
  4. 4 US Centers for Disease Control and Prevention, “Parasites – African Trypanosomiasis (also known as Sleeping Sickness), Epidemiology & Risk Factors,” 2012. www.cdc.gov/parasites/sleepin...kness/epi.html.
  5. 5 Carruthers, Vern B., and Yasuhiro Suzuki, “Effects of Toxoplasma gondii Infection on the Brain,” Schizophrenia Bulletin 33, no. 3 (2007): 745-51.
  6. 6 Uppal, Gulshan, “CNS Toxoplasmosis in HIV,” 2015. emedicine.medscape.com/articl...98-overview#a3.
  7. 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 Toxoplasma gondii to the Central Nervous System,” Nature Microbiology 1 (2016): 16001.
  8. 8 DeGiorgio, Christopher M., Marco T. Medina, Reyna Durón, Chi Zee, and Susan Pietsch Escueta, “Neurocysticercosis,” Epilepsy Currents 4, no. 3 (2004): 107-11.

Contributor

  • Nina Parker, (Shenandoah University), Mark Schneegurt (Wichita State University), Anh-Hue Thi Tu (Georgia Southwestern State University), Philip Lister (Central New Mexico Community College), and Brian M. Forster (Saint Joseph’s University) with many contributing authors. Original content via Openstax (CC BY 4.0; Access for free at https://openstax.org/books/microbiology/pages/1-introduction)


Parasitic Diseases: Nervous System Effects

Encyclopedia of Neuroscience. ed. / Larry R Squire Thomas D Albright Floyd E Bloom Fred H Gage Nicholas C Spitzer. 2nd. ed. Oxford, United Kingdom : Elsevier, 2010. p. 435 - 439.

Research output : Chapter in Book/Report/Conference proceeding › Encyclopaedia / Dictionary Entry › Research › peer-review

T1 - Parasitic Diseases: Nervous System Effects

N2 - Of the large number of parasites that may infect humans, some have a characteristic predilection for involvement of the nervous system, whereas other infections are only rarely associated with neurological manifestations. This article does not exhaustively list all parasites reported to have possible neurological effects, but instead discusses those infections that are most likely to present with symptoms related to the nervous system. Specific infections covered include malaria, toxoplasmosis, amebic encephalitis, microsporidiosis, African and American trypanosomiasis, angiostrongyliasis, gnathostomiasis, strongyloidiasis, trichinellosis, visceral larva migrans, schistosomiasis, paragonimiasis, fascioliasis, cysticercosis, and echinococcosis.

AB - Of the large number of parasites that may infect humans, some have a characteristic predilection for involvement of the nervous system, whereas other infections are only rarely associated with neurological manifestations. This article does not exhaustively list all parasites reported to have possible neurological effects, but instead discusses those infections that are most likely to present with symptoms related to the nervous system. Specific infections covered include malaria, toxoplasmosis, amebic encephalitis, microsporidiosis, African and American trypanosomiasis, angiostrongyliasis, gnathostomiasis, strongyloidiasis, trichinellosis, visceral larva migrans, schistosomiasis, paragonimiasis, fascioliasis, cysticercosis, and echinococcosis.


Cryptococcocal Meningitis

Cryptococcus neoformans 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 virulence factor , inhibiting clearance by phagocytosis. Most C. neoformans cases result in subclinical respiratory infections that, in healthy individuals, generally resolve spontaneously with no long-term consequences (see Respiratory Mycoses). In immunocompromised patients or those with other underlying illnesses, the infection can progress to cause meningitis and granuloma formation in brain tissues. Cryptococcus antigens can also serve to inhibit cell-mediated immunity and delayed-type hypersensitivity.

Cryptococcus can be easily cultured in the laboratory and identified based on its extensive capsule (Figure 27.18). C. neoformans is frequently cultured from urine samples of patients with disseminated infections.

Prolonged treatment with antifungal drugs is required to treat cryptococcal infections. Combined therapy is required with amphotericin B plus flucytosine for at least 10 weeks. Many antifungal drugs have difficulty crossing the blood-brain barrier 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 Cryptococcus infections because of their compromised immune state. AIDS 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.

Figure 27.18. An India ink-negative stain of C. neoformans showing the thick capsules around the spherical yeast cells. (credit: modification of work by Centers for Disease Control and Prevention)

  • Why are neuromycoses infections rare in the general population?
  • How is a cryptococcal infection acquired?

Coccidioidomycosis

Epidemiology, Microbiology, and Pathology

Clinical Characteristics, Clinical Laboratory Tests, and Diagnosis

Studies done on military recruits in the 1940s, using skin testing to diagnose acute infection, provided detailed data on infection in the normal host. Only 40 percent of these patients experienced acute respiratory symptoms [Smith et al., 1946], typically within 3 weeks after exposure and accompanied by fever, chills, night sweats, cough, anorexia, and weight loss. Dissemination of the infection from the pulmonary focus to distant sites usually occurs 1–6 months after primary infection in approximately 0.5 percent of cases half of these are meningitis [Banuelos et al., 1996]. Other sites of dissemination include skin, lymph nodes, bones, and joints.

The clinical characteristics of coccidioidal meningitis are nonspecific and prompt diagnosis can be difficult [Caudill et al., 1970]. The most prevalent manifestations are headache, fever, malaise, and weight loss meningismus may be absent [Saitoh et al., 2000]. Findings can include confusion, personality changes, focal neurological deficits, ataxia, obtundation, and coma. Brain and spinal cord abscesses can occur with or without concurrent meningitis [Banuelos et al., 1996]. Spinal cord symptoms may also occur in conjunction with coccidioidal osteomyelitis of the cervical vertebra [Jackson et al., 1964].

CSF abnormalities include mononuclear pleocytosis, increased protein content, increased chloride concentration, and normal or decreased glucose concentration. Diagnosis can be confirmed by either direct microscopy or culture of the CSF (Figure 82-2). Unfortunately, CSF cultures and microscopy are often negative in C. immitis meningitis, requiring indirect evidence of infection through serologic testing of serum and CSF. Complement fixation and precipitin tests are dependable and provide accurate diagnosis in more than 99 percent of patients with disseminated infection [Pappagianis, 1976]. Any discernible titer of complement fixation antibody in spinal fluid is considered diagnostic [Lyons and Andriole, 1986]. The coccidioidin skin test is not currently used for diagnosis of acute disease.

Management

The 2008 IDSA guidelines for treatment of coccidioidal meningitis recommend fluconazole or itraconazole by mouth for all patients intrathecal amphotericin was recommended by some clinicians but was graded C-III (poor evidence) by the IDSA [Ampel et al., 2009]. Fluconazole is well tolerated in both children and adults, and the oral form is highly bioavailable. Patients with C. immitis meningitis must be treated indefinitely with fluconazole to prevent relapse, and should be managed in conjunction with an infectious disease specialist.


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The Curated Reference Collection in Neuroscience and Biobehavioral Psychology. ed. / George Adelman Barry H Smith. 3rd. ed. Philadelphia, USA : Elsevier, 2016. p. 435-439.

Research output : Chapter in Book/Report/Conference proceeding › Chapter (Book) › Other › peer-review

T1 - Parasitic diseases, nervous system effects

N2 - Of the large number of parasites that may infect humans, some have a characteristic predilection for involvement of the nervous system, whereas other infections are only rarely associated with neurological manifestations. This article will not exhaustively list all parasites reported to have possible neurological effects, but instead will discuss those infections that are most likely to present with symptoms related to the nervous system. Specific infections covered include malaria, toxoplasmosis, amoebic encephalitis, microsporidiosis, African and American trypanosomiasis, angiostrongyliasis, gnathostomiasis, strongyloidiasis, trichinellosis, visceral larva migrans, schistosomiasis, paragonimiasis, fascioliasis, cysticercosis, and echinococcosis.

AB - Of the large number of parasites that may infect humans, some have a characteristic predilection for involvement of the nervous system, whereas other infections are only rarely associated with neurological manifestations. This article will not exhaustively list all parasites reported to have possible neurological effects, but instead will discuss those infections that are most likely to present with symptoms related to the nervous system. Specific infections covered include malaria, toxoplasmosis, amoebic encephalitis, microsporidiosis, African and American trypanosomiasis, angiostrongyliasis, gnathostomiasis, strongyloidiasis, trichinellosis, visceral larva migrans, schistosomiasis, paragonimiasis, fascioliasis, cysticercosis, and echinococcosis.


Diseases of the nervous system (neurology)

The list of definitions can be continued, but here is a special medical term - causalgia - which means severe prolonged pains of a burning character.

Among organic cerebral pathologies, such a congenital anomaly in the development of the brain as lissencephaly stands out, the essence of which lies in the almost smooth surface of the cortex of its hemispheres - with an insufficient number of convolutions and grooves.

A decrease in skeletal muscle tone (residual tension and muscle resistance to passive stretching) with a deterioration in its contractile function is defined as muscle hypotonia.

In neurology, spinal or spinal shock is defined as a clinical syndrome arising from an initial neurological response to traumatic spinal cord injury - with a reversible loss or reduction of all of its functions below the level of the injury.

Peroneal muscle atrophy, syndrome or Charcot-Marie-Tooth disease is a whole group of chronic hereditary diseases with damage to peripheral nerves.

If the doctor diagnoses "ventriculitis", then this means that a complication has developed that threatens not only the health, but also the patient's life. Pathology is an inflammatory reaction that affects the walls of the cerebral ventricles: this is a serious intracranial infectious disease


Delayed (Type IV) Hypersensitivity

Delayed hypersensitivity, or type IV hypersensitivity, is basically a standard cellular immune response. In delayed hypersensitivity, the first exposure to an antigen is called sensitization, such that on re-exposure, a secondary cellular response results, secreting cytokines that recruit macrophages and other phagocytes to the site. These sensitized T cells, of the Th1 class, will also activate cytotoxic T cells. The time it takes for this reaction to occur accounts for the 24- to 72-hour delay in development.

The classical test for delayed hypersensitivity is the tuberculin test for tuberculosis, where bacterial proteins from M. tuberculosis are injected into the skin. A couple of days later, a positive test is indicated by a raised red area that is hard to the touch, called an induration, which is a consequence of the cellular infiltrate, an accumulation of activated macrophages. A positive tuberculin test means that the patient has been exposed to the bacteria and exhibits a cellular immune response to it.

Another type of delayed hypersensitivity is contact sensitivity, where substances such as the metal nickel cause a red and swollen area upon contact with the skin. The individual must have been previously sensitized to the metal. A much more severe case of contact sensitivity is poison ivy, but many of the harshest symptoms of the reaction are associated with the toxicity of its oils and are not T cell mediated.


Algal Diversity

​Although the algae and protozoa were formerly separated taxonomically, they are now mixed into supergroups. The algae are classified within the Chromalveolata and the Archaeplastida. Although the Euglenozoa (within the supergroup Excavata) include photosynthetic organisms, these are not considered algae because they feed and are motile.

The dinoflagellates and stramenopiles fall within the Chromalveolata. The dinoflagellates are mostly marine organisms and are an important component of plankton. They have a variety of nutritional types and may be phototrophic, heterotrophic, or mixotrophic. Those that are photosynthetic use chlorophyll a, chlorophyll c2, and other photosynthetic pigments (Figure 1). They generally have two flagella, causing them to whirl (in fact, the name dinoflagellate comes from the Greek word for “whirl”: dini). Some have cellulose plates forming a hard outer covering, or theca, as armor. Additionally, some dinoflagellates produce neurotoxins that can cause paralysis in humans or fish. Exposure can occur through contact with water containing the dinoflagellate toxins or by feeding on organisms that have eaten dinoflagellates.

When a population of dinoflagellates becomes particularly dense, a red tide (a type of harmful algal bloom) can occur. Red tides cause harm to marine life and to humans who consume contaminated marine life. Major toxin producers include Gonyaulaxand Alexandrium, both of which cause paralytic shellfish poisoning. Another species, Pfiesteria piscicida, is known as a fish killer because, at certain parts of its life cycle, it can produce toxins harmful to fish and it appears to be responsible for a suite of symptoms, including memory loss and confusion, in humans exposed to water containing the species.

Figure 1. The dinoflagellates exhibit great diversity in shape. Many are encased in cellulose armor and have two flagella that fit in grooves between the plates. Movement of these two perpendicular flagella causes a spinning motion. (credit: modification of work by CSIRO)​

​The stramenopiles include the golden algae (Chrysophyta), the brown algae (Phaeophyta), and the diatoms (Bacillariophyta). Stramenopiles have chlorophyll a, chlorophyll c1/c2, and fucoxanthin as photosynthetic pigments. Their storage carbohydrate is chrysolaminarin. While some lack cell walls, others have scales. Diatoms have flagella and frustules, which are outer cell walls of crystallized silica their fossilized remains are used to produce diatomaceous earth, which has a range of uses such as filtration and insulation. Additionally, diatoms can reproduce sexually or asexually. One diatom genus, Pseudo-nitzschia, is known to be associated with harmful algal blooms.

Brown algae (Phaeophyta) are multicellular marine seaweeds. Some can be extremely large, such as the giant kelp (Laminaria). They have leaf-like blades, stalks, and structures called holdfasts that are used to attach to substrate. However, these are not true leaves, stems, or roots (Figure 2). Their photosynthetic pigments are chlorophyll a, chlorophyll c, β-carotene, and fucoxanthine. They use laminarin as a storage carbohydrate.

The Archaeplastids include the green algae (Chlorophyta), the red algae (Rhodophyta), another group of green algae (Charophyta), and the land plants. The Charaphyta are the most similar to land plants because they share a mechanism of cell division and an important biochemical pathway, among other traits that the other groups do not have. Like land plants, the Charophyta and Chlorophyta have chlorophyll a and chlorophyll b as photosynthetic pigments, cellulose cell walls, and starch as a carbohydrate storage molecule. Chlamydomonasis a green alga that has a single large chloroplast, two flagella, and a stigma(eyespot) it is important in molecular biology research (Figure 2).

Chlorellais a nonmotile, large, unicellular alga, and Acetabulariais an even larger unicellular green alga. The size of these organisms challenges the idea that all cells are small, and they have been used in genetics research since Joachim Hämmerling(1901–1980) began to work with them in 1943. Volvox is a colonial, unicellular alga (Figure 2). A larger, multicellular green alga is Ulva, also known as the sea lettuce because of its large, edible, green blades. The range of life forms within the Chlorophyta—from unicellular to various levels of coloniality to multicellular forms—has been a useful research model for understanding the evolution of multicellularity. The red algae are mainly multicellular but include some unicellular forms. They have rigid cell walls containing agar or carrageenan, which are useful as food solidifying agents and as a solidifier added to growth media for microbes.

Figure 2. (a) These large multicellular kelps are members of the brown algae. Note the “leaves” and “stems” that make them appear similar to green plants. (b) This is a species of red algae that is also multicellular. (c) The green alga Halimeda incrassata, shown here growing on the sea floor in shallow water, appears to have plant-like structures, but is not a true plant. (d) Bioluminesence, visible in the cresting wave in this picture, is a phenomenon of certain dinoflagellates. (e) Diatoms (pictured in this micrograph) produce silicaceous tests (skeletons) that form diatomaceous earths. (f) Colonial green algae, like volvox in these three micrographs, exhibit simple cooperative associations of cells. (credit a, e: modification of work by NOAA credit b: modification of work by Ed Bierman credit c: modification of work by James St. John credit d: modification of work by “catalano82”/Flickr credit f: modification of work by Dr. Ralf Wagner)​

Poliomyelitis

Poliomyelitis (polio), caused by poliovirus, is a primarily intestinal disease that, in a small percentage of cases, proceeds to the nervous system, causing paralysis and, potentially, death. Poliovirus is highly contagious, with transmission occurring by the fecal-oral route or by aerosol or droplet transmission. Approximately 72% of all poliovirus infections are asymptomatic another 25% result only in mild intestinal disease, producing nausea, fever, and headache. [12] However, even in the absence of symptoms, patients infected with the virus can shed it in feces and oral secretions, potentially transmitting the virus to others. In about one case in every 200, the poliovirus affects cells in the CNS. [13]

After it enters through the mouth, initial replication of poliovirus occurs at the site of implantation in the pharynx and gastrointestinal tract. As the infection progresses, poliovirus is usually present in the throat and in the stool before the onset of symptoms. One week after the onset of symptoms, there is less poliovirus in the throat, but for several weeks, poliovirus continues to be excreted in the stool. Poliovirus invades local lymphoid tissue, enters the bloodstream, and then may infect cells of the CNS. Replication of poliovirus in motor neurons of the anterior horn cells in the spinal cord, brain stem, or motor cortex results in cell destruction and leads to flaccid paralysis. In severe cases, this can involve the respiratory system, leading to death. Patients with impaired respiratory function are treated using positive-pressure ventilation systems. In the past, patients were sometimes confined to Emerson respirators, also known as iron lungs (Figure 4).

Direct detection of the poliovirus from the throat or feces can be achieved using reverse transcriptase PCR (RT-PCR) or genomic sequencing to identify the genotype of the poliovirus infecting the patient. Serological tests can be used to determine whether the patient has been previously vaccinated. There are no therapeutic measures for polio treatment is limited to various supportive measures. These include pain relievers, rest, heat therapy to ease muscle spasms, physical therapy and corrective braces if necessary to help with walking, and mechanical ventilation to assist with breathing if necessary.

Figure 4. (a) An Emerson respiratory (or iron lung) that was used to help some polio victims to breathe. (b) Polio can also result in impaired motor function. (credit b: modification of work by the Centers for Disease Control and Prevention)

Two different vaccines were introduced in the 1950s that have led to the dramatic decrease in polio worldwide (Figure 5). The Salk vaccine is an inactivated polio virus that was first introduced in 1955. This vaccine is delivered by intramuscular injection. The Sabin vaccine is an oral polio vaccine that contains an attenuated virus it was licensed for use in 1962. There are three serotypes of poliovirus that cause disease in humans both the Salk and the Sabin vaccines are effective against all three.

Figure 5. (a) Polio is caused by the poliovirus. (b) Two American virologists developed the first polio vaccines: Albert Sabin (left) and Jonas Salk (right). (credit a: modification of work by the Centers for Disease Control and Prevention)

Attenuated viruses from the Sabin vaccine are shed in the feces of immunized individuals and thus have the potential to infect nonimmunized individuals. By the late 1990s, the few polio cases originating in the United States could be traced back to the Sabin vaccine. In these cases, mutations of the attenuated virus following vaccination likely allowed the microbe to revert to a virulent form. For this reason, the United States switched exclusively to the Salk vaccine in 2000. Because the Salk vaccine contains an inactivated virus, there is no risk of transmission to others (see Vaccines). Currently four doses of the vaccine are recommended for children: at 2, 4, and 6–18 months of age, and at 4–6 years of age.

In 1988, WHO launched the Global Polio Eradication Initiative with the goal of eradicating polio worldwide through immunization. That goal is now close to being realized. Polio is now endemic in only a few countries, including Afghanistan, Pakistan, and Nigeria, where vaccination efforts have been disrupted by military conflict or political instability.

The Terror of Polio

In the years after World War II, the United States and the Soviet Union entered a period known as the Cold War. Although there was no armed conflict, the two super powers were diplomatically and economically isolated from each other, as represented by the so-called Iron Curtain between the Soviet Union and the rest of the world. After 1950, migration or travel outside of the Soviet Union was exceedingly difficult, and it was equally difficult for foreigners to enter the Soviet Union. The United States also placed strict limits on Soviets entering the country. During the Eisenhower administration, only 20 graduate students from the Soviet Union were allowed to come to study in the United States per year.

Yet even the Iron Curtain was no match for polio. The Salk vaccine became widely available in the West in 1955, and by the time the Sabin vaccine was ready for clinical trials, most of the susceptible population in the United States and Canada had already been vaccinated against polio. Sabin needed to look elsewhere for study participants. At the height of the Cold War, Mikhail Chumakov was allowed to come to the United States to study Sabin’s work. Likewise, Sabin, an American microbiologist, was allowed to travel to the Soviet Union to begin clinical trials. Chumakov organized Soviet-based production and managed the experimental trials to test the new vaccine in the Soviet Union. By 1959, over ten million Soviet children had been safely treated with Sabin’s vaccine.

As a result of a global vaccination campaign with the Sabin vaccine, the overall incidence of polio has dropped dramatically. Today, polio has been nearly eliminated around the world and is only rarely seen in the United States. Perhaps one day soon, polio will become the third microbial disease to be eradicated from the general population [small pox and rinderpest (the cause of cattle plague) being the first two].

Think about It

  • How is poliovirus transmitted?
  • Compare the pros and cons of each of the two polio vaccines.

6. Conclusion

The choice of models to investigate human disease is often a trade-off between how well the model mimics the human condition and how easy it is to manipulate the system. Invertebrate models such as C. elegans and D. melanogaster have been invaluable for the study of development, signaling pathways, and many other aspects of biology. In this chapter, we have outlined several examples that illustrate the ease of such C. elegans studies. Some of the features that have rendered C. elegans such a powerful research organism include the ease of genetics (forward genetic screening, transgenic animal construction, mutation mapping), cell biology (using GFP in a transparent organism with a fully-described and invariant cell lineage), genomics (RNAi and other techniques), modifier screens (enhancement and suppression), and the ability to mimic many human diseases. We also have highlighted how more and more frequently, follow-up studies in mammals have validated these nematode findings. The tools and ease-of-use of C. elegans and other “simple” model organisms continues to make them invaluable for research, and these organisms will continue to play an important role in our understanding of human disease and human disease gene discovery in the future.


Watch the video: Parasitic Diseases Of the Central Nervous System: Toxoplasmosis (July 2022).


Comments:

  1. Aashish

    Your topic has been like a parable of voyazytsya all over the Internet for a month now. It is also sometimes called the bearded boyan. But in general, thanks kaneshn

  2. Ban

    magnificent thought

  3. Corwine

    I join. All of the above is true. Let's discuss this issue. Here or at PM.

  4. Tojazragore

    Agree, a useful piece

  5. Henrik

    Not to everybody.



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