cns -fugi - prion and ab Fsces e3.pptx

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1. Cryptococcal meningitis Cryptococcal meningitis caused by Cryptococcus neoformans . C. neoformans is main cause of fungal meningitis Cryptococcosis is the most common, life-threatening invasive fungal disease worldwide. Cryptococcal meningitis occurs most commonly in immunocompromised patients, such as those with acquired immunodeficiency syndrome (AIDS ) and transplant recipients taking immunosuppressive drugs. Pathogen and Virulence Factors Cryptococcus neoformans is a spherical, single-celled yeast, surrounded by a wide polysaccharide capsule, which resistant to phagocytosis . C . neoformans normally lives widely in soil, and grows abundantly in soil containing bird (especially pigeon) droppings , The birds are not infected .

2. Pathogenesis and Epidemiology After inhalation of dust containing spores and/or dried yeast . → The thick polysaccharide capsule surrounding these microbes enables them to avoid clearance by the alveolar macrophage → pulmonary infections → Produce Initial symptoms. • In immunocompromised patients → pulmonary infections often disseminate via blood to the brain → meningitis . It can infects both meninges and brain tissue . In most individuals , alveolar macrophage in the lungs limit spread of the yeast.

3. Incubation period : variable from 2-9 moths Sign and Symptoms : • Initial symptoms → fever, fatigue, and a dry cough. • If disseminate to brain → meningitis → headaches, neck stiffness, sensitivity to light, and confusion. After weeks or months of slow progression of these symptoms, vomiting, weight loss, paralysis, seizures, and coma may appear. In people with immunodeficiency ( AIDS patients and transplant recipients ), acute onset of rapidly fatal cryptococcal meningitis occurs .

4. Diagnosis, Treatment, and Prevention The CSF usually has a slightly high protein, low glucose and a raised number of lymphocytes. Detection of fungal antigen ( capsular antigen ) in CSF . In AIDS patients , antigen can be detected in serum as well. Fungal stains (such as India ink ) revealing the presence of encapsulated yeast in CSF are highly suggestive of cryptococcal meningitis, even if no obvious symptoms are present. Treatment : intravenous amphotericin B in combination with oral 5-fluorocytosine for at least four weeks. The two drugs enhance one another, allowing to use lower doses of amphotericin B , which is toxic (renal toxicity ) to humans; however, toxicity is not eliminated. No vaccine against Cryptococcus is available.

5. Degenerative disorders Long incubation periods Slow progressive spongiform encephalopathy Fatal outcome Encephalopathy refers to altered brain function in the absence of inflammation or immune responses to the infections. Spongiform because they leave the brains of their victims so full of holes they resemble sponges due to the loss of nerve cells and other changes . Prion diseases involve wild and domestic (sheep, goats and cattle) animals and humans. Prion diseases

6. Diseases caused by prions Creutzfeldt-Jakob Disease (CJD ), a human disease variant Creutzfeldt-Jakob disease ( vCJD ) , infect humans who ate infected beef, derived from cattle. kuru , a human disease bovine spongiform encephalitis (BSE) , so-called mad cow disease , which can spread from cattle to people; scrapie in sheep ; Prions are causative agents Prions are infectious protein that lacks nucleic acids and replicates by converting similar normal proteins into new prions (change in protein shape) Prions are highly resistant to heat, radiation and disinfectants.

7. Normal prions (c- PrP ) play a role in transporting massages between certain brain cells

8. CJD is one of the human transmissible spongiform encephalopathies . CJD is caused by prions, a misfolded protein , thereby altering the function of the protein and leading to death of neurons. CJD : genetic disease, occurs at about age 60 . Mutations of genes encoding these proteins can be inherited CJD occurs sporadically worldwide that spontaneously strikes about one person in a million Prions may remain dormant for more than 60 years . Pathogenesis Prions replicate in dendritic cells in various parts of the body by converting normal protein to more prions ; → transmission to the brain ; → aggregation into masses forming vacules in neurons- → causing malfunction and cell death-  spongiform encephalopathy ( Swiss chesse -like) Creutzfeldt-Jakob disease (CJD)

9. Symptoms Behavioral changes , anxiety, insomnia , fatigue, progressing over weeks or months to muscle jerks , lack of coordination, dementia . The death is inevitable. Epidemiology:- Human-to-human transmission iatrogenically by corneal transplant, m edical procedures such as transplants, blood transfusion from an infected person, use of contaminated surgical instruments CJD does not have any relationship to the ingestion of any food, unlike variant CJD, . Creutzfeldt-Jakob disease (CJD)

10. Definitive diagnosis is made by observing spongiform changes in brain biopsy followed by histochemical staining with anti-prion antibodies. Prevention and treatment: There is no drug treatment for CJD and no vaccine . It is difficult to destroy prions even outside the body. Medical instruments contaminated by prions may remain infectious even after normal autoclaving; boiling; exposure to formaldehyde, glutaraldehyde , or ethylene oxide; or 24 hours of dry heat at 160°C. Autoclaving at 132°C in concentrated sodium hydroxide for one hour or Prionzyme are required to eliminate prions safely and completely from contaminated medical instruments . Creutzfeldt-Jakob disease (CJD)

11. Variant CJD: is a contagious form of the disease, derived from cattle , to distinguish it from the naturally occurring (CJD). is acquired by the ingestion of prion-containing beef. It is declining as a result of the ban on the addition of animal products to cattle feed . As British farmers and ranchers learned, destruction of potentially infected sheep and cattle herds is mandatory to prevent the spread of vCJD . Further, governments have initiated strict laws and inspection procedures to prevent the use of contaminated animal protein in food supplements for herbivores.

12. Kuru is a spongiform encephalopathy found in the Fore tribe in New Guinea . It is now very rare because the eating rituals that transmitted the agent are no longer practiced . kuru , is associated with cannibalism ( eating human brain ) , as formerly practiced by some New Guinea natives

13. Congenital CNS infections Intrauterine infections: toxoplasma, rubella, cytomegalovirus, syphilis During birth: herpes simplex, hepatitis B HIV