Microbial Diseases of the Nervous System The Nervous System Blood Brain Barrier - network of capillaries - selective barrier

- restricts entry of some chemicals & microscopic objects(bacteria)

Microbes enter the Nervous System via: 1. Trauma - skull or backbone fracture 2. Medical Procedures – Surgery, Spinal tap 3. Moving along the peripheral nerve 4. Invasion through the blood & lymph  Bacteria can grow in the cerebrospinal fluid in the subarachnoid space of the CNS  Meningitis  Inflammation of meninges  Encephalitis  Inflammation of the brain Bacterial Diseases of the Nervous System Signs & Symptoms: - Fever, headache, stiff neck - Followed by nausea and vomiting - May progress to convulsions and coma - Diagnosis by Gram stain of CSF - Treated with cephalosporins

Haemophilus influenzae Meningitis - Occurs mostly in children (6 months to 4 years) - when level of antibody from the mother decreases - Gram-negative aerobic bacteria, normal throat microbiota - causes: pneumonia otitis media epiglotittis - Prevented by Hib vaccine Neisseria Meningitis, Meningococcal Meningitis  Gram-negative aerobic cocci, N. meningitidis(Meningococcus)  Polysaccharide capsule

 10% of people are healthy nasopharyngeal carriers  Children under 2 years old  Symptoms are due to endotoxin  Begins as throat infection, rash Bacteremia Meningitis Antibiotics like penicillin and cephalosporin can be used. Streptococcus pneumoniae Meningitis, Pneumococcal Pneumonia  Gram-positive diplococci,encapsulated  70% of people are healthy nasopharyngeal carriers  Most common in children (1 month to 4 years)  Leading cause of bacterial meningitis  Mortality: 30% in children, 80% in elderly  Prevented by vaccination

 Prompt treatment of any type of bacterial meningitis is important.  Antibiotics are given on suspected cases even before the causative bacteria is identified  For diagnosis – CSF from spinal tap - gram stain - culture or sensitivity testing Listeriosis  Listeria monocytogenes  Gram-negative aerobic rod  Usually foodborne(Dairy products, grows in refrigerators), can be transmitted to fetus  Reproduce in phagocytes 2 forms : 1. Adults – Mild, Assymptomatic - may invade the CNS causing meningitis - AIDS - Those taking immuno-suppresive medicines 2. Disease in pregnant woman - mild, flu-like symptoms - infects the fetus via the placenta Abortion/ Stillbirth - may affect the infant after birth causing meningitis Tetanus  Clostridium tetani  Gram-positive, endospore-forming, obligate anaerobe  Found in soil contaminated by animal feces  Grows in deep wounds  Tetanospasmin neurotoxin released upon death & lysis of the bacteria

enters the CNS via peripheral nerves & blood blockage of relaxation pathways so that muscles continuously contract Lockjaw – if jaw muscles are affected Opisthotonos - back muscles Gradually affecting other muscles Death due to spasm of respiratory muscle 1. Improperly cleaned deep wound 2. Deep punctured wound Anaerobic conditions that favor the growth of Cl. tetani Prevention: 1. Debridement 2. DPT 3. Tetanus Toxoid 4. HTIG(Human tetanus immune globulin )ATS - active immunization - For extensive wounds in patients with unknown or low immunity Botulism  Clostridium botulinum  Gram-positive, endospore-forming, obligate anaerobe  Soil and freshwater sediments  Ingestion of spores may cause infant botulism  Intoxication due to ingestion of the toxin produced  In anaerobic environment (scaled cans ) produces exotoxin (Botulinum toxin/ Botulinal toxin)  Infant botulism results from C. botulinum growing in intestines  Wound botulism results from growth of C. botulinum in wounds. Botulinum toxin - neurotoxin - specific for the synaptic ends of nerves Blocks the release of Acetylcholine Flaccid Paralysis Respiratory/Cardiac Failure  Botulinum toxin is destroyed through boiling-"botulinum cook" at 121 °C (250 °F) for 3 mins  Foodborne botulism has more frequently been from home-canned foods with low acid content, such as carrot juice, asparagus, green beans, beets, and corn. Treatment: Supportive care Antibiotics are almost of no use Antitoxin A, B and E Leprosy  Hansen’s disease  Mycobacterium leprae  Acid-fast rod that grows best at 30°C  Grows in peripheral nerves and skin cells

 Transmission requires prolonged contact with an infected person - secretions containing the pathogen - nasal mucosa

Secretions with pathogen Prefers the outer cooler portions of the human body Pathogen survives ingestion by macrophages Invades cells of the PNS causing nerve damage 2 forms of Leprosy: 1. Tuberculoid (Neural) form - Loss of sensation in skin areas - spontaneously heal - positive lepromin test 2. Lepromatous (Progressive) form - Disfiguring nodules over body - negative lepromin test

Prevention: *A single dose of rifampicin is able to reduce the rate of leprosy in contacts by 57% to 75% *BCG is able to offer a variable amount of protection against leprosy as well as against tuberculosis Treatment: Dapsone, Rifampicin, Clofamizine WHO Recommendation: - The first was a 24-month treatment using rifampicin, clofazimine, and dapsone. - The second was a six-month treatment using rifampicin and dapsone VIRAL DISEASES OF THE NERVOUS SYSTEM  Poliovirus, Polio or Infantile Paralysis

 Transmitted by ingestion, person to person, the fecal-oral route - Initial symptoms: sore throat and nausea - Viremia may occur; if persistent, virus can enter the CNS; destruction of motor cells and paralysis occurs in <1% of cases Outcomes of poliovirus infection Outcome Proportion of cases  Asymptomatic 90–95%  Minor illness 4–8%  Non-paralytic aseptic  meningitis 1–2%  Paralytic poliomyelitis 0.1–0.5% Factors that increase the risk of polio infection or affect the severity of the disease: 1. Immune deficiency 2. Malnutrition 3. Tonsillectomy 4. Physical activity immediately following the onset of paralysis 5. Skeletal muscle injury due to injection of vaccines or therapeutic agents 6. Pregnancy

Diagnosis: Recovery of poliovirus from a stool sample or a swab of the pharynx Prevention: BCG 1. Salk vaccine/ IPV (Inactivated Polio Vaccine) 2. Sabin vaccine / 0PV(Oral Polio Vaccine) Rabies virus (Rhabdovirus)  Rhabdovirus “bullet shaped” Mode of transmission: 1. Bite of an infected animal - Any mammal may become infected with the rabies virus and develop symptoms, including humans. - bats, monkeys, raccoons, foxes, skunks, cattle, wolves, dogs, mongoose (normally yellow mongoose) or cats. 2. Lick from an infected animal on scratches 3. Aerosol – Bats  Hydrophobia - spasm of muscles of the mouth and pharynx triggered by the sight of liquid - extensive damage to nerves and spinal cord leads to difficulty in swallowing, increase in salivation. Diagnosis: *The reference method for diagnosing rabies is by performing PCR or viral culture on brain samples taken after death.

*Inclusion bodies called Negri bodies are 100% diagnostic for rabies infection Treatment: Preexposure prophylaxis: Human diploid cells vaccine Postexposure treatment: Vaccine + immune globulin Arboviral Encephalitis  Arboviruses are arthropod-borne viruses that belong to several families  Vertebrate infection occurs when the infected arthropod takes a blood meal.  Arboviral encephalitides have a global distribution - eastern equine encephalitis (EEE) - western equine encephalitis (WEE) - St. Louis encephalitis (SLE) - La Crosse (LAC) encephalitis - Japanese encephalitis (JE) * transmitted by mosquitoes, ticks, • Most cases of arboviral encephalitis occur from June through September, when arthropods are most active. • The majority of human infections are asymptomatic or may result in a nonspecific flu-like syndrome.  Onset may be insidious or sudden with fever, headache, myalgias, malaise and occasionally prostration.  Infection may, however, lead to encephalitis, with a fatal outcome or permanent neurologic sequelae. Fungal Disease of the Nervous System Cryptococcus neoformans Meningitis (Cryptococcosis) - Spherical cells resembling yeast - Soil fungus associated with pigeon and chicken dropping - Transmitted by the respiratory route; spreads through blood to the CNS - Mortality up to 30% - Chronic meningitis - in immunosuppressed individuals - On steroids  Tx: Amphotericin B Flucytosine

Parasitic Infection of the Nervous System African Trypanosomiasis  Sleeping sickness or human African trypanosomiasis is a parasitic disease of people and animals, caused by protozoa of species Trypanosoma brucei  transmitted by the tsetse fly  The disease is endemic in certain regions of Sub-Saharan Africa,  Signs & Symptoms: fever, headaches, and joint pains parasites enter through both the blood and lymph

lymph nodes often swell up to tremendous sizes. Winterbottom's sign - swollen lymph nodes along the back of the neck, If untreated, symptoms spread to include anemia, endocrine, cardiac, and kidney diseases and disorders. enters a neurological phase when the parasite passes through the blood-brain barrier. - confusion and reduced coordination - the sleep cycle is disturbed with bouts of fatigue punctuated with manic periods progressing to daytime slumber and nighttime insomnia. (Sleeping Sickness)

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Trypanosoma brucei gambiense infection is chronic (2 to 4 years) T. b. rhodesiense infection is more acute (few months) Prevention: elimination of the vector Treatment: Eflornithine blocks an enzyme necessary for the parasite

Naegleria fowleri  also known as "the brain-eating amoeba“  can invade and attack the human nervous system  Protozoan infects nasal mucosa from swimming water  N. fowleri can invade and attack the human nervous system; although this occurs rarely[1], such an infection will nearly always result in the death of the victim.  invade the central nervous system via the nose, more specifically the olfactory mucosa and nasal tissues.  results in significant necrosis of and hemorrhaging in the olfactory bulbs.  climb along nerve fibers through the floor of the cranium via the cribriform plate and into the brain.  Primary Amoebic Meningoencephalitis (PAM or PAME). - changes in olfactory perception (taste and smell) - followed by vomiting, nausea, fever, headache - rapid onset of coma and death in two weeks. • occurs in healthy children or young adults with no prior history of immune compromise • exposed to bodies of fresh water(swimming pool) Tx: - Amphotericin B is effective against N. fowleri - survival remains less than 1%.

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