Microbial Diseases of the Nervous System PDF

MANILA CENTRAL UNIVERSITY College of Pharmacy MICROBIAL DISEASES OF THE NERVOUS SYSTEM At the end of the lesson the students will be able to: 1. Illustrate the anatomical structure of the nervous system. 2. Determine the etiological agents affecting...

MANILA CENTRAL UNIVERSITY College of Pharmacy MICROBIAL DISEASES OF THE NERVOUS SYSTEM At the end of the lesson the students will be able to: 1. Illustrate the anatomical structure of the nervous system. 2. Determine the etiological agents affecting the nervous system. 3. Explain the drug of choice for a specific disease At a more integrative level, the primary function of the nervous system is to control and communicate information throughout the body. Subdivisions of the Nervous System Central Nervous System (CNS) – which is comprised of the brain and the spinal cord Peripheral Nervous System (PNS) - consists of the nerves and ganglia outside of the brain and spinal cord Microbial Diseases of the Nervous System: Meningitis Botulism Leprosy Tetanus Rabies Poliomyelitis Arboviral Encephalitis Ricekettsial Diseases Lyme Disease Plague Cryptococcosis African Trypanosomiasis PHARMACEUTICAL MICROBIOLOGY WITH PARASITOLOGY 1 PREPARED BY: CHRISTINE MARIE S. TERRADO, RPh, MSPh  MANILA CENTRAL UNIVERSITY College of Pharmacy Meningitis Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs. Meningitis can be life-threatening because of the inflammation’s proximity to the brain and spinal cord. Therefore, the condition is classified as a medical emergency. The most common symptoms of meningitis are headache and neck stiffness associated with fever, confusion or altered consciousness, vomiting, and an inability to tolerate light (photophobia) or loud noises (phonophobia). Children often exhibit only nonspecific symptoms, such as irritability and drowsiness. If a rash is present, it may indicate a particular cause of meningitis. For instance, meningitis caused by the bacterium Neisseria meningitidis (known as “meningococcal meningitis”) can be differentiated from meningitis with other causes by a rapidly spreading petechial rash, which may precede other symptoms. A lumbar puncture can help diagnose meningitis. A needle is inserted into the spinal canal to extract a sample of cerebrospinal fluid (CSF) which envelopes the brain and spinal cord. The first treatment in acute meningitis consists of antimicrobial and sometimes antiviral therapy. In addition, corticosteroids can also be used to prevent complications from excessive inflammation. Botulism Botulism is a rare, but sometimes fatal, paralytic illness caused by botulinum toxin. It can affect a wide range of mammals, birds and fish. This toxin is a protein produced under anaerobic conditions by the bacterium Clostridium botulinum. The toxin enters the human body in one of three ways: by colonization of the digestive tract by the bacterium in children (infant botulism) or adults (adult intestinal toxemia) by ingestion of toxin from foods (foodborne botulism) by contamination of a wound by the bacterium (wound botulism) C. botulinum is an anaerobic, Gram positive, spore-forming rod. Botulinium toxin is one of the most powerful known toxins: about one microgram is lethal to humans. It acts by blocking nerve function (neuromuscular blockade) through inhibition of the release of the excitatory neurotransmitter acetyl choline from the presynaptic membrane of neuromuscular junctions in the somatic nervous system. PHARMACEUTICAL MICROBIOLOGY WITH PARASITOLOGY 2 PREPARED BY: CHRISTINE MARIE S. TERRADO, RPh, MSPh  MANILA CENTRAL UNIVERSITY College of Pharmacy Leprosy Leprosy, also known as Hansen’s disease, is a chronic bacterial disease caused by Mycobacterium leprae and Mycobacterium lepromatosis. Named after physician Gerhard Armauer Hansen, leprosy is primarily a granulomatous disease of the peripheral nerves and mucosa of the upper respiratory tract. Skin lesions are the primary external sign. Left untreated, leprosy can be progressive, causing permanent damage to the skin, nerves, limbs, and eyes. Leprosy: A 23-year-old man infected with leprosy. Symptoms include: Runny nose Dry scalp Eye problems Skin lesions Muscle weakness Reddish skin Smooth, shiny, diffuse thickening of skin on the face, ears, and hands Loss of sensation in fingers and toes Thickening of peripheral nerves Flat nose due to destruction of nasal cartilage In 1988, Jacinto Convit was nominated for the Nobel Prize in Medicine for developing a vaccine to fight leprosy using a combination of tuberculosis (TB) vaccines with Mycobacterium Leprae. A number of synthetic pharmaceuticals that are effective against leprosy have now been identified, allowing doctors a flexible choice of treatments. PHARMACEUTICAL MICROBIOLOGY WITH PARASITOLOGY 3 PREPARED BY: CHRISTINE MARIE S. TERRADO, RPh, MSPh  MANILA CENTRAL UNIVERSITY College of Pharmacy Tetanus Tetanus is a medical condition characterized by a prolonged contraction of skeletal muscle fibers. The primary symptoms are caused by tetanospasmin, a neurotoxin produced by the Gram-positive, rod- shaped, obligate anaerobic bacterium Clostridium tetani. Infection generally occurs through wound contamination and often involves a cut or deep puncture wound. C. tetani is not invasive, and the infection is normally confined to a wound. Here the bacteria multiply and produce tetanospasmin, which is able to travel throughout the body. Early symptoms of the disease include: restlessness irritability difficulty swallowing As the infection progresses, muscle spasms develop in the jaw (thus the name “lockjaw”) and elsewhere in the body. Infection can be prevented by proper immunization and by post-exposure prophylaxis. Tetanus often begins with mild spasms in the jaw muscles (lockjaw). The spasms can also affect the chest, neck, back, and abdominal muscles. Back muscle spasms often cause arching, called opisthotonos. Prolonged muscular action causes sudden, powerful, and painful contractions of muscle groups. This is called tetany. Opisthotonus: Muscular spasms (specifically opisthotonos) in a patient suffering from tetanus. Painting by Sir Charles Bell, 1809. Tetanus can be prevented by vaccination with tetanus toxoid. PHARMACEUTICAL MICROBIOLOGY WITH PARASITOLOGY 4 PREPARED BY: CHRISTINE MARIE S. TERRADO, RPh, MSPh  MANILA CENTRAL UNIVERSITY College of Pharmacy Rabies Rabies is a viral disease that causes acute encephalitis (inflammation of the brain) in warm-blooded animals. Rabies literally means “madness” in Latin. The disease is zoonotic and can be transmitted from one species to another, commonly by a bite from an infected animal. In humans, rabies is almost invariably fatal if postexposure prophylaxis is not administered prior to the onset of severe symptoms. The rabies virus infects the central nervous system, travelling from the peripheral nerves to the brain. In humans, the incubation period between infection and the first sign of symptoms is typically two to 12 weeks, although periods as short as four days and longer than six years have been documented. Early-stage symptoms include: Malaise Headache Fever Violent movements Uncontrolled excitement Depression Confusion Agitation Anxiety Hydrophobia Late stage symptoms extend to paranoia, terror, mania, and hallucinations progressing into delirium. Rabid Dog: Close-up of a dog’s face during late-stage “dumb” paralytic rabies. Animals with “dumb” rabies appear depressed, lethargic, and uncoordinated. Gradually they become completely paralyzed. When their throat and jaw muscles are paralyzed, the animals will drool and have difficulty swallowing. Rabies may be diagnosed by PCR or viral culture of brain samples. PHARMACEUTICAL MICROBIOLOGY WITH PARASITOLOGY 5 PREPARED BY: CHRISTINE MARIE S. TERRADO, RPh, MSPh  MANILA CENTRAL UNIVERSITY College of Pharmacy Poliomyelitis Poliomyelitis, often called polio or infantile paralysis, is an acute, viral, infectious disease spread from person to person, primarily via the fecal-oral route. Although approximately 90% of polio infections cause no symptoms at all, affected individuals can exhibit a range of symptoms if the virus enters the blood stream. In about 1% of cases, the virus enters the central nervous system, preferentially infecting and destroying motor neurons, leading to muscle weakness and acute flaccid paralysis. Spinal polio is the most common form, characterized by asymmetric paralysis that most often involves the legs. Polio: Man on street with atrophy and paralysis of the right leg and foot due to polio. Jonas Salk (1914–1995) became a national hero when he allayed the fear of the dreaded disease with his polio vaccine, approved in 1955. Although it was the first polio vaccine, it was not to be the last; Albert Bruce Sabin (1906–1993) introduced an oral vaccine in the United States in the 1960s that replaced Salk's. PHARMACEUTICAL MICROBIOLOGY WITH PARASITOLOGY 6 PREPARED BY: CHRISTINE MARIE S. TERRADO, RPh, MSPh  MANILA CENTRAL UNIVERSITY College of Pharmacy Arboviral Encephalitis Arboviral encephalitis are a group of arthropod-transmitted viruses that cause encephalitis (acute swelling in the brain). The word “arbovirus” directly refers to an ARthropod-BOrne virus. Arthropod vectors transmit the virus upon biting, allowing the virus to enter the circulatory system and replicate and shed additional infection into the bloodstream. The majority of the arboviruses are spherical in shape although a few are rod-shaped. They are 17-150 nm in diameter and most have an RNA genome (the single exception is African swine fever virus, which has a DNA genome). Treatment is therefore only supportive, attempting to deal with problems such as swelling of the brain, loss of the automatic breathing, and activity of the brain. Rickettsial Diseases Rickettsia is a genus of bacteria that can be transmitted by arthropod vectors to humans, causing disease. Rickettsia species are non-motile, Gram-negative, non-sporeforming, highly pleomorphic bacteria that can present as cocci (0.1 μm in diameter), rods (1–4 μm long), or thread-like (10 μm long). They are obligate intracellular parasites, and must replicate within the cytoplasm of eukaryotic host cells. Unlike viruses, Rickettsia possess true cell walls and are similar to other gram-negative bacteria. Despite a similar name, Rickettsia bacteria do not cause rickets, which is a result of vitamin D deficiency. Rickettsia species are carried by many ticks, fleas, and lice, and cause diseases in humans such as typhus, rickettsialpox, Boutonneuse fever, African tick bite fever, Rocky Mountain spotted fever, Flinders Island spotted fever, and Queensland tick typhus (Australian Tick Typhus). Lyme Disease Lyme disease (aka Lyme borreliosis) is caused by bacteria from the Borrelia genus, and is the most common tick-borne disease in the Northern Hemisphere. Borrelia burgdorferi sensu stricto is the main cause of Lyme disease in North America, whereas Borrelia afzelii and Borrelia garinii cause most European cases. Borrelia is transmitted to humans through the bite of infected ticks belonging to a few species of the genus Ixodes “hard ticks”. Lyme disease begins with a localized infection, affecting the area at the site of the tick bite with a circular, outwardly expanding rash called erythema chronicum migrans (EM), which gives the appearance of a bullseye. Lyme Disease: Erythematous rash in the pattern of a “bull’s-eye” from Lyme disease. PHARMACEUTICAL MICROBIOLOGY WITH PARASITOLOGY 7 PREPARED BY: CHRISTINE MARIE S. TERRADO, RPh, MSPh  MANILA CENTRAL UNIVERSITY College of Pharmacy Left untreated, Borrelia bacteria begins to spread through the bloodstream within days to weeks after the onset of local infection, progressing symptoms to the joints, heart, and central nervous system. Plague The plague is an infectious disease caused by the Gram-negative rod-shaped bacteria Yersinia pestis. Human Y. pestis infection is manifested in three main forms: Pneumonic plague Septicemic plague Bubonic plague All three forms are widely believed to have been responsible for a number of high-mortality epidemics throughout human history, including the Plague of Justinian in 542, and the Black Death that accounted for the death of at least one-third of the European population between 1347 and 1353. Y. pestis is spread most commonly between rodents (both urban and wild) and fleas. Any infected animal can transmit the infection to humans through contact with skin tissue. Humans can also spread the bacteria to other humans through sneezing, coughing, or with direct contact with infected tissue. The traditional first line treatment for Y. pestis has been the antibiotics streptomycin, chloramphenicol, tetracycline, and fluoroquinolones. Antibiotic treatment alone is insufficient for some patients, who may also require circulatory, ventilator, or renal support. Cryptococcosis Cryptococcosis, or cryptococcal disease, is a potentially fatal fungal disease. It is caused by one of two species: Cryptococcus neoformans and Cryptococcus gattii. Cryptococcal meningitis is caused when the disease-causing fungus gets in the membranes around the brain. Cryptococcosis is an opportunistic infection, it often affects people who are immunocompromised, such as people who have AIDS. As people who get cryptoccosis often have other health problems, even treatment with anti- fungal agents may not cure the infection. Because of its large polysaccharide capsule, it can be visualized by the India Ink stain. Organisms that possess a polysaccharide capsule exhibit a halo around the cell against the black background created by the India Ink. PHARMACEUTICAL MICROBIOLOGY WITH PARASITOLOGY 8 PREPARED BY: CHRISTINE MARIE S. TERRADO, RPh, MSPh  MANILA CENTRAL UNIVERSITY College of Pharmacy African Trypanosomiasis Human African trypanosomiasis, sleeping sickness, African lethargy, or Congo trypanosomiasis is a parasitic disease of people and animals, caused by protozoa of the species Trypanosoma brucei and transmitted by the tsetse fly. Trypanosoma brucei in a mammalian blood system become a trypomastigote and travels throughout the host mammalian and infects spinal fluid and lymph nodes. PHARMACEUTICAL MICROBIOLOGY WITH PARASITOLOGY 9 PREPARED BY: CHRISTINE MARIE S. TERRADO, RPh, MSPh