22: Microbial Diseases of the Nervous System Learning Objectives 1. Define central nervous system and blood-brain barrier. 2. Differentiate meningitis from encephalitis. 3. Discuss the epidemiology of meningitis caused by H. influenzae, S. pneumoniae, N. meningitidis, and L. monocytogenes. 4. Explain how bacterial meningitis is diagnosed and treated. 5. Discuss the epidemiology of tetanus, including mode of transmission, etiology, disease symptoms, and preventive measures. 6. State the causative agent, symptoms, suspect foods, and treatment for botulism. 7. Discuss the epidemiology of leprosy, including mode of transmission, etiology, disease symptoms, and preventive measures. 8. Discuss the epidemiology of poliomyelitis, rabies, and arboviral encephalitis, including mode of transmission, etiology, and disease symptoms. 9. Compare the Salk and Sabin vaccines. 10. Compare preexposure and postexposure treatments for rabies. 11. Explain how arboviral encephalitis can be prevented. 12. Identify the causative agent, reservoir, symptoms, and treatment for cryptococcosis. 13. Identify the causative agent, vector, symptoms, and treatment for African trypanosomiasis and amebic meningoencephalitis. 14. List the characteristics of diseases caused by prions. 15. List some possible causes of chronic fatigue syndrome. New in this Edition • Lyssavirus-related encephalitis is included. • Expanded discussion of amebic encephalitis including primary amebic meningoencephalitis and granulomatous amebic encephalitis. • A new Clinical Problem Solving box describes a recent case of human rabies. Chapter Summary Structure and Function of the Nervous System (p. 643) 1. The central nervous system (CNS) consists of the brain, which is protected by the skull bones, and the spinal cord, which is protected by the backbone. 2. The peripheral nervous system (PNS) consists of the nerves that branch from the CNS. 3. The CNS is covered by three layers of membranes called meninges: the dura mater, arachnoid mater, and pia mater. Cerebrospinal fluid (CSF) circulates between the arachnoid mater and the pia mater in the subarachnoid space. 4. The blood–brain barrier normally prevents many substances, including antibiotics, from entering the brain. 5. Microorganisms can enter the CNS through trauma, along peripheral nerves, and through the bloodstream and lymphatic system. 6. An infection of the meninges is called meningitis. An infection of the brain is called encephalitis. Bacterial Diseases of the Nervous System (pp. 643–652) Bacterial Meningitis (pp. 644–647) 1. Meningitis can be caused by viruses, bacteria, fungi, and protozoa. 2. The three major causes of bacterial meningitis are Haemophilus influenzae, Streptococcus pneumoniae, and Neisseria meningitidis. 3. Nearly 50 species of opportunistic bacteria can cause meningitis. Haemophilus influenzae Meningitis (p. 645) 4. H. influenzae is part of the normal throat microbiota. 5. H. influenzae requires blood factors for growth; there are six types of H. influenzae based on capsule differences. 6. H. influenzae type b is the most common cause of meningitis in children under 4 years old. 7. A conjugated vaccine directed against the capsular polysaccharide antigen is available. Neisseria Meningitis (Meningococcal Meningitis) (pp. 645–646) 8. N. meningitidis causes meningococcal meningitis. This bacterium is found in the throats of healthy carriers. 9. The bacteria probably gain access to the meninges through the bloodstream. The bacteria may be found in leukocytes in CSF. 10. Symptoms are due to endotoxin. The disease occurs most often in young children. 11. Purified capsular polysaccharide vaccine against serotypes A, C, Y, and W-135 is available. Streptococcus pneumoniae Meningitis (Pneumococcal Meningitis) (p. 646) 12. S. pneumoniae is commonly found in the nasopharynx. 13. Hospitalized patients and young children are most susceptible to S. pneumoniae meningitis. It is rare but has a high mortality rate. 14. A conjugated vaccine is available. Diagnosis and Treatment of the Most CommonTypes of Bacterial Meningitis (pp. 646–647) 15. Cephalosporins may be administered before identification of the pathogen. 16. Diagnosis is based on Gram stain and serological tests of the bacteria in CSF. 17. Cultures are usually made on blood agar and incubated in an atmosphere containing reduced oxygen levels. Listeriosis (p. 647) 18. Listeria monocytogenes causes meningitis in newborns, the immunosuppressed, pregnant women, and cancer patients. 19. Acquired by ingestion of contaminated food, it may be asymptomatic in healthy adults. 20. L. monocytogenes can cross the placenta and cause spontaneous abortion and stillbirth. Tetanus (pp. 647–649) 21. Tetanus is caused by a localized infection of a wound by Clostridium tetani. 22. C. tetani produces the neurotoxin tetanospasmin, which causes the symptoms of tetanus: spasms, contraction of muscles controlling the jaw, and death resulting from spasms of respiratory muscles. 23. C. tetani is an anaerobe that will grow in deep, unclean wounds and wounds with little bleeding. 24. Acquired immunity results from DPT immunization that includes tetanus toxoid. 25. Following an injury, an immunized person may receive a booster of tetanus toxoid. An unimmunized person may receive (human) tetanus immune globulin. 26. Debridement (removal of tissue) and antibiotics may be used to control the infection. Botulism (pp. 649–651) 27. Botulism is caused by an exotoxin produced by C. botulinum growing in foods. 28. Serological types of botulinum toxin vary in virulence, with type A being the most virulent. 29. The toxin is a neurotoxin that inhibits the transmission of nerve impulses. 30. Blurred vision occurs in 1 to 2 days; progressive flaccid paralysis follows for 1 to 10 days, possibly resulting in death from respiratory and cardiac failure. 31. C. botulinum will not grow in acidic foods or in an aerobic environment. 32. Endospores are killed by proper canning. The addition of nitrites to foods inhibits growth after endospore germination. 33. The toxin is heat labile and is destroyed by boiling (100°C) for 5 minutes. 34. Infant botulism results from the growth of C. botulinum in an infant’s intestines. 35. Wound botulism occurs when C. botulinum grows in anaerobic wounds. 36. For diagnosis, mice protected with antitoxin are inoculated with toxin from the patient or foods. Leprosy (pp. 651–652) 37. Mycobacterium leprae causes leprosy, or Hansen’s disease. 38. M. leprae has never been cultured on artificial media. It can be cultured in armadillos and mouse footpads. 39. The tuberculoid form of the disease is characterized by loss of sensation in the skin surrounded by nodules. The lepromin test is positive. 40. Laboratory diagnosis is based on observations of acid-fast rods in lesions or fluids and the lepromin test. 41. In the lepromatous form, disseminated nodules and tissue necrosis occur. The lepromin test is negative. 42. Leprosy is not highly contagious and is spread by prolonged contact with exudates. 43. Untreated individuals often die of secondary bacterial complications, such as tuberculosis. 44. Patients with leprosy are made noncontagious within 4 to 5 days with sulfone drugs and then treated as outpatients. 45. Leprosy occurs primarily in the tropics. Viral Diseases of the Nervous System (pp. 652–660) Poliomyelitis (pp. 652–654) 1. The symptoms of poliomyelitis are usually headache, sore throat, fever, stiffness of the back and neck, and occasionally paralysis (fewer than 1% of cases). 2. Poliovirus is transmitted by the ingestion of water contaminated with feces. 3. Poliovirus first invades lymph nodes of the neck and small intestine. Viremia and spinal cord involvement may follow. 4. Diagnosis is based on isolation of the virus from feces and throat secretions. 5. The Salk vaccine (an inactivated polio vaccine, or IPV) involves the injection of formalin- inactivated viruses and boosters every few years. The Sabin vaccine (an oral polio vaccine, or OPV) contains three live, attenuated strains of poliovirus and is administered orally. 6. Polio is a good candidate for elimination through vaccination. Rabies (pp. 654–658) 7. Rabies virus (a rhabdovirus) causes an acute, usually fatal, encephalitis called rabies. 8. Rabies may be contracted through the bite of a rabid animal, by inhalation of aerosols, or invasion through minute skin abrasions. The virus multiplies in skeletal muscle and connective tissue. 9. Encephalitis occurs when the virus moves along peripheral nerves to the CNS. 10. Symptoms of rabies include spasms of mouth and throat muscles followed by extensive brain and spinal cord damage and death. 11. Laboratory diagnosis may be made by direct FA tests of saliva, serum, and CSF or brain smears. 12. Reservoirs for rabies in the United States include skunks, bats, foxes, and raccoons. Domestic cattle, dogs, and cats may get rabies. Rodents and rabbits seldom get rabies. 13. Current postexposure treatment includes administration of human rabies immune globulin (RIG) along with multiple intramuscular injections of vaccine. 14. Preexposure treatment consists of vaccination. 15. Other genotypes of Lyssavirus cause rabies-like diseases. Arboviral Encephalitis (pp. 658–660) 16. Symptoms of encephalitis are chills, headache, fever, and eventually coma. 17. Many types of viruses (called arboviruses) transmitted by mosquitoes cause encephalitis. 18. The incidence of arboviral encephalitis increases in the summer months, when mosquitoes are most numerous. 19. Notifiable arboviral infections are eastern equine encephalitis (EEE), western equine encephalitis (WEE), St. Louis encephalitis (SLE), California encephalitis (CE), and West Nile virus (WNV). 20. Diagnosis is based on serological tests. 21. Control of the mosquito vector is the most effective way to control encephalitis. Fungal Disease of the Nervous System (p. 660) Cryptococcus neoformans Meningitis (Cryptococcosis) (p. 660) 1. Cryptococcus neoformans is an encapsulated yeastlike fungus that causes cryptococcosis. 2. The disease may be contracted by inhalation of dried infected pigeon or chicken droppings. 3. The disease begins as a lung infection and may spread to the brain and meninges. 4. Immunosuppressed individuals are most susceptible to Cryptococcus neoformans meningitis. 5. Diagnosis is based on latex agglutination tests for cryptococcal antigens in serum or CSF. Protozoan Diseases of the Nervous System (pp. 660–662) African Trypanosomiasis (pp. 660–661) 1. African trypanosomiasis is caused by the protozoa Trypanosoma brucei gambiense and T. b. rhodesiense and transmitted by the bite of the tsetse fly. 2. The disease affects the nervous system of the human host, causing lethargy and eventually coma. It is commonly called sleeping sickness. 3. Vaccine development is hindered by the protozoan’s ability to change its surface antigens. Amebic Meningoencephalitis (pp. 661–662) 4. Encephalitis caused by the protozoan Naegleria fowleri is almost always fatal. 5. Granulomatous amebic encephalitis, caused by Acanthamoeba spp. and Balamuthia mandrillaris, is a chronic disease. Nervous System Diseases Caused by Prions (pp. 662–664) 1. Diseases of the CNS that progress slowly and cause spongiform degeneration are caused by prions. 2. Sheep scrapie and bovine spongiform encephalopathy (BSE) are examples of diseases caused by prions that are transferable from one animal to another. 3. Creutzfeldt-Jakob disease and kuru are human diseases similar to scrapie. They are transmitted between humans. 4. Prions are self-replicating proteins with no detectable nucleic acid. Disease Caused by Unidentified Agents (pp. 664–665) Chronic Fatigue Syndrome (pp. 664–665) 1. Chronic fatigue syndrome (CFS) may be caused by an unidentified infectious agent. The Loop For a taxonomic approach, pages can be assigned as follows: Bacterial diseases of the nervous system pp. 643–652 Viral diseases of the nervous system pp. 652–660; 664 Fungal diseases of the nervous system pp. 660 Protozoan diseases of the nervous system pp. 660–662 Diseases caused by prions pp. 662–664 Answers Review 1. Meningitis is an infection of the meninges; encephalitis is an infection of the brain itself. 2. Mode of Causative Agent Susceptible Population Transmission Treatment N. meningitidis Children; military recruits Respiratory Penicillin H. influenzae Children Respiratory Rifampin S. pneumoniae Children; elderly Respiratory Penicillin L. monocytogenes Anyone Foodborne Penicillin C. neoformans Immunosuppressed individuals Respiratory Amphotericin B 3. “Haemophilus” refers to the requirement of this genus for growth factors found in blood (X and V factors) (Chapter 11). “Influenzae” because it was thought to be the causative agent of influenza. 4. The symptoms of tetanus are not due to bacterial growth (infection and inflammation) but to neurotoxin. 5. Salk Sabin Composition Formalin-inactivated viruses Live, attenuated viruses Advantages No reversion to virulence Oral administration Disadvantages Booster dose needed; injected Reversion to virulence 6. a. Vaccination with tetanus toxoid. b. Immunization with antitetanus toxin antibodies. 7. ―Cleaned‖ because C. tetani is found in soil that might contaminate a wound. ―Deep puncture‖ because it is likely to be anaerobic. ―No bleeding‖ because a flow of blood ensures an aerobic environment and some cleansing. 8. Clostridium botulinum. Canned foods. Paralysis. Supportive respiratory care; antitoxin. Anaerobic, nonacidic environment. Diagnosis is made by detecting toxin in foods or patient by inoculating mice with suspect samples. Prevention: use of adequate heat in canning; boiling food before consumption to inactivate toxin. 9. Etiology—Mycobacterium leprae. Transmission—Direct contact. Symptoms—Nodules on the skin; loss of sensation. Treatment—Dapsone and rifampin. Prevention—BCG vaccine. Susceptible—People living in the tropics; genetic predisposition. 10. Etiology—Picornavirus (poliovirus). Transmission—Ingestion of contaminated water. Symptoms—Headache, sore throat, fever, nausea; rarely paralysis. Prevention—Sewage treatment. These vaccinations provide artificially acquired active immunity because they cause the production of antibodies, but they do not prevent or reverse damage to nerves. 11. Etiology—Rhabdovirus. Transmission—Bite of infected animal; inhalation. Reservoirs—Skunks, bats, foxes, raccoons. Symptoms—Muscle spasms, hydrophobia, CNS damage. 12. Postexposure treatment—Passive immunization with antibodies followed by active immunization with HDCV. Preexposure treatment—Active immunization with HDCV. Following exposure to rabies, antibodies are needed immediately to inactivate the virus. Passive immunization provides these antibodies. Active immunization will provide antibodies over a longer period of time, but they are not formed immediately. 13. Disease Etiology Vector Symptoms Treatment Arboviral Togaviruses, Mosquitoes Headache, Immune serum encephalitis Arboviruses (Culex) fever, coma African Trypanosoma Tsetse fly Decreased physical Suramm; trypanosomiasis brucei gambiense, activity and mental melarsoprol T. b. rhodesiense acuity 14. Most antibiotics cannot cross the blood-brain barrier. 15. The causative agent of Creutzfeldt–Jakob disease (CJD) is transmissible. Although there is some evidence for an inherited form of the disease, it has been transmitted by transplants. Similarities with viruses are (1) the prion cannot be cultured by conventional bacteriological techniques and (2) the prion is not readily seen in patients with CJD. Critical Thinking 1. The term rusty nail implies that the sharp object has been contaminated with soil and possibly C. tetani. C. tetani can grow in deep puncture wounds, and a nail is capable of producing such a wound. 2. Both diseases are caused by species of Mycobacterium. 3. The only cases of polio in the United States during the last ten years have been caused by OPV. Clinical Applications 1. Haemophilus influenzae meningitis, treated with rifampin. 2. Cryptococcus neoformans. Need microscopic observation of the fungus from cerebrospinal fluid or culture. 3. Naegleria fowleri meningitis; treated with amphotericin B, miconazole, and rifampin. Case History: An Outbreak of Food Poisoning Background On October 15, a 40-year-old man was admitted to the hospital. He had a ―splitting‖ headache, his legs were unsteady, and his vision was blurred. During examination, it was apparent that there was something wrong with his throat. It wasn’t sore, but it felt stiff and tight, and it was almost impossible for him to speak. Over the next seven days, 28 persons with similar symptoms were admitted to the hospital. Twelve of these patients required ventilatory support; no deaths were reported. During the investigation, it became apparent that the illnesses were due to meals consumed between October 14 and 16 at one restaurant. Detailed food histories were obtained from the patients. An additional case-control study was conducted on well people who had consumed food at the restaurant during the same three-day period. Repeated news media announcements aided health personnel in locating 18 other people who had eaten virtually the same foods at the restaurant. The meals consisted of the following foods: Patty Melt. Frozen hamburger patties purchased from a restaurant distributor. Patties were removed from the freezer and fried as ordered. Presliced pasteurized American cheese purchased from a distributor was kept refrigerated, and a slice was melted on each cooked hamburger patty. Meat and cheese were served on rye bread purchased from a local bakery. Sauteed Onions. Onions were purchased fresh from a farmer. Fresh whole onions were sliced and then sauteed with margarine, paprika, garlic salt, and a chicken-based powder. After the initial cooking, the onions were held uncovered in a pan on a warm stove (<60°C) along with a large volume of melted margarine; they were not reheated before serving. French-Fried Potatoes. Precut frozen potatoes were deep-fried in two- or three-serving batches as needed. Potato Salad. Potatoes were purchased from a farmer. They had been stored in a root cellar and were transported loose in a pickup truck. The potatoes were washed, peeled, diced, and boiled. Cooled, drained potato cubes were mixed with oil, vinegar, dry mustard, and garlic salt, and kept refrigerated. Individual servings were removed from the container as needed. Lettuce and Tomato Salad. Produce was delivered every other day. Lettuce and tomatoes were cut in the morning, refrigerated, and mixed with oil and vinegar for serving. Questions 1. On one page, identify the etiologic agent of this outbreak of food poisoning. 2. Was it food infection or intoxication? 3. What item was contaminated, and how did it become contaminated? 4. Briefly explain how you arrived at your conclusion. How did you eliminate the other major causes of food poisoning? Hints 1. Make a summary table of the persons not ill. 2. Make a table of the onset of symptoms following eating. Data Symptoms Foods Eaten Case Sex Age R H V W D N C Dd Dy M Rd 1 2 3 4 5 1 M 25 26 20 N x x x x x x x x 2 F 20 14 15 Y x x x x x x x x x 3 M 40 15 17 Y x x x x x x x x 4 M 55 14 17 Y x x x x x x x x 5 F 72 15 16 N x x x x x x x x x 6 M 43 15 17 N x x x x x x x 7 F 37 16 17 Y x x x x x x x x x 8 F 51 15 16 Y x x x x x x x x 9 F 25 14 16 N x x x x x x x x x 10 M 40 16 — — x x x x x 11 F 35 14 — — x x x 12 F 39 15 — — x x x x 13 M 54 15 18 N x x x x x x 14 F 34 15 18 Y x x x x x x x x x 15 M 45 14 16 Y x x x x x x x x 16 M 27 16 — — x x x 17 F 37 14 15 Y x x x x x x x x x x 18 M 34 14 — — x x 19M 30 15 — — x x x 20 F 22 16 20 Y x x x x x x x x x 21 F 39 14 17 N x x x x x x x x 22 M 45 16 — — x x x x 23 M 53 14 — — x x x x 24 F 41 15 20 N x x x x 25 F 42 14 16 N x x x x x x x 26 F 54 16 18 Y x x x x x x x x x 27 M 42 16 — — x x x x x x 28 F 43 16 19 N x x x x x x 29 M 42 15 — — x x x x x x 30 F 65 15 — — x x x x x 31 F 33 16 21 N x x x x x x x 32 M 52 14 — — x x x x 33 F 26 14 — — x x x x x x x 34 F 40 15 18 N x x x x x 35 F 22 15 19 Y x x x x x x x x 36 M 63 16 20 N x x x x x x x 37 M 35 15 — — x x x x 38 M 56 15 17 Y x x x x x x x x 39 F 60 15 17 N x x x x x x 40 M 37 15 — — x x x 41 F 28 15 19 N x x x x x 42 M 19 15 — — x x x x 43 F 28 15 — — x x x x 44 F 55 15 17 N x x x x 45 M 28 15 — — x x 46 F 45 15 18 N x x x x x Legend: R = Date at restaurant, H = Date hospitalized, V = Ventilated? Symptoms: W = Weakness, lassitude, D = Diarrhea, N = Nausea, vomiting, C = Constipation, Dd = Diplopia, Dy = Dysphagia, dysphonia, M = Muscle weakness, Rd = Respiratory difficulty. Food: 1–Patty Melt, 2–Sauteed Onions, 3–French-Fried Potatoes, 4–Potato Salad, 5–Lettuce and Tomato Salad. The Solution 1. Clostridium botulinum. 2. Intoxication. 3. The onions were contaminated by C. botulinum from soil. 4. Of the 28 patients, 24 recalled eating the patty melt. All 24 patients, but only 10 of 18 controls, reported eating the sauteed onions. The original batch of sauteed onions was not available for culture or toxin testing, but type A botulinal toxin was detected in an extract made from washings of a discarded foil wrapper used by one of the patients to take a patty melt home. Type A botulinal spores were cultured from 5 of 75 skins of whole onions taken from the restaurant. No other ingredients of the sauteed onions contained toxin or spores.