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Nervous System and Blood Infections Meningococcal Meningitis • Symptoms • First symptoms similar regardless of agent • Mild cold followed by onset of throbbing headache • Fever • Pain and stiffness of neck and back • Nausea and vomiting • Deafness and alteration in consciousness may appear progressing to coma • Small hemorrhages called petechiae may appear on skin • Infected person may develop shock and die within 24 hours • Usually progression of disease is slower allowing time for treatment Meningococcal Meningitis • Pathogenesis • Acquired by inhaling infected respiratory droplets • Bacteria adhere to mucous membranes via pili and multiply • Invade bloodstream by passing through respiratory epithelium • Bloodstream carries organisms to CSF • Organisms phagocytized by PMNs • Enter fluid in large numbers • Inflammation causes swelling and infarcts to brain tissue • Can also cause obstruction of outflow of CSF • Causes brain to squeeze against skull • Release of endotoxin causes drop in blood pressure leading to shock Meningococcal Meningitis • Causative agent • Neisseria meningitids • Gram negative diplococci • 12 antigenic serotypes • Most serious infections due to types A,B,C and Y • Epidemiology • N. meningitis more prone to cause epidemics • Reasons unknown • Can spread rapidly in crowded stressed places • Human only source of infection • Transmission can occur with disease or asymptomatic carrier • Organism recovered from 5% 15% of healthy individuals Meningococcal Meningitis • Prevention and Treatment • Vaccine is available • Used to control epidemics • Not given routinely due to ineffectiveness in children less than 2 years of age • Effect is not long lasting • Mass prophylaxis with antibiotics helpful at controlling epidemics in small populations • Individuals immediately exposed given antibiotic rifampin • Can usually be cured unless brain injury or shock present • Mortality is less than 10% in treated populations Listeriosis • Symptoms • Most cases asymptomatic • Symptoms include • Fever and muscle aches • Sometimes nausea and diarrhea • 75% of cases coming to medical attention have meningitis • With typical symptoms of meningitis • Pregnant women who become infected often miscarry or deliver terminally ill infants Listeriosis • Causative agent • Listeria monocytogenes • Motile, non-spore forming, facultative Gram (+) rod • Pathogenesis • Mode of entry usually obscure • Generally thought to enter through GI tract • Bacteria penetrate intestinal mucosa then enter the bloodstream • Leads to bacteriemia • Organism can cross the placenta • Produces abscesses in fetal tissues • Babies usually develop meningitis after 1-4 week incubation period Listeriosis • Epidemiology • • • • Widespread in natural waters and vegetation Can be carried asymptomatically in animals and humans Occurs on all continents except Antarctica Pregnant women, elderly and immuncompromised at highest risk • Advised to refrain from soft cheeses and reheat leftovers • Epidemics have resulted from contaminated foods • Organism can survive in commercially prepared foods and at refrigeration temperatures Hansen’s Disease (leprosy) • Symptoms • Begins gradually • Usually with onset of increased or decreased sensation in certain areas of skin • These areas usually have changes in pigmentation • Affected areas later enlarge and thicken • Loss of hair, ability to sweat and sensation • Nerves in extremities visibly enlarge • Usually accompanied with pain that proceeds to numbness, muscle wasting, ulceration • Loss of fingers and toes follows • Changes most obvious in face • Thickening of nose and ears with deep wrinkling Hansen’s Disease (leprosy) • Causative agent • Mycobacterium leprae • Aerobic, acid-fast, rod shaped • Grows slowly • Generation time approximately 12 days Hansen’s Disease (leprosy) • Pathogenesis • Earliest detectable findings in humans is infection of small nerves of skin • Generally via biopsy of skin lesion • Only know human pathogen to preferentially attack peripheral nerves • Grows slowly within macrophages • Course of infection depends on immune response • Macrophages limit growth of organism • Disease may spontaneously stop progressing • Nerve damage although permanent doesn’t progress • Tuberculoid leprosy • Rarely transmitted to others • Uncommon form termed lepromatous leprosy • High numbers of bacteria mucous membranes with very little inflammation Hansen’s Disease (leprosy) • Epidemiology • Transmission via direct human-to-human contact • Disease develops in small number of people • Controlled by body defenses • Natural infections occur in wild nine banded armadillos and mangabey monkeys • Armadillos not a source of human infection • Prevention and Treatment • No proven vaccine • Dapsone and rifampin used to arrest tuberculoid leprosy • Treated for 6 months • Lepromatous treated for 2 years • Combination therapy required to control resistance Botulism • Symptoms • Begins 12 to 36 hours post ingestions of contaminated foods • Begins with dizziness, dry mouth and blurred vision • Abdominal symptoms include pain, nausea, vomiting and diarrhea or constipation • Progressive paralysis ensues • Paralysis of respiratory muscles most common cause of death • Paralysis distinguishes botulism from other forms of food poisoning Botulism • Causative agent • Clostridium botulinum • Gram (+), spore forming rod shaped • Endospores generally resist boiling for hours • Killed by autoclaving • Produces toxin • 7 different toxins • A, B, C1, D, E, F, G • All produced by different strains • A, B, E, F responsible for most human cases Botulism • Pathogenesis • Spores germinate in favorable environment • Bacterial growth results in toxin release • Toxin resist digestion and is absorbed by small intestine • Toxin can circulate in blood stream for 3 weeks or more • Toxin is neurotoxin • Acts against nervous system • One of most powerful poisons known • Toxin attaches to motor nerves blocking function of neurotransmitter • Causes paralysis • Toxin is AB toxin • B portion binds and A portion enters nerve cell Botulism • Epidemiology • Widely distributed in soils and aquatic sediments • In early 20th century foodborne outbreaks common • Strict controls on commercially canned foods decreases incidence Botulism • Intestinal botulism more common than foodborne • Intestinal occurs in small children to 6 months of age • Results in mild disease ranging from mild lethargy to respiratory insufficiency. • Flaccid Baby Syndrome Botulism • Prevention and Treatment • Prevention depends on proper sterilization and sealing of canned food • Heating food to 100°C for 15 minutes just prior to eating generally makes food safe to eat • Can’t rely on smell, taste or appearance to detect contamination • Treated by intravenous administration of antitoxin ASAP • Antitoxin only neutralizes circulating toxin • Affected nerves recover slowly • Gastric washing and surgical removal of tissues removes unabsorbed toxin • Artificial respiration may be required for prolonged periods Viral Meningitis • Symptoms • Typically abrupt in onset • Characterized by • • • • • • Fever Severe headache above or behind eyes Stiff neck with increased pain on forward flexion Sensitivity to light Nausea and vomiting May have sore throat, chest pain, swollen parotid gland and skin rash • Depends on causative agent Viral Meningitis • Causative agent • Small, non-enveloped RNA virus • Member of the enterovirus subgroup of picornavirus family • Responsible for at least half of viral meningitis cases • Most common offenders are coxsackie virus and echovirus • Pathogenesis • Begins with infection of throat and intestinal epithelium • Progresses to lymphoid tissue in the bloodstream • Viremia results in meningeal infection • May also be responsible for rash and chest pain Viral Meningitis • Epidemiology • Relatively stable in environment • Can survive in chlorinated water • Infected often eliminate virus in feces • Often for weeks • Transmission via fecal-oral route • Mumps virus transmitted via respiratory droplets • Prevention and Treatment • Handwashing and avoidance of crowded swimming pools • When aseptic disease present in community • No vaccine against coxsakievirus and echoviruses • Mumps virus controlled via immunization Viral Encephalitis • Symptoms • Onset usually abrupt • Characterized by • • • • fever Headache Vomiting one or more nervous system abnormalities • Disorientation, localized paralysis, deafness, seizures or coma Viral Encephalitis • Causative agent • Arboviruses • Arthropod borne viruses • Transmitted by insects, mites and ticks • Viruses enveloped single stranded RNA viruses Viral Encephalitis • Pathogenesis • Knowledge of pathogenesis incomplete • Viruses multiply at site of bite and in local lymph nodes • Produces viremia • Virus crosses blood-brain barrier • Mechanism unknown • Causes extensive damage to brain tissue in severe cases • Progression of disease halted with appearance of neutralizing antibody • Mortality ranges from 2% to 50% depending of type of infecting agent • Disabilities often present in those who recover Viral Encephalitis • Epidemiology • Only minority infected develop encephalitis • Other develop viral meningitis • Disease are all zoonoses • Maintained naturally in birds and rodents • Humans are accidental hosts • LaCrosse encephalitis usually causes most cases of encephalitis Viral Encephalitis • Prevention and Treatment • Animals often used to identify emergence of disease • Equine encephalitis generally infects horses 1 – 2 weeks before first human case seen • Sentinel chickens serve same function • Prevention directed towards • Avoiding outdoor activities at night when mosquito populations highest • Make sure windows and porches properly screened • Use insect repellents and insecticides • No proven antiviral therapy Infantile Paralysis, Polio • Symptoms • Usually begins with symptoms of meningitis • Pain and spasm of muscles generally occur • This is usually followed by paralysis • Paralyzed muscles shrink and bones do not form normally • In severe cases respiratory muscles become paralyzed • Artificial respiration is required • Some recovery if patient survives acute stage Infantile Paralysis, Polio • Causative agent • Poliovirus • There are three types • 1, 2 and 3 • Distinguished via anitsera • Small, enveloped, single-stranded RNA virus • Member of picornavirus • Subgroup enterovirus Infantile Paralysis, Polio • Pathogenesis • Enter body orally • Virus infects the throat and intestinal tract • Then moves to bloodstream • Immune system conquers infection in most people • Viruses enters nervous system of small percentage of people • Virus attacks motor nerves • Infected cells are destroyed upon cell release • Post-polio syndrome • Development of muscle weakness and pain many years after acute disease Infantile Paralysis, Polio • Epidemiology • Virus widespread in areas where sanitation is poor • Virus usually spread via fecal-oral route • In endemic areas people generally do not escape childhood without contracting disease • These individuals develop immunity • Babies receive antibodies transplacentally • Babies develop disease within 2 to 3 months of age • Develop lifelong immunity Infantile Paralysis, Polio • Prevention and Treatment • Virus stable under natural conditions • Inactivated by pasteurization and chlorination • Control directed at vaccination • Oral vaccine until 1999 • Vaccine cause of some cases of polio • Oral vaccine discontinued • New injectable vaccine introduced in 1999 Rabies • Symptoms • • • • • • Fever Head and muscle ache Sore throat Fatigue Nausea Tingling or twitching at site of viral entry • Characteristic symptom • Early symptoms begin 1 to 2 months post infection • Progress rapidly to secondary symptoms of • Encephalitis, agitation, confusion, hallucinations, seizure, increased sensitivity to light and touch • Body temperature rises with increased salivation and difficulty swallowing • Results in frothing of mouth • Hydrophobia occurs in 50% of cases • Coma develops • About 50% of patients die within 4 days Rabies • Causative agent • Rabies virus • Member of rhabdovirus family • Sticking bullet shape • Enveloped, single-stranded RNA genome • Pathogenesis • Mode of transmission primarily via saliva of rabid animal • Usually due to bite or abrasion • Can be contacted via inhalation • Virus multiples in muscle cells at site of infection • Virus reaches brain via infected nerve • Virus multiplies extensively in brain • Negri bodies form at sites of replication Rabies • Epidemiology • Widespread in wild animals • 5,000 cases reported annually in United States • Skunks, raccoons and bats considered chief reservoir • Raccoons most infected • Almost all human cases due to contact with infected bats • Zero to 4 reported cases in U.S annually • Only 25% have history of dog bite • Long incubation period of virus make history unreliable Rabies • Prevention and Treatment • Wash wound immediately and thoroughly • Use soap and water and apply antiseptic • Risk of developing rabies from bite of rabid dog is approximately 30% • Risk can be lowered considerably if vaccine is administered as soon as possible after exposure • Presumably vaccine provokes better immune response • Bitten individual should receive series of 5 injections at wound site and intramuscularly • Shots should be given even if biting animal presumed to be rabid • No effective treatment for rabies • Only six know survivors of disease Cryptococcal Meningioencephalitis • Symptoms • Develop gradually in healthy individuals • Generally consist of • • • • Difficulty thinking Dizziness Intermittent headache Slight or no fever • Slow progression of disease results in other symptoms • • • • • Vomiting Weight loss Paralysis Seizures coma Cryptococcal Meningioencephalitis • Causative agent • Yeast form of Filobasidiella neoformans fungus • Small, spherical yeast • Generally surrounded by large capsule Cryptococcal Meningioencephalitis • Pathogenesis • Fungus becomes airborne in dust • Enters body via inhalation and establishes infection first in lung • Infection often eliminated by body defenses • Organism multiplies and enters bloodstream • Capsule inhibits phagocytosis and neutralizes opsonins • Organisms typically cause thickening of meninges • This can often impede the flow of CSF • Also invade brain tissue producing abscesses Cryptococcal Meningioencephalitis • Epidemiology • Distributed worldwide in soil and vegetation • Numerous in soil where pigeon droppings accumulate • For every one case of disease millions are infected with organism • Symptomatic infection often the first indicator of AIDS • Person-to-person spread does not occur Cryptococcal Meningioencephalitis • Prevention and Treatment • No vaccine or other preventative measures • Treatment with amphotericin B is effective • Often given concurrently with flucytosine or itraconazole • Amphotericin B does not reliably cross blood-brain barrier • Drug administered through tube inserted through the skull into lateral ventricle African Sleeping Sickness • Symptoms • First symptoms appear within a week after bite from tsetse fly • Nodule develops at site of bite • Regional lymph nodes enlarge • Symptoms may disappear spontaneously • Weeks or years later recurrent fevers develop • CNS involvement marked by gradual loss of interest in everything • Marked by decreased activity and indifference to food • Eyelids droop and individual falls asleep during everyday tasks • Speech becomes slurred followed by coma and death African Sleeping Sickness • Causative agent • Trypanosoma brucei • Flagellated protozoan • Slender with wavy undulating membrane • Two subspecies • T. brucei rhodesiense • Occurs mainly in cattleraising areas of East Africa • T. brucei gambiense • Occurs mainly in forested areas of Central and West Africa • Transmitted by tsetse fly African Sleeping Sickness • Pathogenesis • Protozoan enters through bite in fly saliva • Organism multiplies at skin and migrates to lymphatic and blood circulation • Body responds with fever and IgM antibody • Symptoms improve • Period followed by recurrent increases in numbers of parasite • Termed parasitemica • Parasitemia and antibody production continue until treatment or death • T. brucei rhodesiense infections progress quickly often with major system involvement with 6 weeks and death in 6 months • T. brucei gambiense infections progress much more slowly African Sleeping Sickness • Epidemiology • Disease occurs on African continent within 15° of equator • 10,000 to 20,000 new cases annually • Occurrence of disease is determined by distribution of tsetse fly • Wild animals main reservoir for Rhodesian form • Humans are main reservoir for Gambian form • Human-to-human transmission more common African Sleeping Sickness • Prevention and Treatment • Prevention measures directed against tsetse fly vectors include • Insect repellents and protective clothing • Traps with bait and insecticide • Clearing brush • • • • Treatment of infected individuals help reduce reservoir Single injection of pentamidine prevents Gambian form Suramin can be used if no CNS involvement Melarsoprol and eflornithine used with CNS involvement Transmissible Spongiform Encephalopathies • Symptoms • Early symptoms • • • • Vague behavioral changes Anxiety Insomnia Fatigue • These symptoms progress weeks to months to hallmark symptoms • • • • • • Muscle jerks Lack of coordination Dementia Deteriorating intellectual function Impaired judgment Memory loss • Disease often progresses to death within a year Transmissible Spongiform Encephalopathies • Causative agent • Proteinaceous infectious particles • a.k.a prions • Appear to be new class of infectious agent • Differ from bacteria, viruses and viroids • Main characteristics • • • • • • • Increase in quantity during incubation period Resist inactivation via UV and ionizing radiation Resist inactivation by formaldehyde and heat Not readily destroyed by proteases Not destroyed by nucleases Much smaller than smallest virus Composed of protein coded by normal cellular gene • Modified after transcription Transmissible Spongiform Encephalopathies • Pathogenesis • No inflammatory or immune response produced • Replication depends on presence of normal cellular protein • Replicate by converting normal protein into copies of themselves • Normal course of infections • Replication in spleen • Most likely in dendritic cells • Then transported to nervous system via nerve axon • Prions aggregate in insoluble masses in nerve cells • Causes malfunction and death Transmissible Spongiform Encephalopathies • Epidemiology • Creutzfeld-Jakob occurs in humans over age 45 • Human-to-human transmission has occurred via corneal transplants • Scrapie found in sheep • Most likely transmitted from ewe to lamb • Mad cow disease result of cattle exposed to scrapie in cattle feed • New varient Creutzfeld-Jakob mostly likely due to exposure of human to mad cow disease • Median age of onset of NVCJ is 28 years Transmissible Spongiform Encephalopathies • Prevention and Treatment • Prions inactivated by autoclaving in 1N NaOH • No treatment • All forms are fatal Subacute Bacterial Endocarditis • Symptoms • Marked fatigue and slight fever • Typically become ill gradually • Slowly lose energy over a period of weeks or months • Abrupt development of stroke may occur • Causative Agent • Usually member of normal bacterial flora of mouth and skin • α-hemolytic viridians streptococci and Staphylococcus epidermis Subacute Bacterial Endocarditis • Pathogenesis • Bacteria gain entry to bloodstream during dental procedures, toothbrushing or other trauma to mouth or skin • Organisms may become trapped in clots formed near deformed heart valves • Organism may multiply and produce biofilms • Organisms inaccessible to phagocytic killing • As organisms multiply more clot is formed • Clot builds to fragile mass • Bacteria break away from clot and are washed away • Clots may block significant vessels • Leads to tissue death, infarction and aneurysm • Masses of organism growing in heart can burrow into tissue and cause abscesses Subacute Bacterial Endocarditis • Epidemiology • Viridians streptococci account for smaller portion of cases • Due to dentist prescribing antibiotics to patients with distinct heart murmurs before treatment • More cases of disease produced by Staphylococcus epidermidis • Occur most often in • Injected-drug users • Patients with intravenous catheter • Particularly if used for extended periods • Individuals with artificial heart valves Subacute Bacterial Endocarditis • Prevention and Treatment • No proven prevention • Antimicrobial treatment to susceptible population previous to dental procedures most notable attempt to prevent • Rigid attention to sterile technique helps prevent occurrence in hospital setting • Only bacteriocidal medication are effective in treatment • Usually two or more given together for prolonged period • Penicillin and gentimicin given over one or more months Gram Negative Septicemia • Symptoms • Violent shaking chills and fever • Often accompanied by anxiety and rapid breathing • In case of septic shock • Urine output drops • Respiration and pulse become more rapid • Arms and legs become cool and dusky colored Subacute Bacterial Endocarditis • Causative agent • • • • Gram (-) bacteria more likely cause of fatal septicemia Shock is common despite treatment Mortality rate nearly 50% Blood cultures from patients usually reveal • E. coli • Gram (-) facultative anaerobe • Ps. Aeruginosa • Gram (-) aerobe • Generally found in natural environment • Bacteroides sp. • Gram (-) aerobe • Part of normal intestinal and upper respiratory flora Subacute Bacterial Endocarditis • Pathogenesis • Generally originates outside of bloodstream • Alterations in normal body defenses may allow organism to infect blood • Endotoxin is released • Antibiotics can enhance endotoxin release • Macrophages respond intensely to endotoxin to try to localize • Exaggerated response considered hypersensitivity • Failed localization allows endotoxin into bloodstream • Causes cascade of harmful events • Lungs particularly susceptible to irreversible damage • Often results in death despite successful treatment of infection Subacute Bacterial Endocarditis • Epidemiology • Mainly a nosocomial disease • Reflects high incidence of Gram (-) bacteriemia in hospitals • General trend to increasing disease that relates to increased life span, antibiotic suppression of normal flora, use of immunosuppressive drugs and biofilm formation of medical devices Subacute Bacterial Endocarditis • Prevention and Treatment • Depends largely on identification and effective treatment of localized infections • Treatment against causative organisms • Treatment methods will vary according to infecting organism Tularemia (Rabbit Fever) • Symptoms • Characterized by development of skin ulcerations and enlargement of regional lymph nodes • Other symptoms include • Fever • Chills • Achiness • Symptoms usually abate in 1 to 4 weeks • Sometimes may become chronic • Mortality rate between 30% and 50% Tularemia (Rabbit Fever) • Causative agent • Francisella tularensis • Non-motile, aerobic, Gram (-) rod • Pathogenesis • Causes ulcer at entry sight • Lymphatic vessels carry organism to regional lymph nodes • Become large, tender and filled with pus • Spread to other body sites via lymphatics and blood vessels • Pneumonia occurs in 10% -15% of lung infections • Mortality rate as high as 30% • Multiplies within phagocytes • Cell mediated immunity responsible for ridding infection • 90% of infected individuals survive in the absence of treatment Tularemia (Rabbit Fever) • Epidemiology • Occurs among wild animals in Northern Hemisphere • In eastern U.S. most infections occur in winter • Result from skinning hunted rabbits • In western U.S. infections increase in summer • Due to bites from fleas and ticks • Other reservoirs for infection include • Muskrats, beavers, squirrels, and deer • Animals generally free of illness Tularemia (Rabbit Fever) • Prevention and Treatment • Uses of Rubber gloves and goggles when working with animal carcasses • Insect repellents and protective clothing • Inspect routinely for ticks after exposure • Vaccine available for workers at higher risk of exposure • Treated with gentimicin Brucellosis (Undulant Fever) • Symptoms • Onset usually gradual and symptoms vague • Symptoms include • Aches and pains • Enlarged lymph nodes • Weight loss • Without treatment most cases recover within 2 months • 15% will be symptomatic for 3 months or longer Brucellosis (Undulant Fever) • Causative agent • Four varieties of genus Brucella cause disease in humans • All fall into a single species Brucella melitensis • Traditionally each variety given own species name depending on preferred host • B. abortus cattle • B. canis dogs • B. melitensis goats • B. suis pigs • Organism is Gram (-) rod Brucellosis (Undulant Fever) • Pathogenesis • Organism penetrates mucous membranes or break in skin • Disseminated via lymphatic or blood vessels • Generally to heart and kidneys • Spleen enlarges in response to infection • Organisms resistant to phagocytic killing • Can grow within phagocytes • These organisms inaccessible to antibodies and some antibiotics • Mortality generally due to endocarditis • Rate is approximately 2% • Osteomyelitis is often serious side effect Brucellosis (Undulant Fever) • Epidemiology • Chronic infection of domestic animals • Generally involving the mammary gland and uterus • Causes contaminated milk and abortions • Abortion not a feature of human disease • Occurs in workers in meat packing industry • Major problem in animals used for food Brucellosis (Undulant Fever) • Prevention and Treatment • Pasteurization most important control measure • Inspection of domestic animals • Protective eyewear and gloves when working with animals or animal carcass • Attenuated vaccine controls disease in domestic animals • Tetracycline combined with rifampin used for treatment • Treatment usually given for 6 weeks Plague (Black Death) • Symptoms • Develop abruptly 1 – 6 days post infection • Transmission via bite from infected flea • Disease characterized by large tender lymph nodes called buboes • Other symptoms include • • • • • High fever Shock Delirium Patchy bleeding under the skin May also have cough and bloody sputum • Only in lungs infected • Pneumonic plague Plague (Black Death) • Causative agent • Yersinia pestis • Facultative intracellular bacteria • Resemble safety pin in stained preparation • Has three kinds of plasmids • Smallest is Pla • Causes protective clots to dissolve via activation of plasminogen activator • Middle plasmid codes Yops proteins and regulators of Yops proteins • Yops interferes with phagocytosis • Last is F1 • Becomes anitphagocytic capsule • Used in plague vaccine Plague (Black Death) • Pathogenesis • • • • Masses of organism obstruct digestive tract of rat fleas Flea regurgitates infected material into bite wound Pla is essential to spread from site of entry Organisms multiply within macrophages • Produce F1 capsule while in macrophages • Macrophages die and release organism • Organism encapsulated and produces Yops proteins and other mechanisms that enhance survival • Inflammation in nodes results in characteristic swelling • Nodes become necrotic and spill organisms • • Septicemic plague Mortality rate of untreated reaches between 50% and 80% Plague (Black Death) • Epidemiology • Endemic on rodent populations in all continents except Australia • Prairie dogs, rock squirrels and their fleas are main reservoir • Hundreds of fleas can transmit plague and can remain infectious for a year • Can spread person to person by household fleas • Organism can remain viable for weeks in dried sputum and flea feces Plague (Black Death) • Prevention and Treatment • Prevention directed by rat control • • • • Proper garbage disposal Rat-proof buildings Guards on mooring ropes Extermination programs • Killed vaccine gives short-term partial protection • Treatment via tetracycline for some exposed individuals to control epidemics • Gentimicin, ciprofloxacin and doxycycline effective on disease if given early Infectious Mononucleosis • Symptoms • Appear after long incubation • Usually 30 to 60 days post infection • Symptoms include fever, sore throat covered with pus, fatigue, enlarged lymph nodes and spleen • Most cases fever and sore throat disappear within 2 weeks, lymph node enlargement within 3 Infectious Mononucleosis • Causative agent • Caused by Epstein-Barr virus • Double stranded DNA virus • Belongs to herpesvirus family • Pathogenesis • Infection begins in cells of throat and mouth and become latent in another cell type • Virus carried to lymph nodes after replication in epithelial cells of mouth, saliva producing glands and throat • Infects B lymphocytes • Infection can be productive or nonproductive • Productive – kills cells • Nonproductive – virus is latent • Virus activates B cells to produce multiple clones • Clones produce immunoglobulin Pathogenesis of Epstein-Barr Virus Infectious Mononucleosis • Epidemiology • Distributed worldwide • Infects individuals in crowded, economically disadvantaged areas • Infects at early age without producing symptoms producing immunity • More affluent populations missed exposure and lack immunity • Occurs almost exclusively in adolescents and adults who lack antibody • Virus present in saliva for up to 18 months • Mouth-to-mouth kissing important mode of transmission • No animal reservoir Infectious Mononucleosis • Prevention and Treatment • Avoiding saliva of another person • No vaccine • Acyclovir inhibits productive infection • Has no activity on latent viruses Yellow Fever • Symptoms • Disease can range from mild to severe • Most common form may be only fever and slight headache lasting a day or two • Severe disease characterized by high fever, nausea, nose bleeds and bleeding into the skin, “black vomit” from GI bleeding and jaundice • Mortality rate of severe disease can reach 50% • Reason for the variation in symptoms is unknown Yellow Fever • Causative agent • Enveloped, single stranded RNA arbovirus • Belongs to flavivirus family • Virus multiplies in mosquitoes • Mosquitoes transmit virus to humans • Pathogenesis • Introduce via bite of Aedes mosquitoes • Multiplies and enters blood stream • Carried to liver • Jaundice results in liver damage • Injury to small blood vessels produces petechiae • Kidney failure is a common consequence of disease Yellow Fever • Epidemiology • Reservoir mainly infected mosquitoes and primates in tropical regions of Central and South America and Africa • Periodically spread to urban areas via mosquito bite • Prevention and Treatment • Control achieved by spraying and elimination of breeding sites • Control almost impossible in jungle regions • Attenuated vaccine available for high risk groups • No proven antiviral treatment Malaria • Symptoms • “flu-like” • Includes fever, headache and pain in the joints and muscles • Generally begin 2 weeks post infection • Transmission via bite of infected mosquito • Symptom pattern changes after 2 to 3 weeks • Fall into three categories • Cold phase – abruptly feels cold and develops shaking • Hot phase – follows cold phase • Temperature rises steeply reaching 104°F • Wet phase – follows hot phase • temperature falls and drenching sweat occurs Malaria • Causative agent • Human malaria caused by four species of genus Plasmodium • P. vivax, P. falciparum, P. malatiae, P. ovale • Infectious form of parasite injected via mosquito • Carried by bloodstream to liver • Infects cells of liver • Thousands of offspring released to produce infection in erythrocytes Malaria • Pathogenesis • Characteristic feature • Recurrent bouts of fever followed by times of wellness • Caused by erythrocytic cycle of growth and release of offspring • Each species has different incubation periods, degrees of severity and preferred host age and range • Spleen enlarges to cope with large amount of foreign material and abnormal RBC • Common cause of splenic rupture • Parasites cause anemia by destroying red RBC and converting iron from hemoglobin to no-usable form • Stimulates immune system • Overworked immune system fails and immunodeficiency develops Malaria • Epidemiology • Once common in both temperate and tropical areas • Now dominantly disease of warm climate • Eliminated from continental U.S. in late 1940’s • Mosquitoes of genus Anopheles are biological vectors • Infected mosquitoes and humans constitute reservoir • Transmission via mosquitoes, blood transfusion and sharing of syringes Malaria • Prevention and Treatment • Treatment is complicated • Due to different stages of mosquito life cycle • Chloroquine • Effective against erythrocyte stage • Will not cure liver infection • Primaquine and tafenoquine • Generally effective against exoerythrocyte stage and certain species gametocytes