Blood and Lymphatic Infections

1. Blood and Lymphatic Infections • Chapter 28

2. Tularemia (Rabbit Fever) • Symptoms • Characterized by development of skin ulcerations and enlargement of regional lymph nodes • Other symptoms include • Fever • Chills • Achiness

3. Tularemia (Rabbit Fever) • Causative agent - Francisella tularensis (aerobic, Gram- rod) • Pathogenesis • Causes ulcer at entry sight • Lymphatic vessels carry organism to regional lymph nodes, which may rupture • 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

4. 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

5. 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 gentamicin

6. 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

7. Brucellosis (Undulant Fever) • Causative agent • Four varieties of genus Brucella cause disease in humans (Gram- rod) • 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

8. 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

9. 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

10. 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

11. 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

12. Plague (Black Death) • Causative agent - Yersinia pestis • Facultative intracellular bacteria • Resemble safety pin in stained preparation • Has three plasmids • Smallest is Pla • Causes protective clots to dissolve via activation of plasminogen activator • Middle plasmid codes Yops (Yersinia outer-membrane proteins) and regulators of Yops proteins • Yops permits entry of organism into macrophageswhere they replicate andinterfere with innate immunity • Last is F1 • Becomes anitphagocytic capsule • Used in plague vaccine • Not very good and notorious for adverse reactions

13. 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 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%

14. 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

15. 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

16. 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

17. 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

18. Pathogenesis of Epstein-Barr Virus

19. 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

20. Infectious Mononucleosis • Prevention and Treatment • Avoiding saliva of another person • No vaccine • Acyclovir inhibits productive infection • Has no activity on latent viruses

21. 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

22. 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

23. 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 antiviral treatment

24. 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

25. Malaria

26. 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

27. 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 an unusable form • Stimulates immune system • Overworked immune system fails and immunodeficiency develops

28. Malaria • Epidemiology • Once common in both temperate and tropical areas • Now dominantly disease of warm climate • Eliminated from continental U.S. in late 1940s • Mosquitoes of genus Anopheles are biological vectors • Infected mosquitoes and humans constitute reservoir • Transmission via mosquitoes, blood transfusion and sharing of syringes

29. 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