RICKETTSIACEAE

1. RICKETTSIACEAE Dr.T.V.Rao MD T Dr.T.V.Rao MD

2. Zinsser, Lice And History • In 1935, Harvard Medical School physician and researcher Hans Zinsser wrote the brilliant and original Rats, Lice and History in which he traced the effects of vermin-borne disease on armies, cities and populations. From his extensive research on head and body lice, Zinsser stated unequivocally that "the body and head louse carry the infection [typhus] from one human to another. Dr.T.V.Rao MD

3. Zinsser, Lice And History Dr.T.V.Rao MD

4. General Characteristics • Small obligate intracellular coccobacilli • Gram negative (poorly), better stained with Giemsa (Blue) • Have cell wall, bigger than virus but smaller than bacteria • Have DNA and RNA • Have an ATP transport system that allows them to use host ATP • Arthropod reservoirs and vectors ( e.g., ticks, mites, lice or fleas). • Sensitive to antibiotics Dr.T.V.Rao MD

5. Category of rickettsia • Genus Rickettsia, Coxiella ,Orientia,Ehrlichia Bartonella • Species Rickettsia prowazekii (epidemic typhus), Rickettsia typhi (endemic typhus), Rickettsia rickettsii (spotted fever), Rochalimaea quintana (trench fever), Coxiella burnetii (Q fever) Dr.T.V.Rao MD

6. History • 17th-19th century • Epidemics in Europe as a result of war, disaster, or in prisoners • 1909: Transmission by lice • 1917-1925: Russia • Estimated 25 million cases • End of WWII • DDT used for control • Vaccine developed Dr.T.V.Rao MD

7. Historical Photograph on Typhus Dr.T.V.Rao MD

8. Structure: of Bacteria • Similar with Gram negative bacteria • Cell wall: outer membrane • peptidoglycan • lipopolysaccharide (LPS) • Microcapsule and polysaccharide • Two antigenically distinct groups: • LPS: heat-stable, cross-reactive with somatic antigens of non-motile Proteus species (Weil-Felix test) • Outer membrane protein: heat-unstable, species-specific Dr.T.V.Rao MD

9. Rickettsia • Small gram negative Bacilli • Obligate intracellular pathogens. • Parasites on - Lice, Fleas, Ticks Mites colonizes the Gut. In vertebrates colonizes Vascular endothelium and Reticuloendothelial system. T.V.Rao MD Dr.T.V.Rao MD

10. Five genera in this class cause human diseases: • Rickettsia • Bartonella • Coxiella (does NOT cause skin rash) • Ehrlichia • Orientia Dr.T.V.Rao MD

11. Replication Dr.T.V.Rao MD

12. Five genera in this class cause human diseases: • Rickettsia • Bartonella • Coxiella (does NOT cause skin rash) • Ehrlichia • Orientia Dr.T.V.Rao MD

13. Dr.T.V.Rao MD

14. Genera • 1.Rikettsia, • 2.Orientia • 3.Ehrcichia Dr.T.V.Rao MD

15. Typhus Group • Murine typhus (also known as endemic • typhus and flea borne typhus) • – Rickettsia mooseri (typhi) • • Epidemic typhus (also known as Brill- • Zinsser disease and louse borne typhus) • – Rickettsia prowazekii • • Scrub typhus (or Chigger fever) • – Rickettsia tsutsugamushi Dr.T.V.Rao MD

16. The Others • Q Fever • – Coxiella burnetii • • Ehrlichiosis • – Ehrlichia canis • – Ehrlichia equi • – Ehrlichia chafeensis • – Several others now identified Dr.T.V.Rao MD

17. RICKETTSIAL INFECTIONS • Fever, headache, malaise, prostration, skin rash & Hepatosplenomegaly • Classified into groups: 1. Typhus Group – Epidemic typhus, Murine typhus, Scrub typhus 2. Spotted Fever Group – RMSF, Rickettsia pox 3. Q Fever 4. Trench fever 5. Ehrlichiosis Dr.T.V.Rao MD

18. Diseases Caused by the Rickettsia Dr.T.V.Rao MD

19. Dr.T.V.Rao MD

20. Rickettsia Prowazekii( Von Prowazekii ) • Humans natural vertebrate hosts • Vector - Human body louse,( Pediculus humans corporis ) • Lice get infected from patients. • Life cycle – get multiplied in gut 1 week • Person – person contact. • Lice bite causes itching and scratching • Enters through respiratory tract / Conjunctivae • Incubation 5- 15 days Dr.T.V.Rao MD

21. Genus -Rickettsia • Two groups Typhus fevers, Spotted fever. Morphology Rickettsia pleomorphic Coco bacillary, Size 0.3 to 0.6 micron x 0.8 - 2 microns. Gram negative, non motile Non capsulate not stained easily Giemsa and Gimenez staining methods. Dr.T.V.Rao MD

22. Typhus Fever Dr.T.V.Rao MD

23. Typhus Fever group • 1. Epidemic Typhus • 2. Recrudescent typhus ( Brill Zinsser’ disease ) • 3. Endemic typhus Dr.T.V.Rao MD

24. EPIDEMIC TYPHUS (LOUSEBORNE TYPHUS) • Etiology: R. prowazekii • severe systemic infection & prostration • more fatal • Brill-Zinsser Disease  recrudescent disease Dr.T.V.Rao MD

25. Epidemic Typhus - 1 • Also known as louse borne typhus because it • is spread human-to-human via the body louse • (which dies of its infection with Rickettsia • prowazekii after about three weeks) • • This is a serious disease consisting of fever, • severe headache, myalgia, and central rash • • Untreated, the mortality ranges from 20-40% • • Major killer in concentration camps of WW II Dr.T.V.Rao MD

26. Cultivation • Needs cell culture lines • Grows in the Cytoplasm • Grows at 32 to 350 c • Grows in yolk sac of developing chick embryo • Grows in mouse fibroblasts, Hela,Hep2 Dr.T.V.Rao MD

27. Cultivation • Rickettsia can not be grown in bacteriological media, Obligate intracellular pathogens. • In continuous cell lines, Guinea pig, Mice • Infect the endothelial cells of vascular system. • Can synthesize ATP Dr.T.V.Rao MD

28. Life Cycle of Rickettsia Dr.T.V.Rao MD

29. Replication Dr.T.V.Rao MD

30. Transmission • Human body louse • Pediculus humanus corporis • Infective for 2-3 days • Infection acquired by feeding on infected person • Excrete R. prowazekii in feces at time of feeding • Lice die within 2 weeks Dr.T.V.Rao MD

31. Transmission • Louse feces rubbed into bite or superficial abrasions • Inhalation of feces • Sylvatic typhus • Flying squirrel • 30 human cases in eastern and central U.S. Dr.T.V.Rao MD

32. PATHOLOGY Multiply in endothelial cells of small blood vessels Vasculitis (skin – rashes;other organs – DIC & vascular occlusion) Swollen & necrotic Thrombosis of the vessels Dr.T.V.Rao MD

33. Antigenic structure • Species differ with Group specific antigens. • Sharing of antigens between Rickettsia and Proteus basis of Weil – Felix Heterophile agglutination Test. • Used Proteus strains 0X 19, OX2 OXK T.V.Rao.MD Dr.T.V.Rao MD

34. Epidemic Typhus Also called as Louse borne Typhus Classical Typhus Russia Eastern Europe Devastating Epidemics in wars Napoleons retreat Russia 3 million deaths 1917 – 1921 India - Kashmir Dr.T.V.Rao MD

35. R. Prowazekii Louse Human Human Louse Epidemic typhus Dr.T.V.Rao MD

36. R. Typhi Rodent Flea Rat TickFlea Human Rodent Murine typhus (much milder than epidemic typhus) Dr.T.V.Rao MD

37. Lesions in Epidemic Typhus Dr.T.V.Rao MD

38. Rickettsia Prowazekii( Von Prowazekii ) • Humans - natural vertebrate hosts • Vector - Human body louse,( Pediculus humans corporis ) • Lice get infected from patients. • Life cycle – get multiplied in gut 1 week • Person – person contact. • Lice bite causes itching and scratching • Enters through respiratory tract / Conjunctivae • Incubation 5- 15 days Dr.T.V.Rao MD

39. Pediculus humanus corporis is the Vector Dr.T.V.Rao MD

40. Clinical Symptoms • Incubation: 7-14 days • High fever, chills, headache, cough, severe myalgia • May lead to coma • Macular eruption • 5-6 days after onset • Initially on upper trunk, spreads to entire body • Except face, palms and soles of feet Dr.T.V.Rao MD

41. Clinical Features • Fever, chills • Rash on 4 th day Spread from Trunk to Limbs Not face palms, sole. • In 2 nd week may into stuporous,delirious state May reach 40 % fatality • Bacteria remain latent in Lymphoid tissue, cloudy state. Because of called as Typhus • May cause Recrudescent Typhus ( Called as Brill Zinser Disease.) Dr.T.V.Rao MD

42. Brill-Zinsser Disease • Occurs years after primary attack • Person previously affected or lived in endemic area • Viable retained organisms reactivated • Milder symptoms • Febrile phase 7-10 days • Rash often absent • Low mortality rate Dr.T.V.Rao MD

43. Brill- Zinser DiseaseRecrudescent typhus fever • Earlier recovery from typhus fever • Latency of the organism in lymphoid tissue • Reactivation leads to recrudescence. • Even louse get infected from patients. • Clinically similar but mild. Dr.T.V.Rao MD

44. Pattern of Temperature chart in Typhus Fever Dr.T.V.Rao MD

45. Endemic TyphusR.mooseri • Also called as Murine or Flea borne typhus • From Rats -Transmitted by Rat flea • Rickettsia multiplies in Gut and shed in feces • Humans bitten by infected Rat flees. • Saliva or feces rubbed on bitten area, may lead to infection. • R.typhi R. Prowazekii similar, Biological and Immunological tests. Dr.T.V.Rao MD

46. Clinical features • Mild disease • Rat act as reservoir. • Vector – Rat flea -Xenopsylla – cheopsis • Rat flea bites rat • Multiplies in the gut of the rat • Fleas un affted. • Man gets infected accidentally • Mexico Kashmir - china T.V.Rao MD Dr.T.V.Rao MD

47. Experiments on Animals Neill-Mooser Reaction • Male guinea pig inoculated intra peritioneally with blood of patients, or isolates of S.typhi produce – Fever, and scrotal swelling, enlarged tests, and cannot be pushed back.-due inflammation and adhesions between layers of Tunica vagina • Test positive in R.typhi Dr.T.V.Rao MD

48. Treatment • Chloramphenicol • Tetracycline • Doxycycline 200mg • Response within 48 hrs. usually • Vaccine • Developed after World War II • Not commercially available Dr.T.V.Rao MD

49. Spotted Fever Group • Rickets 1906 • Rickettsia of this group, multiplies in Nucleus and Cytoplasm • Ticks transmit Dr.T.V.Rao MD

50. Dr.T.V.Rao MD