1. Hemorrhagic Fevers Ashry Gad Mohamed Prof. of Epidemiology Medical College and KKUH

2. Group of diseases characterized by fever and bleeding n Causes: n Viruses (RVF, DF …etc) n Rickettsia (Rouky Mountain Spotted Fever) n Bacteria (Plaque) n Spirochates (Relapsing fever) n Protozoa (African trypanosomiasis)

3. Virsuses Arboviruses Bunyaviruses All are mosquito borne Sandfly fever Rift valley fever Cramean –Congo fever Group A Togaviruses e.g. encephalitis Group B Togaviruses By Mosquito Yellow fever, Denque fever By Ticks Russian fever E. Spring Summer fever

4. Dengue fever

5. n A disease caused by any one of four closely related viruses. n Characterized by fever, severe headache, backache, joint pains, nausea and vomiting, eye pain and rash n Younger children have milder disease than older children and adults.

6. Dengue Clinical Syndromes n Undifferentiated fever n Classic dengue fever n Dengue hemorrhagic fever n Dengue shock syndrome

7. Undifferentiated Fever n May be the most common manifestation of dengue n Prospective study found that 87% of students infected were either asymptomatic or only mildly symptomatic n Other prospective studies including all age- groups also demonstrate silent transmission DS Burke, et al. A prospective study of dengue infections in Bangkok. Am J Trop Med Hyg 1988; 38:172-80.

8. Clinical Characteristics of Dengue Fever n Fever n Headache n Muscle and joint pain n Nausea/vomiting n Rash n Hemorrhagic manifestations

9. Hemorrhagic Manifestations of Dengue n Skin hemorrhages: petechiae, purpura, ecchymoses n Gingival bleeding n Nasal bleeding n Gastro-intestinal bleeding: hematemesis, melena, n Hematuria n Increased menstrual flow

10. Clinical Case Definition for Dengue Hemorrhagic Fever n Fever, or recent history of acute fever n Hemorrhagic manifestations n Low platelet count (100,000/mm 3 or less) n Objective evidence of “leaky capillaries:” elevated hematocrit (20% or more over baseline) elevated hematocrit (20% or more over baseline) low albumin low albumin pleural or other effusions pleural or other effusions 4 Necessary Criteria:

11. Clinical Case Definition for Dengue Shock Syndrome n 4 criteria for DHF n Evidence of circulatory failure manifested indirectly by all of the following: Rapid and weak pulse Rapid and weak pulse Narrow pulse pressure ( 20 mm Hg) OR hypotension for age Narrow pulse pressure (  20 mm Hg) OR hypotension for age Cold, clammy skin and altered mental status Cold, clammy skin and altered mental status n Frank shock is direct evidence of circulatory failure

12. Four Grades of DHF n Grade 1 Fever and nonspecific constitutional symptoms Fever and nonspecific constitutional symptoms Positive tourniquet test is only hemorrhagic manifestation Positive tourniquet test is only hemorrhagic manifestation n Grade 2 Grade 1 manifestations + spontaneous bleeding Grade 1 manifestations + spontaneous bleeding n Grade 3 Signs of circulatory failure (rapid/weak pulse, narrow pulse pressure, hypotension, cold/clammy skin) Signs of circulatory failure (rapid/weak pulse, narrow pulse pressure, hypotension, cold/clammy skin) n Grade 4 Profound shock (undetectable pulse and BP) Profound shock (undetectable pulse and BP)

13. Danger Signs in Dengue Hemorrhagic Fever n Abdominal pain - intense and sustained n Persistent vomiting n Abrupt change from fever to hypothermia, with sweating and prostration n Restlessness or somnolence Martínez Torres E. Salud Pública Mex 37 (supl):29-44, 1995.

14. Unusual Presentations of Severe Dengue Fever n Encephalopathy n Hepatic damage n Cardiomyopathy n Severe gastrointestinal hemorrhage

15. Signs and Symptoms of Encephalitis/Encephalopathy Associated with Acute Dengue Infection n Decreased level of consciousness: lethargy, confusion, coma n Seizures n Nuchal rigidity n Paresis

16. Incubation period 3-14 days (commonly 4-7 days)

17. Epidemiology

18. History n China : 265-420 A.D. : water poison n French West indies 1635 n Panama 1699 n Jakarta 1779 n Cairo 1779 n Philadelphia 1780 1780 Infrequent large epidemics 1940 1780 Infrequent large epidemics 1940

19. World War II Chinese India (South East Asia). n Manila 1953-54 n India n Pakistan (the leading cause of hospitalization and death among children in SEA 1970s). (the leading cause of hospitalization and death among children in SEA 1970s). n Americas 1970

20. Africa n Before 1980. n 1980 West Africa. n 1980s Central Africa n 1991 Djibouti n --------------------------------- n 1994 Saudi Arabia n 1997 Worldwide disease

21. n Dengue is currently classified as an emerging or re-emerging infectious disease 1. Overcrowded population. 2. Unplanned & uncontrolled urbanization. 3. Lack of effective mosquito control. 4. Increased air travel. 5. Decay of public health measures.

22. n Dengue fever (DF) and dengue haemorrhagic fever/dengue shock syndrome (DHF/DSS) occur in over 100 countries n More than 2.5 billion people at risk and an estimated 50 million infections per year. n The disease is endemic in all WHO Regions except the European Region (EUR).

23. n The major disease burden is found in south-east Asia and the western Pacific. n 1998 1,295,985 3628 n 1999 441,727 681 n 2000 504,114 801 n 2001 525,913 496

24. World Distribution of Dengue 1999 Areas infested with Aedes aegypti Areas with Aedes aegypti and recent epidemic dengue

25. Denque fever in KSA Year N. of suspected cases N. of confirmed cases 199419951996199719981999200020012002673136576231261707112896215003004 Total1020319

26. Risk Factors Reported for DHF n Virus strain DHF risk is greatest for DEN-2, followed by DEN-3, DEN-4 and DEN-1 DHF risk is greatest for DEN-2, followed by DEN-3, DEN-4 and DEN-1 n Pre-existing anti-dengue antibody Persons who have experienced a dengue infection develop serum antibodies that can neutralize the dengue virus of that same (homologous) serotype

27. Risk Factors for DHF (continued) n Higher risk in secondary infections n Higher risk in locations with two or more serotypes circulating simultaneously at high levels (hyperendemic transmission)

28. Virus

29. Dengue Virus n Causes dengue and dengue hemorrhagic fever n Is an arbovirus n Transmitted by mosquitoes n Composed of single-stranded RNA n Has 4 serotypes (DEN-1, 2, 3, 4)

30. Dengue Viruses n Each serotype provides specific lifetime immunity, and short-term cross-immunity n All serotypes can cause severe and fatal disease n Genetic variation within serotypes n Some genetic variants within each serotype appear to be more virulent or have greater epidemic potential

31. Vector and Transmission

32. Transmission of Dengue Virus by Aedes aegypti Viremia Extrinsic incubation period DAYS 0581216202428 Human #1Human #2 Illness Mosquito feeds / acquires virus Mosquito refeeds / transmits virus Intrinsic incubation period Illness

33. Replication and Transmission of Dengue Virus (Part 1) 1. Virus transmitted to human in mosquito saliva 2. Virus replicates in target organs 3. Virus infects white blood cells and lymphatic tissues 4. Virus released and circulates in blood 3 4 1 2

34. Replication and Transmission of Dengue Virus (Part 2) 5. Second mosquito ingests virus with blood 6. Virus replicates in mosquito midgut and other organs, infects salivary glands 7. Virus replicates in salivary glands 6 7 5

35. Aedes aegypti Mosquito

36. Aedes aegypti n Dengue transmitted by infected female mosquito n Highly domesticated tropical mosquito. n Prefer to lay eggs in artificial containers e.g. flower vases, automobile tires…etc. n Prefer to rest indoors. n Prefer to feed on humans during daytime hours.

37. n Have two peaks of biting activity 2-3hours after daybreak. 2-3hours after daybreak. 2-3 hours before dark. 2-3 hours before dark. n Female mosquito are very nervous feeder: feed on several persons during a single blood feed on several persons during a single blood meal. meal. n Single infective mosquito may cause an outbreak.

38. Prevention

39. n Elimination & destruction of mosquitos and larval habitat: Space Spraying of insecticide is not usually effective. Space Spraying of insecticide is not usually effective. Spraying residual insecticides in-door. Spraying residual insecticides in-door. Larval source reduction : Cover water holding Larval source reduction : Cover water holding containers. containers. n Personal protection against mosquito biting: Screening Screening Protective clothing Protective clothing Repellents Repellents n Centralized, vertically-structured programs with military-type organization, strict supervision, high level of discipline

41. للتبليغ عن أماكن تجمّع المياه الراكدة، يمكن التواصل مع أمانة محافظة جدة على الرقم التالي: (940)

42. n Report to health authority. n Isolation of patients: blood precautions n Need to promote dengue as a priority among health officials and the general public n Investigate for source of infection.: patient residence during the two weeks before the illness.

43. n The most cost effective approach to denque fever is tetravalent vaccine. n Promising candidates attenuated virus vaccines have been developed, but not yet evaluated. n Up to date it is unlikely that an effective, safe, and economical vaccine will be available in the near future..

44. Health education n First must educate the public in the basics of dengue, such as: Where the mosquito lays her eggs Where the mosquito lays her eggs The link between larvae and adult mosquitoes The link between larvae and adult mosquitoes General information about dengue transmission, symptoms and treatment General information about dengue transmission, symptoms and treatment