1. Viral Hemorrhagic Fever In KSA (1)
Prof. Marwan Jabr Alwazzeh
KFHU-University of Dammam

2. Viral Hemorrhagic Fever
Virus Genus
Name of Hemorrhagic Fever
Arenaviridae
Guanarito
Venezuelan
Junin 
Argentinian
Machupo
Bolivian
Lassa
Lassa (West Africa)
Sabia
Brazilian or Sao Paulo
Bunyaviridae 
Nairovirus
Crimean-Congo
Phlebovirus 
Rift Valley
Hantaan virus
Korean
Hantavirus pulmonary syndrome
Flaviviridae
Flavivirus
Yellow
Dengue
Omsk
Kyasanur
Alkhurma
Filoviridae 
Marburg 
Ebola

3. Viral Hemorrhagic Fever In KSA
Dengue Fever
Alkhurma Hemorrhagic fever and Kyasanur Forest disease
Chikungunya fever

4. Dengue Fever
Four immunologically related, single positive-stranded RNA viruses known as dengue viruses (DENV-1 through DENV-4) of the genus Flavivirus, family Flaviviridae
Infection with one DENV produces lifelong immunity against reinfection with that one virus and short-term (≤9 months), partial cross-protection against the other three dengue viruses

5. Dengue Virus

6. Dengue Fever
Dengue fever in recent decades has become a major international public health concern
There is good evidence that sequential infection increases the risk of developing DHF
WHO currently estimates:
50 million dengue infections worldwide every year
people with DHF require hospitalization each year
2.5% of those affected die

7. Dengue Transmission Vectors
Aedes albopictus
Aedes aegypti

8. Dengue Transmission
Whereas Ae. aegypti is confined within the tropics and sub-tropics, Ae. albopictus also occurs in temperate and even cold temperate regions
In recent decades Ae. albopictus has spread from Asia to become established in areas of Africa, Europe and the Americas
Both species are found biting outdoors, but Ae. aegypti will also readily feed indoors and is often found in dark, cool places such as in closets, under beds, behind curtains, and in bathrooms.

9. Dengue Transmission Vectors
The bite of one infected mosquito can result in infection
The risk of being bitten is highest during the early morning after daybreak, and in the late afternoon before sunset, because the female mosquito typically feeds (bites) during these hours

10. Dengue Transmission
In Africa several other mosquito vectors have been implicated in disease transmission, including species of the A. furcifer-taylori group and A. luteocephalus
There is evidence that some animals, including non-primates, may act as reservoirs

11. Dengue Transmission Vectors

12. Dengue Transmission Vectors

13. Dengue Transmission Vectors

14. Dengue cycles
After virus incubation for 8 to 10 days, an infected mosquito is capable, during probing and blood feeding, of transmitting the virus for the rest of its life
There is transovarial transmission
Infected humans serving as a source of the virus for uninfected mosquitoes
Monkeys in some parts of the world play a similar role in transmission

15. Dengue cycles

16. Mosquito Life-Cycle

17. Mosquito Life-Cycle
Natural / plant containers – rain-filled (cavities in trees, bamboo internodes, leaf-axils of plants)

18. Mosquito Life-Cycle
Artificial containers: Rain-filled Small, discarded containers (bottles, food packaging, dishes, cups)

19. Artificial containers Water added or collect by humans
Mosquito Life-Cycle
Artificial containers Water added or collect by humans

21. Clinical Presentation
The incubation period is typically 4–7 days (range 3–14 days)
The clinical manifestations range from mild, undifferentiated febrile illness to classic DF or DHF

22. Clinical Presentation
Dengue fever is defined clinically by an acute febrile illness with two or more of the following symptoms: headache, retro-orbital pain, muscle or joint pain, rash, hemorrhagic manifestation, or leucopenia
Other signs and symptoms include flushed facies (usually during the first 24–48 hours), nausea, and vomiting

23. Clinical Presentation
The rash usually appears as the fever subsides and lasts 2–4 days
The rash is either macular or maculopapular and generalized

24. Clinical Presentation
Approximately 1% of patients with DF develop DHF as the fever subsides (usually 3–7 days following the onset of fever)
Dengue hemorrhagic fever is defined by the presence of all the following symptoms:
Fever or recent history of fever lasting 2–7 days
Any hemorrhagic manifestation
Thrombocytopenia (i.e., platelet count <100,000/mm³)
Evidence of increased vascular permeability (i.e., hemoconcentration, pleural or abdominal effusion, hypoalbuminemia, or hypoproteinemia)

25. Clinical Presentation
Thrombocytopenia can occur with classic DF and does not by itself indicate DHF
Dengue Shock Syndrome (DSS) is defined as a syndrome in any case patient who meets the criteria for DHF and has hypotension, narrow pulse pressure (≤20 mm Hg), or frank shock

26. Dengue Fever Dengue infection among pregnant women:
The infant can be born with dengue infection or acquire dengue during labor and delivery and then develop the clinical manifestations of DF or DHF
Transplacental transfer of maternal antidengue antibodies (from a previous maternal infection) may place infants at greater risk for DHF with their first dengue infection.

27. Diagnosis
The diagnosis can be laboratory confirmed by one of the following means:
From serum or tissue samples by (RT-PCR)
Anti-dengue antibody titer:
Seroconversion from negative to positive
Four-fold or greater change
dengue viral antigen identification in autopsy tissue samples by immunofluorescence or immunohistochemical analysis

28. Diagnosis
Caution should be exercised when using anti-dengue IgM or IgG antibody positivity from a single sample for diagnosis because there is cross-reactivity between anti-dengue IgM and IgG antibodies with antibodies from other flaviviruses
Previous infection or vaccination with another flavivirus may also result in false-positive anti-dengue antibody results

29. Management No specific therapeutic agents exist for dengue infections
Encourage bed rest and maintenance of fluids to prevent dehydration
Control fever with acetaminophen
Headache, back pain and muscle aching may be so severe as to require narcotics
Acetylsalicylic acid and other nonsteroidal anti-inflammatory drugs should be avoided

30. Management
Ask patients to watch for warning signs of DHF or DSS as fever declines 3–7 days after onset of symptoms:
Abrupt change from fever to hypothermia
Severe abdominal pain
Persistent vomiting
Bleeding
Breathing difficulties
Altered mental status (e.g., irritability, confusion, lethargy)

31. Prevention and control
No drugs for preventing infection are available
Have secure screens on windows and doors to keep mosquitoes out
During outbreaks, insecticides may be sprayed to kill flying mosquitoes
Insecticide treated mosquito nets afford good protection
Wear clothing that adequately covers the arms and legs, especially during the early morning and late afternoon

32. Prevention and control
Proper solid waste disposal and improved water storage practices
Small, mosquito-eating fish have also been used with some success

33. Prevention and control
Repellents can be applied to exposed skin or to clothing in strict accordance with product label instructions
Repellents should contain:
DEET (N, N-diethyl-3-methylbenzamide),
IR3535 (3-[N-acetyl-N-butyl]-aminopropionic acid ethyl ester)
Icaridin (1-piperidinecarboxylic acid, 2-(2-hydroxyethyl)-1-methylpropylester)
Oil of lemon eucalyptus

34. Prevention and control Immunization
There is no vaccine to protect against dengue
Developing a vaccine against the disease is challenging:
With four closely related viruses
With limited understanding of how the disease typically behaves and how the virus interacts with the immune system
With lack of laboratory animal models available to test immune responses

35. Dengue virus infection In KSA What’s new?
Significant differences in the clinical presentation of dengue virus (DENV) infection, indicative of a variation in disease severity from dengue fever (DF) to dengue hemhorrhagic fever (DHF)/dengue shock syndrome (DSS), were noted over the years. Possible reasons are infection with different serotypes, concurrent/sequential infection of more than one serotype, and differences in host immune responses associated with host genetic variations. .
Clinical profile of dengue fever infection in King Abdul Aziz University Hospital Saudi Arabia. Ahmed MM J Infect Dev Ctries Sep 3;4(8):503-10

36. Dengue virus infection In KSA What’s new?
Distribution and seasonal activity of mosquitoes in al Madinah Al Munwwrah, Saudi Arabia:
The population density started to increase in March, with a peak in August when temperature was 36 degress C. The activity started to decrease in October, and minimum activity was in January, when temperature was below 5 degrees C. The seasonal abundance of adult mosquitoes was not affected by rainfall. A. aegypti, vector of Dengue fever virus, Cx. tritaeniorhynchus, vector of Rift Valley fever and Cx. univittatus, vector of sindbis virus were reported for the first time in Al Madinah Al Munawwrah Region. These vectors constituted a major health problem, and every effort should be made for feasible control. .
Distribution and seasonal activity of mosquitoes in al Madinah Al Munwwrah, Saudi Arabia. Kheir SM, Alahmed AM, Al Kuriji MA, Al Zubyani SF. J Egypt Soc Parasitol Apr;40(1):

37. Dengue virus infection In KSA What’s new?
During February 1994-December 2002, a total of 1,020 suspected clinical cases were examined by laboratory methods. Dengue virus infection was confirmed in 319 (31.3%) cases, 209 by virus isolation and the rest by serological techniques. DEN-1, DEN-2 and DEN-3 were detected between 1994 and 2002 in that order of frequency. Using IgG immunofluorescent assay or haemagglutination–inhibition (HI) test, the prevalence of dengue reactive antibodies in the suspected group was confirmed in 515 (50.5%) of the 1,020 samples tested
Dengue in Jeddah, Saudi Arabia, Mazen Fakeeh and Ali M Zaki. Dengue Bulletin – Vol 27, 2003

38. Chikungunya fever

39. Chikungunya fever
Chikungunya is a mosquito-borne viral disease first described during an outbreak in southern Tanzania in 1952
Chikungunya virus was first isolated from the blood of a febrile patient in Tanzania in 1953
The name ‘chikungunya’ derives from a root verb in the Kimakonde language, meaning "to become contorted" and describes the stooped appearance of sufferers with joint pain

40. Chikungunya virus

41. Chikungunya fever
Chikungunya virus is an alphavirus of the family Togaviridae.
Chikungunya virus is spread by the bite of an infected mosquito Aedes aegypti and Aedes albopictus.
Monkeys, and possibly other wild animals, may also serve as reservoirs of the virus.
In recent decades mosquito vectors of chikungunya have spread to Europe and the Americas

43. Epidemiology
In there was a large outbreak in the Democratic Republic of the Congo, and in 2007 there was an outbreak in Gabon
Starting in February 2005, a major outbreak of chikungunya occurred in islands of the Indian Ocean
A large outbreak of chikungunya in India occurred in 2006 and 2007

44. Epidemiology
Several other countries in South-East Asia were also affected
In 2007 transmission was reported for the first time in Europe, in a localized outbreak in north-eastern Italy

46. Epidemiology
Co-circulation of dengue fever in many areas may mean that chikungunya fever cases are sometimes clinically misdiagnosed as dengue infections, therefore the incidence of chikungunya fever could be much higher than what has been previously reported
There is “Silent” chikungunya; but how commonly this happens is not yet known
Chikungunya virus infection is thought to confer life-long immunity

47. Signs and symptoms
The incubation period can be 2-12 days, but is usually 3-7 days
Often symptoms in infected individuals are mild and the infection may go unrecognized, or be misdiagnosed in areas where dengue occurs
Chikungunya is characterized by:
An abrupt onset of fever frequently accompanied by very debilitating joint pain
muscle pain
headache
nausea
Fatigue: some patients have prolonged fatigue lasting several weeks
rash

48. Signs and symptoms
Most patients recover fully, but in some cases joint pain may persist for several months, or even years
Occasional cases of eye, neurological and heart complications have been reported
Serious complications are not common, but in older people, the disease can contribute to the cause of death
No hemorrhagic cases related to chikungunya virus infection have been conclusively documented

49. Chikungunya and pregnancy
Most infections occurring during pregnancy will not result in the virus being transmitted to the fetus
The highest risk for infection of the fetus/child occurs when a woman has viremia at the time of delivery
There are also rare reports of first trimester abortions
Currently, there is no evidence that the virus is transmitted through breast milk

50. Diagnosis
Serological tests (ELISA) confirm the presence of IgM and IgG anti-chikungunya antibodies
IgM antibody levels are highest three to five weeks after the onset of illness and persist for about two months
The virus may be isolated from the blood during the first few days of infection
RT–PCR methods are available but are of variable sensitivity

51. Treatment
There is no specific antiviral treatment currently available for chikungunya fever.
Treatment is symptomatic and can include rest, fluids, and medicines to relieve symptoms of fever and aching

52. Prevention and control
There is no commercial chikungunya vaccine
A person with chikungunya fever should limit their exposure to mosquito bites to avoid further spreading the infection

53. Alkhurma Hemorrhagic Fever (AHFV)

54. Alkhurma Hemorrhagic Fever (AHFV)
To know what's going on in Alkhurma we should know what happened in Kyasanur

55. Kyasanur forest disease (KFD)
A hemorrhagic disease caused by Kyasanur forest disease virus (KFDV), a member of the virus family Flaviviridae

56. Kyasanur Forest disease Areas of Karnataka State, India

57. Kyasanur forest disease (KFD)
Macaca radiata
Presbytis entellus

58. Kyasanur Forest disease Haemaphysalis spinigera

59. Kyasanur forest disease (KFD)
March 1957
466 human cases and 5 deaths
1981
> 550 cases and 15 deaths
1983
an outbreak (326 cases, 29 fatal)
1555 cases and 180 deaths
1999
an outbreak (10 cases)
2000
outbreaks in endemic areas (9 deaths)
2002
an outbreak (98 cases, 6 fatal)
2003
2004
an outbreak (27 cases, 1 fatal)
22.4% of people living in the Andaman and Nicobar Islands are seropositive

60. Kyasanur forest disease (KFD)
Incubation period of 3-8 days
The symptoms of KFD begin suddenly with fever, headache, severe muscle pain, cough, dehydration, gastrointestinal symptoms and bleeding problems
Patients may experience abnormally low blood pressure, and low platelet, red blood cell, and white blood cell counts
The disease has a morbidity rate of 2-10%

61. Alkhurma Hemorrhagic Fever (AHFV)
Alkhurma Hemorrhagic fever virus Isolated for the first time in 1994 in Alkhumra district (south of Jeddah), Makkah province, Saudi Arabia
AHFV is Flavivirus Genetically very closely related to Kyasanur forest disease (KFD) virus

62. Alkhurma Hemorrhagic fever Vector
Available data are in favour of ticks bite transmission:
AHFV is genetically and serologically closely Related to tick-borne flaviviruses
Tick bite has been associated with clinical cases
AHFV RNA was recently detected in ticks (Ornithodoros savignyi) collected on a camel resting place in Jeddah
O. savignyi were found where AHFV infected cases were reported

63. Alkhurma Hemorrhagic fever Vector
The hypothesis that mosquitoes could also be vectors was mentioned but no data were provided

64. Alkhurma Hemorrhagic fever
Reservoir: Not documented. Probably sheep, camels, goats.
Geographical distribution: Unknown. Reported only in Saudi Arabia in Makkah and Najran provinces

65. Alkhurma Hemorrhagic fever Transmission
Transcutaneous, by contact with infected blood on a skin wound or by infective tick bite, which is probably under-estimated
Digestive, by consumption of unpasteurised dairy products from infected animals
To date, no human-to-human transmission has been reported (as for KFD)

66. Epidemiology
The climatic conditions in Makkah and Najran provinces are warm and dry
Each year, during Hajj’s period, a large number of livestock are imported to Makkah city, through Jeddah’s seaport
In the absence of a specific AHFV surveillance system epidemiological data are scarce and provided by few studies

68. Seasonality
Seasonality Annual distribution of 11 AHFV infections in Saudi Arabia, 1994–1999 (Charrel, Zaki et al., 2005)

69. Alkhurma Hemorrhagic fever
Incubation period: Probably 3-8 days
Clinical manifestations: Acute febrile flulike illness with
Hepatitis (100%)
Hemorrhagic manifestations (55%)
Encephalitis (20%)
The potential existence of paucisymptomatic and asymptomatic forms is unknown but probable
Lethality: 25-30% of reported cases

70. Alkhurma Hemorrhagic fever
Diagnostic:
Direct diagnosis is done by detection of viral genome by RT-PCR, and/or isolation on cell culture.
Serological detection of specific IgM can be performed (possible cross reactions with other flaviviruses)
Treatment: Only symptomatic
Vaccine: No vaccine

71. Alkhurma Hemorrhagic fever What’s new?
2 cases identified in 2003, 1 case in 2004, 4 cases in 2005, 1 cases in 2007, 12 cases in 2008, and 58 cases in 2009
5 Jan 2010:
Laboratory tests in Jeddah identified 4 cases of Alkhurma hemorrhagic fever [AHFV] disease
1 Feb 2010:
The Ministry of Health has confirmed 7 cases of the Alkhurma hemorrhagic influenza in Makkah and Najran

72. Alkhurma Hemorrhagic fever What’s new?
After its first appearance in Alkhumra district of Jeddah in , and then in Makkah in , the new hemorrhagic fever virus, known as Alkhumra (misnamed as Alkhurma) virus (ALKV), has subsequently been reported from Najran, in the south border of Saudi Arabia.
ALKV infection has now been recognized outside its original boundaries in Saudi Arabia which may herald its identification in other countries.
Alkhumra (Alkhurma) Virus Outbreak In Najran, Saudi Arabia: Epidemiological, Clinical, And Laboratory Characteristics. Madani TA, Azhar EI, Abuelzein ET, Kao M, Al-Bar HM, Abu-Araki H, Niedrig M, Ksiazek TG. J Infect Oct 1.

73. COMMENTS
There is a lack of epidemiological, veterinary and entomological data
The cycle of transmission is also still poorly known
In absence of active detection (seroprevalence survey), the circulation of the virus in other areas (inside or outside the country) cannot be excluded