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Viral Hemorrhagic FeverIn KSA (1)
Prof. Marwan Jabr Alwazzeh
KFHU-University of Dammam
Viral Hemorrhagic FeverVirus Genus Name of Hemorrhagic FeverArenaviridae
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 Flavivirus Dengue Flavivirus Omsk Flavivirus Kyasanur Flavivirus Alkhurma
Filoviridae Marburg Marburg Ebola Ebola
Viral Hemorrhagic FeverIn KSA
Dengue FeverAlkhurma Hemorrhagic fever and Kyasanur
Forest disease
Chikungunya fever
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
Dengue Virus
Dengue FeverDengue fever in recent decades has become a
major international public health concern There is good evidence that sequential infection
increases the risk of developing DHFWHO currently estimates:
50 million dengue infections worldwide every year 500 000 people with DHF require hospitalization each
year 2.5% of those affected die
Dengue Transmission Vectors
Aedes albopictus Aedes aegypti
Dengue TransmissionWhereas 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.
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
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
Dengue Transmission Vectors
Dengue Transmission Vectors
Dengue Transmission Vectors
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 transmissionInfected humans serving as a source of the
virus for uninfected mosquitoes Monkeys in some parts of the world play a
similar role in transmission
Dengue cycles
Mosquito Life-Cycle
Natural / plant containers – rain-filled (cavities in trees, bamboo internodes, leaf-axils of plants)
Mosquito Life-Cycle
Artificial containers: Rain-filled Small, discarded containers (bottles, food packaging, dishes, cups)
Mosquito Life-Cycle
Artificial containers Water added or collect by humans
Mosquito Life-Cycle
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
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
Clinical Presentation
The rash usually appears as the fever subsides and lasts 2–4 days
The rash is either macular or maculopapular and generalized
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 daysAny hemorrhagic manifestationThrombocytopenia (i.e., platelet count <100,000/mm³)Evidence of increased vascular permeability (i.e.,
hemoconcentration, pleural or abdominal effusion, hypoalbuminemia, or hypoproteinemia)
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
Dengue FeverDengue 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.
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
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
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
ManagementAsk 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)
Prevention and controlNo drugs for preventing infection are availableHave secure screens on windows and doors to keep
mosquitoes out During outbreaks, insecticides may be sprayed to
kill flying mosquitoesInsecticide treated mosquito nets afford good
protection Wear clothing that adequately covers the arms and
legs, especially during the early morning and late afternoon
Prevention and controlProper solid waste disposal and improved
water storage practices Small, mosquito-eating fish have also
been used with some success
Prevention and controlRepellents 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
Prevention and control Immunization
There is no vaccine to protect against dengueDeveloping 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
Dengue virus infection In KSAWhat’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. 2010 Sep 3;4(8):503-10
Dengue virus infection In KSAWhat’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. 2010 Apr;40(1):215-27.
Dengue virus infection In KSAWhat’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, 1994-2002. Mazen Fakeeh and Ali M Zaki. Dengue Bulletin – Vol 27, 2003
Chikungunya fever
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
Chikungunya virus
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
In 1999-2000 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
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
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
Epidemiology
Signs and symptomsThe 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
Signs and symptomsMost 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 reportedSerious 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
Chikungunya and pregnancyMost 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
DiagnosisSerological 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
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
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
Alkhurma Hemorrhagic Fever (AHFV)
Alkhurma Hemorrhagic Fever (AHFV)
To know what's going on in Alkhurma we should know what
happened in Kyasanur
Kyasanur forest disease (KFD)
A hemorrhagic disease caused by Kyasanur forest disease virus (KFDV), a member of
the virus family Flaviviridae
Kyasanur Forest diseaseAreas of Karnataka State, India
Kyasanur forest disease (KFD)Macaca radiata Presbytis entellus
Kyasanur Forest disease Haemaphysalis spinigera
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)
1983-84 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 an outbreak (98 cases, 6 fatal)
2004 an outbreak (27 cases, 1 fatal)
22.4% of people living in the Andaman and Nicobar Islands are seropositive
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%
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
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 JeddahO. savignyi were found where AHFV infected cases were
reported
Alkhurma Hemorrhagic fever Vector
The hypothesis that mosquitoes could also be vectors was mentioned but no data were provided
Alkhurma Hemorrhagic fever
Reservoir: Not documented. Probably sheep, camels, goats.
Geographical distribution: Unknown. Reported only in Saudi Arabia in Makkah and Najran provinces
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)
EpidemiologyThe climatic conditions in Makkah and
Najran provinces are warm and dryEach 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
Seasonality
Seasonality Annual distribution of 11 AHFV infections in Saudi Arabia, 1994–1999 (Charrel, Zaki et al., 2005)
Alkhurma Hemorrhagic feverIncubation period: Probably 3-8 daysClinical 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
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
Alkhurma Hemorrhagic feverWhat’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] disease1 Feb 2010:
The Ministry of Health has confirmed 7 cases of the Alkhurma hemorrhagic influenza in Makkah and Najran
Alkhurma Hemorrhagic feverWhat’s new?
After its first appearance in Alkhumra district of Jeddah in 1994-1995, and then in Makkah in 2001-2003, 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. 2010 Oct 1.
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
