kDHF (DENGUE HEMORRHAGE FEVER)

Presented by:
Alivia Mulia Adzhari.
Andriani Putri Wulandari.
Bella Rosliyana Tahiya.
Dodi.
Fauziyah Farah Rahmawati.
Ita Lestari.
Nia Humairoh.
Marlina.
Wulan Suci Liandani.
Chapter 1 BACKGROUND
Infection with on of the four serotypes of dengue virus (DENV)
causes a wide spectrum of clinical disease ranging from asymptomatic
infection, undifferentiated fever, dengue fever (DF) to dengue
hemorrhagic fever (DHF). DHF occurs in a minority of patients and is
characterized by bleeding and plasma leakage which may lead to shock.
There are currently no reliable clinical or laboratory indicators that
accurately predict the development of DHF. Human studies have shown
that high viral load and intense activation of the immune system are
associated with DHF. Recently, endothelial cells and factors regulating
vascular permeability have been demonstared to play a role. In the
absence of animal models that closely mimic DHF, human studies are
essential in identifying predictors of severe illness.

A. Definition of DHF
Dengue and DHF are viral diseases transmitted by mosquitoes in
tropical and subtropical regions of the world. Dengue
hemorrhagic fever (DHF) is an infectious disease, cause by four
antigenically related serotypes of dengue virus. Aedes aegypti
mosquito is the main vector in dengue epidemics. Aedes
albopictus and Aedes polynesienses may also be involved in
virus transmission.
Dengue is a mosquito-borne disease caused by any one of
four closely realated dengue viruses (DENV-1, -2, -3, and -4).
Infection with one serotype of DENC provides immunity to that
serotype for life, but provides no long-term immunity to other
serotypes. Thus, a person can be infected as many as four times,
once with each serotype.
DHF is characterized by the acute onset of high fever and is
associated with signs and symptoms similiar to DF in the early
febrile phase. Plasma leakage is the hallmark of DHF which
occurs soon after the end of the febrile phase. There is a
tendency to develop hypovolemic shock (dengue shock
syndrome) due to plasma leakage.

B. History of DHF
The first epidemics of dengue fever were reported in 1770 in Asia, Africa, and
North America. Infections thereafter were periodic and infrequent, and intervals of
10 to 40 years often separated epidemics due to their slow spread by sailing
vessels. Since the early 1980s, however, dengue has been at pandemic levels, its
rapid spread fueled by an expansion of the geographical range of both the
mosquito vector and all of the virus serotypes. Hyperendemicity is growing as
multiple serotypes occupy the same region, resulting in the emergence of more
deadly manifestations of infection, dengue hemorrhagic fever and dengue shock
syndrome.
The modern DF pandemic began in Southeast Asia during the Second World War
as a result of the movement of military equipment that trapped rainwater and led
to the spread of the mosquito vector to previously uninfected regions. During the
war, many water systems were destroyed and the number of water storage
facilities increased, providing new niches for mosquito larvae to exploit. The
outbreak was further spurred by the transit of hundreds of thousands of uninfected.
Japanese and Allied soldiers into infected areas. Mosquito hosts moved into most
of the central and southern islands of the Pacific, although their isolation and
small human population kept dengue epidemics brief. Larger Pacific islands were
also effected, and in 1953 and 1954, an epidemic of DHF occurred in Manila in
the Philippines, having previously appeared in Bangkok, Thailand, in 1950.
Earlier clinical reports of illnesses similar to DHF and DSS appear in medical
records from northeastern Australia in 1987 and Greece in 1982.
Several decades after World War II, DHF again struck Asia in Sri Lanka, India,
Pakistan, Taiwan, China, and Singapore as the range of the virus and its mosquito
vector spread. Multiple serotypes were present during this epidemic, with the
DEN-3 serotype predominating. The responsible viral strain was distinct from
previous isolates. By 1975, DHF was leading cause of hospitalization and death in
children. About 900,000 cases of DHF and DSS occurred in Thailand between the
years of 1958 and 1990. Since then, the incidence of dengue disease in Southeast
Asia has continued to increase in intensity as the presence of multiple viral
serotypes in a given area became more frequent. Four times as many cases of
DHF were reported in the past 15 years than were reported during the previous 30
years.
In Africa, dengue-related disease is also increasing. The surveillance system in the
area is imperfect, but the number of DF epidemics has been raising since1980,
most notably in East Africa (Kenya, Mozambique, Sudan, Djibouti, and Somalia)
and in Saudi Arabia. All four serotypes are active in these regions. Although
sporadic cases of DHF have been reported in several of these countries, no
epidemic of severe disease has occurred. In western Africa and parts of Southeast
Asia, dengue virus also circulates in monkey populations.
Dengue was unknown in the Western Hemisphere until the advent of European
colonization and the African slave trade. In the Americas, programs directed by
the Pan-American Health Organization wiped out the mosquito vector, virtually
eliminating yellow fever and decreasing the incidence of dengue until only
sporadic cases of DF occurred in island areas that failed to eridicate the vector
entirely. During the 1970s, these mosquito control programs were abandoned; as a
result, the incidence of DF is now greater than before the vector control program
began. In 1970, the DEN-2 and DEN-3 serotypes were found in the Americas, and
the latter caused several epidemics in Puerto Rico and Columbia in the mid-1970s.
DEN-1 was introduced into the area in 1977, resulting in epidemics of DF in
Jamaica, Cuba, Puerto Rico, and Venezuella in 1977 and 1978 before spreading
throughout the Caribbean, north into Mexico and Texas, and south into Central
America and northern South America. DEN-4 was imported into the eastern
Caribbean in 1981 and caused major epidemics throughout the surrounding areas.
The same year, a new strain of DEN-2 originating in Southeast Asia (most likely
in Vietnam) was imported into Cuba, leading to the first major epidemic of DHF
in the Americas. Over 10,000 cases of DHF occurred during this outbreak;
however; large-scale hospitalization and effective fluid replacement therapy
limited the number of deaths to 158 people. The next major epidemic of DHF
began in Venezuella in 1989 and 1990, resulting in more than 6,000 cases of
disease and 73 deaths. Between 1990 and 1995, DEN-2 led to a series of smaller
epidemics in Colombia, Brazil, Puerto Rico, and Mexico. By 1997, 18 countries in
the region had reported DHF cases. A novel strain of DEN-3 from Sri Lanka
appeared in 1994 and led to an outbreak of DF in Costa Rica and Panama and
DHF in Nicaragaua. Yellow fever incidence has increased in the tropical areas of
the Americas as well.

Chapter 2 PREVALENCE
A. Global Prevalence of DHF
Regional dengue activity is variable. Malaysia continues to report a
greater number of reported cases in 2014 compared to 2013, for the
same time period. However, cases appear to be decreasing. Singapore has
reported a similar number of cases in 2014 compared to 2013.
Australia, Cambodia, Lao PDR, the Philippines and Viet Nam reported
lower levels of dengue activity in 2014 compared to 2013.

Dengue virus infection in the Pacific Region
High level of dengue activity is being observed in Fiji, French Polynesia,
Solomon Islands and Tuvalu. Dengue virus serotype 3 (DENV-3), to which
a large proportion of the population of the Pacific Islands is likely to be
susceptible has been recently isolated in the Region and is now co-
circulating with serotype 1 (DENV-1). DENV-3 has recently re- emerged in
several countries and territories in the South Pacific after nearly 20 years.
WHO is closely monitoring the situation in the Region, especially with
regard to serotype circulation.

In Fiji, the outbreak since last December has affected over 20,000
individuals, including
13 deaths. Most cases have occurred in the Central Division. The Ministry
of Health, in collaboration with other government sectors and health
partners including WHO, has embarked on controlling and responding to
the outbreak.

In French Polynesia, a dengue outbreak is ongoing. Since February 2013,
there have been 1,906 positive cases of dengue as of 4 April 2014. In the
month of March, all cases serotyped were dengue serotype-1 and the rate
of hospitalization and severe cases has increased.

In Solomon Islands, 754 cases of dengue have been reported since
January 2014 (138 additional cases reported this week). A post disaster
epidemic surveillance system was set up in Honiara and Guadalcanal
Province following flash flooding on 4 April 2014. Rapid reference
laboratory testing of samples by the Institut Louis Malarde, French
Polynesia, confirmed the dengue serotype as type 3. As this is the same
type that caused the large dengue outbreak in 2013, and because
infection with one serotype results in life-long immunity to that specific
serotype, the likelihood of an explosive and widespread outbreak is lower
than if another serotype was identified.
In Tuvalu, a dengue outbreak is occurring with nine confirmed cases out
of 43 dengue- like illness (DLI cases), as of 10 April 2014. The Ministry of
Health has embarked on an extensive clean-up campaign.

B. Local Prevalences of DHF
In 2012, the amount of dengue patients reported as much as 90 245 cases
by the number of deaths 816 (Incidence Rate = 37.11 per 100,000
populations and CFR = 0.90%). There is an increased numbers of cases in
2012 compared in 2011 which amounted to 65 725 cases with IR 27.67.
renstra target of DHF incidence rate cases in 2012 was 53 per 100,000
populations, therefore Indonesia has reached the Renstra target 2012.
Following trends during the period of dengue IR From 2007 to 2012.
You can see pic 3.39 Incidence rate based on province in 2012

Source: Indonesia Ministry of Health, 2013
Picture 3.38
The Incidence rate of DHF
Per 100.000 population in 2008-2012










The strategic plan of Ministry of Health in 2014 for incidence rate of DHF
is <35 per 100,000 population. Accordingly, based on the picture above,
in 2012 there were 15 provinces (45.45%) who reached the Renstra target
in 2012. Meanwhile, based on the target in strategic plan the Ministry of
Health in 2012, which amounted <53 per 100,000 populations, as much
as 22 provinces (66.67%) had reach the target.
In 2012 there were five provinces that have high CFR due to dengue fever
(> 2%) that is Province of West Papua, Maluku, Gorontalo, Bangka Belitung
Island and Jambi. It is shows that still needs efforts to improve the
quality of health services, governance management of patients in health
service facilities, increased quality and quantity of health human
resources in hospitals and clinics (doctors, nurses etc.) including
increased diagnostic support facilities and management for patients in
health care facilities.
In line with the increase in the number / Incidence rate, the number of
regencies / cities infected DHF in 2012 also increased, from 374 (75.25%)
to 417 Regency / City (83.9%) in 2012. This increase was show more
extent of the spread of dengue. Here is an overview the number of
regencies / cities infected in 2008-2012. During the period in 2005 to
2012 the number of regencies / cities dengue is likely to increase.



Picture 3.39
The Incidence rate of DHF
Per 100.000 population in Indonesia period 2012

Picture 3.40
Amount Regencies/cities who had DHF
In Indonesia period 2008-2012

Total of amount regency/cities who get infeced Dengue Haemorrhagic Fever
Based on province in 2012


Incidence rate 100.000/ people, death cases, and case fatality rate (%)
Dengue Hemorrhagic Fever
Based on province in 2012
Chapter 3 MECHANISM OF DHF

Dengue virus that has entered into the body, the patient will cause
viremia. This causes the activation of complement, resulting in antibody
immune complex - will set up a viral reactivation and release substances
(3a, C5a, bradykinin, serotonin, thrombin, histamine), which will
stimulate PGE2 in the hypothalamus resulting in thermo regulation
instable that hyperthermia would increase the reabsorption Na + and
water resulting in hypovolemi. Hypovolemi can also be caused by
increasing the permeability of blood vessel walls causing leakage
plasma. The presence of immune complex antibody - virus also cause
platelet aggregation resulting in impaired platelet function,
thrombocytopenia, and coagulopathy. The third thing that causes
excessive bleeding occurs if shock persists and if the shock is not
resolved, there will be tissue hypoxia and metabolic acidosis finally
happened. Metabolic acidosis also caused due to the leakage of plasma
that eventually occurred systemic circulation thus weakening decreased
tissue perfusion and if not resolved can lead to tissue hypoxia.
Dengue virus incubation period of 3-15 days, an average of 5-8
days. Viruses can only live in a living cell, so it must compete with
human cells, especially in protein requirements. The competition is very
dependent on the human immune system. As a reaction to the infection
occurs:
1) activation of the complement system that excluded
substances that cause an increase anafilaktosin capillary
permeability resulting in leakage of plasma from the
intravascular to the extravascular space,
2) decreased platelet aggregation, would continue if these
abnormalities cause abnormal platelet function as a result
there will be young platelets cell mobilization from bone
marrow and
3) Damage to vascular endothelial cells to stimulate or activate
clotting factors.

These three factors will lead to
1) an increase in capillary permeability;
2) abnormalities of hemostasis, which is caused by
vasculopathy;thrombocytopenia; and kuagulopati



Chapter 4 - SYMPTOMS DHF
After being bitten by a dengue mosquito infected with the dengue virus,
it usually takes between 3 to 14 days to start experiencing symptoms.
During this time you are able to pass the virus on to other dengue
mosquitoes, so if a dengue mosquito bites you it can catch the virus and
go on to infect other people. That is why it is very important to visit a
doctor as soon as you feel unwell.

A. General Symptom DHF
Early symptoms of dengue hemorrhagic fever are similar to those of
dengue fever. But after several days the patient becomes
irritable, restless, and sweaty. These symptoms are followed by a shock-
like state.
Dengue fever has many symptoms, and people usually experience a
combination of symptoms. Common symptoms of dengue fever are:
sudden fever and extreme tiredness
intense headache (especially behind the eyes)
muscle and joint pain
loss of appetite
vomiting, diarrhoea, abdominal pain
a metallic taste in the mouth
red or macular (small, flat red spots) rash occurs in half of cases
minor bleeding from nose and gums
Most symptoms last up to a week and in some cases the fever may return
for another 2-3 days. Dengue fever symptoms affect everyone differently.
They can range from mild, and can even go unnoticed (often in children),
to very severe and potentially fatal. Most people will experience a certain
amount of discomfort, regardless of their specific symptoms, and usually
need to spend a few days resting at home. This is important, not only for
recovery but to reduce the risk of spreading the virus.


B. Specific Symptom DHF
Specific symptoms for DHF are followed by:
1. Bleeding problems such as easy bruising.
2. Low blood presure.
3. Skin hemorrhages.
4. Increased menstrual flow.
5. Bleeding from the nose or gums, and
6. Possible bleeding of the internal organs.
Chapter 5 - TREATMENT FOR DHF
A. Medical Treatment for DHF
Treatment according to groups A-C
1. Group A - patients who may be sent home.
These are patients who are able to tolerate adequate volumes of
oral fluids and pass urine at least once every six hours, and do not
have any of the warning signs, particularly when fever subsides.
Ambulatory patients should be reviewed daily for disease
progression (decreasing white blood cell count, defervescence and
warning signs) until they are out of the critical period. Those with
stable haemotocrit can be sent home after being advised to return
to the hospital immediately if they develop any of the warning
signs and to adhere to the following action plan:
Encourage oral intake of oral rehydration solution (ORS), fruit
juice and other fluids containing electrolytes and sugar to
replace losses from fever and vomiting. Adequate oral fluid
intake may be able to reduce the number of hospitalizations.
[caution: fluids containing sugar/glucose may exacerbate
hyperglycaemia of physiological stress from dengue and
diabetes mellitus]
Give paracetamol for high fever if the patient is
uncomfortable. The interval of paracetamol dosing should
not be less than six hours. Tepid sponge if the patient still
has high fever. Do not give acetylsalicylic acid (aspirin),
ibuprofen or other non-steroidal anti-inflammatory agents
(NSAIDs) as these drugs may aggravate gastritis or bleeding.
Acetylsalicylic acid (aspirin) may be associated with Reyes
Syndrome.
Instruct the care-givers that the patient should be brought to
hospital immediately if any of the following occur: no clinical
improvement deterioration around the time of defervescence,
severe abdominal pain, persistent vomiting, cold and clammy
extremities, lethargy or irritability/restlessness, bleeding(e.g.
black stools or coffee-ground vomiting0, not passing urine
for more than 4-6 hours.
Patients who are sent home should be monitored daily by health
care providers for temperature pattern, volume of fluid intake and
losses, urine output (volume and frequency), warning signs, signs
of plasma leakage anf bleeding, haemotocrit, and white blood cell
and platelet counts.


2. Group B - patients who should be referred for in-hospital
management
Patients may need to be admitted to a secondary health care centre
for close observation, particularly as they approach the critical
phase. These include patients with warming signs, those with co-
exiting conditions that may make dengue or its management more
complicated (such as pregnancy, infancy, old age, obesity, diabetes
mellitus, renal failure, chronic haemolytic diseases), and those with
certain social circumstances (such as living alone, or living for from
a health facility without reliable means transport).
If the patient has dengue with warning signs, the action plan
should be as follows:
Obtain a reference haematocrit before fluid therapy. Give
only isotonic solutions such as 0.9% saline, Ringers locate, or
Hartmanns solution. Start with 5-7ml/kg/hour for 1-2 hours,
then reduce to 3-5ml/kg/hr for 2-4 hours, and then reduce to
2-3ml/kg/hr or less according to the clinical response.
Reassess the clinical status and repeat the haematocrit. If the
haematocrit remains the same or rises only minimally,
continue with the same rate (2-3 ml/kg/hr) for another 2-4
hours. If the vital signs are worsening and haematocrit is
rising rapidly, increase the rate to 5-10 ml/kg/hour for 1-2
hours. Reassess the clinical status, repeat the haematocrit
and review fluid infusion rates accordingly.
Give the minimum intravenous fluid volume required to
maintain good perfusion and urine output of about 0.5
ml/kg/hr. intravenous fluid are usually needed for only 24-48
hours. Reduce intravenous fluids gradually when the rate of
plasma leakage decreases towards the end of the critical
phase. This is indicated by urine output and/ or oral fluid
intake that is/ are adequate, or haematocrit decreasing below
the baseline value in a stable patient.
Patients with warning signs should ne monitored by health
care providers untuil the period of risk is over. A detailed
fluid balance should be maintained. Parameters that should
be monitored include vital signs and peripheral perfusion (1-
4 hourly until the patient is out of the critical phase), urine
output (4-6 hourly), haematocrit (before and after fluid
replacement, then 6-12 hourly), blood glucose, and other
organ functions (such as renal profile, liver profile,
coagulation profile, as indicated).
If the patient has dengue without warning signs, the action plan
should be as follows:
Encourage oral fluids. If not tolerated, start intravenous
fluid therapy of 0.9% saline or Ringers locate with or
without at maintenance rate. For obese and overweight
patients, use the ideal body weight for calculation of fluid
infusion (Textboxes J and K). Patients may be able to take
oral fluids after a few hours of intravenous fluid therapy.
Thus, it is necessary to revise the fluid infusion frequently.
Give the minimum volume required to maintain good
perfusion and urine output. Intravenous fluids are usually
needed only for 2448 hours.
Patients should be monitored by health care providers for
temperature pattern, volume of fluid intake and losses,
urine output (volume and frequency), warning signs,
haematocrit, and white blood cell and platelet counts
(Textbox L). Other laboratory tests (such as liver and renal
functions tests) can be done, depending on the clinical
picture and the facilities of the hospital or health centre.
3. Group C patients who require emergency treatment and urgent
referral when they have severe dengue.
Patient require emergency treatment and urgent referral when
they are in the critical phase of disease, i.e. when they have:
severe plasma leakage leading to dengue shock and/or
fluid accumulation with respiratory distress;
severe haemorrhages;
severe organ impairment (hepatic damage, renal
impairment, cardiomyopathy, encephalopathy or
encephalitis).
All patients with severe dengue should be admitted to a
hospital with access to intensive care facilities and blood
transfusion. Judicious intravenous fluid resuscitation is the
essential and usually sole intervention required. The crystalloid
solution should be isotonic and the volume just sufficient to
maintain an effective circulation during the period of plasma
leakage. Plasma losses should be replaced immediately and
rapidly with isotonic crystalloid solution or, in the case of
hypotensive shock, colloid solutions (Textbox M). If possible,
obtain haematocrit levels before and after fluid resuscitation.
There should be continued replacement of further plasma losses
to maintain effective circulation for 2448 hours. For overweight
or obese patients, the ideal body weight should be used for
calculating fluid infusion rates (textboxes J and K). A group and
cross- match should be done for all shock patients. Blood
transfusion should be given only in cases with suspected/severe
bleeding.
Fluid resuscitation must be clearly separated from simple fluid
administration. This is a strategy in which larger volumes of fluids
(e.g. 1020 ml boluses) are administered for a limited period of
time under close monitoring to evaluate the patients response
and to avoid the development of pulmonary oedema. The degree
of intravascular volume deficit in dengue shock varies. Input is
typically much greater than output, and the input/ output ratio is
of no utility for judging fluid resuscitation needs during this
period.
The goals of fluid resuscitation include improving central and
peripheral circulation (decreasing tachycardia, improving blood
pressure, pulse volume, warm and pink extremities, and
capillary refill time <2 seconds) and improving end-organ
perfusion i.e. stable conscious level (more alert or less restless),
urine output 0.5 ml/kg/hour, decreasing metabolic acidosis.


B. Non Medical Treatment for DHF
How to treat Dengue Fever:
1. Avoiding mosquito bites (use of insecticides, repellents, body
covering with clothing, screening of house, destruction of the
vector breeding sites, using mosquito nets).
2. Eliminaton of larva habitats
3. Planting a plant that mosquito doesnt like such as lavender,
rosemarry, etc. Because mosquito doesnt like strong scent like
eucalyptus, rosemarry, lemon, etc.
4. Placing fish in containers to eat the larvae
5. Do a fogging.
6. Do 3M plus which is closing, draining and hoarding.
Chapter 6 - MANAGEMENT CARE OF DHF
1. Use screen on doors and windows.
2. Remove all sources of stagnant water.
3. Throw away, turn over, empty or store under roof any container
that may accumulate rain water.
4. Remove water in plant pot plates. Clean and scrub the plate
throughly to remove mosquito eggs. Avoid the use of plant pot
plates, if posible
5. Use patio insecticides such as Permethrin (pesticide and repellent)
and Allethrin (candles and lanterns. Wear long sleeve shirts, long
pants, socks and closed shoes to avoid mosquito bites at dusk and
dawn especially.
6. Planting a plant that mosquito dont like.
7. Do a fogging
8. Use mosquito repellents. Use repellents containing DEET (N, N-
diethyl-m-toluamide) or Picardin on your clothing and exposed skin.
Follow manufacturers instructions and CDC recomendations.

Chapter 7 CONCLUSION
Dengue hemorrhagic Fever or DHF is a disease caused by a vector
called Aedes aegypti.
Dengue transmitted by female mosquito.
DHF first reported in 1770 in Asia, Africa, and North America.
Epidemic dengue / dengue hemorrhagic fever (DHF) is a major
public health problem in tropical and sub-tropical countries in
South-East Asia, Westren Pasific, Latin and Central America.
General symptom for DHF is High fever for 2-7 days, Severe
headache, nausea and vomitting, etc. Specific symptoms for DHF is
skin hemorrhages, low blood preasure, etc.
For the medicine treatment you can used antipyretics and
analgetics such as paracetamol.
Never give aspirin and non-steroidal anti inflamantory, beacause
they increased the risk of hemorrhage.
For non medicine treatment is do a fogging, planting a plant that
mosquito doesnt like such as eucalyptus,lavender, rosemarry, etc.
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