Dengue Haemorrhagic Fever, Essays (university) of Medicine

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DENGUE HEMORRHAGIC FEVER

3.1. Dengue Fever

3.1.1. Definition

Dengue fever is the most common fever in the age group of children, adolescents

and adults. In general, dengue fever is an acute febrile condition, which sometimes has a

biphasic pattern and is accompanied by severe headaches, myalgias, arthralgias, skin

rashes, leukopenia and thrombocytopenia. Even though dengue fever is actually a harmless

condition, it can cause sufferers to be unable to do activities due to severe headaches,

muscle, joint and bone pain (break-bone fever), especially in adults. Sometimes atypical

bleeding occurs, such as gastrointestinal bleeding, hypermenorrhea, and massive epistaxis.

In areas experiencing dengue fever epidemics, transmission of dengue fever rarely occurs

between local residents

Dengue hemorrhagic fever (DHF) is more common in children under 15 years of

age in hyperendemic areas, and it is associated with recurrent dengue infection. However,

its incidence in adults is also increasing. DHF is characterized by a high fever with an

acute onset with symptoms and signs similar to the symptoms and signs of dengue fever in

the initial phase. In DHF, abnormalities in bleeding can be found, for example, a positive

tourniquet (rumple leed) test, petechiae, bruises and gastrointestinal bleeding in more

severe cases.

At the end of the febrile phase, there is a threat of hypovolemic shock (dengue

shock syndrome) due to plasma leakage. The emergence of warning signs such as

persistent vomiting, abdominal pain, lethargy, restlessness, irritability, and oliguria is an

important thing to be followed up immediately in order to prevent shock. Hemostatic

disorders and plasma leakage are the main pathophysiological processes in DHF.

Thrombocytopenia and increased hematocrit/hemoconcentration are features that are

invariably encountered before a reduction in fever/onset of shock. DHF mostly occurs in

children who get a second infection with the dengue virus. There are also reports of DHF

cases occurring in the first infections with DENV-1 and DENV-3 viruses as well as

infections in infants. 6

Most infections in the United States are brought in from other countries. Risk

factors for dengue include having antibodies to the dengue virus from a previous infection

(Vyas, et al, 2014). Dengue virus belongs to the genus Flavirus, family flaviridae, there are

4 serotypes of the virus with DEN-1, DEN-2, DEN-3 and DEN-4, all four of which are

found in Indonesia with the most den-3 serotypes. Infection with one serotype will produce

antibodies against the serotype in question, while the antibodies formed against the other

serotypes are very lacking, so they cannot provide adequate protection against other

serotypes. A person living in the epidermal area of dengue can be infected by 3 or 4

serotypes during his life. The four serotypes of dengue virus can be found in various

regions in Indonesia.

3.1.3. Symptom

Clinical features Dengue fever After an incubation period of an average of 4-

days (range, 3-16 days), various non-specific constitutional symptoms as well as

headache, back pain and malaise begin to appear. The uniqueness of the onset of dengue

fever is fever that rises suddenly with a sharp increase in temperature and is often

accompanied by facial flushing and headache. Occasionally, chills accompany a sudden

rise in temperature. After that, retro-orbital pain can appear which is especially felt when

moving the eyeball or if pressure is applied to the eyeball, photophobia, back pain,

muscle pain and bone/joint pain. Other symptoms that often appear are anorexia and

changes in tongue taste sensation, constipation, colicky abdominal pain. groin area pain,

sore throat and depression. These symptoms usually persist for several days to several

weeks. It is important to note that the symptoms of dengue fever vary widely in terms of

frequency and severity

Fever: body temperature usually ranges from 39 oC - 40 oC, fever has a biphasic

pattern, and lasts 5-7 days in most cases.

Skin rash: a diffuse rash of short duration appearing on the face, neck and chest in

the first 2 to 3 days; later, a marked rash appears as maculopapular or rubelliform lesions

on the 3rd and 4th day. At the end of the feverish period, or as soon as the temperature

begins to drop, the diffuse rash will disappear, and clusters of localized petechiae will

appear in such locations as the soles of the feet, feet, palms and arms. This healing rash has

the characteristic, namely, scattered petechiae between the surrounding areas of pale, and

normal surrounding skin. 11. Itchiness in the rash can be found

Bleeding manifestations: skin bleeding may be seen as a positive tourniquet test

and/or petechiae. Other bleeding such as massive epistaxis, hypermenorrhea and

gastrointestinal bleeding rarely occur in DD which is exacerbated by thrombocytopenia.

Disease course: the duration and severity of DD varies between individuals in each

epidemic area. The recovery phase may be reached in a short time and without serious

problems but sometimes it is also often ongoing. In adults, it sometimes lasts for several

weeks and may be accompanied by asthenia and depression. Bradycardia often occurs

during the healing phase. Bleeding due to complications of DF, such as epistaxis, bleeding

gums, gastrointestinal bleeding, hematuria and hypermenorrhoea, is rare. However, heavy

bleeding (DD with unusual bleeding) is an important cause of death in DF. Dengue fever

with bleeding manifestations must be differentiated from dengue hemorrhagic fever

3.1.4. Illness Course

A. Dengue infection course

Dengue is an infection with complex manifestations with an incubation period of

4 to 10 days, and has 3 phases in the course of the disease, namely the febrile phase,

the critical phase, and the recovery phase (Figure 2). Accuracy and speed of

management as well as patient monitoring since the febrile phase, can reduce the risk

of death in severe dengue patients to <0.5%

: D e g r e e s C e l s i u s ( ° C )

1. Fever Phase

The febrile phase is characterized by sudden

onset of high fever (can reach 40oC), continuous,

sometimes biphasic, and lasts 2–7 days. Fever is

accompanied by other common symptoms such as

facial flushing, headache, retroorbital pain, anorexia,

myalgia, and arthralgia. Other symptoms that may be

encountered are heartburn, nausea, vomiting, pain in

the right subcostal area or diffuse abdominal pain,

sometimes accompanied by sore throat. Redness of

the pharynx and conjunctiva (pharyngeal injection

and ciliary injection) may be found on physical

examination. In the early febrile phase, it is difficult

to distinguish clinically dengue from other non-

dengue febrile illnesses. A differential diagnosis is

deemed necessary so that appropriate management

can be carried out.

Table 1. Differential Diagnosis of Dengue in the Fever Phase

Dengue-like condition in the Fever Phase

Flue like syndrome Colds, influenza, measles, chikungunya, infections

mononucleosis, COVID-19, HIV seroconversion

Fever and rash Rubella, measles, fever scarlatina,

infection

meningococci, chikungunya, drug reactions

Diarrhea Rotavirus, another intestinal infection

Disease with

neurological manifestations

Meningoencephalitis, febrile seizures

Source: WHO. Dengue guidelines for diagnosis, treatment

and control, 2009.

Mild bleeding manifestations such as

petechiae and bleeding of the mucous membranes (eg

epistaxis and bleeding gums) may occur. Changes in

the results of a complete peripheral blood count

during the febrile phase in the form of a progressive

decrease in the number of leukocytes (leukopenia)

can guide clinicians to diagnose dengue. In dengue

infection the total number of leukocytes, neutrophils

and platelets is lower when compared to patients with

fever caused by other viruses in dengue endemic

areas.

2. Critical Phase

The critical phase occurs when the fever

drops (time of fever defervescence), that is, when the

body temperature drops to 37.5–38o C or less and

remains below that temperature. This is when plasma

leakage occurs so that the patient can experience

hypovolemic shock. This symptom marks the

beginning of the critical phase. Danger signs

generally occur towards the end of the febrile phase,

form of increased capillary permeability together with an

increase in hematocrit levels. Warning signs are signs of

worsening dengue that need to be watched out for

Every time you find a patient with fever with

suspicion of dengue, it is necessary to do a serial

examination of the peripheral blood. The presence of

progressive leukopenia followed by a rapid decrease in the

number of platelets generally precedes plasma leakage. The

presence of severe plasma leakage (pleural effusion, ascites,

hemoconcentration, hypoalbumin and hypoproteinemia) is a

risk for shock. The patient's clinical condition worsened as

indicated by the presence of warning signs, referred to as

dengue with warning signs (Table 3).

Most cases of dengue with warning signs will

improve with early intravenous fluids, although some may

develop severe dengue.

Setting clear definitions for warning signs and the severity

of dengue infection is important to avoid unnecessary

hospitalization, especially during an outbreak.

Table 3. Warning signs

Parameter Description Explanation

Clinical Throw up Keep going-continuously

(persistent)

≥3 episodes of vomiting within 12 hours

and no

can tolerate oral fluids

Pain or tenderness

Abdomen

Abdominal pain is continuous and intensity

increased to interfere with activity

Restless/lethargic decreased consciousness and/or irritability

Mucosal bleeding 1) nosebleed/epistaxis

2. gum bleeding

3. petechial skin bleeding

4. purpura

5)bleeding in the conjunctiva,

subconjunctiva

Hepatomegaly >2cm An enlarged liver is palpable on

examination

physical > 2cm

Clinical found

fluid accumulation

palpebral edema, pleural effusion, ascites

Laboratory Hematocrit level and platelet count Enhancement hematocrit

comparedearlier,

accompanied by a rapid decline in

numbers

thrombocyte.

Source: Morra ME, et al. Definitions for warning signs and

signs of severe dengue according to the WHO 2009

classification: Systematic review of literature. Rev Med

Virol. 2018 Jul;28(4):e1979.

Pleural effusion and ascites can be detected

clinically depending on the level of plasma leakage

and volume. Chest X-ray examination (especially the

right lateral decubitus position) and abdominal

ultrasonography are useful adjuncts for diagnosis.

The degree of increase in the hematocrit level above

normal often indicates the severity of plasma leakage.

Persistent vomiting and severe abdominal pain

are early signs of plasma leakage, and may worsen or

persist when the patient is in shock. The patient

appears increasingly lethargic, but generally remains

conscious. Spontaneous mucosal bleeding or bleeding

at the site of blood collection is an important and

common bleeding manifestation. Hepatomegaly and

abdominal pain are also common. The findings of

signs and symptoms that are more severe than the

warning signs in (Table 3), indicate the condition and

classification of the patient as severe dengue.

A prospective multicenter clinical study in a

WHO/TDR-supported dengue endemic area pooled

evidence to establish criteria for classifying dengue

according to severity. The study findings confirm that

using a single set of clinical and/or laboratory parameters

can assess a clear difference between patients with severe

and non-severe dengue. However, for practical reasons,

the group of patients with non-severe dengue was divided

into two subgroups

namely dengue patients with warning signs and

without warning signs, for this reason the classification

of dengue diagnosis is as follows (Figure 4)11:

a) Dengue without warning signs.

b) Dengue with warning signs.

c) Severe dengue.

Figure 4. Classification of Dengue Infection

Source: WHO. Dengue guidelines for

diagnosis, treatment and control, 2009.

Dengue severity classification can be used practically

by doctors in determining management, how closely patients

need to be monitored during triage and hospitalization, for

more consistent reporting on a national and international

scale, and as a final step in vaccine trials and drug research.

Dengue patients without warning signs may develop severe

dengue. Comorbid factors in patients with dengue infection

allow the condition of dengue without warning signs to

progress to warning signs or severe dengue.

1. Severe Dengue

Severe dengue cases in Southeast Asia occupy

the highest place, namely 15% of all severe dengue

cases. Among the severe cases of dengue, 244 (90%)

had plasma leakage, 39 (14%) severe bleeding, and 28

(10%) severe organ dysfunction. The highest frequency

of plasma seepage occurs in the age group <15 years.

Severe dengue is defined as one or more of the

following conditions, (a) plasma leakage causing shock

(dengue shock) and/or accumulation of liquid

with/without respiratory distress, and/or(b) heavy

bleeding (c) severe organ damage

Increased vascular permeability is followed by severe

hypovolemia until shock occurs, occurring during

defervescence. Early in shock, compensatory

mechanisms occur to maintain a normal systolic

pressure, causing tachycardia and peripheral

pulse

narrowed

Parameter Circulation

Stable

Compensated

Shock

Decompensated

Shock

Pressure

pulsenormally fit

age

Postural

hypotension

Blood pressure is not

detected

Breathing

frequency

Frequency

breath

normalaccording to

age

Tachypnea Acidosis metabolic/

hyperpnea/Kussmaul

breathing

Diuresis Normal

 For BB patient

<30 kgs

hence diuresis

ml/kgbb/hour m

 For BB

patient 

kg hence

diuresis

ml/kgbb/hour

There is a

decrease in

diuresis from

normal values

Anuria

Explanation of the normal values of

respiratory rate, heart rate and blood pressure in the

age group of infants and children:

Age Normal

breath rate

(upper limit)

Normal

heart rate

(upper limit)

Normal

systolic BP

(lower limit)

Normal MAP

(lower limit)

1 month 35 (55) 120 (175) 60 (50) 45 (35)

1 year 30 (40) 110 (170) 80 (70) 55 (40)

2 years 25 (30) 100 (160) 90+2*age#

(70+ 2* ages)#

55+ 1.5* age#

(40+1.5* ages)#

6 years 20 (25) 90 (130) 90+2*age#

(70+ 2* ages)#

55+ 1.5* age#

(40+1.5* ages)#

12 years

old

Source: European Pediatric Advanced Life Support. ERC Guidelines

2015 edition.

To recognize shock, when examining patients with

dengue infection, it is enough for health workers to simply

hold the patient's hand for 30 seconds to assess

hemodynamics in the form of adequacy of peripheral

perfusion and cardiac output, otherwise known as "the 5-in-

maneuver" magic touch (Figure 5). ).

Figure 5. The “5-in-1 maneuver” magic touch–CCTV-R

Source: Dengue clinical management: facilitator's

training manual. WHO 2013.

acute renal failure, encephalopathy or encephalitis,

cardiomyopathy or other unusual manifestations).

Further explanation regarding the definition of shock

and organ involvement in dengue infection is as follows: 12

a. Shock:

1. Poor capillary perfusion is characterized by

increased pulse rate (tachycardia), capillary refill

time of more than two seconds, cold extremities.

2. Pulse pressure narrows (<20 mm Hg).

3. Hypotension or until immeasurable.

4. The pulse feels weak and small until it can't be felt.

b. Hypotension:

A decrease in systolic blood pressure >40 mm Hg or

<2 SD below normal for the age group.

c. Respiratory distress (shortness of breath):

1. Respiratory rate increases with age.

2. Increased work of breathing (dyspnea).

3. Kussmaul breath.

Saturation 0 2 ≤94% without administration 02.

5. Respiratory failure.

d. Cardiac involvement in the form of:

1. myocarditis.

2. Cardiomyopathy.

3. Heart failure.

e. Involvement of the central nervous system, in the form of:

1. Decreased consciousness without finding

metabolic disturbances or other explanations, or

finding the following signs:

1. cerebrospinal fluid leukocytes >5/L; 2) focal

neurological signs, and 3) seizures (not simple

febrile seizures).

2. Encephalopathy.

3. Encephalitis.

f. Renal involvement, in the form of:

1. Serum creatinine ≥2x compared to the upper limit of normal

value.

2. Serum creatinine >1.2 mg/dL.

Assessment of AKI using the criteria of pediatric

RIFLE (RIFLE, an acronym for Risk of renal

dysfunction, Injury to the kidney, Failure of

kidney function, Loss of kidney function, and

End-stage Renal Disease

g. Liver involvement, in the form of:

1. Fail heart I which be marked with

jaundice,thromboplastin time <20%, and

encephalopathy.

2. Enhancement function heart without