MODULE 5: Case Classification and

Differential Diagnosis

Dengue Clinical Management

Acknowledgements
This curriculum was developed with technical assistance from the University of Malaya Medical Centre. Materials were contributed by the
Ministry of Health, Singapore, the United States Centers for Disease Control and Prevention, and the University of Malaya Medical Centre.
 Dengue case classification by severity

Dengue has a wide spectrum of clinical presentations with often

unpredictable evolution:
• Self-limiting disease in most patients
• Severe disease in a small proportion of patients, characterized by
plasma leakage with/without haemorrhage

WHO proposed a dengue case classification system in 2009:

• Supported by set of clinical and/or laboratory parameters
• Aim to show clear-cut difference between patients with non-
severe versus severe dengue
• Classification levels would help clinicians in decision making
about intensity of treatment and observation
Dengue case classification (2009)

Dengue Severe dengue

• 1. Severe plasma leakage

With
Without • 2. Severe haemorrhage
warning signs
• 3. Severe organ impairment
 Dengue case definition (2009)
Probable dengue
Live in and/or travelled to a dengue-endemic area
Fever and two of the following criteria:
• Nausea, vomiting (new)
• Rash
• Aches and pains (combined)
• Tourniquet test positive
• Leucopenia
• Any warning sign

Laboratory-confirmed dengue
(Important when there is no sign of plasma leakage)
 Dengue case classification (2009)
Dengue ± warning signs Severe dengue

• 1. Severe plasma leakage

With
Without warning signs • 2. Severe haemorrhage
• 3. Severe organ impairment

Criteria for dengue ± warning signs Criteria for severe dengue

Probable dengue Warning signs* 1. Severe plasma leakage leading to:
Live in or travelled to dengue- • Abdominal pain or tenderness • Shock (DSS)
endemic area. Fever and two of Fluid accumulation with respiratory
• Persistent vomiting
•

the following criteria: distress

• Mucosal bleed
• Nausea, vomiting (new)
• Lethargy; restlessness 2. Severe bleeding
• Rash
• Liver enlargement >2 cm Bleeding that causes hemodynamic
• Aches and pains (combined)
• Clinical fluid accumulation instability and may require blood
• Tourniquet test positive
• Increase in HCT with rapid decrease transfusion
• Leucopenia
in platelet count 3. Severe organ involvement
• Any warning sign

• Liver: AST or ALT ≥1000

* Requiring strict observation and medical
Laboratory-confirmed dengue intervention • CNS: Impaired consciousness
(important when no sign of plasma leakage)
• Impaired cardiac function
 Dengue mimics many clinical syndromes

Flu-like illness
Clues to diagnose dengue:

Viral exanthem Understanding the

dynamic and systemic
Acute abdomen nature of dengue

Infections Dengue Knowing its various

manifestations as the
disease progresses from
Autoimmune febrile phase to critical
diseases phase and evolves into
recovery phase
Haematological
disorders
Conditions that mimic the febrile phase of dengue

Influenza, measles, rubella

Chikungunya, West Nile virus
Enterovirus
Viral infections Other viral haemorrhagic fever
Infectious mononucleosis
Acute HIV seroconversion illness

Leptospirosis
Bacterial infections Typhoid
Rickettsia infections (typhus, scrub typhus, etc.)

Parasitic infections Malaria

Measles, rubella
Infectious mononucleosis, enterovirus
Chikungunya, West Nile virus,
Febrile illness with Scarlet fever, meningococcal infection
a rash Leptospirosis, typhoid
Rickettsia infections (typhus, scrub typhus, etc.)
Syphilis, acute HIV seroconversion illness
Autoimmune diseases (e.g. SLE)
Adverse drug reaction
Rotavirus
Diarrhoeal diseases Salmonellosis
Other enteric infections
Conditions that mimic the critical phase of dengue
Acute appendicitis
Acute cholecystitis
Acute abdomen Perforated viscus
Diabetic ketoacidosis

Diabetic ketoacidosis
Acidotic breathing/ Lactic acidosis
respiratory distress Renal failure
Acute respiratory distress syndrome (ARDS)

Sepsis, septic shock

Acute gastroenteritis
Infections Leptospirosis, typhoid, typhus, malaria
Viral hepatitis
Acute HIV seroconversion illness

Systemic lupus erythematosus

Idiopathic thrombocytopenic purpura
Autoimmune diseases Thrombotic thrombocytopenic purpura
Systemic vascultis

Acute leukaemia
Malignancies Lymphoma
Other malignancies

Liver cirrhosis with portal hypertension

Others Adverse drug reaction
 Differentiating dengue from leptospirosis
Dengue
Causative organism Dengue virus
Source of infection
Mosquito bites
WHO case definitions Rash
Headache
Retro-orbital eye pain
Hemorrhagic manifestation
Arthralgia
Myalgia
Leukopenia
Definitive therapy Early detection of warning
signs, supportive care and
judicious use of IVFs
Leptospirosis
Leptospira spirochete
Contact with urine-
contaminated water or soil
(e.g. flood water, puddles)
Rash
Menigeal irritation
Conjunctiva suffusion
Hemorrhagic manifestation
Cardiac arrhythmia or
failure
Cough/hemoptysis
Anuria/oliguria
Jaundice
Antibiotics (doxycycline,
penicillin, tetracycline,
erythromycin)
 Differentiating dengue from leptospirosis
Clinical features Leptospirosis Dengue

Fever (≥38°C)* +++ +++

Myalgia +++ +++
Headache +++ +++
Rash + ++
Jaundice ++ +/-
Hyperbilirubinemia (T.Bili >1.3) ++ +/-
Elevated blood urea nitrogen (BUN >25) or Creatinine >2 + +/-
Leukocytosis (WBC >10 000)† ++ +/-
Positive tourniquet test + +++

Anaemia +++ +

Thrombocytopenia + +++
*Mean frequency of symptoms from studies where the two diseases were directly compared among patient seeking care; +++ =
70%–100% of patients; ++ = 40%–69%; + = 10%–39%; +/- = <10%; - = 0%. Sources: Bruce MG et. al. Acta Tropica, 2005; Libraty DH et.
al. PLoS, 2007; LaRocque RC et al. EID, 2005; Ellis T et. al. VBZD, 2008.
**Leptospirosis cases may be more likely to have intermittent fever, but both infections may have biphasic fevers.
† Leptospirosis cases may be more likely to have a higher percentage of neutrophils and a higher absolute neutrophil count.
 Differentiating dengue from malaria

Clinical features P. falciparum P. vivax Dengue

Fever (≥38°C)* +++ +++ +++
Myalgia + + +++
Headache +++ +++ +++
Rash +/- +/- ++
Jaundice + +/- +/-
Vomiting ++ + +
Abdominal pain + + +/-
Hepatomegaly + + +/-
Splenomegaly + + +/-
Leukopenia +/- +/- +++
Anaemia ++ ++ +
Thrombocytopenia ++ ++ +++
*Mean frequency of symptoms from studies where the two diseases were directly compared among patient seeking care; +++ = 70%–
100% of patients; ++ = 40%–69%; + = 10%–39%; +/- = <10%; - = 0%. Sources: Nimmannitya S et al. Am J Trop Med Hyg, 1969; 18:954–
971. Halstead SB et al. Am J Trop Med Hyg, 1969; 18:972–983. Beg et al. Int J Inf Dis, 2008; 12:37–42. Robinson et al. J Travel Med,
2001; 8(2):76– 81. Luxemburger et al. Tran R Soc Trop Med Hyg, 1998; 92:42-49.
 Differentiating dengue from chikungunya

Clinical Features Chikungunya virus infection Dengue virus infection

Fever (>102°F) +++ ++

Myalgia + ++

Arthalgias/arthritis +++ +/-

Headache ++ ++

Rash ++ +

Bleeding dyscrasias +/- ++

Shock - +/-

Leukopenia ++ +++

Neutropenia + +++

Lymphopenia +++ ++

Thrombocytopenia + +++
*Mean frequency of symptoms from studies where the two diseases were directly compared among patient seeking care; +++ =
70%–100% of patients; ++ = 40%–69%; + = 10%–39%; +/- = <10%; - = 0%. Sources: Nimmannitya S et al. Am J Trop Med Hyg, 1969;
18:954–971. Halstead SB et al. Am J Trop Med Hyg, 1969; 18:972–983.
Differentiating dengue from surgical acute abdomen

Dengue-related acute abdomen Surgical acute abdomen

Fever precedes pain and may

Fever may occur after onset of pain
become afebrile

Guarded abdomen with rebound

Tender but not guarded
tenderness in perforated viscus

May be distended in plasma leakage May or may not be distended

Fluid resuscitation is imperative in

May require fluid resuscitation
severe dengue

Pain improves with fluid Pain remains after fluid

resuscitation in severe dengue resuscitation
 Differentiating dengue shock from septic shock
Dengue shock
Temperature - Occurs after defervescence
- Temperature is often subnormal or
normal
- Temperature may be high in those
with reactive haemophagocytic
syndrome
Pulse - Small or weak pulse volume
- Narrowed pulse pressure
- Cold extremities
Full blood - Usually leukopenic and
count thrombocytopenic
- Leukocytosis maybe observed in
those with active bleeding
C-reactive - Normal or mildly elevated CRP
protein
Septic shock
- Temperature is usually high
- But could be subnormal in late
stage of septic shock
(decompensation)
- Bounding pulse
- Widened pulse pressure with
warm extremities in the early stage
of septic shock
- Usually leukocytosis
- But could be leukopenic and/or
thrombocytopenic
- Markedly elevated CRP