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 Leptospirosis
Causative organism Dengue virus Leptospira spirochete
Source of infection Contact with urine-
Mosquito bites contaminated water or soil
(e.g. flood water, puddles)
WHO case definitions Rash Rash
Headache Menigeal irritation
Retro-orbital eye pain Conjunctiva suffusion
Hemorrhagic manifestation Hemorrhagic manifestation
Arthralgia Cardiac arrhythmia or
Myalgia failure
Leukopenia Cough/hemoptysis
Anuria/oliguria
Jaundice
Definitive therapy Early detection of warning Antibiotics (doxycycline,
signs, supportive care and penicillin, tetracycline,
judicious use of IVFs 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 Septic shock
Temperature - Occurs after defervescence
- Temperature is often subnormal or - Temperature is usually high
normal - But could be subnormal in late
- Temperature may be high in those stage of septic shock
with reactive haemophagocytic (decompensation)
syndrome
Pulse - Small or weak pulse volume - Bounding pulse
- Narrowed pulse pressure - Widened pulse pressure with
- Cold extremities warm extremities in the early stage
of septic shock
Full blood - Usually leukopenic and - Usually leukocytosis
count thrombocytopenic - But could be leukopenic and/or
- Leukocytosis maybe observed in thrombocytopenic
those with active bleeding
C-reactive - Normal or mildly elevated CRP - Markedly elevated CRP
protein
