Differentials
Zika virus infection
SIGNS / SYMPTOMS
Residence in/travel from a Zika-affected region in the previous 2 weeks, or unprotected sexual contact with infected individual.
Conjunctivitis (usually non-purulent) or conjunctival hyperaemia.
No signs of bleeding or haemorrhage.
Mild cases may be difficult to distinguish from dengue fever without specific diagnostic testing.
It is imperative to differentiate dengue fever from Zika virus infection in pregnancy as the latter is known to be associated with microcephaly in newborns.[83]
INVESTIGATIONS
Reverse transcriptase-polymerase chain reaction (RT-PCR) for Zika: positive.
Serology for Zika: positive (note: risk of cross-reaction with dengue antibodies).
The US Centers for Disease Control and Prevention (CDC) recommends molecular and/or serological testing for dengue and Zika viruses in patients who are at risk of infection with both viruses.[90]
The World Health Organization (WHO) has produced a tool to help physicians differentiate between dengue, chikungunya, and Zika virus infection.[85]
Chikungunya virus infection
SIGNS / SYMPTOMS
Peripheral arthralgia and/or arthritis occurs in almost all patients. Pain is usually severe and most commonly affects the distal joints (e.g., wrists, ankles, hands, feet). It is usually symmetric. May be prominent signs of joint inflammation (swelling, warmth, rubor).
Dermatological manifestations including hyperpigmentation of the skin (predominantly on the face), desquamation of the skin (especially the palms of hands and soles of feet), well-demarcated ulcers in the intertrigo/perigenital/perianal regions, and oral aphthous ulcers are common.
Absence of bleeding tendency and circulatory failure.[91][92]
May be difficult to distinguish from dengue fever without specific diagnostic testing.
INVESTIGATIONS
Serology for chikungunya: positive.
The WHO has produced a tool to help physicians differentiate between dengue, chikungunya, and Zika virus infection.[85]
Rickettsial diseases
SIGNS / SYMPTOMS
History of tick, flea, or mite bite.
Discrete maculopapular and erythematous rash, which mainly involves the soles of the feet, palms of the hands, and limbs in Rocky Mountain spotted fever, and the trunk in other Rickettsial infections.
Characteristic eschar is seen.[93]
Arthritis/arthralgia of large joints may occur.
INVESTIGATIONS
FBC: WCC and platelet count usually normal; however, thrombocytopenia can occur in severe disease.
Serology (indirect immunofluorescent antibody) for Rickettsial infections: positive.
Leptospirosis
SIGNS / SYMPTOMS
History of working or bathing in muddy or stagnant water or handling animals.
Conjunctival injection.[94]
INVESTIGATIONS
FBC: leukocytosis.
Urinalysis: haematuria.
Serum bilirubin: elevated.
Urea: elevated.
Serology (microscopic agglutination test) for leptospirosis: positive.
Polymerase chain reaction (PCR) assay for leptospirosis: positive.
Measles infection
SIGNS / SYMPTOMS
Koplik spots (i.e., red spots often with a bluish-white central dot on erythematous buccal mucosa).
Upper respiratory tract symptoms (e.g., cough, coryza) more common.
Conjunctivitis.
Maculopapular rash, predominantly on the face and ears.
INVESTIGATIONS
Serology (measles-specific IgM and IgG enzyme-linked immunosorbent assay [ELISA]) for measles: positive.
Rubella
SIGNS / SYMPTOMS
Maculopapular rash, which usually begins on the face and spreads from the head to the feet.
Lymphadenopathy (often posterior cervical).
Arthralgia.
Conjunctivitis.
INVESTIGATIONS
Serology (antirubella IgM or IgG): positive.
Viral culture or reverse transcription-polymerase chain reaction (RT-PCR): may be positive.
Infectious mononucleosis
SIGNS / SYMPTOMS
Long-standing fever (i.e., 1-2 weeks, rarely up to 5 weeks).
Cervical or generalised lymphadenopathy.
Pharyngitis.
Variable skin rash that worsens with use of beta-lactam antibiotics.
INVESTIGATIONS
FBC: lymphocytosis or atypical lymphocytosis.
Epstein-Barr virus (EBV)-specific antibodies: positive.
Meningococcal disease
SIGNS / SYMPTOMS
Neck pain and/or stiffness.
Photophobia.
Altered consciousness.
Seizures.
Haemorrhagic rash.
INVESTIGATIONS
Blood culture: positive forNeisseria meningitides.
Typhoid infection
SIGNS / SYMPTOMS
Travel history to endemic area.
Fever sometimes occurs in a stepwise fashion.
Constipation.
Rose spots (blanching erythematous maculopapular lesions) are rare; usually seen on abdomen.
Relative bradycardia (although this is neither sensitive or specific for typhoid).
Splenomegaly.
INVESTIGATIONS
Blood/urine/stool culture: positive forSalmonella enterica (S typhi serotype).
Serology (Widal test) for typhoid: positive.
Hantavirus infection
SIGNS / SYMPTOMS
Exposure to rodent excreta.
Dyspnoea or severe respiratory distress.
INVESTIGATIONS
Serology (IgM and IgG for Sin Nombre virus) for hantavirus: positive.
Yellow fever
SIGNS / SYMPTOMS
Conjunctival injection.
Jaundice.
Relative bradycardia.
INVESTIGATIONS
Serology (IgM ELISA or haemagglutination inhibition): positive, increasing IgG titres.
West Nile virus
SIGNS / SYMPTOMS
Lymphadenopathy.
Conjunctival injection.
Encephalitis.
INVESTIGATIONS
Serology (West Nile virus-specific IgM ELISA) or specific viral detection for West Nile virus: positive in CSF and serum.
Malaria
SIGNS / SYMPTOMS
Travel history to endemic area.
Characteristic paroxysms of chills and rigors followed by fever and sweats may be described.
Absence of rash.
INVESTIGATIONS
Giemsa-stained thick and thin blood smears: positive for the malaria parasite.
Rapid diagnostic tests: detection of parasite antigen or enzymes.
Crimean-Congo haemorrhagic fever
SIGNS / SYMPTOMS
History of tick bite or handling animals.
Travel history to endemic area.
Haemorrhagic signs.
Disseminated intravascular coagulation.
May be difficult to distinguish from dengue fever without specific diagnostic testing.
INVESTIGATIONS
Serology or specific viral detection for Crimean-Congo virus: positive.
Lassa fever
SIGNS / SYMPTOMS
Exposure to mouse excreta.
Travel history to endemic area.
Haemorrhagic signs.
Encephalopathy.
May be difficult to distinguish from dengue fever without specific diagnostic testing.
INVESTIGATIONS
Serology or specific viral detection for Lassa virus: positive.
Ebola virus infection
SIGNS / SYMPTOMS
Travel history to endemic area.
Haemorrhagic signs.
May be difficult to distinguish from dengue fever without specific diagnostic testing.
INVESTIGATIONS
Serology or specific viral detection for Ebola virus: positive.
Marburg virus infection
SIGNS / SYMPTOMS
Travel history to endemic area.
Haemorrhagic signs.
May be difficult to distinguish from dengue fever without specific diagnostic testing.
INVESTIGATIONS
Serology or specific viral detection for Marburg virus: positive.
South American haemorrhagic fevers
SIGNS / SYMPTOMS
Travel history to endemic area.
Haemorrhagic signs.
May be difficult to distinguish from dengue fever without specific diagnostic testing.
INVESTIGATIONS
Serology or specific viral detection for Junin, Guanarito, Machupo, Chapare, or Sabia virus: positive.
Rift Valley fever
SIGNS / SYMPTOMS
Travel history to endemic area.
Haemorrhagic signs.
May be difficult to distinguish from dengue fever without specific diagnostic testing.
INVESTIGATIONS
Serology or specific viral detection for Rift Valley fever virus: positive.
Coronavirus disease 2019 (COVID-19)
SIGNS / SYMPTOMS
Important to consider the current epidemiologic situation. May give history of unwell contacts.
Respiratory symptoms may be prominent.
INVESTIGATIONS
Real-time reverse transcription polymerase chain reaction (RT-PCR): positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. Rapid antigen tests may also be used.
Use of this content is subject to our disclaimer