Differentials

Dengue fever

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Residence in/travel from dengue-endemic region.

Biphasic fever and rash.

Signs of hemorrhage (e.g., petechiae, purpura, epistaxis, gingival bleeding, hematemesis, melena, vagina bleeding) or plasma leakage in dengue hemorrhagic fever.

Diffuse skin flushing of face, neck, and chest early in infection course.

Milder cases may be difficult to distinguish from Zika virus infection without diagnostic testing.

INVESTIGATIONS

Reverse transcriptase-polymerase chain reaction (RT-PCR): positive for dengue virus RNA.

Nonstructural protein 1 (NS1) detection: positive.

The World Health Organization (WHO) has produced a tool to help physicians differentiate between Zika, dengue, and chikungunya virus infection. [151]

Chikungunya virus

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Residence in/travel from chikungunya-endemic region.

Almost always symptomatic.

Prominent joint symptoms.

Hyperpigmentation of skin and intertriginous lesions are common.

Difficult to distinguish from Zika virus infection without diagnostic testing.

INVESTIGATIONS

ELISA/indirect fluorescent antibody (IFA): positive for chikungunya antibodies.

RT-PCR: positive for chikungunya viral RNA.

WHO has produced a tool to help physicians differentiate between Zika, dengue, and chikungunya virus infection. [151]

West Nile virus

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Residence in/travel from West Nile virus-endemic region.

Visual disturbances are common.

Rarely causes neuroinvasive disease (e.g., encephalitis, meningitis, flaccid paralysis syndrome).

INVESTIGATIONS

West Nile virus-specific IgM in serum or CSF: positive.

Yellow fever

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Residence in/travel from Yellow fever virus-endemic region.

Absence of Yellow fever vaccination.

Also transmitted by Haemagogus species of mosquito.

Relative bradycardia (Faget sign) may be present.

Hemorrhagic signs.

Biphasic course: after a remission period lasting up to 24 hours, some patients develop a period of intoxication with jaundice, liver and kidney failure, coagulopathy, shock, and death.

High mortality rate.

INVESTIGATIONS

Serology: positive for yellow fever virus antibodies.

Malaria infection

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Residence in/travel from malaria-endemic region.

Inadequate or absent malaria chemoprophylaxis.

INVESTIGATIONS

Giemsa-stained blood film: positive for Plasmodium species.

Rapid diagnostic tests: positive for Plasmodium species.

Leptospirosis

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Zoonosis transmitted by direct or indirect contact with urine of infected animals.

Residence in/travel from endemic region.

History of water sports.

Outbreaks during flooding and natural disasters.

High remitting fever and biphasic course of illness.

Bilateral conjunctival suffusion pathognomonic for leptospirosis.

Pulmonary symptoms.

Affected individuals can present with an extensive spectrum of clinical manifestations ranging from subclinical illness in approximately 90% of cases to renal and hepatic failure and pulmonary hemorrhages.

INVESTIGATIONS

Darkfield examination: direct visualization of spirochete in blood or urine.

Blood/CSF culture: positive for leptospires.

RT-PCR: positive Leptospira RNA.

Serology (indirect hemagglutination test, microagglutination test, or dipstick test): positive.

Antigen detection in urine: positive.

Rubella

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Incomplete or absence of rubella vaccination.

Exposure to infectious contact.

Rash is erythematous, discrete, maculopapular, and sometimes mildly pruritic, and may be accentuated by heat. Usually begins on face and spreads to head and feet. May be petechial.

Lymphadenopathy may precede rash.

Mild upper respiratory symptoms are common.

Maternal infection during pregnancy may cause spontaneous abortion, fetal death, or multiple congenital anomalies (congenital rubella syndrome).

INVESTIGATIONS

Anti-rubella IgM: positive.

Erythema infectiosum (parvovirus B19 infection)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Exposure to infectious contact.

Classic bright red macular erythema of bilateral cheeks sparing the nasal ridge and perioral areas.

Infection in pregnant women may result in fetal anemia, hydrops fetalis, or intrauterine death.

INVESTIGATIONS

Diagnosis is usually clinical.

Serology: positive for parvovirus B19 antibodies.

Rocky Mountain spotted fever

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Transmitted by tick bite.

Rash may be petechial.

Nausea/vomiting common.

INVESTIGATIONS

Serology: positive for Rickettsia species.

Group A streptococcal infection

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

May manifest as sepsis, cutaneous conditions such as cellulitis, or pharyngitis.

INVESTIGATIONS

Blood or tissue cultures: positive.

Rapid antigen detection tests: allow immediate point-of-care assessment of group A streptococcal pharyngitis.

Other alphavirus infections

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Includes Mayaro virus disease, Ross River fever, Barmah Forest virus, O'nyong-nyong virus, and Sindbis virus.

Residence in/travel from endemic region.

Difficult to distinguish from Zika virus infection without diagnostic testing.

INVESTIGATIONS

Antibody detection for specific virus.

Other causes of fetal microcephaly

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

There may be a history of in utero drug/toxin exposure, family history of genetic factor, or other pregnancy-associated infection (such as CMV or syphilis).

INVESTIGATIONS

Targeted testing for suspected etiologies.

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