Differentials
Dengue fever
SIGNS / SYMPTOMS
Residence in/travel from dengue-endemic region.
Biphasic fever and rash.
Signs of haemorrhage (e.g., petechiae, purpura, epistaxis, gingival bleeding, haematemesis, melena, vagina bleeding) or plasma leakage in dengue haemorrhagic 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: positive for dengue virus RNA.
Serology (dengue IgM antibody test): positive.
The World Health Organization has produced a tool to help physicians differentiate between Zika, dengue, and chikungunya virus infection.[137]
Chikungunya virus
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
Enzyme-linked immunosorbent assay (ELISA)/indirect fluorescent antibody: positive for chikungunya antibodies.
Reverse transcriptase-polymerase chain reaction: positive for chikungunya viral RNA.
The World Health Organization has produced a tool to help physicians differentiate between Zika, dengue, and chikungunya virus infection.[137]
West Nile virus
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 cerebrospinal fluid: positive.
Yellow fever
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's sign) may be present.
Haemorrhagic 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
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.
Oropouche virus disease
SIGNS / SYMPTOMS
Residence in/travel from Oropouche virus-endemic region (or area with an ongoing outbreak).
Endemic to the Amazon region, but has spread to other countries in the Americas in recent years.
Clinical signs and symptoms are similar to other arboviral diseases so it is difficult to differentiate without laboratory testing.[187]
Most cases are mild; however, haemorrhagic manifestations or neuroinvasive disease can occur rarely.
Vertical transmission has been reported with adverse pregnancy outcomes, including fetal deaths and congenital abnormalities.[187]
INVESTIGATIONS
Reverse transcriptase-polymerase chain reaction: positive for oropouche virus RNA.
Serological testing: positive. Plaque reduction neutralisation testing to detect virus-specific neutralising antibodies in serum or cerebrospinal fluid, with titres ≥10 considered positive.[188]
Leptospirosis
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 haemorrhages.
INVESTIGATIONS
Darkfield examination: direct visualisation of spirochete in blood or urine.
Blood/cerebrospinal fluid culture: positive for leptospires.
Reverse transcriptase-polymerase chain reaction: positive Leptospira RNA.
Serology (indirect haemagglutination test, microagglutination test, or dipstick test): positive.
Antigen detection in urine: positive.
Rubella
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
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 anaemia, hydrops fetalis, or intrauterine death.
INVESTIGATIONS
Diagnosis is usually clinical.
Serology: positive for parvovirus B19 antibodies.
Rocky Mountain spotted fever
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
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
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
There may be a history of in utero drug/toxin exposure, family history of genetic factor, or other pregnancy-associated infection (e.g., cytomegalovirus or syphilis).
INVESTIGATIONS
Targeted testing for suspected aetiologies.
Coronavirus disease 2019 (COVID-19)
SIGNS / SYMPTOMS
Important to consider the current epidemiological situation. May give history of unwell contacts.
Respiratory symptoms may be prominent.
INVESTIGATIONS
Real-time reverse transcription polymerase chain reaction: positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. Rapid antigen tests may also be used.
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