Differentials
Malaria infection
SIGNS / SYMPTOMS
Most common cause of non-specific febrile illness in returning travellers.[36]
Residence in/travel from malaria-endemic region.
Inadequate or no malaria chemoprophylaxis.
INVESTIGATIONS
Giemsa-stained thick and thin blood smears: positive for Plasmodium species.
Rapid diagnostic tests: positive for Plasmodium species.
Typhoid infection
SIGNS / SYMPTOMS
There are no differentiating signs or symptoms.
Absence of typhoid fever vaccination.
Travel history to endemic area (i.e., less-developed countries with poor sanitary conditions and untreated water supplies).
INVESTIGATIONS
Blood/urine/stool culture: positive for Salmonella typhi or Salmonella paratyphi.
Ebola virus infection
SIGNS / SYMPTOMS
There are no differentiating signs or symptoms.
Epidemiological features can help differentiate between the viral haemorrhagic fevers.
INVESTIGATIONS
Reverse transcription-polymerase chain reaction (RT-PCR): positive for Ebola virus.
It is recommended that appropriate confirmatory tests for Ebola virus infection are performed before, or in tandem with, differentiating tests if Ebola is suspected.
Marburg virus infection
SIGNS / SYMPTOMS
There are no differentiating signs or symptoms.
Epidemiological features can help differentiate between the viral haemorrhagic fevers.
Transmitted via exposure to fruit bat, cave/mining exposure, or close contact with infected persons in the last 21 days.
INVESTIGATIONS
RT-PCR: positive for Marburg virus.
Hantavirus cardiopulmonary syndrome
SIGNS / SYMPTOMS
Exposure to rodent excreta.
Dyspnoea or severe respiratory distress.
INVESTIGATIONS
Serology: positive IgM and IgG for hantavirus.
Crimean-Congo haemorrhagic fever (CCHF)
SIGNS / SYMPTOMS
There are no differentiating signs or symptoms.
Epidemiological features can help differentiate between the viral haemorrhagic fevers.
Animal butchering, tick bite, or exposure to infected animals are the main routes of transmission to humans.
INVESTIGATIONS
RT-PCR: positive for CCHF virus.
Rift Valley fever
SIGNS / SYMPTOMS
There are no differentiating signs or symptoms, particularly in early disease.
Short incubation period (2-6 days).
Transmitted via mosquitoes or contact with the blood or tissues of infected animals.
INVESTIGATIONS
RT-PCR: positive for Rift Valley fever virus RNA.
Serology: positive for IgM or IgG.
Yellow fever
SIGNS / SYMPTOMS
Residence in/travel from yellow fever virus-endemic region.
Absence of yellow fever vaccination.
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.
Dengue fever
SIGNS / SYMPTOMS
There are no differentiating signs or symptoms.
INVESTIGATIONS
Serology: positive IgM or IgG.
Non-structural protein (NS1) detection by rapid diagnostic test: positive.
RT-PCR: positive for dengue virus.
Chikungunya virus infection
SIGNS / SYMPTOMS
Residence in/travel from chikungunya virus-endemic region.
Almost always symptomatic.
Prominent joint symptoms.
Hyperpigmentation of skin and intertriginous lesions are common.
INVESTIGATIONS
ELISA/indirect fluorescent antibody: positive for chikungunya antibodies.
RT-PCR: positive for chikungunya viral RNA.
West Nile virus infection
SIGNS / SYMPTOMS
Residence in/travel from West Nile virus-endemic region.
Visual disturbances are common.
Causes neuroinvasive disease (e.g., encephalitis, meningitis, flaccid paralysis syndrome).
INVESTIGATIONS
West Nile virus-specific IgM in serum or cerebrospinal fluid: positive.
Leptospirosis
SIGNS / SYMPTOMS
There are no differentiating signs or symptoms; however, a history of exposure may be helpful.
Exposure to water or soil contaminated by infected rodents.
More common in tropical climates.
INVESTIGATIONS
PCR: positive for leptospira.
Serology (microscopic agglutination test): positive for leptospira antibodies.
Rickettsial diseases
SIGNS / SYMPTOMS
Includes murine typhus, African tick-bite fever, and epidemic typhus.
Eschar is typical.
Lymphadenopathy may be present.
Discrete rash.
INVESTIGATIONS
Serology: positive for Rickettsia species.
Eschar PCR: positive for Rickettsia species.
Measles infection
SIGNS / SYMPTOMS
Unvaccinated.
There are no differentiating signs or symptoms in the prodromal phase.
Koplik's spots (red spots with bluish-white central dot) on buccal mucosa.
Rash typically starts on the face and spreads craniocaudally.
INVESTIGATIONS
Serology: positive for measles virus antibodies.
PCR: positive for measles virus.
Gastroenteritis (E coli enterotoxigenic or enterohaemorrhagic)
SIGNS / SYMPTOMS
In the correct epidemiological context, this can present in a similar way to Lassa fever; however, features such as rash and conjunctival injection are very rare in gastroenteritis.
INVESTIGATIONS
Stool culture, PCR, or rapid antigen testing: positive.
Shigella infection
SIGNS / SYMPTOMS
Usually in children attending day care centre; also acquired from eating contaminated vegetables.
Fever may develop, followed by diarrhoea that is watery and becomes mucoid and bloody; stool: small in amount, ranges from 10 to 12 per day; fever and tenesmus in one third of patients.
Abdominal examination: generalised tenderness, distension, or absent bowel sounds, dependent on severity.
Rectal examination: tender, and rarely rectal prolapse.
INVESTIGATIONS
Faecal leukocytes: positive.
Stool culture: positive.
Sepsis
SIGNS / SYMPTOMS
Bacterial sepsis with an unclear origin is a common presentation in developing countries. Often turns out to be a localised infection that is difficult to determine on initial examination, such as deep abdominal infection, upper urinary tract infection, endocarditis, or discitis.
Diarrhoea is often absent.
INVESTIGATIONS
Blood cultures: positive.
Influenza infection
SIGNS / SYMPTOMS
Respiratory signs or symptoms (e.g., cough, nasal congestion) are more common.
INVESTIGATIONS
PCR or rapid diagnostic test: positive for influenza virus.
FBC: normal.
Coronavirus disease 2019 (COVID-19)
SIGNS / SYMPTOMS
Residence in/travel to a country/area or territory with local transmission, or close contact with a confirmed or probable case of COVID-19, in the 14 days prior to symptom onset.
The situation is evolving rapidly; see our COVID-19 topic for further information.
INVESTIGATIONS
Real-time reverse transcription polymerase chain reaction (RT-PCR): positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA.
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