Differentials

Malaria infection

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Most common cause of non-specific febrile illness in returning travellers.[18]

Residence in/travel from Malaria-endemic region.

Inadequate malaria chemoprophylaxis.

INVESTIGATIONS

Rapid diagnostic tests: positive for Plasmodium species.

Giemsa-stained thick and thin blood smears: positive for Plasmodium species.

Ebola virus infection

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

There are no differentiating signs and symptoms.

Epidemiological features can help differentiate between the viral haemorrhagic fevers, including differences in endemic regions. In general, Ebola virus is endemic to West and Central Africa and Marburg virus to Central and East Africa though outbreak settings may be different.

INVESTIGATIONS

Reverse transcriptase PCR (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 virus infection is suspected.

Crimean-Congo haemorrhagic fever (CCHF)

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

There are no differentiating signs and symptoms.

Epidemiological features can help differentiate between the viral haemorrhagic fevers.

Animal butchering, tick bite, or exposure to animals.

INVESTIGATIONS

RT-PCR: positive for CCHF virus.

Lassa fever

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

There are no differentiating signs and symptoms.

Epidemiological features can help differentiate between the viral haemorrhagic fevers.

Exposure to rats in endemic areas.

INVESTIGATIONS

RT-PCR: positive for Lassa virus.

Typhoid fever

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

There are no differentiating signs and symptoms.

INVESTIGATIONS

Blood or stool culture: positive for Salmonella enterica.

Serological testing with rising titres of Salmonella antibodies. Testing may be negative in the presence of disease.

Shigella infection

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Diarrhoea, often bloody, is the main symptom.

Usually due to faecal-oral contact or ingestion of contaminated food or water.

Most commonly seen in children <5 years of age.

INVESTIGATIONS

Stool culture: positive for Shigella species.

Rickettsial diseases

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Includes murine typhus, African tick-bite fever, and epidemic typhus.[32]

Eschar is typical.

Lymphadenopathy may be present.

Discrete rash.

Disease is usually less severe than filovirus disease in late stages.

INVESTIGATIONS

Serology: positive for Rickettsia species RNA.

Eschar PCR: positive for Rickettsia species RNA.

Dengue fever

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

There are no differentiating signs and symptoms, although epidemiological clues may be helpful (i.e., Caribbean, Southeast Asia, Oceania, Central and South America, sub-Saharan Africa).

INVESTIGATIONS

Serology: positive IgM or IgG.

Nonstructural protein (NS1) detection: positive.

RT-PCR: positive for dengue virus RNA.

Measles infection

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Unvaccinated.

There are no differentiating signs and symptoms in prodromal phase.

Koplik spots (red spots with bluish-white central dot) on buccal mucosa.

Rash typically starts on face and spreads craniocaudally.

INVESTIGATIONS

Serology: positive for measles virus IgM.

Leptospirosis

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

In early phases, there are no differentiating signs and symptoms; however, a history of exposure may be helpful.

Exposure to contaminated water or soil contaminated by infected rodents.[33]

More common in tropical climates.

INVESTIGATIONS

PCR: positive for leptospira RNA.

Serology: positive for leptospira IgM.

Influenza infection

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Respiratory signs and symptoms (e.g., cough, nasal congestion) are more common.

INVESTIGATIONS

Viral culture or PCR: detection of seasonal influenza virus or viral RNA.

FBC: may be normal.

Gastroenteritis

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

In the correct epidemiological context, this can present in a similar way to Marburg virus infection. However, features such as rash and conjunctival injection are very rare in gastroenteritis.

INVESTIGATIONS

Stool culture, PCR, or rapid antigen testing: positive for causative agent.

Sepsis

SIGNS / SYMPTOMS
INVESTIGATIONS
SIGNS / SYMPTOMS

Bacterial sepsis with an unclear origin is a common presentation in developing countries. May be deep abdominal infection, upper urinary tract infection, endocarditis, or discitis.

Diarrhoea is often absent.

INVESTIGATIONS

Blood cultures: positive, although positive blood cultures may occur in Marburg virus infection as well.

Coronavirus disease 2019 (COVID-19)

SIGNS / SYMPTOMS
INVESTIGATIONS
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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