Malaria differential diagnosis

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: João André Alves Silva, M.D. [2]; Alison Leibowitz [3]

Overview

Malaria must be differentiated from other diseases that cause fever, chills, nausea, anemia and vomiting, such as Ebola, Typhoid fever, Shigellosis and Lassa fever.

Differentiating Malaria from other Diseases

The table below summarizes the findings that differentiate Malaria from other conditions, which also cause fever and vomiting:

Disease	Findings
Ebola	Manifests with fever, chills, vomiting, diarrhea, generalized pain or malaise, and sometimes internal and external bleeding, which follow an incubation period of 2-21 days.
Typhoid fever	Manifests with fever, headache, rash, gastrointestinal symptoms, lymphadenopathy, relative bradycardia, cough and leucopenia, and occasionally sore throat. Blood and stool culture can confirm the presence of the causative bacteria.
Shigellosis & other bacterial enteric infections	Manifests with diarrhea, possibly bloody, accompanied by fever, nausea, and sometimes toxemia, vomiting, cramps, and tenesmus. Frequently, Stool contains blood and mucous. A search for possible sites of bacterial infection, together with cultures and blood smears, should be initiated. The presence of leucocytosis distinguishes bacterial infections from viral infections.
Lassa fever	Disease onset is usually gradual, with fever, sore throat, cough, pharyngitis, and facial edema in the later stages. Frequently, there is inflammation and exudation of the pharynx and conjunctiva.
Yellow fever and other Flaviviridae	Manifests with hemorrhagic complications. Epidemiological investigation may reveal disease transmission by an insect vector. Virus isolation and serological investigations aid in distinguishing these viruses. History of a previous yellow fever vaccination will likely rule out yellow fever.
Others	Viral hepatitis, leptospirosis, rheumatic fever, typhus, and mononucleosis can manifest with signs and symptoms that may be confused with Ebola in the early stages of infection.

Differential diagnosis of Malaria	Symptoms					Signs			Diagnosis	Additional Findings
	Fever	Rash	Diarrhea	Abdominal pain	Weight loss	Painful lymphadenopathy	Hepatosplenomegaly	Arthritis	Lab Findings
Brucellosis	✔	✔	✘	✔	✔	✔	✔	✔	Relative lymphocytosis	Night sweats, often with characteristic smell, likened to wet hay
Typhoid fever	✔	✔	✘	✔	✘	✘	✔	✔	Decreased hemoglobin	Incremental increase in temperature initially and than sustained fever as high as 40°C (104°F)
Malaria	✔	✘	✔	✔	✘	✘	✔	✔	Microcytosis, elevated LDH	"Tertian" fever: paroxysms occur every second day
Tuberculosis	✔	✔	✘	✔	✔	✔	✔	✔	Mild normocytic anemia, hyponatremia, and hypercalcemia	Night sweats, constant fatigue
Lymphoma	✔	✘	✘	✔	✔	✘	✔	✘	Increase ESR, increased LDH	Night sweats, constant fatigue
Mumps	✔	✘	✘	✘	✘	✔	✘	✘	Relative lymphocytosis, serum amylase elevated	Parotid swelling/tenderness
Rheumatoid arthritis	✘	✔	✘	✘	✘	✘	✘	✔	ESR and CRP elevated, positive rheumatoid factor	Morning stiffness
SLE	✘	✔	✘	✔	✔	✘	✘	✔	ESR and CRP elevated, positive ANA	Fatigue
HIV	✘	✘	✘	✔	✔	✔	✘	✔		Constant fatigue