Signs and Symptoms of Falciparum Malaria

Malaria is generally transmitted by the bite of an infected female Anopheles mosquito (although rarely, cases of transfusion-related and congenital malaria can occur). The infecting sporozoite travels to the liver, and in 8 hours is undetectable in the blood. Within the hepatocytes, the sporozoites divide and form a cyst-like structure called a schizont that contains thousands of merozoites. When the schizont matures, it ruptures, releasing the merozoites into the bloodstream where it invades red blood cells.

This period between the bite of the mosquito and the invasion of RBCs by malaria parasites is called the prepatent period. Again, for the sake of simplicity, I will concentrate on P. falciparum malaria on this blog. It's important to establish the species of malaria prior to beginning treatment, and to keep in mind that patients can be infected with multiple species of malaria parasites. (Will come back to this later! Please stay tuned!)

In falciparum malaria, this process lasts from 8 to 25 days (on average, usually around 10). 90% of returning travelers with falciparum malaria present with symptoms within 30 days of departure from the malaria-endemic area.

Symptoms of malaria are often vague, and can resemble flu-like symptoms with fever, headache, and malaise. Semi-immune patients (and non-immune patients on chemoprophylaxis) generally have lower levels of parasitemia, shorter fever duration, as well as shorter parasite clearance time. Fever is the main presenting symptom, although the severe headache may also prompt patients to seek care.

Classic Paroxysm of Malaria:

Cold Stage (1-2 hours) – the patient shivers or has frank rigor; the temperature rises sharply
Hot Stage (2-6 hours) – the patient is flushed, tachycardic, and has sustained high temperature
Sweating Stage (2-4 hours) – the patient is diaphoretic, and the temperature falls rapidly

Rigors are associated with the lysis of RBCs and the release of TNF-alpha. The cycling of fever and chills is dependent on the synchronization of parasitic invasion and RBC lysis. This process can take a week to develop and in falciparum malaria, the development of disease is often too rapid to allow the classic paroxysms to develop.

Percentage of patients reporting:

Fever 92%
Headache 53%
Myalgesia/Arthralgia 34%
Fatigue 27%
Emesis 18%
Diarrhea 17%

Clinical Signs:

The Malarial Triad: Fever, Anemia, Hepato-splenomegaly. Additionally, some patients may exhibit jaundice. In complicated malaria, anemia may be severe, and patients may have acidosis and hypoglycemia. The term “Blackwater Fever” used to be used to refer to patients with discolored urine resulting from haemoglobinuria and renal failure. Disseminated Intravascular Coagulation (DIC) is an occasional complication in adults.

Cerebral Malaria is the most important complication of malaria, and even with hospitalization in modern intensive care units, the mortality rate is approximately 20 percent. The case definition is “an unrousable coma in the presence of peripheral parasitemia where other causes of encephalopathy have been excluded.” Patients make exhibit seizures (note: malaria seizures can occur at any temperatures), focal neurological signs, retinal hemorrhages, and brainstem signs such as doll’s eyes. Neurological sequelae are found in 5% of survivors (10% of children) and may include cortical blindness, hypotonia, hemiparesis, and mental retardation.

The natural history of untreated malaria differs with each species. After the first instance of infection with P. falciparum, the patient will either die in the acute attack, or survive with the development of some immunity and residual anemia. Unlike other species of malaria, falciparum does not have a dormant liver stage (hypnozoites), although small numbers of mereozoites can persist in the blood stream and cause recurrent attacks (recrudescence) for up to 12 months.


Source: "Lecture Notes: Tropical Medicine" by Geoff Gil and Nick Beeching. (2009 ed.)