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Clinical Characteristics and Pathology

Characteristically there is fever, splenomegaly, and anemia, but the clinical spectrum is very broad, and reliance on the classical combination of recurring chills and fevers will result in many missed diagnoses. For example, the spleen may not enlarge, or when there is cerebral involvement, seen in patients infected with P. falciparum, the presenting symptoms may be confusion and convulsions, particularly in children. There may be increasingly deep coma and a wide variety of abnormal neurological signs, including even decerebrate rigidity in severe cases. Lumbar puncture to exclude other causes is essential; in the majority of patients with malaria the CSF pressure is normal and the fluid clear, even when the patient has become comatose.
In other patients, hemolysis causes hemoglobinuria, oliguria, and albuminuria. The blackwater fever so often mentioned in the historical accounts of the tropical explorers is a severe complication of falciparum malaria.

Malaria has been known for many years to affect the kidneys, causing predominately glomerular lesions in P. malariae and P. falciparum infections. Although malaria is extremely common worldwide, renal disease is quite uncommon. It may perhaps require some altered immunology, such as an associated bacterial or viral infection. Malnutrition may be another factor, which may be why children are the most frequently affected. In P. malariae infection renal complications are more likely to be chronic and progressive, initially focal but eventually becoming diffuse glomerulosclerosis and leading to chronic renal failure in a few years. This does not respond well to antimalarial treatment, except early in the infection. When the malaria is due to P. falciparum there can be acute renal failure or glomerulonephritis. This may occur in any age group, but is most common in children. The clinical presentation is with proteinuria, microscopic hematuria, and urinary casts. Some patients develop intravascular coagulation. Unlike the P. malariae infections, the falciparum nephropathy is usually reversible with treatment and seldom progresses. In addition to renal failure, there may be an enlarged and tender liver and spleen, jaundice, and severe anemia.

In any form of malaria, respiratory symptoms, sufficiently severe to cause acute dyspnea, may be an alternative presentation. Noncardiogenic pulmonary edema has a grave prognosis. Involvement of the alimentary tract may cause pain, vomiting, hematemesis, abdominal cramps, and diarrhea. Some patients present with features of vasomotor collapse, hypertension, cyanosis, and a clammy skin (algid malaria). These widely differing symptoms may occur singly or, more often, together. Malaria is therefore a protean disease and should be suspected in any patient of any age returning from the tropics or who is resident there. The classical recurring fever is the most prominent feature only in the nonimmune patient.

The clinical and pathological findings in malaria result from the invasion and destruction of red cells, the consequent release of hemoglobin and debris, and the accumulation of malarial pigment in the phagocytic cells of the reticuloendothelial system. P. falciparum, the most virulent species, produces electron-dense knobs on the surface of the erythrocytes which adhere to the capillary endothelium and, when severe, block capillaries and cause microinfarction. This reduces the number of circulating parasites, leading to underestimation of the severity of the infection. Disseminated intravascular coagulation (DIC), presenting with spontaneous systemic hemorrhage, is a fatal complication which has been reported in approximately 10% of patients. Yet where malaria is edemic there are other effects which are less easily recognized. Certain lymphomas are increased in frequency, whereas autoimmune diseases are less common. In malarial areas the syndrome of "idiopathic tropical splenomegaly" occurs frequently: where P. malariae is common there is an associated nephrotic syndrome. Malaria contributes to the maintenance of high gamma globulin levels after the first year of life. It must be remembered that there is already geographic variation in the normal level of gamma globulin in neonates in the tropics. Some innate resistance to malaria occurs in patients with sickle cell hemoglobin or glucose-6-phosphate dehydrogenase (G-6-APD) deficiency. A racial immunity (particularly to P. vivax) has also been postulated, although the exact mechanism is unknown.

Thus, malaria is a very complex disease with many fascinating aspects but it would be out of place in a radiological text to describe all the clinical and therapeutic problems of malaria in any detail. There are many excellent reviews, including several WHO publications with much useful clinical information. The malarial parasite is carried throughout the body and can affect any part: it must therefore be a very variable disease clinically, complicated by cellular and immune responses. Relapse after a brief interval is due to the release of merozoites from malarial parasites which have survived within red cells. Long-term relapse is probably due to release from the liver. The interrelationship of malnutrition, or of good nutrition, and of other parasitic infections affects the clinical course of malaria and requires study. Radiologists should remember that P. malariae, P. ovale, and P. vivax infections are seldom fatal, unless unrecognized and untreated: the cause of death in nonimmune patients is almost always P. falciparum: it is this parasite which causes cerebral malaria. Clinically this must be differentiated from the cerebral symptoms caused by the high fever and liver damage. Brain damage results from the blockage of cerebral microvessels, but the very complex mechanisms are not well understood. Computed tomographic (CT) and magnetic resonance imaging (MRI) scans have confirmed the cerebral edema, reduced blood flow, infarction, and inflammation which may occur. There may also be metabolic changes.

The pulmonary complications, which can be fatal, are of particular importance for radiologists: pulmonary symptoms develop in 3%-5% of all patients with acute falciparum malaria, and up to 10% of other malarial infections. These may range from insignificant and mild upper respiratory tract complaints to fatal and overwhelming pulmonary edema (Figs. 46.2, 46.3).

Fig. 46.2. Severe pulmonary edema in a patient with severe P. falciparum malaria. This edema can develop even while the patient is being treated for malaria, is unresponsive to any therapy, and is usually fatal.

Fig. 46.3. Malarial lung with marked septal interstitial edema, chronic interstitial inflammation, and congestion of vessels by parasitized red cells. AFIP 66-6728. x42. (From Marty and Andersen 1995).

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