Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (515 page)

   Who Should Be Suspected?

   Fever, sweats, anemia, and splenomegaly are the usual signs and symptoms of acute malaria. The classical presentation of malaria is the malarial paroxysm, which occurs cyclically with erythrocyte lysis, but these fever cycles are often not seen. Fevers recur every 48 hours in
P. vivax
and
P. ovale
infection and every 72 hours with
P. malariae
infection.
Plasmodium falciparum
infections also have a 48-hour cycle, but erythrocyte lysis is usually not synchronized. The erythrocyte cycle for
P. knowlesi
is only 24 hours. Nonimmune individuals and pregnant women are at greatest risk for severe and complicated infection.

   
Plasmodium falciparum
infection is associated with the greatest risk of severe and complicated disease. Anemia is common and may be severe with high levels of parasitemia. Hypoglycemia and acidosis are seen as a complication of severe malaria. Hyperthermia (T >41°C) may be seen, especially related to severe anemia, hypoglycemia, and cerebral malaria. Cerebral malaria, usually manifested by coma and/or seizures, is caused by multiple factors, including microvascular obstruction by parasites and metabolic disorders. Cerebral malaria is associated with high morbidity. Oliguric renal failure (blackwater fever) may complicate severe malaria and is associated with high mortality. Pulmonary edema, caused by capillary leak syndrome, may be seen, usually in combination with other symptoms of complicated malaria. Microvascular sequestration of parasitized erythrocytes may cause intestinal dysfunction, resulting in diarrhea. The complications of falciparum malaria are not well correlated to the level of parasitemia.

   Laboratory Findings

Direct detection
:

   Diagnosis is usually achieved by examination of thin and thick blood smears stained with Giemsa, Wright, or Wright-Giemsa stain. Giemsa is recommended because most morphologic descriptions are based on Giemsa staining. Thick smears of peripheral blood or bone marrow provide the most sensitive method for detection, and the thin smears are used for speciation.

   Multiple specimens should be examined to rule out malaria. Smears should be made every 6–12 hours for 3 consecutive days. Requests for malaria diagnosis should be considered as representing a potential medical emergency, so specimens should be transported and tested in a “stat” manner. Capillary blood is recommended if thin and thick smears can be prepared at the bedside. EDTA-anticoagulated blood may be used, but stippling may be lost if the smears are not prepared quickly.

Serology
: Limited value in acute infection.

Molecular tests
: PCR methods have been developed that are very sensitive and species specific, but FDA-approved tests are not yet available.

Core laboratory
: Hemolytic anemia (average 2.5 million erythrocytes per microliter in chronic cases); usually hypochromic; may be macrocytic in severe chronic disease. Reticulocyte count is increased. Thrombocytopenia is commonly seen. Leukocytes may be decreased. ESR is increased. There is increased serum indirect bilirubin and other evidence of hemolysis. Serum globulin is increased (especially euglobulin fraction); albumin is decreased. Biologic false-positive test for syphilis is frequent. Proteinuria and hematuria may be seen. Renal complications of malaria may result in acute tubular necrosis with casts on microscopic examination, azotemia, and oliguria progressing to anuria. Liver function tests may be moderately elevated.

MICROSPORIDIOSIS

   Definition

The microsporidia are obligate intracellular protozoan species capable of infecting a wide variety of vertebrate and invertebrate species.
Enterocytozoon bieneusi
is the most common human pathogen. Infection is usually acquired by oral ingestion of the microsporidia, rarely by inhalation.

   Who Should Be Suspected?

   
Enterocytozoon bieneusi
has emerged as a significant pathogen for patients with AIDS. Clinical disease is similar to that of
Cryptosporidium
and
Isospora
, with frequent, watery diarrhea with nausea and anorexia. Stools are not bloody. Complications of diarrhea may occur in severe cases, with dehydration, hypovolemia, electrolyte imbalance, and malabsorption. A significant number of patients with proven intestinal microsporidiosis may be coinfected with
Cryptosporidium
. Microsporidia have been identified in lower respiratory secretions of AIDS patients.

   Self-limited intestinal disease has been described in patients with intact immune systems. Microsporidia other than
E. bieneusi
are more likely to be responsible for extraintestinal microsporidiosis (e.g., keratoconjunctivitis, hepatitis, sclerosing cholangitis, peritonitis, respiratory tract infection, sinusitis, myositis, kidney disease).