Acalculous Cholecystitis Associated with Plasmodium falciparum Malaria

Sir—We read with interest the report by Dylewski and Al-Azragi [1] that describes a patient with acalculous cholecystitis (AC) and Plasmodium falciparum malaria, which has not been previously described. We present another patient with the same condition and comment on the pathogenesis of AC and P. falciparum malaria, an underdiagnosed condition.

A 24-year-old Spanish woman was admitted to the hospital because of a 1-week history of diarrhea and fever after a 15-day tourist visit to Punta Cana, Dominican Republic. On admission, she was lethargic, her temperature was 39°C, her pulse 105/min, and her blood pressure 90/50 mm Hg. A general physical examination showed tenderness in the right upper abdominal quadrant without any other abnormalities. Laboratories studies disclosed the following values: hemoglobin, 8.9 g/dL; leukocytes, 6200/mm³; platelets, 11.000/mm³; prothrombin time, 22 s; partial thromboplastin time, 120 s; fibrinogen, 80 mg/dL; antithrombin III, 36%; total bilirubin, 6.9 mg/dL (direct bilirubin, 6.5 mg/dL); lactate dehydrogenase, 928 U/L; aspartate aminotransferase, 214 U/L; alanine aminotransferase, 254 U/L; and alkaline phosphatase, 423 U/L. A test for fibrin degradation products was positive. Other routine laboratory data and the chest x-ray were normal. Abdominal ultrasonography revealed a stone-free gallbladder with a thickened wall surrounded by a thin layer of fluid. A diagnosis of AC cholecystitis was made. Examination of 3 blood smears for parasites was negative. A hematological study revealed anemia with normal iron metabolism, a negative Coombs test, and absence of hemolysis signs. Freshly frozen plasma was administered for the severe coagulation abnormalities, and empirical therapy with ceftriaxone and metronidazole was initiated. Cultures of blood, stool specimen, and urine were negative. Two serologic studies separated by 1 week were negative for Salmonella, Yersinia, amoeba, Leptospira, and HIV.

After 1 week of antibiotic treatment, although the fever continued, abdominal symptoms had improved, and the gallbladder ultrasonography was normal. A thoracic and abdominal CT showed a moderate splenomegaly. On day 21, the patient became apyretic; the antibiotics were stopped, and she was discharged. Four days later, the clinical symptoms reappeared. On readmission, 1 of 3 blood cultures grew Shigella sonnei, whereas stool cultures remained negative. Again therapy with ceftriaxone was begun. Despite a normal abdominal ultrasonography, the patient had a persistent fever, anemia, hyperbilirubinemia, and increased levels of lactate dehydrogenase without hemolysis. A second set of blood smears revealed infestation with ring trophozoites typical of Plasmodium falciparum and merozoites. Several days later, a positive serology of P. falciparum at a titer of 1:360 was received. A diagnosis of imported malaria was made, and treatment with quinine and doxicycline was started, with resolution of the diarrhea and fever, as well as normalization of the laboratory data.

An enteric fever was initially suspected, despite negative cultures and serology. The patient had recently traveled to the Caribbean islands, her clinical features were compatible, and she had developed an AC and had a good response to ceftriaxone. During the second admission to the hospital, the patient's fever and diarrhea relapsed and, although S. sonnei was isolated in a blood culture, specific treatment failed, and symptoms persisted until malaria treatment was administered. The clinical presentation with AC and the concept that Punta Cana in the Altagracia province of the Dominican Republic was not a malaria area led to the delay of the diagnosis. On 22 December 1999, the Centers for Disease Control and Prevention reported in its travel web page (www.cdc.gov/travel/blusheet.htm) an outbreak of P. falciparum malaria in the Altagracia province. This outbreak involved >250 cases during 1999 and has been associated with climatic changes induced by Hurricane George. It has also been associated with worker emigration, usually illegal and without sanitary control, from endemic areas (Haiti) to tourist zones in the Dominican Republic.

The pathogenesis of AC [2] involves a combination of bile stasis and ischemia. As in Dylewski's patient, our patient presented hypotension that probably contributed to gallbladder damage. Etiology of AC [2] includes trauma, vascular diseases (polyarteritis nodosa), and infectious agents, such as Salmonella, cytomegalovirus, Cryptosporidium, and microsporidium. To the best of our knowledge, S. sonnei has never been associated with AC. The S. sonnei bacteremia was probably related to a transient immunosuppression induced by malaria [3]. The contribution of malaria to AC in this patient seems evident, but secondary bacterial infections are common in malaria. It remains to be determined whether AC is directly related to malaria or to a secondary gallbladder bacterial infection that could not be identified. We agree with Dylewski and Al-Azragi that malaria, although the pathogenesis remains controversial, should be included among the differential diagnoses of AC, especially in endemic zones of malaria.

• © 2000 by the Infectious Diseases Society of America