A 43-year-old man in the advanced stages of AIDS begins to experience watery diarrhea and intermittent abdominal pain, along with nausea, anorexia, and fever. The diarrhea persists over a period of four weeks, with no signs of letting up. In fact, the diarrhea is often profuse, with the patient producing 15-20 liters of fluid (as many as 30-40 stools) per day. The patient experiences weight loss, wasting, and increased diffuse abdominal pain along with the persistent diarrhea. Near the end of the four-week period, additional symptoms appear. The patient develops a mild jaundice, has repeated incidents of nausea and vomiting, and is still febrile. The physical examination reveals pain and tenderness in the right epigastrium. Palpation of the right upper quadrant elicits marked tenderness and stoppage of inspired breath, along with a guarding response. Microscopic examination of stool samples reveals the presence of structures that might be relatively small cysts or oocysts. These structure stain red when an acid-fast stain is applied to the fecal smear.

Question 10.1: What is your preliminary diagnosis?

The presence of possible cysts or oocysts in the stool suggests a protozoan disease, and this one appears to have become chronic. The protozoa that are most frequently associated with chronic gastroenteritis in AIDS patients and other immunocompromised individuals include Cryptosporidium parvum, Isospora belli, and several genera of the Microspora. The general gastroenteritis related symptoms in this case are reasonably consistent with any of these causative agents, so it is difficult to make a more specific diagnosis without additional information. Some of the later-developing symptoms (jaundice, vomiting, pain and tenderness in the right epigastrium, etc.) are suggestive of gallbladder or other biliary involvement.

Question 10.2: What tests should you do?

The lab should be asked to identify the cyst-like structures in the stool. Lab tests should include CBC with differential, alkaline phosphatase, ALT, AST, bilirubin, and amylase. Imaging should also be done if gallbladder involvement is suspected. Ultrasound or nuclear imaging (HIDA) are possibilities.

Test Results

The lab identifies the objects in the stool as Cryptosporidium parvum oocysts. The CBC shows marked leukocytosis (19,000/microliter). Alkaline phosphatase, ALT, and AST are somewhat elevated. Total bilirubin is elevated 6 mg/dL, amylase is within the normal range. Imaging does not detect gallstones, although the gallbladder is enlarged.

Question 10.3: How did the causative agent produce the symptoms seen here?

Intestinal epithelial cells harbor the C. parvum in an intracellular vacuole, but the actual mechanism by which this organism produces a secretory diarrhea remains uncertain. Biopsies do not reveal any characteristic pathologic changes. In immunocompetent individuals, the infection almost always is limited to the GI tract, and it is usually self-limiting (typically subsiding after 1-2 weeks). In immunocompromised individuals, especially AIDS patients, the microbe can invade the biliary tract and cause acute cholecystitis (as seen in the present case). Other possible manifestations of biliary tract involvement include papillary stenosis or sclerosing cholangitis. More widely disseminated infections are also possible in immunocompromised patients.

Question 10.4: How is this disease transmitted?

Cryptosporidium species are distributed worldwide. Infection has been reported in a wide variety of animals, including mammals, reptiles, and fish, so some Cryptosporidium infections are zoonotic. Oocysts are immediately infective when they are passed in feces, so person-to-person transmission occurs in day-care centers and among household contacts and medical providers. Waterborne transmission accounts for infections in travelers and for common-source epidemics (such as the huge outbreak that took place in Milwaukee, Wisconsin some years ago). Drinking water and recreational water (e.g., pools and water slides) can both serve as sources of infection. The oocysts are resistant to standard drinking water purification methods like chlorination, and this enhances the likelihood of large common-source outbreaks. Cryptosporidium parvum can also be transmitted by oral-anal sexual practices.

Question 10.5: How is this organism identified by the lab?

Cryptosporidium oocysts, which are 4-5 (m in diameter, can be identified by direct microscopic examination of stool samples. The cysts are numerous in patients with acute symptoms. Identification is based on morphology and the fact that they stain a red color with a modified acid-fast staining procedure. Alternative methods for identification are now available and include direct immunofluorescent stains and enzyme immunoassays (ELISA).