Step Perspective, Volume 5, Number 1; A Publication Of The Seattle Treatment Education Project - February 1993
Laury McKean

People with normal immune systems can contract this infection and prevalence studies have shown it to be the cause of 1.4 to 7.9 percent of infectious diarrhea (gastroenteritis), most commonly in children in developing countries. It is probably one of the causes of "traveler's diarrhea." The incidence of infection in people with HIV is reported by the CDC (Centers for Disease Control) at four percent, but it is probably higher as the organism is not routinely looked for or diagnosed. In Haiti, the incidence is 41 percent in people with AIDS, and is about the same in children with AIDS in the United States. The likelihood of infection is roughly correlated with the degree of damage to the immune system. Since 1982, the CDC has included in its definition of AIDS those people who have had intestinal cryptosporidiosis for longer than one month and in whom no other cause of immunosuppression exists.

Cryptosporidiosis is a highly infectious disease spread most commonly from person to person, either through routine contract or through unsafe sexual practices. The organism is found in a number of animals (dogs, cats, calves, lambs, turkeys, chickens, birds, goats, pigs, rabbits, monkeys, and rodents), and it is felt that contact with animals is a risk factor. Cryptosporidiosis can also be acquired from contaminated water supplies, food, and environmental surfaces. The organism is very hardy and resistant to various disinfectants. The incubation period is thought to be two to ten days.

The severity and duration of cryptosporidiosis are directly dependent on the immune status of the person infected. In immunocompetent people, and perhaps people with HIV in earlier phases of the disease, the illness is an acute, self-limiting diarrhea lasting 10 to 14 days. But, in most people with AIDS< the disease is much more severe. The primary symptom is diarrhea, which is profuse (six to 25 bowel movements per day), non-bloody, and often chronic. The disease is often accompanied by accelerated weight loss, as much as 20-30 percent of total body weight within a few weeks. Vomiting and crampy abdominal pain, at times severe, occur frequently as the illness persists. Anorexia (loss of appetite), flatulence, and muscle aches occur, but fever usually does not.

Cryptosporidium is typically found in the intestines, but biliary- tract involvement has been reported in 10 percent of the cases. The biliary tract, which is located between the liver, gall bladder, and small intestine, may act as a reservoir of infection, defeating efforts to cure the disease. Cases of inflamed gall bladder have occurred, with persistent vomiting and localized pain in the upper right quadrant. Cryptosporidium is also implicated in pancreatitis (inflammation of the pancreas). The organism has been found in the respiratory tract, but its significance is unclear and probably not pathogenic.

Prior to 1983, intestinal biopsy was necessary to detect the infection, but it can now be identified in stool samples treated with a modified acid-fast stain (Kinyoun). It is recommended that three specimens be submitted over several days time. concentration techniques are not thought to be important for those with diarrhea, as the oocysts are shed in large numbers. However, specialized techniques may be helpful to recognize low-intensity infection which might be important in future drug trials and for earlier treatment of people in early stages of infection. Blood tests are not useful in the diagnosis of acute infection, but are used in epidemiological studies. Recently, a monoclonal antibody reagent has become commercially available and may prove to be superior to staining techniques in oocyst detection.

In some people with cryptosporidiosis, special tests such as CT scans (computerized tomography) and ultrasound may be necessary to diagnose involvement of the gall bladder or pancreas.

Treatment

In the past, therapy was largely unsuccessful and futile, but now a number of drugs are showing encouraging results. Perhaps the most promising of these treatments is the drug paromomycin (Humatin). It is an intraluminal agent, which means it goes through the gastrointestinal tract with little absorption into the bloodstream. Hence, toxicity is controlled. It should be noted that it is possible for paromomycin to reach the bloodstream if intestinal ulcers are present, which could lead to hearing loss or kidney toxicity. In one study of 23 individuals treated with paromomycin, 16 people responded completely to the drug, and the other seven individuals had a marked reduction in their stools. In another study of 22 people who had 31 episodes of gastrointestinal cryptosporidiosis (GIC), 30 of the 31 episodes improved with 500 mg of paromomycin given four times daily for four to 30 days with excellent tolerance. Weight gain was seen in 23 of the 30 episodes. Relapse occurred in five individuals, but all responded successfully to re treatment. In addition to these published studies, STEP has received a number of anecdotal reports from local care providers who are seeing positive results with this drug. Paromomycin is available through prescription.

Letrazuril is another drug which looks promising for the treatment of cryptosporidiosis. Letrazuril is a derivative of diclazuril (a drug which has been found to be ineffective for cryptosporidiosis due to poor bioavailability) but is much more readily absorbed. A small Spanish study reported that 50 mg of letrazuril a day substantially decreased diarrhea in individuals who had already tried and failed numerous other treatments. The diarrhea did return when treatment with letrazuril was discontinued. Studies are also underway in the United States.

Azithromycin is also under investigation for the treatment of cryptosporidiosis. It is an oral antibiotic that is also under investigation for toxoplasmosis and MAC. Preliminary results of 28 patients from a study under way at the Cornell Medical Center suggests that azithromycin is effective in some individuals and most tolerate the therapy well. However, another pilot study showed no change in stool frequency and volume, of the number of cryptosporidial oocysts in the stool in 13 of 15 individuals. Diarrhea did stop in two of the 15 individuals, but cryptosporidia were still present. Further studies are underway. Azithromycin is available through prescription, however, because cryptosporidiosis is not an officially approved use of the drug, insurance companies may not pay for it. Physicians can obtain azithromycin, free of charge, on a compassionate use basis through the manufacturer (Pfizer) by calling 1-800-742-3029.

Roxithromycin, a cousin of azithromycin, is also being studied as a possible treatment option for cryptosporidiosis. It showed surprisingly good results in four individuals in Argentina. Diarrhea stopped after two to ten days of treatment in all four individuals. The diarrhea recurred in one person after treatment was stopped. Stool cultures were negative for cryptosporidium after treatment in three of the individuals, and the numbers reduced in the fourth individual. No side effects were reported. Larger studies are needed to confirm the efficacy of roxithromycin.

Other drugs currently being studied for use in cryptosporidiosis include octreotide acetate, erythromycin, 566, and Bovine anti- cryptosporidium Immunoglobulin (BACI). In addition, one physician reported successfully treating four patients with fluconazole, although the mechanism of action for fluconazole against cryptosporidiosis is unknown.

Because fluid losses in cryptosporidiosis are often so severe, increasing oral fluid intake via juices, water, bouillon, and oral rehydration solutions is very important. When dehydration occurs, hospitalization is necessary for IV fluids and correction of electrolyte imbalances. Sometimes total parental nutrition (TPN) is used for fluid replacement and nutritional maintenance.

Anti-diarrheal medications have not been consistently effective and appear to increase abdominal pain in some patients. However, in one study, diphenoxylate (Lomotil) seemed beneficial.

It is important to maximize caloric intake to combat malnutrition, and to utilize a lactose-free and low-fat diet as these nutrients seem to increase the diarrhea.
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