Opportunistic Infections Research - National Institute of Allergy and Infectious Diseases
Acquired immunodeficiency syndrome (AIDS) is an infectious disease of the immune system. Since its identification in 1981, AIDS has become a worldwide epidemic. In the United States alone, an estimated 1 million Americans are infected with the human immunodeficiency virus (HIV), the virus that causes AIDS. More than 150,000 persons have been diagnosed with AIDS, and more than 100,000 deaths have been attributed to the disease.
People infected with HIV often have no symptoms for years. The eventual destruction of the immune system by HIV makes these persons particularly susceptible to the development of opportunistic infections (OIs), including a variety of protozoal, viral, fungal, and bacterial diseases. The most devastating gastrointestinal infection seen in persons with AIDS is severe diarrhea caused by the protozoan Cryptosporidium.
In persons who have normally functioning immune systems, the body is able to overcome infection with Cryptosporidium. In persons with AIDS, however, Cryptosporidium infection can be severe and even life-threatening because the body's immune system is damaged. Even persons taking AZT (zidovudine, Retrovir,) the only drug approved to treat HIV, are not protected. Consequently, safe and effective methods are needed to prevent and treat this OI in people infected with HIV.
The National Institute of Allergy and Infectious Diseases (NIAID) has the principal responsibility in the federal government for research on AIDS. A major focus of the NIAID program is the development and evaluation of promising drugs for OIs, including Cryptosporidium-induced diarrhea.
NATURE OF THE DISEASE
Cryptosporidiosis is a major cause of diarrheal illness in humans worldwide. The parasite lives in cattle and domestic animals and is excreted in feces. It can be transmitted to humans from animals or via contact with feces, contaminated water, or food. In persons with normal immune systems, Cryptosporidium causes acute diarrhea with flu-like intestinal symptoms that go away after a week or more without treatment.
In persons with AIDS, cryptosporidiosis is a serious, debilitating illness. Along with chronic, watery, sometimes uncontrollable diarrhea, other symptoms include abdominal cramps, nausea, vomiting, fever, and headache. Weakness and weight loss often accompany bouts of the disease, which can persist for weeks or months. Fluid loss may be so massive as to be life-threatening. The infection can spread to other digestive organs such as the gallbladder, causing nausea, vomiting, and severe localized pain. A diagnosis of cryptosporidiosis is made by microscopic examination of stool specimens (treated with special stains) for the organism.
Approximately 50 percent of persons with AIDS in the United States suffer from some form of diarrhea, but only 4 percent are reported to have cryptosporidiosis at the time of their initial diagnosis of AIDS. The actual number of patients who develop cryptosporidiosis later in the course of their HIV infection is believed to be higher. Cryptosporidiosis is more common in AIDS patients in other countries.
A variety of agents have been used against cryptosporidiosis, but none have been effective. Supportive therapy with fluids and nutrients given orally or intravenously is used to treat severe illness.
In some people, cryptosporidial infections seem to respond to an oral form of spiramycin, an antibiotic similar to erythromycin. The oral from of the drug, however, is poorly absorbed, which may limit its effectiveness. A study of intravenous spiramycin has recently completed enrollment in NIAID's AIDS Clinical Trials Group (ACTG).
Other agents being tested against cryptosporidiosis in various medical centers include diclazuril, hyperimmune bovine colostrum, and a synthetic form of the hormone somatostatin. In some people, these treatments help control the diarrhea temporarily but do not eliminate the organism that causes the disease. The inability to grow this organism in the laboratory has limited clinical exploration of a broader range of agents.
No preventive treatment is yet available for diarrhea caused by Cryptosporidium. Careful handwashing after contact with potentially infected animals or humans offers the best protection against infection.
SCOPE OF THE NIAID EFFORT
One of the primary goals of the NIAID is the development of new therapeutic approaches for HIV-related OIs. The NIAID research effort ranges from preclinical study to clinical investigations in HIV-infected persons. NIAID has given a high priority to basic research for finding better ways to treat the infectious diseases associated with HIV. NIAID has established several National Cooperative Drug Discovery Groups (NCDDGs) specifically to identify and develop treatments for HIV-related OIs. Like the NCDDGs that focus on HIV therapies, each NCDDG-OI consists of a multidisciplinary team with the skills needed to design, synthesize, and evaluate, at the preclinical level, potential therapeutic agents for the treatment of HIV-related OIs, including cryptosporidiosis.
NIAID sponsors a number of clinical studies to evaluate agents for the prevention and treatments of AIDS-related infections, including cryptosporidiosis. NIAID studies are conducted by the ACTG at sites located at academic research centers throughout the country.
NIAID sponsors the following ACTG trial:
o Evaluation of the safety and effectiveness of intravenous spiramycin in treating AIDS-related cryptosporidial diarrhea (ACTG 113). This study is closed to enrollment and its data are being analyzed.
Information about ACTG studies may be obtained by calling 1-800-TRIALS-A