Clinical trials to test the safety of a first-of-its-kind human hookworm vaccine

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Jan 27 2005

Clinical trials to test the safety of a first-of-its-kind human hookworm vaccine will begin in the Washington, DC area in a couple of months after the U.S. Food and Drug Administration conferred investigational new drug status on the vaccine.

No current vaccine is available to prevent hookworm disease, which is one of the most common chronic infections of humans with an estimated 740 million cases in areas of rural poverty in the tropics and subtropics.

The Human Hookworm Vaccine Initiative is sponsored by the Albert B. Sabin Vaccine Institute, and is funded by the Bill & Melinda Gates Foundation. The research is conducted at The George Washington University Medical Center. Peter J. Hotez, MD, PhD, professor and chair of GW's Department of Microbiology and Tropical Medicine leads the scientific team and has been responsible for the development of the vaccine. "Approval to begin safety trials is a major milestone for the human hookworm vaccine project," Hotez said. "It has taken an amazing amount of our team's effort to get us to the current stage of vaccine development. Of course, our ultimate goal is to take this research to developing countries where the vaccine will be tested in individuals who suffer from hookworm infection."

Human hookworm infection is caused by parasitic worms that fasten onto the inner layers of the small intestine using their teeth-like projections and cause blood loss at the attachment site. Hookworm disease refers to the iron deficiency anemia that results from moderate and heavy infections. Because women and young children have the lowest iron stores, they are the most vulnerable to chronic hookworm blood loss. In children, chronic hookworm disease contributes to physical growth retardation and cognitive impairment. Hookworm is considered a major health threat to adolescent girls, women of reproductive age, and to outcomes in pregnancy and is a major contributor to misery and suffering in the poorest of the poor.

This first phase of clinical research will assess the initial safety of the new hookworm vaccine, as well as the immune system's response to vaccination. Several more years of subsequent research on the vaccine's effect will be required before it can be licensed for use. Looking towards the future, the Sabin Vaccine Institute signed a memorandum of understanding this past fall with federal and state vaccine production facilities in Brazil for clinical development of the vaccine. A Human Hookworm Vaccine Initiative team based in Brazil is now assembling baseline data in a rural area impacted by hookworm disease. In just more than a year, that data and data from safety and tolerability trials in the United States, will serve as required groundwork for a wider clinical trial, to ascertain the efficacy and safety of the new vaccine.

The Human Hookworm Vaccine Initiative of the Sabin Vaccine Institute and the Bill & Melinda Gates Foundation is being conducted at The George Washington University Medical Center.

What is hookworm?

Hookworm is an intestinal parasite of humans that usually causes mild diarrhea or cramps. Heavy infection with hookworm can create serious health problems for newborns, children, pregnant women, and persons who are malnourished. Hookworm infections occur mostly in tropical and subtropical climates and are estimated to infect about 1 billion people -- about one-fifth of the world's population.

Where are hookworms commonly found?

One of the most common species, Ancylostoma duodenale (an-cy-CLO-sto-ma doe-AH-den-al), is found in southern Europe, northern Africa, northern Asia, and parts of South America. A second species, Necator americanus (ne-KAY-tor am-er-i-CON-us), was widespread in the southeastern United States early in this century. The Rockefeller Sanitary Commission was founded in response, and hookworm infection has been largely controlled.

How do I get a hookworm infection?

You can become infected by direct contact with contaminated soil, generally through walking barefoot, or accidentally swallowing contaminated soil.

Hookworms have a complex life cycle that begins and ends in the small intestine. Hookworm eggs require warm, moist, shaded soil to hatch into larvae. These barely visible larvae penetrate the skin (often through bare feet), are carried to the lungs, go through the respiratory tract to the mouth, are swallowed, and eventually reach the small intestine. This journey takes about a week. In the small intestine, the larvae develop into half-inch-long worms, attach themselves to the intestinal wall, and suck blood. The adult worms produce thousands of eggs. These eggs are passed in the feces (stool). If the eggs contaminate soil and conditions are right, they will hatch, molt, and develop into infective larvae again after 5 to 10 days.

Who is at risk?

People who have direct contact with soil that contains human feces in areas where hookworm is common are at high risk of infection. Children --because they play in dirt and often go barefoot-- are at high risk. Since transmission of hookworm infection requires development of the larvae in soil, hookworm cannot be spread person to person. Contact among children in institutional or child care settings should not increase the risk of infection.

What are the symptoms of hookworm?

Itching and a rash at the site of where skin touched soil or sand is usually the first sign of infection. These symptoms occur when the larvae penetrate the skin. While a light infection may cause no symptoms, heavy infection can cause anemia, abdominal pain, diarrhea, loss of appetite, and weight loss. Heavy, chronic infections can cause stunted growth and mental development.

Can a hookworm infection cause any serious health problems?

Yes. The most serious results of hookworm infection are the development of anemia and protein deficiency caused by blood loss. When children are continuously infected by many worms, the loss of iron and protein can retard growth and mental development, sometimes irreversibly. Hookworm infection can also cause tiredness, difficulty breathing, enlargement of the heart, and irregular heartbeat. Sometimes hookworm infection is fatal, especially among infants.

What should I do if I think I have a hookworm infection?

Visit your health care provider. Infection is diagnosed by identifying hookworm eggs in a stool sample.

What is the treatment for hookworm?

In countries where hookworm is common and reinfection is likely, light infections are often not treated. In the United States, hookworm infections are generally treated for 1-3 days with medication prescribed by your health care provider. The drugs are effective and appear to have few side effects. For children under the age of 2, the decision to treat should be made by their health care provider.

Another stool exam should be repeated 1 to 2 weeks after therapy. If the infection is still present, treatment will be given again. Iron supplements will be ordered if you have anemia.