New Treatment Patch For Traveler's Diarrhea

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Main Category: GastroIntestinal / Gastroenterology
Also Included In: Clinical Trials / Drug Trials;  Nutrition / Diet
Article Date: 12 Jun 2008 - 0:00 PDT

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A new study published online in The Lancet reports promising results for patches that vaccinate travelers against diarrhea. A team of researchers, led by Dr Gregory Glenn and Dr Sarah Frech (IOMAI Corporation, Gaithersburg, MD, USA), has demonstrated that patches containing Escherichia coli toxins can not only help to prevent traveler's diarrhea, but also can reduce severity and shorten episodes if the ailment is contracted.

People who travel to endemic areas and young children who live in developed countries often suffer from diarrhea due to enterotoxigenic E coli (ETEC) - a form of the bacterium that is toxic to the digestive system. Some 380,000 of the 210 million children who are affected by acute diarrhea die each year die, and about 27 million travelers are also affected by acute diarrhea every year. The condition is characterized by 4 to 5 days of frequent loose stool, nausea, vomiting, abdominal cramps, prostration, and dehydration. People contract the disease through contaminated food or drinks, whereby the ETEC organisms colonize the small intestine and secrete two types of toxins that threaten the digestive tract: heat-labile enterotoxin (LT, 66% of cases) or heat-stable enterotoxin (ST).

According to existing research, anti-LT vaccines are capable of providing short-term protection against diarrhea. Though it is an ideal antigen, LT cannot be administered by oral, nasal, or intravenous routes due to its toxicity. To test the efficacy of a different administration route, Glenn, Frech, and colleagues studied travelers who used vaccine skin patches containing LT from ETEC. The researchers focused on the rate of diarrhea attacks, safety, and feasibility of the vaccine.

Patients in the phase II randomized trial consisted of healthy adults (age 18 to 64) who planned to travel to Mexico or Guatemala and who were near a US regional vaccination center. Randomization created two groups in a 2:1 ration: the first received 37 μg of LT and a second received placebo, both through patches. Two to three weeks before travel, 178 (out of 201) participants received patches and traveled, and 170 of these were assessed. Participants utilized diary cards to keep track of stool output during their travels; if diarrhea occurs, participants provided stool samples so researchers could identify the pathogen responsible. Diarrhea severity was evaluated using a scale that used the number of loose stools in previous 24 hours: 3 loose stools is mild; 4 or 5 is moderate, at least 6 is severe (at least six).

Results of the study are summarized below:

• 22% (24 of 111) of the placebo group had diarrhea, 11 (10%) had ETEC diarrhea.
• 15% (9 of 59) in the LT patch group had diarrhea, 3 (5%) had ETEC diarrhea.
• 21% of placebo group compared to 5% of the LT patch group had moderate-to-severe of any cause - a 75% protective efficacy for the LT patch
• 11% of the placebo group compared to 2% of the LT patch group had severe diarrhea - an 84% protective efficacy for the LT patch

In addition, participants who received the LT-patch and still had diarrhea had shorter episodes (by 1.6 days) and 6.8 fewer loose stools than those in the placebo group.

"The LT patch vaccine conferred some protective efficacy against moderate-to-severe travellers' diarrhoea of any cause, severe diarrhoea, and moderate-to-severe ETEC diarrhoea. Furthermore, recipients of the LT patch who became ill had a milder course of illness, with reduced stool output and duration of diarrhoea illness compared with placebo. Taken together, the LT patch conferred a meaningful benefit to the recipients," write the authors.

"In addition to the biological rationale for delivering antigen to the skin, the transcutaneous patch lends itself to a simple and needle-free application, use of the vaccine outside the cold chain, and has been designed to be suitable for both travellers and use in the developing world. This study suggests that transcutaneous immunisation with LT in a patch could protect travellers against this common, debilitating ailment but the recorded efficacy will need confirmation in a phase III trial," they conclude.

Use of a patch containing heat-labile toxin from Escherichia coli against travellers' diarrhoea: a phase II, randomised, double-blind, placebo-controlled field trial
Sarah A Frech, Herbert L DuPont, A Louis Bourgeois, Robin McKenzie, Jaime Belkind-Gerson, Jose F Figueroa, Pablo C Okhuysen, Norma H Guerrero, Francisco G Martinez-Sandoval, Juan H M Meléndez-Romero, Zhi-Dong Jiang, Edwin J Asturias, Jane Halpern, Olga R Torres, Ana S Hoffman, Christina P Villar, Raniya N Kassem, David C Flyer, Bo H Andersen, Kazem Kazempour, Sally A Breisch, Gregory M Glenn
The Lancet (2008).
DOI:10.1016/S0140-6736(08)60839-9
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Written by: Peter M Crosta
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