ILLNESS/INFLAMMATION/IMMUNITY/

COMMUNICABLE DISEASECase Presentation

CHOLERACHOLERA

MUAMIR ALI ALINGANBSN4A

INTRODUCTION

• Cholera is an acute, bacterial, diarrheal disease with profuse watery stools, occasional vomiting, and rapid dehydration.

• If untreated, circulatory collapse, renal failure and death may occur.

• More than 50% of untreated people with severe cholera die.

• It occurs worldwide, with periodic epidemics and pandemics.

• A recent Western Hemisphere cholera pandemic started in Peru in 1991. By 1994, more than 950,000 cases had been reported in 21 countries in the Western Hemisphere.

• Only 5 new U.S. cases were reported to the CDC in 2004. Most U.S. cases involve the ingestion of raw or undercooked seafood (e.g., oysters) from the coastal waters of Louisiana and Texas.

• The Philippines were infected in 1858.• The 1902-1904 cholera epidemic claimed

200,000 lives in the Philippines.• In the Philippines, there is an incidence rate of

approximately one person in 86,241,697.

Etiologic agent. Certain biotypes of Vibrio cholerae serogroup

01 which are curved, Gram-negative bacilli that secrete an enterotoxin (a toxin that adversely affects cells in the intestinal tract) called choleragen. Other Vibrio spp. (Vibrio parahaemolyticus, Vibrio vulnificus) also cause diarrheal diseases. Vibrios are halophilic and are thus found in marine environments.

Vibrio cholerae

Cholera Toxin. The delivery region (blue) binds membrane carbohydrates to get into cells. The toxic part (red) is activated inside the cell .

Reservoirs and Mode of Transmission.• Infected humans and aquatic reservoirs.• Transmission is via the fecal-oral route, contact

with feces or vomitus of infected people, ingestion of fecally contaminated water and foods especially raw or undercooked shellfish and other seafood and flies.

Diagnosis.Rectal swabs or stool specimens should

be inoculated onto thio-sulfate-citrate-bile-sucrose (TCBS) agar; different Vibrio spp. produce different reactions on this medium. Biochemical tests are used to identify the various species. Biotyping is accomplished using commercially available antisera.

ANATOMY AND PHYSIOLOGY OF THE SYSTEM INVOLVED

The organs of the digestive system can be separated into two main groups: those forming the alimentary canal and the accessory digestive organs. The alimentary canal performs the whole menu of digestive functions (ingests, digests, absorbs, and defecates). The accessory organs (teeth, tongue, and several large digestive glands) assist the process of digestive breakdown in various ways.

Organs of the Alimentary Canal

The alimentary canal, also called the gastrointestinal (GI) tract, is a continuous, coiled, hollow, muscular tube that winds through the ventral body cavity and is open at both ends. Its organs are the mouth, pharynx, esophagus, stomach, small intestine, and large intestine. The large intestine leads to the terminal opening, or anus.

MOUTHFood enters the digestive tract through the

mouth, or oral cavity, a mucous membrane-lined cavity. The lips (labia) protect its anterior opening, the cheeks form its lateral walls, the hard palate forms its anterior roof, and the soft palate forms its posterior roof. The uvula is a fleshy fingerlike projection of the soft palate, which extends downward from its posterior edge. The space between the lips and cheek externally and the teeth and gums internally is the vestibule.

` The area contained by the teeth is the oral cavity proper. The muscular tongue occupies the floor of the mouth. The tongue has several bony attachments-two of these are to the hyoid bone and the styloid processes of the skull. The lingual frenulum, a fold of mucous membrane, secures the tongue to the floor of the mouth and limits its posterior movements.

At the posterior end of the oral cavity are paired masses of lymphatic tissue, the palatine tonsils. The lingual tonsil covers the base of the tongue just beyond. The tonsils, along with other lymphatic tissues, are part of the body’s defense system. When the tonsils become inflamed and enlarged, they partially block the entrance into the throat (pharynx), making swallowing difficult and painful.

PHARYNXThe pharynx or throat is a tubular structure

that extends from the base of the skull to the esophagus and is situated immediately in front of the cervical vertebrae. The oropharynx and laryngopharynx are food passageways connecting the oral cavity to the esophagus. No digestion takes place in the pharynx. Its only related function is swallowing, the mechanical movement of food. When the bolus of food is pushed backward by the tongue, the constrictor muscles of the pharynx contract as part of the swallowing reflex.

ESOPHAGUSThe esophagus , or gullet, is a muscular

tube of approximately 25cm in length and 2cm in diameter. It extends from the pharynx to the stomach after passing through an opening in the diaphragm. The esophagus functions primarily as a transport medium between compartments.

The walls of the alimentary canal organs from the esophagus to the large intestine are made up of the same four basic tissue layers, or tunics:

1.The mucosa is the innermost layer, a moist membrane that lines the cavity, or lumen, of the organ. It consists primarily of a surface epithelium, plus a small amount of connective tissue (lamina propria) and a scanty smooth muscle layer.

2. The submucosa is found just beneath the mucosa. It is a soft connective tissue layer containing blood vessels, nerve endings, lymph nodules and lymphatic vessels.

3. The muscularis externa is a muscle layer typically made up of an inner circular layer and an outer longitudinal layer of smooth muscle cells.

4. The serosa is the outermost layer of the wall. It consists of a single layer of flat serous fluid-producing cells, the visceral peritoneum. The visceral peritoneum is continuous with the slick, slippery parietal peritoneum, which lines the abdominopelvic cavity by way of a membrane extension, the mesentery.

STOMACHThe stomach is a C shaped expanded bag,

located just left of the midline between the esophagus and small intestine. It has two borders called the greater and lesser curvatures. The first section is the cardia which surrounds the cardial orifice where the esophagus enters the stomach. The fundus is the superior, dilated portion of the stomach. The body is the largest section between the fundus and the curved portion of the C.

The pylorus is the curved base of the stomach. Gastric contents are expelled into the proximal duodenum via the pyloric sphincter. The inner surface of the stomach is contracted into numerous longitudinal folds called rugae. These allow the stomach to stretch and expand when food enters.

The functions of the stomach include: • The short-term storage of ingested food. • Mechanical breakdown of food by churning

and mixing motions. • Chemical digestion of proteins by acids and

enzymes. • Stomach acid kills bugs and germs. • Some absorption of substances such as

alcohol.

SMALL INTESTINE The small intestine is about 1 inch (2.5

cm) in diameter and approximately 20 feet (6m) long and extends from the stomach to the cecum of the large intestine.

The duodenum is the first 10 inches (25 cm) of the small intestine. The jejunum is about 8 feet long, and the ileum is about 11 feet in length.

Digestion is completed in the small

intestine, and the end products of digestion are absorbed in the blood and lymph. The mucosa has simple columnar epithelium that includes cells with microvilli and goblets cells that secretes mucos. Enteroendocrine cells secrete the hormones of the small intestine. Lymph nodules called peyer’s patches are especially abundant in the ileum to destroy absorbed pathogens.

LARGE INTESTINEThe large intestine is horse-shoe shaped and

extends around the small intestine like a frame. It consists of the appendix, cecum, ascending, transverse, descending and sigmoid colon, and the rectum. It has a length of approximately 1.5m and a width of 7.5cm. The cecum is the expanded pouch that receives material from the ileum and starts to compress food products into fecal material. Food then travels along the colon. The wall of the colon is made up of several pouches (haustra) that are held under tension by three thick bands of muscle (taenia coli).

The rectum is the final 15cm of the large intestine. It expands to hold fecal matter before it passes through the anorectal canal to the anus. Thick bands of muscle, known as sphincters, control the passage of feces.

The functions of the large intestine can be summarized as: • The accumulation of unabsorbed material to form feces. • Some digestion by bacteria. The bacteria are responsible

for the formation of intestinal gas. • Reabsorption of water, salts, sugar and vitamins

Accessory Digestive Organs

SALIVARY GLANDSThree pairs of salivary glands which are the

parotid, submandibular and sublingual glands communicate with the oral cavity. Each is a complex gland with numerous acini lined by secretory epithelium. The acini secrete their contents into specialized ducts. Each gland is divided into smaller segments called lobes.

TEETHThe function of the teeth is chewing. This is

the process that mechanically breaks food into smaller pieces and mixes with saliva.

TONGUEIt is the principal organ of the sense of taste

that also assist in the mastication and deglutition of food.

The pancreas is a lobular, pinkish-grey organ that lies behind the stomach. Its head communicates with the duodenum and its tail extends to the spleen. The organ is approximately 15cm in length with a long, slender body connecting the head and tail segments. It is made up of numerous acini (small glands) that secrete contents into ducts which eventually lead to the duodenum.

PANCREAS

LIVERThe liver is a large, reddish-brown organ situated

in the right upper quadrant of the abdomen. It is divided into four lobes namely the right, left, caudate and quadrate lobes. The liver has important functions. It acts as a mechanical filter by filtering blood that travels from the intestinal system. It detoxifies several metabolites including the breakdown of bilirubin and estrogen. In addition, the liver has synthetic functions, producing albumin and blood clotting factors. However, its main roles in digestion are in the production of bile and metabolism of nutrients.

GALL BLADDERThe gallbladder is a hollow, pear shaped

organ that sits in a depression on the posterior surface of the liver's right lobe. The main functions of the gall bladder are storage and concentration of bile.

RISK FACTORSPrecipitating factors:•Contaminated food and water (contact with flies, feces )•Raw or undercooked seafood (e.g., shellfish)•Poor hygiene and sanitation•Overcrowding(e.g., refugee camps, impoverished countries, and areas devastated by famine, war or natural disasters)•Poverty•Malnutrition•Compromised Immunity•Reduced or nonexistent stomach acid (hypochlorhydria or achlorhydria)

Predisposing factors:•Age: children and older adults• People who have had gastric surgery, who have untreated Helicobacter pylori infection, or who are taking antacids, H-2 blockers or proton pump inhibitors for ulcers•Type O blood•Household exposure•International travel (Latin America, Africa, Asia, Gulf of Mexico, Middle East)

PATHOPHYSIOLOGY

Adherence of Vibrio cholerae to the small intestinal epithelium

Adherence of Vibrio cholerae to the small intestinal epithelium

Multiplication of the organisms on the epithelial cells (colonization)

Multiplication of the organisms on the epithelial cells (colonization)

Production of cholera enterotoxin by the bacteria

Production of cholera enterotoxin by the bacteria

Survival of virulent organisms that pass through the stomach and into the small

intestine

Survival of virulent organisms that pass through the stomach and into the small

intestine

Entry of Vibrio cholerae through oral route (entry)

Entry of Vibrio cholerae through oral route (entry)

leads to

causes

results to

leads to

Manifestations of cholera (disease)Manifestations of cholera (disease)

Normal shedding of intestinal cells eventually gets rid of the toxin (exit)

Normal shedding of intestinal cells eventually gets rid of the toxin (exit)

Binding of toxin to the plasma membrane of intestinal epithelial cells

Binding of toxin to the plasma membrane of intestinal epithelial cells

Release of an enzymatically active subunit called adenylate cyclase

Release of an enzymatically active subunit called adenylate cyclase

A rise in cyclic adenosine monophosphate (cAMP) production

A rise in cyclic adenosine monophosphate (cAMP) production

Massive secretion of electrolytes and water into the intestinal lumen

Massive secretion of electrolytes and water into the intestinal lumen

results in

leads to

causes

results in

causes

leads to

CLINICAL MANIFESTATIONS

Stage 1: Diarrheal Stage• Abrupt onset of painless, severe, watery diarrhea

that is often voluminous, flecked with mucus and dead cells, and has a pale, milky appearance that resembles water in which rice has been rinsed (rice-water stool)

• Vomiting without nausea that may persist for hours at a time

• Muscle cramps

Stage 2: Dehydration Stage• Dehydration• Irritability• Lethargy • Sunken eyes• Dry mouth• Extreme thirst• Dry, shriveled skin that's slow to bounce back when pinched into

a fold• Little or no urine output• Low blood pressure• Irregular heartbeat (arrhythmia)• Shock

NURSING CARE MANAGEMENT

• Assess severity, quality, region and time of muscle cramps.• Assess for signs of dehydration. Observe for excessively dry

skin and mucous membranes, decreased skin turgor, slowed papillary refill.

• Note number, color, amount, consistency and characteristic of stool and vomitus.

• Note generalized muscle weakness or cardiac dysrhythmias.• Observe for overt bleeding and test stool daily for occult

blood.• Monitor input and output strictly.• Monitor vital signs. Blood pressure, pulse, respiration and

temperature.• Weigh daily.• Increase fluid intake.• Estimate fluid volume losses like diaphoresis.

• Measure urine specific gravity and observe for oliguria.• Maintain oral restrictions, bed rest and avoid exertion.• Provide bed pan or bedside commode.• Provide a bland diet.• Assist patient in ambulating to the bathroom.• Medical septic protective care must be provided.• Contact precautions must be observed.• A thorough and careful personal hygiene must be provided.• Stool, urine and other infected secretions must be properly

disposed of.• Concurrent disinfection must be applied.• Food must be properly prepared.• Environmental sanitation must be observed.

Treatment:Cholera requires immediate treatment because the disease can

cause death within hours.• Rehydration. The goal is to replace fluids and electrolytes

lost through diarrhea using a simple rehydration solution, Oral Rehydration Salts (ORS), that contains specific proportions of water, salts and sugar. The ORS solution is available as a powder that can be reconstituted in boiled or bottled water. Without rehydration, approximately half the people with cholera die. With treatment, the number of fatalities drops to less than 1 percent.

• Intravenous fluids. During a cholera epidemic, most people can be helped by oral rehydration alone, but severely dehydrated people may also need intravenous fluids.

• Antibiotics. Recent studies show that a single dose of azithromycin (Zithromax, Zmax) in adults or children with severe cholera helps shorten diarrhea duration and decreases vomiting.

• Zinc supplements. Research has shown that zinc may decrease and shorten the duration of diarrhea in children with cholera.

Prevention:• Wash your hands. Frequent hand washing is the best way

to control cholera infection. Wash your hands thoroughly with hot, soapy water, especially before eating or preparing food, after using the toilet, and when you return from public places. Carry an alcohol-based hand sanitizer for times when water isn't available.

• Avoid untreated water. Contaminated drinking water is the most common source of cholera infection. For that reason, drink only bottled water or water you've boiled or disinfected yourself. Coffee, tea and other hot beverages, as well as bottled or canned soft drinks, wine and beer, are generally safe. Carefully wipe the outside of all bottles and cans before you open them and ask for drinks without ice..

• Eat food that's completely cooked and hot. Cholera bacteria can survive on room temperature food for up to five days and aren't destroyed by freezing. It's best to avoid street vendor food, but if you do buy it, make sure your meal is cooked in your presence and served hot.

• Avoid sushi. Don't eat raw or improperly cooked fish and seafood of any kind.

• Be careful with fruits and vegetables. When you're traveling, make sure that all fruits and vegetables that you eat are cooked or have thick skins that you peel yourself. Avoid lettuce in particular because it may have been rinsed in contaminated water.

• Be wary of dairy foods. Avoid ice cream, which is often contaminated, and unpasteurized milk.

• Cholera vaccine. Because travelers have a low risk of contracting cholera and because the traditional injected vaccine offers minimal protection, no cholera vaccine is currently available in the United States. A few countries offer two oral vaccines that may provide longer and better immunity than the older versions did. If you'd like more information about these vaccines, contact your doctor or local office of public health. Keep in mind that no country requires immunization against cholera as a condition for entry.

JOURNALS

Sari Cloth a Simple Sustainable Protector from Cholera

ScienceDaily (May 20, 2010) — A five-year follow up study in Bangladesh finds that women are literally wearing the answer to better health for themselves, their families and even their neighbors. Using the simple sari to filter household water protects not only the household from cholera, but reduces the incidence of disease in neighboring households that do not filter. The results of this study appear in the inaugural issue of mBio™, the first online, open-access journal published by the American Society for Microbiology (ASM).

"A simple method for filtering pond and river water to reduce the incidence of cholera, field tested in Matlab, Bangladesh, proved effective in reducing the incidence of cholera by 48 percent. This follow-up study conducted 5 years later showed that 31 percent of the village women continued to filter water for their households, with both an expected and an unexpected benefit," says Rita Colwell of the University of Maryland, College Park, a researcher on the study.

In 2003, Colwell and her colleagues reported the results of a field study that demonstrated by simply teaching village women responsible for collecting water to filter the water through folded cotton sari cloth, they could reduce the incidence of cholera in that group by nearly half. Though the results were promising at the time of the research, there was concern that the practice of sari water filtration would not be sustained in later years.

Five years later they conducted the follow-up study to determine whether sari water filtration continued to be practiced by the same population of participants and, if it were, whether there would continue to be a beneficial effect of reduced incidence of cholera.

Over 7,000 village women collecting water daily for their households in Bangladesh were selected from the same population used in the previous study. Survey data showed that 31 percent continued to filter their water, of which 60 percent used a sari. Additionally, they found that of the control group (the one that did not receive any education or training in the first study) 26 percent of households now filter their water.

"This is a clear indication of both compliance with instructions and the sustainability of the method, but it also shows the need for continuing education in the appropriate use and benefits of simple filtration," says Colwell.

The researchers also looked at the incidence of cholera in households during the 5-year follow-up period. While not statistically significant, they found the incidence of hospitalizations for cholera during that period reduced by 25 percent.

"With the lower rate of filtration in this follow-up study, it is not surprising that the observed reduction in disease rate was not as high as the 48 percent observed in the original trial, suggesting that active reinforcement would have been effective in ensuring higher protection," says Colwell.

They also found an indirect benefit. Households that did not filter their water but were located in neighborhoods where water filtration was regularly practiced by others also had a lower incidence of cholera.

"Results of the study showed that the practice of filtration not only was accepted and sustained by the villagers but also benefited those who filtered their water, as well as neighbors not filtering water for household use, in reducing the incidence of cholera," says Colwell.

New Insight Into Predicting Cholera Epidemics in the Bengal DeltaScienceDaily (Nov. 16, 2009) — Cholera, an acute diarrheal

disease caused by the bacterium Vibrio cholerae, has reemerged as a global killer. Outbreaks typically occur once a year in Africa and Latin America. But in Bangladesh the epidemics occur twice a year -- in the spring and again in the fall.

Scientists have tried, without much success, to determine the cause of these unique dual outbreaks -- and advance early detection and prevention efforts -- by analyzing such variables as precipitation, water temperature, fecal contamination and coastal salinity. Now, researchers from Tufts University, led by Professor of Civil and Environmental Engineering Shafiqul Islam, have proposed a link between cholera and fluct uating water levels in the region's three principal rivers -- the Ganges, Brahmaputra and Meghna.

"What we are establishing is a way to predict cholera outbreaks two to three months in advance," says Islam, who also holds an appointment as professor of water and diplomacy at The Fletcher School at Tufts. "It's not a microbiological explanation. The key is the river discharge and regional climate."

The Tufts researchers' findings were reported in the latest issue of Geophysical Research Letters, published October 10, 2009.

Understanding cholera's environmental catalystsVibrio cholerae lives and thrives among phytoplankton and

zooplankton in brackish estuaries where rivers come into contact with the sea. The Bengal Delta, which scientists have considered the native land of cholera, is fed by three rivers.

Almost all of the rainfall in the region occurs during the four-month monsoon season between June and September. Water levels in the river system rise, causing floods that cover 20 percent of the land in an average year. Water levels then fall rapidly, though low-lying, depressed areas remain submerged for weeks.

The Tufts team tracked the month-by-month incidence of cholera using data from the International Center for Diarrhoeal Disease Research, a treatment center that recorded incidences of cholera for the biggest population center of Bangladesh from 1980 to 2000.

The Tufts team correlated these cholera incidence statistics with an analysis of water discharges from the three rivers. Their findings suggested two distinctive epidemic patterns that are associated with the seasonal cycles of low river flows and floods.

A spring outbreak occurs in March, during the period of low river flow in Bangladesh. The low river flow allows seawater from the Bay of Bengal to move inland, transporting bacteria-carrying plankton.

A second epidemic occurs in September and October, after monsoon rains have raised water levels. Here, a different dynamic takes place. Floodwaters have mixed water from sewers, reservoirs and rivers. As the floods recede, contamination is left behind..

Predicting cholera before it happensIslam and his team linked the incidence of cholera cases to the

level of water flow in the rivers. In order to confirm their findings, the researchers looked for a consistent pattern. They analyzed the incidence of cholera in five years of severely low river flow from 1980 to 2000 and compared it with five years of average and below average river flow. The same analysis was done for extreme, average and below average floods to study the fall epidemic.

The researchers found a relationship between the magnitude of cholera outbreaks and the severity of the region's seasonal low river flow and floods. "The more severe the low river flow, the larger the spring epidemic," says Islam. "The same thing is true with flooding during the fall." Islam says that the findings will contribute to the development of systems to anticipate and predict cholera outbreaks based on the hydroclimate of the region.

This research was funded in part by the National Science Foundation and a National Institutes of Health Fellowship. Researchers included engineering doctoral students Ali S. Akanda and Antarpreet S. Jutla.

‘

How Cholera Bacteria Becomes InfectiousScienceDaily (Feb. 12, 2010) — In a new study, Dartmouth

researchers describe the structure of a protein called ToxT that controls the virulent nature ofVibrio cholerae, the bacteria that causes cholera. Buried within ToxT, the researchers were surprised to find a fatty acid that appears to inhibit ToxT, which prevents the bacteria from causing cholera. Cholera, which causes acute diarrhea, can be life threatening, and, according to the World Health Organization, cholera remains a serious threat to global health.

Doctors have known that bile, found in the intestine, inhibits the expression of the virulence genes in V. cholerae, but until now, the mechanism behind this was not completely understood. This study provides a direct link between the environment of the gut and the regulation of virulence genes, and it also identifies the regulatory molecule.

"Finding a fatty acid in the structure was quite a surprise," says F. Jon Kull, associate professor of chemistry at Dartmouth and senior author on the paper. Kull is also a 1988 graduate of Dartmouth. "The exciting thing about this finding is that we might be able to use a small, natural molecule to treat and/or prevent cholera. We will also use the structure of the fatty acid as a framework to try and design a small molecule inhibitor of ToxT."

Kull's co-authors on the paper are Michael Lowden and Maria Pellegrini with the Department of Chemistry at Dartmouth; Michael Chiorazzo, a summer undergraduate research fellow; and Karen Skorupski and Ronald Taylor with the Department of Microbiology and Immunology at Dartmouth Medical School.

The researchers used X-ray crystallography to determine the structure of ToxT. The process involves taking DNA from V. cholerae and using non-pathogenic E. coli bacteria to produce large amounts of the target protein, in this case, ToxT. Once protein has been purified, it is concentrated and crystallized. Then the crystal, which is an ordered array of protein molecules, is subjected to a powerful X-ray beam. The pattern of diffracted X-rays is collected on a detector and then analyzed using mathematical algorithms, eventually revealing the atomic structure of the protein.

Co-author Taylor also notes that "The results of the study are exciting from the points of view of both the mechanistic aspect of the complex regulation of V. cholerae virulence gene expression and the potential medical impact as we now move forward to apply this new knowledge to influence this mechanism to control infection in humans."

This study was funded by the National Institutes of Health, Institute of Allergy and Infectious Diseases.

Designing Probiotics That Ambush Gut PathogensScienceDaily (Sep. 8, 2009) — Researchers in Australia are

developing diversionary tactics to fool disease-causing bacteria in the gut. Many bacteria, including those responsible for major gut infections, such as cholera, produce toxins that damage human tissues when they bind to complex sugar receptors displayed on the surface of cells in the host's intestine.

At the Society for General Microbiology's meeting at Heriot-Watt University, Edinburgh, Professor James Paton and colleagues from the University of Adelaide explained how they had added molecular mimics of these host cell receptors onto the surface of harmless bacteria capable of surviving in the human gut. If given during an infection caused by a toxin-producing bacterium, these "receptor-mimic probiotics" will bind the toxins in the gut very strongly, thereby preventing the toxins from interacting with receptors on host intestinal cells and causing disease.

Effective vaccines are not yet available for many diarrhoeal diseases; and trying to control or treat these diseases with antibiotics can lead to the development of drug-resistance. One advantage of this approach to treatment is that the pathogenic bacteria are unlikely to develop a resistance to it, as that would destroy the basic mechanism by which they cause disease.

A further advantage is that the receptor-mimic bacteria bind toxins more strongly than previous technologies in which synthetic receptors were displayed on inert silica particles. They are also more cost effective, as the bacteria can be grown cheaply in large-scale fermenters.

"We initially developed this technology to prevent disease caused by strains of E. coli bacteria that produce Shiga toxin. These include the infamous E. coli O157 strain, which causes outbreaks of severe bloody diarrhoea and the potentially fatal haemolytic uraemic syndrome. Our prototype receptor mimic probiotic provided 100% protection against otherwise fatal E. coli disease in an animal model." said Professor Paton, "We have also developed similar receptor mimic probiotics that are capable of preventing cholera and travellers' diarrhoea. As well as being able to treat disease, these probiotics could be given to vulnerable populations following natural disasters to help prevent outbreaks of diseases like cholera".

New Vaccine Could Be Lethal Weapon Against Malaria, CholeraScienceDaily (Jan. 27, 2010) — Mankind may finally have a

weapon to fight two of the world's deadliest diseases.A University of Central Florida biomedical researcher has

developed what promises to be the first low-cost dual vaccine against malaria and cholera.

There is no FDA approved vaccine to prevent malaria, a mosquito-borne illness that kills more than 1 million people annually. Only one vaccine exists to fight cholera, a diarrheal illness that is common in developing countries and can be fatal. The lone vaccine is too expensive to prevent outbreaks in developing countries after floods, and children lose immunity within three years of getting the current vaccine.

"I'm very encouraged because our technique works well and provides an affordable way to get vaccines to people who need them most and can least afford them," said lead scientist Henry Daniell.

Daniell's team genetically engineered tobacco and lettuce plants to produce the vaccine. Researchers gave mice freeze-dried plant cells (orally or by injection) containing the vaccine. aThey then challenged the mice with either the cholera toxin or malarial parasite. The malaria parasite studies were completed in fellow UCF professor Debopam Chakrabarti's lab.

Untreated rodents contracted diseases quickly, but the mice who received the plant-grown vaccines showed long-lasting immunity for more than 300 days (equivalent to 50 human years).

Results from the National Institutes of Health-funded research are published in this month's Plant Biotechnology, the top-ranked journal in the field.

Clinical trials are needed, and Daniell is hopeful that the results with mice will translate to humans. It could be yet another example of plants delivering life-saving medicines.

The dual vaccine follows a string of other "green" vaccines developed in Daniell's lab. He's created vaccines against anthrax and black plague that generated a congratulatory call from the top U.S. homeland security official and was featured on the Discovery Channel. He's also successfully grown insulin in plants to find what could be a long-lasting cure for diabetes. Daniell's team continues to research these vaccines and is looking for investors to help fund clinical trials.

Producing vaccines in plants is less expensive than traditional methods because it requires less labor and technology, Daniell said.

"We're talking about producing mass quantities for pennies on the dollar," he said. "And distribution to mass populations would be easy because it could be made into a simple pill, like a vitamin, which many people routinely take now. There is no need for expensive purification, cold storage, transportation or sterile delivery via injections."

For Daniell, his research is more than his day job. His passion to find vaccines for the world's top 10 diseases as defined by the World Health Organization comes from growing up in India. He watched many of his childhood friends contract malaria, cholera and other diseases.

Daniell, a father of two, joined UCF's Burnett School of Biomedical Sciences in the College of Medicine in 1998. His research led to the formation of the university's first biotechnology company. Daniell also became only the 14th American in the last 222 years to be elected the Italian National Academy of Sciences. In 2007 he was named a Fellow of the American Association for the Advancement of Sciences.

"I'm not done yet," he said. "I still have more diseases to attack."