ILLNESS/INFLAMMATION/

IMMUNITY/
COMMUNICABLE DISEASE
Case Presentation

MUAMIR A. ALINGAN
BSN-4A
 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.
Short History

Cholera has killed millions of people since it emerged out of the filthy water and
living conditions of Calcutta India in the early 1800s. The Italian doctor Filippo Pacini
was the first to discover the cholera bacteria (Vibrio cholerae) in 1854 when cholera hit
Florence,Italy. Pacini became very interested in the disease. Immediately following the
death of cholera patients, he performed an autopsy and with his microscope, conducted
histological examinations of the intestinal mucosa. During such studies, Pacini first
discovered a comma-shaped bacillus which he described as a Vibrio. Three decades later,
unaware of the fact that Pacini had already done the same research at the University of
Florence and had obtained significant results, Robert Koch, one of the “fathers” of
microbiology and bacteriology, was also researching the microorganism causing
cholera,he went to different countries like in India which was a cholera hotspot and
performed analyses on the bodies of the victims of the disease and he found a bacillus,
the same one that Pacini had found, in the intestinal mucosa. The observations and
discoveries that Koch performed led him to become a hero in the field and for years, he
was given complete credit for the discovery and isolation of Vibrio cholera.

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.

Laboratory Test:
darkfield/phase-contrast microscopy, which may yield a large quantity
of curved bacilli on examination of saline suspensions from fresh
stool samples. V cholerae are usually variable in size from 1 to 3
micrometres in length to 0.5 to 0.8 micrometres in diameter, with
single polar flagellum and typical shooting star motility.

Gram-stain examination of stool culture is cheap and widely available

but not a particularly helpful subsequent laboratory test. Smears can
demonstrate small, curved gram-negative rods.

Full blood count may show elevated haematocrit in non-anaemic

patients as a result of volume depletion, and a high neutrophil count
may be present in severe infection.
 Blood chemistry tests are important in assessing the degree of volume
depletion; urea and creatinine levels are frequently elevated due to
volume depletion.

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.
MOUTH
 Food 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.
PHARYNX
The 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.

ESOPHAGUS
The 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.
STOMACH
The 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 INTESTINE
The 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 GLANDS
Three 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.

TEETH
The function of the teeth is chewing. This is the process that mechanically
breaks food into smaller pieces and mixes with saliva.
TONGUE
It is the principal organ of the sense of taste that also assist in the
mastication and deglutition of food.

PANCREAS
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.

LIVER
The 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 BLADDER
The 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 FACTORS
Precipitating 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)
Entry of Vibrio cholerae through oral route
(entry) PATHOPHYSIOLOGY
 Leads to
Survival of virulent organisms that pass through the
stomach and into the small intestine

Adherence of Vibrio cholerae to the small intestinal

Causes
epithelium

Multiplication of the organisms on the epithelial

cells (colonization) Result to

Leads to Production of cholera enterotoxin by the bacteria

Result in
Binding of toxin to the plasma membrane of
intestinal epithelial cells

Leads to Release of an enzymatically active subunit called

adenylate cyclase

A rise in cyclic adenosine monophosphate Causes

(cAMP) production

Massive secretion of electrolytes and water into

Result in
the intestinal lumen

Manifestations of cholera (disease) Causes

Leads to Normal shedding of intestinal cells eventually

gets rid of the toxin (exit)

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 Delta

ScienceDaily (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 catalysts

Vibrio 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 happens
Islam 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 Infectious

ScienceDaily (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.

New Vaccine Could Be Lethal Weapon Against Malaria, Cholera

ScienceDaily (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."