cholera ppt final

8/9/2019 Cholera Ppt Final

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ILLNESS/INFLAMMATION/

IMMUNITY/COMMUNICABLE DISEASE

Case Presentation

CHOLERACHOLERA

MUAMIRALIALINGAN

BSN4A


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INTRODUCTION


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Cholera is an acute, bacterial, diarrheal disease withprofuse watery stools, occasional vomiting, and rapid

dehydration. If untreated, circulatory collapse, renal failure and

death may occur.

More than 50% of untreated people with severecholera die.

It occurs worldwide, with periodic epidemics andpandemics.


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A recent Western Hemisphere cholera pandemic started in

Peru in 1991. By 1994, more than 950,000 cases had beenreported 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 Louisianaand Texas.


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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.


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Etiologic agent.

Certain biotypes of Vibrio cholerae serogroup 01 whichare curved, Gram-negative bacilli that secrete an enterotoxin

(a toxin that adversely affects cells in the intestinal tract)called choleragen. OtherVibrio spp. (Vibrio parahaemolyticus,Vibrio vulnificus) also cause diarrheal diseases. Vibrios arehalophilic and are thus found in marine environments.


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Vibrio cholerae


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Cholera Toxin.

The delivery region(blue) binds membranecarbohydrates to get intocells. The toxic part (red)is activated inside the

cell .


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Reservoirs and Mode of Transmission.

Infected humans and aquatic reservoirs.

Transmission is via the fecal-oral route, contact withfeces or vomitus of infected people, ingestion of fecallycontaminated water and foods especially raw orundercooked shellfish and other seafood and flies.


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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 identifythe various species. Biotyping is accomplished usingcommercially available antisera.


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ANATOMY AND PHYSIOLOGY OFTHESYSTEM INVOLVED


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The organs of the digestive system can beseparated into two main groups: those forming thealimentary canal and the accessory digestive organs.The alimentary canal performs the whole menu ofdigestive functions (ingests, digests, absorbs, anddefecates). The accessory organs (teeth, tongue, andseveral large digestive glands) assist the process of

digestive breakdown in various ways.


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Organs of the Alimentary Canal

The alimentary canal, also called the gastrointestinal(GI) tract, is a continuous, coiled, hollow, muscular tubethat winds through the ventral body cavity and is open atboth ends. Its organs are the mouth, pharynx, esophagus,

stomach, small intestine, and large intestine. The largeintestine leads to the terminal opening, oranus.


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MOUTHFood enters the digestive tract through the mouth, ororal

cavity, a mucous membrane-lined cavity. The lips (labia) protectits anterior opening, the cheeks form its lateral walls, the hard

palate forms its anterior roof, and the soft palate forms itsposterior roof. The uvula is a fleshy fingerlike projection of thesoft palate, which extends downward from its posterior edge.The space between the lips and cheek externally and the teethand gums internally is the vestibule.


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` The area contained by the teeth is the oral cavityproper. The muscular tongue occupies the floor of themouth. The tongue has several bony attachments-two of

these are to the hyoid bone and the styloid processes ofthe skull. The lingual frenulum, a fold of mucousmembrane, secures the tongue to the floor of the mouthand limits its posterior movements.


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At the posterior end of the oral cavity are pairedmasses of lymphatic tissue, the palatine tonsils. Thelingual tonsil covers the base of the tongue just beyond.

The tonsils, along with other lymphatic tissues, are partof the bodys defense system. When the tonsils becomeinflamed and enlarged, they partially block the entranceinto the throat (pharynx), making swallowing difficult

and painful.


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PHARYNX

The pharynx or throat is a tubular structure that extendsfrom the base of the skull to the esophagus and is situatedimmediately in front of the cervical vertebrae. The oropharynx

and laryngopharynx are food passageways connecting the oralcavity to the esophagus. No digestion takes place in thepharynx. Its only related function is swallowing, the mechanicalmovement of food. When the bolus of food is pushed backwardby the tongue, the constrictor muscles of the pharynx contract

as part of the swallowing reflex.


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ESOPHAGUS

The esophagus , or gullet, is a muscular tube ofapproximately 25cm in length and 2cm in diameter. It

extends from the pharynx to the stomach after passingthrough an opening in the diaphragm. The esophagusfunctions primarily as a transport medium betweencompartments.


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The walls of the alimentary canal organs from the

esophagus to the large intestine are made up of thesame four basic tissue layers, or tunics:

1. The mucosa is the innermost layer, a moist membranethat lines the cavity, or lumen, of the organ. It consistsprimarily of a surface epithelium, plus a small amount ofconnective tissue (lamina propria) and a scanty smoothmuscle layer.


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

3. The muscularis externa is a muscle layer typically madeup of an innercircular layer and an outer longitudinallayerof smooth muscle cells.


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

membrane extension, the mesentery.


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STOMACHThe stomach is a C shaped expanded bag, located just left

of the midline between the esophagus and small intestine. It hastwo borders called the greater and lesser curvatures. The first

section is the cardia which surrounds the cardial orifice wherethe esophagus enters the stomach. The fundus is the superior,dilated portion of the stomach. The body is the largest sectionbetween the fundus and the curved portion of the C.


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The pylorus is the curved base of the stomach. Gastriccontents are expelled into the proximal duodenum viathe pyloric sphincter. The inner surface of the stomach iscontracted into numerous longitudinal folds called rugae.These allow the stomach to stretch and expand whenfood enters.


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The functions of the stomach include: The short-term storage of ingested food.

Mechanical breakdown of food by churning andmixing motions.

Chemical digestion of proteins by acids andenzymes.

Stomach acid kills bugs and germs.

Some absorption of substances such as alcohol.


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SMALL INTESTINE

The small intestine is about 1 inch (2.5 cm) indiameter and approximately 20 feet (6m) long andextends from the stomach to the cecum of the largeintestine.

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


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Digestion is completed in the small intestine, and the

end products of digestion are absorbed in the blood andlymph. The mucosa has simple columnar epithelium thatincludes cells with microvilli and goblets cells thatsecretes mucos. Enteroendocrine cells secrete the

hormones of the small intestine. Lymph nodules calledpeyers patches are especially abundant in the ileum todestroy absorbed pathogens.


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LARGE INTESTINE

The large intestine is horse-shoe shaped and extendsaround the small intestine like a frame. It consists of theappendix, cecum, ascending, transverse, descending andsigmoid colon, and the rectum. It has a length of approximately

1.5m and a width of 7.5cm. The cecum is the expanded pouchthat receives material from the ileum and starts to compressfood products into fecal material. Food then travels along thecolon. The wall of the colon is made up of several pouches

(haustra) that are held under tension by three thick bands ofmuscle (taenia coli).


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The rectum is the final 15cm of the large intestine. It expands to

hold fecal matter before it passes through the anorectal canal to theanus. Thick bands of muscle, known as sphincters, control thepassage 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


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Accessory Digestive Organs

SALIVARY GLANDSThree pairs of salivary glands which are the parotid,

submandibular and sublingual glands communicate with theoral cavity. Each is a complex gland with numerous acini lined

by secretory epithelium. The acini secrete their contents intospecialized ducts. Each gland is divided into smaller segmentscalled lobes.


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TEETH

The function of the teeth is chewing. This is the processthat mechanically breaks food into smaller pieces and mixeswith saliva.

TONGUEIt is the principal organ of the sense of taste that also

assist in the mastication and deglutition of food.


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The pancreas is a lobular, pinkish-grey organ that liesbehind the stomach. Its head communicates with theduodenum and its tail extends to the spleen. The organ isapproximately 15cm in length with a long, slender body

connecting the head and tail segments. It is made up ofnumerous acini (small glands) that secrete contents intoducts which eventually lead to the duodenum.

PANCREAS


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IVER

The liver is a large, reddish-brown organ situated in the rightupper quadrant of the abdomen. It is divided into four lobesnamely the right, left, caudate and quadrate lobes. The liver hasimportant functions. It acts as a mechanical filter by filtering

blood that travels from the intestinal system. It detoxifies severalmetabolites including the breakdown of bilirubin and estrogen. Inaddition, the liver has synthetic functions, producing albumin andblood clotting factors. However, its main roles in digestion are inthe production of bile and metabolism of nutrients.


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GALL BLADDER

The gallbladder is a hollow, pear shaped organ that sitsin a depression on the posterior surface of the liver's rightlobe. The main functions of the gall bladder are storage andconcentration of bile.


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Hormones Source Stimulus forSecretion

Actions

Gastrin Stomach Food in stomach(chemical stimulus)

Stimulates releaseof gastric juice.

Stimulates mobilityof small intestine.Relaxes ileocecalvalve.

Histamine Stomach Food in stomach Activates parietalcells to secretehydrochloric acid.

Somatostatin Stomach Food in stomach Inhibits secretion of

gastric juice andpancreatic juice.Inhibits emptying ofstomach andgallbladder.


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Hormones Source Stimulus forSecretion

Actions

Secretin Duodenum Acidic chyme andpartially digested

foods induodenum

Increases output of pancreaticjuice rich in bicarbonate ions.Increases bile output by liver.Inhibits gastric mobility andgastric gland secretion.

Cholecystokinin Duodenum Fatty chyme andpartially digestedproteins induodenum.

Increases output of enzyme

rich pancreatic juice.Stimulates gallbladder to expelstored bile.Relaxes the sphincter of theduodenal papillae to allow bilein pancreatic juice to enter theduodenum.

Gastric InhibitoryPeptide

Duodenum Fatty chyme andduodenum.

Inhibits gastric mobility andsecretions of gastric juice.


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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., refugeecamps, impoverished countries,and areas devastated by famine,war or natural disasters)PovertyMalnutritionCompromised ImmunityReduced or nonexistent stomachacid (hypochlorhydria orachlorhydria)

Predisposing factors:

Age: children and older adults People who have had gastricsurgery, who have untreatedHelicobacter pylori infection, orwho are taking antacids, H-2

blockers or proton pump inhibitorsfor ulcersType O bloodHousehold exposureInternational travel (LatinAmerica, Africa, Asia, Gulf ofMexico, Middle East)


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PATHOPHYSIOLOGY


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Adherence of Vibrio cholerae to the small intestinalepithelium

Multiplication of the organisms on theepithelial cells (colonization)

Production of cholera enterotoxin by the

bacteria

Survival of virulent organisms that pass throughthe stomach and into the small intestine

Entry of Vibrio cholerae through oral route(entry)

leads to

causes

results to

leads to

lt i


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Manifestations of cholera (disease)

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

Binding of toxin to the plasma membrane ofintestinal epithelial cells

Release of an enzymatically activesubunit called adenylate cyclase

A rise in cyclic adenosine monophosphate (cAMP) production

Massive secretion of electrolytes and waterinto the intestinal lumen

results in

leads to

causes

results in

causes

leads to


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CLINICAL MANIFESTATIONS


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S

tage 1: DiarrhealS

tage Abrupt onset of painless, severe, watery diarrhea that is

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

Vomiting without nausea that may persist for hours at a time

Muscle cramps


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S

tage 2: DehydrationS

tage 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


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NURSINGCARE MANAGEMENT


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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.


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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.

F

ood must be properly prepared. Environmental sanitation must be observed.


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Treatment:

Cholera requires immediate treatment because the disease can cause deathwithin hours.

Rehydration. The goal is to replace fluids and electrolytes lost throughdiarrhea using a simple rehydration solution, Oral Rehydration Salts(ORS), that contains specific proportions of water, salts and sugar. The

OR

S solution is available as a powder that can be reconstituted in boiledor bottled water. Without rehydration, approximately half the peoplewith cholera die. With treatment, the number of fatalities drops to lessthan 1 percent.


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Intravenous fluids. During a cholera epidemic, most people can be helped byoral 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 shortendiarrhea duration and decreases vomiting.

Zinc supplements. Research has shown that zinc may decrease and shorten

the duration of diarrhea in children with cholera.


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Prevention:

Wash your hands. Frequent hand washing is the best way to controlcholera infection. Wash your hands thoroughly with hot, soapy water,especially before eating or preparing food, after using the toilet, andwhen you return from public places. Carry an alcohol-based handsanitizer for times when water isn't available.

A

void untreated water. Contaminated drinking water is the mostcommon source of cholera infection. For that reason, drink only bottledwater or water you've boiled or disinfected yourself. Coffee, tea andother hot beverages, as well as bottled or canned soft drinks, wine andbeer, are generally safe. Carefully wipe the outside of all bottles and cans

before you open them and ask for drinks without ice..


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

Avoid sushi. Don't eat raw or improperly cooked fish and seafood of anykind.

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


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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 minimalprotection, no cholera vaccine is currently available in the UnitedStates. A few countries offer two oral vaccines that may providelonger and better immunity than the older versions did. If you'd likemore information about these vaccines, contact your doctor or localoffice of public health. Keep in mind that no country requiresimmunization against cholera as a condition for entry.


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JOURNALS


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Sari Cloth a Simple Sustainable Protector from Cholera

ScienceDaily (May 20, 2010) A five-year follow up study in Bangladesh finds thatwomen are literally wearing the answer to better health for themselves, their families andeven their neighbors. Using the simple sari to filter household water protects not only thehousehold from cholera, but reduces the incidence of disease in neighboring households thatdo 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 villagewomen continued to filter water for their households, with both an expected and anunexpected benefit," says Rita Colwell of the University of Maryland, College Park, aresearcher on the study.

In 2003, Colwell and her colleagues reported the results of a field study thatdemonstrated by simply teaching village women responsible for collecting water to filter thewater through folded cotton sari cloth, they could reduce the incidence of cholera in thatgroup 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


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continued to be practiced by the same population of participants and, if it were, whether there wouldcontinue to be a beneficial effect of reduced incidence of cholera.

Over 7,000 village women collecting water daily for their households in Bangladesh were selectedfrom the same population used in the previous study. Survey data showed that 31 percent continued tofilter 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 filtertheir 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 simplefiltration," says Colwell.

The researchers also looked at the incidence of cholera in households during the 5-year follow-upperiod. 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 observedreduction in disease rate was not as high as the 48 percent observed in the original trial, suggesting thatactive 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 inneighborhoods where water filtration was regularly practiced by others also had a lower incidence ofcholera.

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


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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 occuronce a year in Africa and Latin America. But in Bangladesh the epidemics occur twice ayear -- in the spring and again in the fall.

Scientists have tried, without much success, to determine the cause of theseunique dual outbreaks -- and advance early detection and prevention efforts -- byanalyzing such variables as precipitation, water temperature, fecal contamination andcoastal salinity. Now, researchers from Tufts University, led by Professor of Civil andEnvironmental Engineering Shafiqul Islam, have proposed a link between cholera andfluct 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 threemonths in advance," says Islam, who also holds an appointment as professor of waterand 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.


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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 scientistshave 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, causingfloods 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 DiseaseR

esearch, a treatment center thatrecorded incidences of cholera for the biggest population center of Bangladesh from1980 to 2000.

The Tufts team correlated these cholera incidence statistics with an analysis ofwater discharges from the three rivers. Their findings suggested two distinctive epidemicpatterns 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 inBangladesh. 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 havei d t l l H diff t d i t k l Fl d t h i d t


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raised water levels. Here, a different dynamic takes place. Floodwaters have mixed waterfrom 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 flowin the rivers. In order to confirm their findings, the researchers looked for a consistentpattern. They analyzed the incidence of cholera in five years of severely low river flowfrom 1980 to 2000 and compared it with five years of average and below average riverflow. The same analysis was done for extreme, average and below average floods tostudy the fall epidemic.

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

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.


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HowCholera Bacteria Becomes InfectiousScienceDaily (Feb. 12, 2010) In a new study, Dartmouth researchers

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

Doctors have known that bile, found in the intestine, inhibits theexpression of the virulence genes in V. cholerae, but until now, the mechanismbehind this was not completely understood. This study provides a direct linkbetween the environment of the gut and the regulation of virulence genes, andit also identifies the regulatory molecule.


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"Finding a fatty acid in the structure was quite a surprise," says F.

Jon Kull, associate professor of chemistry at Dartmouth and seniorauthor on the paper. Kull is also a 1988 graduate of Dartmouth. "Theexciting 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 thestructure of the fatty acid as a framework to try and design a smallmolecule inhibitor of ToxT."

Kull's co-authors on the paper are Michael Lowden and MariaPellegrini with the Department of Chemistry at Dartmouth; MichaelChiorazzo, a summer undergraduate research fellow; and KarenSkorupski and Ronald Taylor with the Department of Microbiology andImmunology at Dartmouth Medical School.


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The researchers used X-ray crystallography to determine the structure ofToxT. The process involves taking DNA from V. cholerae and using non-

pathogenic E. coli bacteria to produce large amounts of the target protein, inthis case, ToxT. Once protein has been purified, it is concentrated andcrystallized. 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 iscollected 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 complexregulation of V. cholerae virulence gene expression and the potential medicalimpact as we now move forward to apply this new knowledge to influencethis mechanism to control infection in humans."

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


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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 thoseresponsible for major gut infections, such as cholera, produce toxins that damage humantissues when they bind to complex sugar receptors displayed on the surface of cells in thehost's intestine.

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

Effective vaccines are not yet available for many diarrhoeal diseases; and trying tocontrol 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 bacteriaare unlikely to develop a resistance to it, as that would destroy the basic mechanism by

which they cause disease.


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

"We initially developed this technology to prevent disease caused bystrains of E. coli bacteria that produce Shiga toxin. These include theinfamous E. coli O157 strain, which causes outbreaks of severe bloodydiarrhoea and the potentially fatal haemolytic uraemic syndrome. Ourprototype 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 capableof preventing cholera and travellers' diarrhoea. As well as being able to treatdisease, these probiotics could be given to vulnerable populations followingnatural disasters to help prevent outbreaks of diseases like cholera".


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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 promisesto be the first low-cost dual vaccine against malaria and cholera.

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

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

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


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Untreated rodents contracted diseases quickly, but the mice who received theplant-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-savingmedicines.

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 acongratulatory call from the top U.S. homeland security official and was featured on theDiscovery Channel. He's also successfully grown insulin in plants to find what could be along-lasting cure for diabetes. Daniell's team continues to research these vaccines and islooking for investors to help fund clinical trials.

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


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"We're talking about producing mass quantities for pennies on the dollar,"he said. "And distribution to mass populations would be easy because it couldbe made into a simple pill, like a vitamin, which many people routinely take now.

There is no need for expensive purification, cold storage, transportation orsterile 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 HealthOrganization comes from growing up in India. He watched many of hischildhood friends contract malaria, cholera and other diseases.

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

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

cholera ppt final

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