Typhoid Fever

(Enteric Fever) by Michelle Badash, MS Definition Typhoid fever and paratyphoid fever are serious illnesses caused by Salmonella bacteria. It may be Salmonella typhi or Salmonella paratyphi . It occurs most often in developing countries where sanitation is poor. Typhoid fever can be fatal, especially when not treated. Causes Typhoid fever is caused by eating foods or drinking beverages contaminated with the Salmonella bacteria. Contamination can occur from:

Food or drinks handled by someone who has no symptoms but carries the bacteria Food or drinks handled by someone who is sick or coming down with typhoid fever Poultry products left unrefrigerated Sewage contamination of water or food Unpasteurized dairy products

Once bacteria enter the body, they infect the intestine. Bacteria can be carried through the bloodstream to other organs. Risk Factors A risk factor is something that increases your chance of getting a disease or condition. Risk factors include:

Drinking contaminated water Eating fruits and vegetables that are raw or have been washed with contaminated water Eating raw shellfish Living in, or recent travel, to a country with poor sanitation

Symptoms Symptoms may include:

Constipation or diarrhea Abdominal pain Chills Dizziness Fatigue or lethargy Fever, often for a prolonged time Loss of appetite

Muscle pains Rose-colored spots on the body Severe headaches Swelling of the neck glands, liver, or spleen

Diagnosis The doctor will ask about your symptoms and medical history. A physical exam will be done. Typhoid fever is usually diagnosed with a blood culture. Treatment Typhoid fever is treated with antibiotics. Typhoid fever is very contagious until treated. In a small number of cases, people may become typhoid carriers even after the illness has subsided. People who are chronic carriers can shed contagious Salmonella bacteria in their stool or urine. This condition can be treated with antibiotics or, in unusual cases, surgery. Prevention There are two main ways to prevent typhoid fever: VaccineA typhoid vaccine is recommended if you are planning to visit a country where typhoid fever is prevalent. However, the vaccine is not always effective and careful food monitoring is just as important. Careful food monitoringWhen you are in an area where typhoid fever is prevalent, always take the following precautions:

Avoid any raw fruits and vegetables that cannot be peeled. Avoid raw shellfish. Avoid unpasteurized dairy products. Drink only bottled water or water that has been boiled for at least one minute. This includes ice. Eat foods while they are still hot, and ensure that they are thoroughly cooked.

Gastrointestinal System

Introduction to the gastrointestinal system Basic structure of the gastrointestinal system Individual components of the gastrointestinal system o Oral cavity o Salivary glands

o o o o o o o

Oesophagus Stomach Small intestine Large intestine Liver Gall bladder Pancreas

Introduction to the gastrointestinal system

The gastrointestinal tract (GIT) consists of a hollow muscular tube starting from the oral cavity, where food enters the mouth, continuing through the pharynx, oesophagus, stomach and intestines to the rectum and anus, where food is expelled. There are various accessory organs that assist the tract by secreting enzymes to help break down food into its component nutrients. Thus the salivary glands, liver, pancreas and gall bladder have important functions in the digestive system. Food is propelled along the length of the GIT by peristaltic movements of the muscular walls.

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The primary purpose of the gastrointestinal tract is to break food down into nutrients, which can be absorbed into the body to provide energy. First food must be ingested into the mouth to be mechanically processed and moistened. Secondly, digestion occurs mainly in the stomach and small intestine where proteins, fats and carbohydrates are chemically broken down into their basic building blocks. Smaller molecules are then absorbed across the epithelium of the small intestine and subsequently enter the circulation. The large intestine plays a key role in reabsorbing excess water. Finally, undigested material and secreted waste products are excreted from the body via defecation (passing of faeces).

In the case of gastrointestinal disease or disorders, these functions of the gastrointestinal tract are not achieved successfully. Patients may develop symptoms of nausea, vomiting, diarrhoea, malabsorption, constipation or obstruction. Gastrointestinal problems are very common and most people will have experienced some of the above symptoms several times throughout their lives.
Basic structure

The gastrointestinal tract is a muscular tube lined by a special layer of cells, called epithelium. The contents of the tube are considered external to the body and are in continuity with the outside world at the mouth and the anus. Although each section of the tract has specialised functions, the entire tract has a similar basic structure with regional variations.

The wall is divided into four layers as follows:

Mucosa The innermost layer of the digestive tract has specialised epithelial cells supported by an underlying connective tissue layer called the lamina propria. The lamina propria contains blood vessels, nerves, lymphoid tissue and glands that support the mucosa. Depending on its function, the epithelium may be simple (a single layer) or stratified (multiple layers). Areas such as the mouth and oesophagus are covered by a stratified squamous (flat) epithelium so they can survive the wear and tear of passing food. Simple columnar (tall) or glandular epithelium lines the stomach and intestines to aid secretion and absorption. The inner lining is constantly shed and replaced, making it one of the most rapidly dividing areas of the body! Beneath the lamina propria is the muscularis mucosa. This comprises layers of smooth muscle which can contract to change the shape of the lumen.

Submucosa

The submucosa surrounds the muscularis mucosa and consists of fat, fibrous connective tissue and larger vessels and nerves. At its outer margin there is a specialized nerve plexus called the submucosal plexus or Meissner plexus. This supplies the mucosa and submucosa.

Muscularis externa This smooth muscle layer has inner circular and outer longitudinal layers of muscle fibres separated by the myenteric plexus or Auerbach plexus. Neural innervations control the contraction of these muscles and hence the mechanical breakdown and peristalsis of the food within the lumen.

Serosa/mesentery The outer layer of the GIT is formed by fat and another layer of epithelial cells called mesothelium.
Individual components of the gastrointestinal system

Oral cavity The oral cavity or mouth is responsible for the intake of food. It is lined by a stratified squamous oral mucosa with keratin covering those areas subject to significant abrasion, such as the tongue, hard palate and roof of the mouth. Mastication refers to the mechanical breakdown of food by chewing and chopping actions of the teeth. The tongue, a strong muscular organ, manipulates the food bolus to come in contact with the teeth. It is also the sensing organ of the mouth for touch, temperature and taste using its specialised sensors known as papillae. Insalivation refers to the mixing of the oral cavity contents with salivary gland secretions. The mucin (a glycoprotein) in saliva acts as a lubricant. The oral cavity also plays a limited role in the digestion of carbohydrates. The enzyme serum amylase, a component of saliva, starts the process of digestion of complex carbohydrates. The final function of the oral cavity is absorption of small molecules such as glucose and water, across the mucosa. From the mouth, food passes through the pharynx and oesophagus via the action of swallowing.

Salivary glands Three pairs of salivary glands communicate with the oral cavity. Each is a complex gland with numerous acini lined by secretory epithelium. The acini secrete their contents into specialised ducts. Each gland is divided into smaller segments called lobes. Salivation occurs in response to the taste, smell or even appearance of food. This occurs due to nerve signals that tell the salivary

glands to secrete saliva to prepare and moisten the mouth. Each pair of salivary glands secretes saliva with slightly different compositions.

Parotids The parotid glands are large, irregular shaped glands located under the skin on the side of the face. They secrete 25% of saliva. They are situated below the zygomatic arch (cheekbone) and cover part of the mandible (lower jaw bone). An enlarged parotid gland can be easier felt when one clenches their teeth. The parotids produce a watery secretion which is also rich in proteins. Immunoglobins are secreted help to fight microorganisms and a-amylase proteins start to break down complex carbohydrates.

Submandibular The submandibular glands secrete 70% of the saliva in the mouth. They are found in the floor of the mouth, in a groove along the inner surface of the mandible. These glands produce a more viscid (thick) secretion, rich in mucin and with a smaller amount of protein. Mucin is a glycoprotein that acts as a lubricant.

Sublingual The sublinguals are the smallest salivary glands, covered by a thin layer of tissue at the floor of the mouth. They produce approximately 5% of the saliva and their secretions are very sticky due to the large concentration of mucin. The main functions are to provide buffers and lubrication.

Oesophagus The oesophagus 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 wall of the oesophagus is made up of inner circular and outer longitudinal layers of muscle that are supplied by the oesophageal nerve plexus. This nerve plexus surrounds the lower portion of the oesophagus. The oesophagus functions primarily as a transport medium between compartments.

Stomach The stomach is a J shaped expanded bag, located just left of the midline between the oesophagus and small intestine. It is divided into four main regions and has two borders called the greater and lesser curvatures. The first section is the cardia which surrounds the cardial orifice where the oesophagus enters the stomach. The fundus is the superior, dilated portion of the stomach that has contact with the left dome of the diaphragm. The body is the largest section between the fundus and the curved portion of the J. This is where most gastric glands are located and where most mixing of the food occurs. Finally 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 stomach can hold up to 1.5 litres of material. The functions of the stomach include:
1. 2. 3. 4. 5. 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.

Most of these functions are achieved by the secretion of stomach juices by gastric glands in the body and fundus. Some cells are responsible for secreting acid and others secrete enzymes to break down proteins.

Small intestine The small intestine is composed of the duodenum, jejunum, and ileum. It averages approximately 6m in length, extending from the pyloric sphincter of the stomach to the ileo-caecal valve separating the ileum from the caecum. The small intestine is compressed into numerous folds and occupies a large proportion of the abdominal cavity.

The duodenum is the proximal C-shaped section that curves around the head of the pancreas. The duodenum serves a mixing function as it combines digestive secretions from the pancreas and liver with the contents expelled from the stomach. The start of the jejunum is marked by a sharp bend, the duodenojejunal flexure. It is in the jejunum where the majority of digestion and absorption occurs. The final portion, the ileum, is the longest segment and empties into the caecum at the ileocaecal junction.

The small intestine performs the majority of digestion and absorption of nutrients. Partly digested food from the stomach is further broken down by enzymes from the pancreas and bile salts from the liver and gallbladder. These secretions enter the duodenum at the Ampulla of Vater. After further digestion, food constituents such as proteins, fats, and carbohydrates are broken down to small building blocks and absorbed into the body's blood stream. The lining of the small intestine is made up of numerous permanent folds called plicae circulares. Each plica has numerous villi (folds of mucosa) and each villus is covered by epithelium with projecting microvilli (brush border). This increases the surface area for absorption by a factor of several hundred. The mucosa of the small intestine contains several specialised cells. Some are responsible for absorption, whilst others secrete digestive enzymes and mucous to protect the intestinal lining from digestive actions.

Large intestine The large intestine is horse-shoe shaped and extends around the small intestine like a frame. It consists of the appendix, caecum, ascending, transverse, descending and sigmoid colon, and the rectum. It has a length of approximately 1.5m and a width of 7.5cm. The caecum is the expanded pouch that receives material from the ileum and starts to compress food products into faecal 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 faecal matter before it passes through the anorectal canal to the anus. Thick bands of muscle, known as sphincters, control the passage of faeces.

The mucosa of the large intestine lacks villi seen in the small intestine. The mucosal surface is flat with several deep intestinal glands. Numerous goblet cells line the glands that secrete mucous to lubricate faecal matter as it solidifies. The functions of the large intestine can be summarised as:
1. The accumulation of unabsorbed material to form faeces. 2. Some digestion by bacteria. The bacteria are responsible for the formation of intestinal gas. 3. Reabsorption of water, salts, sugar and vitamins.

Liver The liver is a large, reddish-brown organ situated in the right upper quadrant of the abdomen. It is surrounded by a strong capsule and divided into four lobes namely the right, left, caudate and quadrate lobes. The liver has several 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 oestrogen. 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. All nutrients absorbed by the intestines pass through the liver and are processed before traveling to the rest of the body. The bile produced by cells of the liver, enters the intestines at the duodenum. Here, bile salts break down lipids into smaller particles so there is a greater surface area for digestive enzymes to act.

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. It consists of a fundus, body and neck. It empties via the cystic duct into the biliary duct system. The main functions of the gall bladder are storage and concentration of bile. Bile is a thick fluid that contains enzymes to help dissolve fat in the intestines. Bile is produced by the liver but stored in the gallbladder until it is needed. Bile is released from the gall bladder by contraction of its muscular walls in response to hormone signals from the duodenum in the presence of food.

Pancreas Finally, 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. The pancreas has both exocrine and endocrine functions. Endocrine refers to production of hormones which occurs in the Islets of Langerhans. The Islets produce insulin, glucagon and other substances and these are the areas damaged in diabetes mellitus. The exocrine (secretrory) portion makes up 8085% of the pancreas and is the area relevant to the gastrointestinal tract. It is made up of numerous acini (small glands) that secrete contents into ducts which eventually lead to the duodenum. The pancreas secretes fluid rich in carbohydrates and inactive enzymes. Secretion is triggered by the hormones released by the duodenum in the presence of food. Pancreatic enzymes include carbohydrases, lipases, nucleases and proteolytic enzymes that can break down different components of food. These are secreted in an inactive form to prevent digestion of the pancreas itself. The enzymes become active once they reach the duodenum.
GASTROINTESTINAL TRACT : Anatomy and physiology of gastrointestinal system

Image:A

Image:B Gastrointestinal tract showing gross anatomy (A) and structure (B).

Anatomy and physiology of Gastrointestinal System:

The gastrointestinal system is primarily involved in reducing food for absorption into the body. This process occurs in 4 main phases: i) Fragmentation ii) Digestion iii) Absorption iv) Elimination of waste products - Initial fragmentation of food occurs along with the secretions of the salivary glands, in the oral cavity forming a bolus. - Bolus of food is then carried to the esophagus by the action of the tongue and pharynxc(deglutition). - Esophagus carries food from mouth to stomach, where fragmentation is completed and digestion initiated. - Digestion is the progressive breakdown of food by enzymes into molecules which are small enough to be absorbed into the circulation (Eg: protein to polypeptides followed by small peptides and aminoacids). - In the stomach food is converted into semi-digested liquid (chyme) which passes through the pylorus, into the duodenum. - Unabsorbed liquid residue enters the cecum through ileo-cecal valve where water is absorbed and become progressively more solid as it passes into the anus.

- Mucosal epithelium consists of three types of cells (Enterocyte ; Goblet and Paneth cells) and is replaced every 3-5 days by gradual maturation of basal enterocytes.

- Mucosa of Gastrointestinal tract consists of 4 basic types: i) Protective - squamous type in the oral cavity, pharynx, esophagus and anal canal. ii) Secretory - gastric mucosa consists of tubular glands iii) Absorptive - intestinal mucosa consists of villi with intervening crypts. iv) Absorptive and protective - mucosa lines the large intestine. This consists of tubular glands to absorb water and goblet cells to secrete mucus to lubricate the passage of faeces.

Typhoid fever is a bacterial infection characterized by diarrhea, systemic disease, and a rash -- most commonly caused by the bacteria Salmonella typhi. Alternative Names

Enteric fever
Causes

S. typhi are spread by contaminated food, drink, or water. Following ingestion, the bacteria spread from the intestine via the bloodstream to the intestinal lymph nodes, liver, and spleen via the blood where they multiply. Salmonella may directly infect the gallbladder through the hepatic duct or spread to other areas of the body through the bloodstream. Early symptoms are generalized and include fever, malaise and abdominal pain. As the disease progresses, the fever becomes higher (greater than 103 degrees Fahrenheit), and diarrhea becomes prominent. Weakness, profound fatigue, delirium, and an acutely ill appearance develop. A rash, characteristic only of typhoid and called "rose spots," appears in some cases of typhoid. Rose spots are small (1/4 inch) red spots that appear most often on the abdomen and chest. Typically, children have milder disease and fewer complications than adults. A few people can become carriers of S. typhi and continue to shed the bacteria in their feces for years, spreading the disease, as in the case of "Typhoid Mary" in New York over 100 years ago. Although typhoid fever is common in developing countries, less than 400 cases are reported in the U.S. each year, most brought in from abroad.

Back to TopSymptoms

Severe headache Fever Loss of Appetite General discomfort, uneasiness, or ill feeling (malaise) Rash (rose spots) appearing on the lower chest and abdomen during the second week of the fever Abdominal tenderness Constipation, then diarrhea Bloody stools Slow, sluggish, lethargic Fatigue Weakness Nosebleed Chills Delirium Confusion Agitation Fluctuating mood Difficulty paying attention (attention deficit) Hallucinations

Back to TopSigns and Tests

An elevated white blood cell count in blood A blood culture during first week of the fever can show S. typhi bacteria A stool culture An ELISA test on urine may show Vi antigen specific for the bacteria A platelet count (decreased platelets ) A fluorescent antibody study (demonstrates Vi antigen, which is specific for typhoid)

Back to TopTreatment

Intravenous fluids and electrolytes may be given. Appropriate antibiotics are given to kill the bacteria. There are increasing rates of antibiotic resistance throughout the world, so the choice of antibiotics should be a careful one.
Back to TopExpectations (prognosis)

The illness usually resolves in 2 to 4 weeks with treatment. The outcome is likely to be good with early treatment, but becomes poor if complications develop. Cases in children are milder, and are more debilitating in the elderly. Relapse may occur if the treatment has not fully eradicated the infection.

Back to TopComplications

Intestinal hemorrhage (severe GI bleeding) Intestinal perforation Kidney failure Peritonitis

Back to TopCalling Your Health Care Provider

Call your health care provider if you have had any known exposure to typhoid fever or if you have been in an endemic area and symptoms of typhoid fever develop. Also call your health care provider if you have had typhoid fever and relapse occurs or if severe abdominal pain, decreased urine output, or other new symptoms develop.
Back to TopPrevention

Vaccines are recommended for travel outside of the U.S., Canada, northern Europe, Australia, and New Zealand, and during epidemic outbreaks. Immunization is not always completely effective and at-risk travelers should drink only boiled or bottled water and eat well cooked food. Experimentation with an oral live attenuated typhoid vaccine is now underway and appears promising. Adequate water treatment, waste disposal, and protection of food supply from contamination are important public health measures. Carriers of typhoid must not be allowed to work as food handlers.

Medical Care
If a patient presents with unexplained symptoms described in Table 1 within 60 days of returning from an typhoid fever (enteric fever) endemic area or following consumption of food prepared by an individual who is known to carry typhoid, broad-spectrum empiric antibiotics should be started immediately. Treatment should not be delayed for confirmatory tests since prompt treatment drastically reduces the risk of complications and fatalities. Antibiotic therapy should be narrowed once more information is available. Compliant patients with uncomplicated disease may be treated on an outpatient basis. They must be advised to use strict handwashing techniques and to avoid preparing food for others during the illness course. Hospitalized patients should be placed in contact isolation during the acute phase of the infection. Feces and urine must be disposed of safely.

Diet
Fluids and electrolytes should be monitored and replaced diligently. Oral nutrition with a soft digestible diet is preferable in the absence of abdominal distension or ileus.

Activity
No specific limitations on activity are indicated for patients with typhoid fever. As with most systemic diseases, rest is helpful, but mobility should be maintained if tolerable. The patient should be encouraged to stay home from work until recovery.

Deterrence/Prevention

Travelers to endemic countries should avoid raw unpeeled fruits or vegetables since they may have been prepared with contaminated water; in addition, they should drink only boiled water. In endemic countries, the most cost-effective strategy for reducing the incidence of typhoid fever is the institution of public health measures to ensure safe drinking water and sanitary disposal of excreta. The effects of these measures are long-term and reduce the incidence of other enteric infections, which are a major cause of morbidity and mortality in those areas.

Patient Education

Because vigilant hand hygiene, vaccination, and the avoidance of risky foods and beverages are mainstays of prevention, educating travelers before they enter a disease-endemic region is important. Because the protection offered by vaccination is at best partial, close attention to personal, food, and water hygiene should be maintained. The US Centers for Disease Control and Prevention dictum to "boil it, cook it, peel it, or forget it" is a good rule in any circumstance. If disease occurs while abroad despite these precautions, one can usually call the US consulate for a list of recommended doctors.

Further Outpatient Care

After discharge, patients should be monitored for relapse or complications for 3 months after treatment has commenced. Five percent to 10% of patients treated with antibiotics experience relapse of typhoid fever after initial recovery. Relapses typically occur approximately 1 week after therapy is discontinued, but relapse after 70 days has been reported. In these cases, the blood culture results are again positive, and high serum levels of H, O, and Vi antibodies and rose spots may reappear. o A relapse of typhoid fever is generally milder and of shorter duration than the initial illness. In rare cases, second or even third relapses occur. Notably, the relapse rate is much lower following treatment with the new quinolone drugs, which have effective intracellular penetration. o S typhi and S paratyphi rarely develop antibiotic resistance during treatment. If an antibiotic has been chosen according to sensitivities, relapse should dictate a search for anatomic, pathologic, or genetic predispositions rather than for an alternate antibiotic. o Previous infection does not confer immunity. In any suspected relapse, infection with a different strain should be ruled out. Depending on the antibiotic used, between 0% and 5.9% of treated patients become chronic carriers. In some cases, the organism evades antibiotics by sequestering itself within gallstones or Schistosoma haematobium organisms that are infecting the bladder. From there, it is shed in

stool or urine, respectively. If present, these diseases must be cured before the bacterium can be eliminated. Untreated survivors of typhoid fever may shed the bacterium in the feces for up to 3 months. Therefore, after disease resolution, 3 stool cultures in one-month intervals should be performed to rule out a carrier state. Concurrent urinary cultures should be considered.

Health Teachings

How can you avoid typhoid fever? Two basic actions can protect you from typhoid fever:
1. 2.

Avoid risky foods and drinks. Get vaccinated against typhoid fever.

It may surprise you, but watching what you eat and drink when you travel is as important as being vaccinated. This is because the vaccines are not completely effective. Avoiding risky foods will also help protect you from other illnesses, including travelers' diarrhea, cholera, dysentery, and hepatitis A.

"Boil it, cook it, peel it, or forget it"

If you drink water, buy it bottled or bring it to a rolling boil for 1 minute before you drink it. Bottled carbonated water is safer than uncarbonated water. Ask for drinks without ice unless the ice is made from bottled or boiled water. Avoid popsicles and flavored ices that may have been made with contaminated water. Eat foods that have been thoroughly cooked and that are still hot and steaming. Avoid raw vegetables and fruits that cannot be peeled. Vegetables like lettuce are easily contaminated and are very hard to wash well. When you eat raw fruit or vegetables that can be peeled, peel them yourself. (Wash your hands with soap first.) Do not eat the peelings. Avoid foods and beverages from street vendors. It is difficult for food to be kept clean on the street, and many travelers get sick from food bought from street vendors.

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Getting vaccinated If you are traveling to a country where typhoid is common, you should consider being vaccinated against typhoid. Visit a doctor or travel clinic to discuss your vaccination options. Remember that you will need to complete your vaccination at least 1-2 weeks (dependent upon vaccine type) before you travel so that the vaccine has time to take effect. Typhoid vaccines lose effectiveness after several years; if you were vaccinated in the past, check with your doctor to see if it is time for a booster vaccination. Taking antibiotics will not prevent typhoid fever; they only help treat it. The chart below provides basic information on typhoid vaccines that are available in the United States. Table 1: Typhoid Vaccines Available in the United States Time immunization Number of Time Minimum Booster How should be Doses Between Age For Needed completed by Given Necessary Doses Vaccination Every... (before possible exposure) 1 4 capsule by mouth 2 days 1 week 6 years 5 years

Vaccine Name

Ty21a (Vivotif Berna, Swiss Serum and Vaccine

Institute) ViCPS Injection 1 (Typhim Vi, Pasteur Merieux) N/A 2 weeks