Typhoid fever

• Typhoid fever is a contagious infection of the intestines that affects the whole body. It is caused by a bacterium called Salmonella typhi that is found in the fecal matter of infected individuals. Drinking water can become contaminated with fecal matter from sewage. Typhoid is spread when a person drinks or eats food and water contaminated by human waste (stool or urine) containing Salmonella typhi bacteria.
• Typhoid fever is characterized by the sudden onset of a fever, severe headache, nausea, and severe loss of appetite. It is sometimes accompanied by hoarse cough and constipation or diarrhea. Death rates of 10% can be reduced to less than 1% with appropriate antibiotic therapy.
• Paratyphoid fever is an infection caused by Salmonella paratyphi. Paratyphoid fever shows similar symptoms, but tends to be milder and the case-fatality rate is much lower. Paratyphoid fever is a serious contagious disease that is also grouped together with typhoid fever under the name enteric fever.
• In developing countries, typhoid often occurs in epidemics (many people get sick at once). Most people in the United States get typhoid as a result of visiting another country, such as in India and Brazil, where the food or water supply has been contaminated.
• A person may become a carrier of typhoid fever, suffering no symptoms, but capable of infecting others. Carriers must be extra careful with their personal hygiene. They should not work in restaurants or places where food is handled until a healthcare provider determines that they are no longer carriers of the bacteria.
• Typhoid fever remains a serious public health problem throughout the world. The World Health Organization (WHO) estimates that there are 16-33 million cases and 500,000-600,000 deaths annually. In virtually all areas that suffer from typhoid outbreaks, typhoid fever occurs most often in children from five to 19 years old. The disease is almost exclusively transmitted by food and water contaminated by the feces and urine of patients and carriers. Developing countries with poor sanitation and sewage treatment are especially vulnerable to typhoid outbreaks. Polluted water is the most common source of typhoid transmission. In addition, shellfish taken from sewage-contaminated beds, vegetables fertilized with human excrement and eaten raw, as well as contaminated milk and milk products have been shown to be a source of infection. Typhoid fever has been virtually eliminated in most areas of the industrialized world with the development of proper sanitary facilities. Individuals can transmit the disease as long as the bacteria remain in their body; most people are infectious prior to and during the first week of bed rest, but 10% of untreated patients will still have bacteria present in the body for up to three months. In addition, 2-5% of untreated patients will become permanent, lifelong carriers of the bacteria in their gall-bladder.

• The cause of typhoid fever is the bacterium Salmonella typhi. S. typhi was identified in the late 19th Century, although it has been infecting humans for millennia. Another bacterium, Salmonella paratyphi, causes paratyphoid fever.
• Fecal-oral route: The bacteria that cause typhoid and paratyphoid fever are both spread through contaminated food or water and occasionally through direct contact with a carrier. In developing nations, where typhoid and paratyphoid are endemic, most cases result from contaminated drinking water and poor sanitation. The majority of people in industrialized countries pick up the typhoid bacteria while traveling and spread it to others through the fecal-oral route. S. typhi and S. paratyphi are passed in the feces of infected people. Individuals can contract the infection if eating food handled by someone with typhoid fever who has not washed carefully after using the toilet. Individuals can also become infected by drinking water contaminated with the bacteria.
• Typhoid carriers: Even after treatment with antibiotics, a small number of people who recover from typhoid fever can continue to carry the bacteria in their intestinal tract or gallbladder, for years. These individuals, called chronic carriers, eliminate the bacteria in their feces and are capable of infecting others, although they are non-symptomatic.

• Typhoid fever remains a serious threat in the developing world, where it affects more than 12 million people annually. The disease is endemic in India, Southeast Asia, Africa, South America, and in certain regions of the former Soviet Union, especially Tajikistan and Uzbekistan. Worldwide, children are at the greatest risk of contracting the disease, although they generally have milder symptoms and fewer complications than adults do. If an individual lives in a country where typhoid and paratyphoid fevers are rare, they are at an increased risk if they: work in or travel to areas where typhoid fever is endemic; have close contact with someone who is infected or has recently been infected with typhoid fever; have an immune system weakened by medications such as corticosteroids or conditions such as pregnancy, human immunodeficiency virus (HIV), or acquired immunodeficiency syndrome (AIDS); or drink water contaminated by sewage that contains S. typhi.

• Although
  some individuals with typhoid fever sometimes become sick suddenly, signs and symptoms are more likely to develop gradually. Symptoms of typhoid fever appear in stages, with treatment being possible in all stages. The rate of recovery depends upon the stage of the condition, with third stage typhoid recovering more slowly.
• First stage: Signs and symptoms often appear one to three weeks after exposure to the bacterium, S. typhi. In some cases, symptoms may take up to two months to appear. individuals may not become sick for as long as two months after exposure. The incubation period for paratyphoid fever is shorter, usually one to 10 days under normal circumstances. Once signs and symptoms do appear, individuals will likely experience: fever, often as high as 103-104 degrees Fahrenheit (39-50 degrees Celsius); headache; weakness and fatigue; a sore throat; abdominal pain; and diarrhea or constipation. Children are more likely to have diarrhea whereas adults may become severely constipated.
• During the second week, individuals may develop a rash of small, flat, rose-colored spots on the lower chest or upper abdomen. The rash is temporary, and usually disappears in three or four days.
• Second stage: If the individual does not receive treatment for typhoid fever, they may enter a second stage during which the individual becomes very ill. The fever will remain high, and the individual may develop either diarrhea that has the color and consistency of pea soup or severe constipation. They may lose considerable weight during this phase, and the abdomen may become extremely distended.
• Third stage or the typhoid state: By the third week, the individual may become delirious, lying motionless and exhausted with their eyes half-closed in what is known as the typhoid state. Life-threatening complications often develop at this time, such as pneumonia.
• Improvement stage: Improvement may come slowly during the fourth week. A fever is likely to decrease gradually until the temperature returns to normal in another week to 10 days. Signs and symptoms can return up to two weeks after the fever has subsided.
• Paratyphoid fever causes signs and symptoms similar to those of typhoid fever, but in a milder form. Complications are not as severe, and individuals generally recover more quickly.

• A doctor is likely to suspect typhoid or paratyphoid fever based on the individual's symptoms and medical and travel history. But the diagnosis is usually confirmed by identifying S. typhi or S. paratyphi in a culture of the blood or other body fluid or tissue.
• Bacterial culture: For the culture, a small sample of blood, stool, urine, or bone marrow is placed on a special medium that encourages the growth of bacteria. In 48-72 hours, the culture is checked under a microscope for the presence of typhoid bacteria. A bone marrow culture often is the most sensitive test for S. typhi, although it is not performed often due to pain and discomfort.
• Enzyme-linked immunosorbent assay (ELISA): An enzyme-linked immunosorbent assay (ELISA) test is a blood test that looks for an antigen that is specific to typhoid bacteria. An antigen is any substance, such as a virus, bacterium, toxin, or foreign protein, which triggers an immune system response in the body.
• Fluorescent antibody test: A fluorescent antibody test checks for antibodies to S. typhi. Antibodies are proteins produced by the immune system in response to foreign substances in the body called antigens. Each antibody is unique and defends the body against a single, specific antigen.

• The most serious complication of typhoid fever is intestinal bleeding or perforation, which may develop in the third week of illness. About 5% of individuals with typhoid fever experience this complication. Intestinal bleeding is often marked by a sudden drop in blood pressure and shock, followed by the appearance of blood in the stool. A perforated intestine occurs when the small intestine or large bowel develops a hole, causing intestinal contents to leak into the abdominal cavity. This triggers signs and symptoms such as severe abdominal pain, nausea, vomiting, and blood stream infection (sepsis). This life-threatening emergency requires immediate medical care. Intestinal perforation causes nearly a quarter of the deaths that occur from typhoid fever.
• Other, less common complications of typhoid fever include: myocarditis or inflammation of the heart muscle (symptoms may include shortness of breath, chest pain, and irregular heart beats); pneumonia (symptoms include shortness of breath, cough, and lung pain); pancreatitis or inflammation of the pancreas (symptoms include nausea, fever, and pain); kidney or bladder infections (symptoms include painful urination and fever); osteomyelitis or infections of the bone (symptoms include pain); meningitis or infection and inflammation of the membranes and fluid surrounding the brain and spinal cord (symptoms include fever, chills, and fatigue); and psychiatric problems such as delirium, hallucinations, and paranoid psychosis.
• With prompt treatment, nearly all individuals in industrialized nations recover from typhoid, but without treatment, some individuals may not survive the above complications of the disease.

• Antibiotics: Antibiotic therapy is the only effective treatment for typhoid and paratyphoid fevers. In the past, the drug of choice was chloramphenicol (Chloromycetin®). Doctors no longer commonly use this antibiotic because of chloramphenicol's severe side effects, a high relapse rate, and widespread bacterial resistance. The existence of antibiotic-resistant bacteria is a serious and growing problem in the treatment of typhoid, especially in the developing world.
• When bacteria prove resistant to standard antibiotics, illnesses last longer, and the risks of complications and death increase. Failure to treat an infection properly leads to longer periods in which an individual is contagious and able to spread the resistant strain to others. Because bacteria mutate much more quickly than researchers can develop new antibiotics, the possibility exists that one day highly lethal strains of resistant bacteria will evolve and doctors will have no effective way to treat them.
• S. typhi has been found to be resistant to other former methods of drug treatment, including trimethoprim-sulfamethoxazole (Bactrim®), ampicillin (Trimox®), and tetracycline (Sumycin®), in addition to chloramphenicol (Chloromycetin®).
• In the United States, most doctors now prescribe ciprofloxacin (Cipro®) for adults other than pregnant women with typhoid fever. However, in some parts of the world, typhoid resistance has begun to extend even to ciprofloxacin. Women who are pregnant and children most often receive ceftriaxone (Rocephin®) injections. All of these drugs can cause side effects, such as nausea and diarrhea, and long-term use can lead to the development of antibiotic-resistant strains of bacteria.
• Other treatments: Other treatment steps aimed at managing symptoms include drinking plenty of fluids (called oral rehydration therapy) and eating a healthy diet, including plenty of fresh fruits and vegetables. Drinking fluids helps prevent the dehydration that results from a prolonged fever and diarrhea. If an individual is severely dehydrated, they may need to receive intravenous (IV, or into the veins) fluids. Non-bulky, high-calorie meals, such as those with rice or carbohydrates, can help replace the nutrients lost when the individual is sick with typhoid.

Note
: There is currently a lack of available clinical studies that support the use of integrative therapies for typhoid fever. The therapies listed below have generally been studied for effects on various types of bacteria, are not to be used in replacement of other more proven therapies for typhoid fever such as antibiotics, and should not delay the time to treatment with more proven therapies.

A

Strong scientific evidence

• Probiotics
  : Probiotics are beneficial bacteria and are sometimes called friendly germs. They help maintain a healthy intestine by keeping harmful bacteria and yeasts in the gut under control. Most probiotics come from food sources, especially cultured milk products. Probiotics can be taken as capsules, tablets, beverages, powders, yogurts, and other foods. An increasing number of studies support the use of probiotics as a supplement to antibiotic therapy. Probiotic supplementation during a course of antibiotics has been studied for reducing adverse effects of antibiotics in the intestinal environment. This includes reducing growth of Clostridium difficile bacteria, which can lead to colitis, a common complication of antibiotics, especially in the elderly. Some probiotics may also help prevent the development of antibiotic resistance. In acutely ill children, synbiotics have been linked to greater weight gain and fewer bacterial illnesses after antibiotics are ended. The evidence consistently supports supplementation of antibiotics with probiotics.
• Probiotics are generally considered to be safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.

B

Good scientific evidence

• Probiotics
  : Limited evidence with day care children suggests supplementation with Lactobacillus GG may reduce number of sick days, frequency of respiratory tract infections, and frequency of related antibiotic treatments.
  Fermented milk (with yogurt cultures and L. casei DN-114001) may reduce the duration of gastrointestinal infections in elderly people. More research is needed to make a firm conclusion.
• Probiotics are generally considered to be safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.

C

Unclear or conflicting scientific evidence

• Blessed thistle
  : Human research of blessed thistle as a treatment for bacterial infections is currently lacking. Laboratory studies report that blessed thistle (and chemicals contained in blessed thistle, such as cnicin and polyacetylene) may have activity against several types of bacterial infections and no effects on some types. Early studies report no activity of blessed thistle against herpes viruses, influenza, or poliovirus. Further evidence is necessary in this area before a firm conclusion can be drawn.
• Blessed thistle is generally considered to be safe when taken by mouth in recommended doses for short periods of time, with few reported side effects such as birth defects, bleeding, breathing problems, bruising, cancer of the nose or throat, increased production of stomach acid, itching, kidney disease, liver toxicity, skin rash, stomach discomfort, stomach ulcers, and vomiting. Allergic reactions to blessed thistle including rash may occur, as well as cross-sensitivity to mugwort and Echinacea. Cross-reactivity may also occur with bitter weed, blanket flower, Chrysanthemum, coltsfoot, daisy, dandelion, dwarf sunflower, goldenrod, marigold, prairie sage, ragweed or other plants in the Asteraceae/Compositae family. Avoid if pregnant or breastfeeding.
• Cranberry
  : Limited laboratory research has examined the antibacterial activity of cranberry. Further research is warranted in this area.
• Avoid if allergic to cranberries, blueberries, or other plants of the Vaccinium species. Sweetened cranberry juice may affect blood sugar levels. Use cautiously with a history of kidney stones. Pregnant and breastfeeding women should avoid cranberry in higher amounts than what is typically found in foods.
• Propolis
  : Propolis is a natural resin created by bees to make their hives. Propolis is made from the buds of conifer and poplar trees and combined with beeswax and other bee secretions. Animal and laboratory studies suggest that propolis may be a beneficial treatment for various types of bacterial infections. Additional research is needed to confirm these findings.
• Avoid if allergic or hypersensitive to propolis, black poplar (Populas nigra), poplar bud, bee stings, bee products, honey, or Balsam of Peru. Severe allergic reactions have been reported. There has been one report of kidney failure with the ingestion of propolis that improved upon discontinuing therapy and deteriorated with re-exposure. Avoid if pregnant or breastfeeding because of the high alcohol content in some products.
• Seaweed, kelp, bladderwrack
  : Bladderwrack (Fucus vesiculosus) is a brown seaweed found along the northern coasts of the Atlantic and Pacific oceans and North and Baltic seas. Another seaweed that grows alongside bladderwrack is Ascophyllum nodosum, and
  it is often combined with bladderwrack in kelp preparations. Laboratory research suggests that bladderwrack may have antibacterial activity. However, reliable human studies to support this use are currently lacking in the available literature.
• Avoid if allergic or hypersensitive to Fucus vesiculosus or iodine. Avoid with a history of thyroid disease, bleeding, acne, kidney disease, blood clots, nerve disorders, high blood pressure, stroke, or diabetes. Avoid if pregnant or breastfeeding.
• Sorrel
  : There is currently not enough evidence on the proposed antibacterial effects of sorrel. More research is needed.
• Avoid large doses of sorrel because there have been reports of toxicity and death. This may be because of the oxalate found in sorrel. Many sorrel tinctures contain high levels of alcohol and should be avoided when driving or operating heavy machinery. These sorrel formulations may cause nausea or vomiting when taken with the prescription drugs metronidazole (Flagyl®) or disulfiram (Antabuse®). Avoid if pregnant or breastfeeding.

D

Fair negative scientific evidence

• Macrobiotic diet
  : A macrobiotic diet has been advocated to preserve intestinal health. However, it apparently does not reduce the incidence of antibiotic resistant bacteria, nor infections caused by resistant strains in the gastrointestinal tract, compared to a diet with animal products.
• Use cautiously with cancer or other medical conditions without expert planning or supplementation. Avoid in children or adolescents without professional guidance or appropriate supplementation. Avoid in pregnant or lactating women due to potential deficiencies, unless properly supplemented.
• Probiotics
  : Bacterial infection translocation, the passage of bacteria from the gut to other areas of the body where they can cause disease, is of special concern in surgery. Limited evidence suggests that supplementation with probiotics may not reduce this problem.
• Probiotics are generally considered to be safe and well-tolerated. Avoid if allergic or hypersensitive to probiotics. Use cautiously if lactose intolerant. Caution is advised when using probiotics in neonates born prematurely or with immune deficiency.

• Healthcare professionals recommend: washing hands well with soap and water after going to the bathroom and before preparing food items; if traveling to a foreign country, it is recommended to drink bottle water or boil the water; avoid raw fruits and vegetables, as they may be washed in unclean water; choose hot foods that are not stored or served at room temperature; and maintain cleanliness and proper sanitation at all times, especially after a flood or other natural disasters. Individuals can be vaccinated against typhoid.
• Vaccination: Individuals can be vaccinated against typhoid fever. Vaccination is not usually needed in the United States. It is usually recommended by healthcare professionals only for international travelers going to developing countries where exposure to contaminated food or water is likely.
• Experts believe that vaccinating high-risk populations, such as those in developing countries, is the best way to control typhoid fever. Safe drinking water, improved sanitation, and adequate medical care are essential in controlling typhoid fever outbreaks. If an individual is traveling to an area where typhoid fever is endemic, they should consider vaccination against S. typhi.
• There is an oral typhoid vaccine and a single-dose injectable vaccine that produces fewer side effects than an older two-dose injectable vaccine. Both vaccines are equally effective and offer 65-75% protection against the disease. The oral vaccine (Vivotif®) contains a live but weakened strain of the Salmonella bacteria that causes typhoid fever. The vaccine consists of four capsules that are taken every other day over a one-week period. The capsule protects the vaccine against stomach acid allowing it to remain active when it reaches the intestine. Immunity develops in the intestines. The oral vaccine can be given either as a first-time dose or as a booster dose. The protection should last about five years, at which time another booster dose would be needed if traveling again. The oral vaccine is not recommended for children under six years old. Side effects may include abdominal cramps, diarrhea, nausea and vomiting, and itchy rash (urticaria).
• The single-dose injectable vaccine, Vi polysaccharide vaccine (ViCPS), contains capsular polysaccharide antigen and offers protection starting two weeks after injection. ViCPS should last for two years. Subsequent booster doses are recommended at two-year intervals. This vaccine can be used in children as young as two years old. Side effects, while greater than those of the oral vaccine, are much less than those experienced with the old two-dose injectable vaccine. Vi polysaccharide vaccine may cause redness or swelling where the vaccine was given, as well as fever and headache.