Typhoid Fever – Causes, Symptoms, Complications, Prevention, Treatment

By Dr Raghuram Y.S. MD (Ay) & Dr Manasa, B.A.M.S

Typhoid fever is an acute illness. It is associated with fever caused by the Salmonella enteric serotype Typhi bacteria. It is also caused by Salmonella paratyphi. Man is the carrier. The bacteria are deposited in water or food by human beings. Later they are spread to other people in the water.
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Causes of Typhoid

Salmonella typhi, virulent bacteria is the causative agent. Consumption of food or water contaminated with bacteria, one can get typhoid.

Fecal-oral transmission route

Salmonella typhi is passed in feces or urine of infected people. Contamination of water supply by stools / urine of people with typhoid are causal. There will be high concentration of bacteria in the stools. The contaminated stools can contaminate food supply too. The bacteria are known to survive for many weeks in contaminated water and dry sewage.

Thus, the bacteria pass from feces to food and food to the human body through oral consumption of contaminated food. Therefore it is called fecal-oral transmission route.

Eating food handled by typhoid patients, especially when they haven’t washed their hands carefully after using toilet, is causal.

People of industrialized countries pick up the bacteria while traveling. These people spread it to others through fecal-oral route.
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Typhoid carriers

In spite of being treated with antibiotics, some people harbor bacteria in their intestines or gallbladders for many years. This happens in spite after their recovery. These people are called chronic carriers. They keep shedding bacteria in their feces. They are thus capable of infecting others. But these people will not be having the signs and symptoms of active disease. Approximately 3-5% people become carriers of bacteria after acute phase of illness.

In other instances, some people will suffer from mild illness which might go undiagnosed. These people may become long-term carriers of bacteria. They may not present with symptoms of typhoid. They may also become source of new outbreaks of typhoid for many years.

Paratyphi – Typhoid is also less commonly caused by Salmonella enteric serotypes paratyphi A, B and C. Paratyphi is more commonly transmitted in food from street vendors. It is common among the newcomers to urban areas because they are probably immunologically naïve to it. The travelers get little or no protection against paratyphi from typhoid vaccines. Most vaccines are targeted towards typhi.
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Symptoms

The symptoms in typhoid develop gradually. They often appear one to three weeks after the exposure to the disease.

Incubation period – roughly 1-2 weeks

Duration of illness – roughly 3-4 weeks

Early illness manifests with the below mentioned signs and symptoms –

  • High Fever – intensity increases daily, reaches as high as 104.9 F or more, remains constant
  • Headache
  • Weakness and fatigue
  • Lethargy
  • Chills
  • Body aches
  • Loss of appetite
  • Diarrhea / constipation
  • Pain abdomen
  • Cough & chest congestion
  • Sweating
  • Rashes

If treated promptly improvement occurs in the 3rd and 4th week.

Later illness –

If typhoid is not promptly treated during its acute phase of illness, the patient may suffer from

  • Delirium
  • Being inert, motionless and exhausted, eyes half closed with toxic look – typhoid state  

Life threatening complications may also develop.

In some people, the fever and other symptoms may go away and may recur after couple of weeks. Symptoms recur after recovery in about 10% people. Relapses are common in those treated with antibiotics.

Development of symptoms week-wise and mode of manifestation

Fever begins 7-14 days after ingesting the organism.

Pattern of fever – stepwise / step-ladder pattern – is characterized by rising temperature over course of each day. It drops by subsequent morning.

During first week –

  • Gastrointestinal manifestations – abdominal pain and tenderness occur. In some cases, there is fierce colicky pain in the right upper quadrant of the abdomen.
  • Inflammation of Peyer’s patches occurs following monocytic infiltration. The bowel lumen becomes narrow.
  • Dry cough, dull frontal headache, delirium and malaise occur.
  • Fever plateaus at 103-104 degree F at the end of the first week.
  • Rose spots which are salmon-colored develop. They are blanching, truncal, macula-papules usually 1-4 cm wide and fewer than 5 in numbers. They generally resolve within 2-5 days.

During second week –

During third week –

  • Severe toxic appearance of the patient
  • Anorexia and weight loss
  • Infection of conjunctiva
  • Tachypnea with thread pulse and crackles over lung bases
  • Severe abdominal distension
  • Foul, green-yellow liquid diarrhea – pea soup diarrhea
  • Typhoid state characterized by – apathy, confusion, psychosis
  • Necrotic Peyer patches – may cause bowel perforation and peritonitis
  • Overwhelming toxemia, myocarditis or intestinal hemorrhage may eventually lead to death
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During fourth week – if the patient survives –

  • Fever, mental state and abdominal distension slowly improve
  • Intestinal and neurological complications may still occur especially in untreated individuals
  • Debilitating weakness and weight loss may stay for months
  • Some of them become asymptomatic S typhi carriers. They have potential to transmit the bacteria.

The stepladder fever pattern that was once the hallmark of typhoid fever now occurs in as few as 12% cases. In most contemporary typhoid presentations, the fever has a steady insidious onset.

Important signs –

  • Coated tongue
  • Rales
  • Dicrotic pulse
  • Thrombophlebitis
  • Hepato-splenomegaly
  • Jaundice
  • Rose spots (rare)

Interesting points about typhoid

Typhoid fever is rare in industrialized countries. It is still a serious health threat in developing world, mainly in children.

Risk Factors

Worldwide, an estimated 26 million or more people are afflicted by typhoid. The disease is established in India, Southeast Asia, South America, Africa and other areas.

Risk factors include –

  • If you are working in or traveling to areas where typhoid is established
  • If your job is microbiologist
  • If you are in contact with infected individuals
  • If you have drunk water contaminated by sewage containing Salmonella typhi

Complications

Neuropsychiatric –

  • Toxic confusion state – disorientation, delirium and restlessness
  • Facial twitching or convulsions
  • Meningitis
  • Stupor or coma – in severe disease
  • Brain abscesses
  • Spastic paraplegia
  • Peripheral or cranial neuritis
  • GB syndrome
  • Schizophrenia like illness, mania, depression
  • Hallucinations
  • Paranoid psychosis etc

Respiratory –

  • Cough
  • Ulceration in posterior pharynx
  • Acute lobar pneumonia – pneumo-typhoid

Cardiovascular –

  • Toxic myocarditis
  • Endocarditis
  • Pericarditis

Hepatobiliary –

  • Jaundice
  • Pancreatitis
  • Hepatitis with hepatomegaly
  • Mild elevation of transaminases

Intestinal –

  • Intestinal hemorrhage – Intestinal bleeding / perforations – which may develop in the third week of illness, are a life threatening complication requiring immediate medical care.
  • Perforation

Genitourinary –

  • S typhi in urine
  • Immune complex glomerulitis and proteinuria
  • Nephritic syndrome
  • Nephrotic syndrome
  • Cystitis
  • Infections of kidney and bladder

Hematologic –

  • Subclinical disseminated intravascular coagulation
  • Hemolytic-uremic syndrome
  • Hemolysis

Musculoskeletal and joint –

  • Zenker degeneration of skeletal muscle
  • Polymyositis
  • Arthritis

Late sequelae –

  • Neurologic – polyneuritis, paranoid psychosis
  • Cardiovascular – thrombophlebitis
  • Genitourinary – Orchitis
  • Musculoskeletal – Periostitis, spinal abscess (typhoid spine)

Diagnosis

Diagnosis is made through stool, blood or urine samples.

The ingested Salmonella bacteria invade small intestine. From there they enter the bloodstream. They are carried by white blood cells into the liver, spleen and bone marrow. Here they multiply. They once again enter the bloodstream. At this instance, symptoms like fever etc manifest. The bacteria invade the gall bladed, bile system and lymphatic tissue of the bowel. They multiply in high numbers. The bacteria pass into the intestinal tract and can be identified in stools. Blood or urine samples may be taken to make the diagnosis sure.

Culture test to diagnose is the mainstay of diagnosis. Cultures are widely considered 100% specific. Culture of bone marrow aspirate is 90% sensitive until at least 5 days after commencement of antibiotics. This technique is extremely painful and may outweigh its benefits.

A test to detect antibodies to typhoid bacteria in your blood is also preferred.

A test to check for typhoid DNA in your blood sample may be asked for.

Blood, intestinal secretions i.e. vomitus or duodenal aspirate and stool culture are positive for S typhi in approximately 85-90% patients who present within first week of onset. In later course of the disease, they decline to 20-30%.

Other samples –

  • Stool culture – less than 50% sensitivity
  • Urine culture – less sensitive than stool culture
  • Punch biopsy samples of rose spots – 63% sensitive
  • Rectal swab culture – detects S typhi in 30-40% of hospitalized patients
  • S typhi has been isolated from CSF, peritoneal fluid, mesenteric lymph nodes, intestine, pharynx, tonsils, abscess and bone

Polymerase Chain Reaction (PCR) – This technique has shown a sensitivity of 82.7% and reported specificity of 100% in diagnosis of typhoid.

Specific serological tests –

  • Assays that identify Salmonella antibodies or antigens
  • Widal test – is neither sensitive nor specific, no longer acceptable
  • Indirect fluorescent Vi antibody
  • Indirect hemagglutination test
  • Indirect ELISA for IgM and IgG antibodies to S typhi polysaccharide

Differential Diagnosis

  • Abdominal abscess
  • Amebic liver / hepatic abscess
  • Appendicitis
  • Brucellosis
  • Dengue
  • Influenza
  • Leishmaniasis
  • Malaria
  • Rickettsial diseases
  • Toxoplasmosis
  • Tuberculosis
  • Tularemia
  • Typhus

Prognosis

Prognosis of typhoid depends on how quickly it is diagnosed and prompt initiation of treatment. Untreated typhoid carries a mortality rate of 15-30%. In properly treated cases mortality is less than 1%.

Many patients experience long term or permanent complications. These include neuropsychiatric symptoms and high rates of gastrointestinal cancers.

Prevention

Measures at community level

  • Safe drinking water
  • Improved sanitation
  • Adequate and immediate medical care
  • Educating people in prone zones
  • Vaccinating high risk population
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Personal care –

  • Wash hands frequently and thoroughly – use hot, soapy water. Wash hands before eating, cooking and after toilet. Carry alcohol-based hand sanitizer always.
  • Avoid drinking untreated water, drink only boiled water or canned water. Carbonated bottled water is safer. Use bottled water to brush teeth. Don’t swallow water in the shower.
  • Avoid raw fruits and vegetables – they might have been washed with unsafe water. Avoid those which you can’t peel, example lettuce.
  • Choose hot foods – Avoid taking stored foods and those at room temperature. The best choice is steaming hot foods.
  • Avoid foods from road-side street vendors.

Measures to be taken if you are recovering from typhoid, to keep others safe –

  • Take antibiotics promptly and finish the scheduled course.
  • Wash hands often.
  • Avoid handling foods and preparing food for others until you are declared ‘no longer contagious’.
  • Take leave if you are working in food industry or health care facility until your tests show that you are not shedding bacteria.

Treatment

Antibiotic therapy – Typhoid is treated with antibiotics and supportive care. With this the mortality has come down to 1-2%. Improvement usually occurs within 1-2 days. Recovery is seen in 7-10 days. For many years Chloramphenicol was the drug of choice. Later it has been replaced with other effective antibiotics.

Commonly prescribed antibiotics –

  • Ciprofloxacin
  • Azithromycin
  • Ceftriaxone etc

Prolonged antibiotic therapy – is given for those who are chronically ill.

Combination of ceftriaxone and ciprofloxacin – is recommended when origin of bacteria is not known.

Floroquinolones are highly effective. They offer better cure rate than cephalosporins. Third generation cephalosporins are preferred in fluroquinolone resistance rates. The third generation fluoroquinolone gatifloxacin is highly effective against all known clinical strains of S typhi, yield better results than cephalosporins.

Guidelines given by Indian Association of Pediatrics in 2006 – Cefixime and azithromycin are choices. Ceftriaxone is recommended in complicated cases. They recommend Aztreonam and imipenem as second line agents.

WHO recommendations – Oral ciprofloxacin for uncomplicated disease and intravenous ciprofloxacin in complicated typhoid are recommended.

Removal of Gall Bladder – Gall bladder is the site of chronic infection. Removal of this organ often provides cure. If antibiotic treatment fails to eradicate hepatobiliary carriage – gallbladder should be resected.

Vaccines – are available for those who are travelling to high risk areas.

Drinking fluids – to prevent dehydration caused due to prolonged fever and diarrhea is necessary. In severe dehydration intravenous fluids may be needed.

Diet – Fluids and electrolytes should be monitored and replaced promptly. Oral nutrition with soft digestible diet is preferable. 

Surgery – if your intestines are perforated.

Small bowel resection – patients with multiple perforations

Care after discharge

After discharge, the patients should be monitored for relapse or complications for 3 months after treatment has commenced. Relapse is generally milder and of shorter duration.

Previous infection does not confer immunity. In suspected relapse infection with a different strain should be ruled out.

Untreated survivors may shed 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. Urine cultures too should be considered.

Epidemiology

In United States, since 1900 there is a steady decrease in the incidence of typhoid fever due to improved sanitation and successful use of antibiotics.

Worldwide, typhoid occurs primarily in developing nations wherein there are poor sanitary conditions. It is endemic in Asia, Africa, Latin America, Caribbean and Oceania. Among these, 80% cases come from Bangladesh, China, India, Indonesia, Nepal, Pakistan or Vietnam. Within these countries, typhoid is most common in underdeveloped areas.

Typhoid fever infects roughly 21.6 million people i.e. incidence of 3.6/1,000 population and kills an estimated 2 lakh people every year.

In US, most cases of typhoid arise in international travelers. Most travelers recorded in between 1999-2006 were from Western hemisphere, Africa, Asia and India.

Mortality and Morbidity – Typhoid is typically a short-term febrile illness with prompt and appropriate antibiotic therapy. It requires a median of 6 days hospitalization. Treated, it has few long term sequelae and 0.2% risk of mortality. Untreated conditions are life threatening and stay for many weeks with long term morbidity. It often involves complications related to central nervous system.

Race – Typhoid has no racial predilection.

Sex – 54% cases in US reported between 1999-2006 involved males.

Age – Most documented cases include schooling children and young adults. The incidence among very young children and infants is higher.

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