Typhoid Fever

Typhoid - What is Typhoid?

Typhoid fever, also known as ''Salmonella typhi" or commonly just typhoid, is a common worldwide illness, transmitted by the ingestion of food or water contaminated with the feces of an infected person. The bacteria then perforate through the intestinal wall and are phagocytosed by macrophages.

The organism is a Gram-negative short bacillus that is motile due to its peritrichous flagella. The bacterium grows best at – human body temperature.

This fever received various names, such as gastric fever, abdominal typhus, infantile remittant fever, slow fever, nervous fever, pythogenic fever, etc. The name of " typhoid " was given by Louis in 1829, as a derivative from typhus.

The impact of this disease falls sharply with the application of modern sanitation techniques.

With an estimated 16–33 million cases of annually resulting in 216,000 deaths in endemic areas, the World Health Organization identifies typhoid as a serious public health problem. Its incidence is highest in children and young adults between 5 and 19 years old.

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Typhoid Symptoms

Typhoid fever is characterized by a slowly progressive fever, profuse sweating, gastroenteritis, and nonbloody diarrhea. Less commonly, a rash of flat, rose-colored spots may appear.

Classically, the course of untreated typhoid fever is divided into four individual stages, each lasting approximately one week.

In the first week, there is a slowly rising temperature with relative bradycardia, malaise, headache and cough.

A bloody nose (epistaxis) is seen in a quarter of cases and abdominal pain is also possible. There is leukopenia, a decrease in the number of circulating white blood cells, with eosinopenia and relative lymphocytosis, a positive diazo reaction and blood cultures are positive for ''Salmonella typhi'' or ''paratyphi''. The classic Widal test is negative in the first week.

In the second week of the infection, the patient lies prostrate with high fever in plateau around and bradycardia (sphygmothermic dissociation), classically with a dicrotic pulse wave.

Delirium is frequent, frequently calm, but sometimes agitated. This delirium gives to typhoid the nickname of "nervous fever". Rose spots appear on the lower chest and abdomen in around a third of patients. There are rhonchi in lung bases.

The abdomen is distended and painful in the right lower quadrant where borborygmi can be heard. Diarrhea can occur in this stage: six to eight stools in a day, green with a characteristic smell, comparable to pea soup. However, constipation is also frequent.

The spleen and liver are enlarged (hepatosplenomegaly) and tender, and there is elevation of liver transaminases. The Widal reaction is strongly positive with antiO and antiH antibodies. Blood cultures are sometimes still positive at this stage.

(The major symptom of this fever is the fever usually rises in the afternoon up to the first and second week.)

In the third week of typhoid fever, a number of complications can occur:

  • Intestinal hemorrhage due to bleeding in congested Peyer's patches; this can be very serious but is usually not fatal.
  • Intestinal perforation in the distal ileum: this is a very serious complication and is frequently fatal. It may occur without alarming symptoms until septicaemia or diffuse peritonitis sets in.
  • Encephalitis
  • Metastatic abscesses, cholecystitis, endocarditis and osteitis

The fever is still very high and oscillates very little over 24 hours. Dehydration ensues and the patient is delirious (typhoid state). By the end of third week the fever has started reducing (defervescence). This carries on into the fourth and final week.

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Typhoid Diagnosis

Diagnosis is made by any blood, bone marrow or stool cultures and with the Widal test (demonstration of salmonella antibodies against antigens O-somatic and H-flagellar).

In epidemics and less wealthy countries, after excluding malaria, dysentery or pneumonia, a therapeutic trial time with chloramphenicol is generally undertaken while awaiting the results of Widal test and cultures of the blood and stool.

The term "enteric fever" is a collective term that refers to typhoid and paratyphoid.

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Typhoid Treatment

The rediscovery of oral rehydration therapy in the 1960s, and proven in the Bangladesh Liberation War, provided a simple way to prevent many of the deaths of diarrheal diseases in general.

Where resistance is uncommon, the treatment of choice is a fluoroquinolone such as ciprofloxacin otherwise, a third-generation cephalosporin such as ceftriaxone or cefotaxime is the first choice. Cefixime is a suitable oral alternative.

Typhoid fever in most cases is not fatal. Antibiotics, such as ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole, Amoxicillin and ciprofloxacin, have been commonly used to treat typhoid fever in developed countries. Prompt treatment of the disease with antibiotics reduces the case-fatality rate to approximately 1%.

When untreated, typhoid fever persists for three weeks to a month. Death occurs in between 10% and 30% of untreated cases. In some communities, however, case-fatality rates may reach as high as 47%.

The common treatment of Typhoid is Mucomelt-Forte which is the combination of Cefixime with Acetylcysteine. Cefixime is the third generation cephalosporin antibiotic which breaks the cell wall of bacteria that is Salmonella typhi and acetylcysteine neutralize the endotoxin which is release by the bacteria as a waste product of metabolism.This endotoxin cause rise in body temperature which is the main symptom of typhoid.

Resistance

Resistance to ampicillin, chloramphenicol, trimethoprim-sulfamethoxazole and streptomycin is now common, and these agents have not been used as first line treatment now for almost 20 years. Typhoid that is resistant to these agents is known as multidrug-resistant typhoid (MDR typhoid).

Ciprofloxacin resistance is an increasing problem, especially in the Indian subcontinent and Southeast Asia. Many centres are therefore moving away from using ciprofloxacin as first line for treating suspected typhoid originating in South America, India, Pakistan, Bangladesh, Thailand or Vietnam.

For these patients, the recommended first line treatment is ceftriaxone. It has also been suggested Azithromycin is better at treating typhoid in resistant populations than both fluoroquinolone drugs and ceftriaxone. Azithromycin significantly reduces relapse rates compared with ceftriaxone.

There is a separate problem with laboratory testing for reduced susceptibility to ciprofloxacin: current recommendations are that isolates should be tested simultaneously against ciprofloxacin (CIP) and against nalidixic acid (NAL), and that isolates that are sensitive to both CIP and NAL should be reported as "sensitive to ciprofloxacin", but that isolates testing sensitive to CIP but not to NAL should be reported as "reduced sensitivity to ciprofloxacin". However, an analysis of 271 isolates showed that around 18% of isolates with a reduced susceptibility to ciprofloxacin (MIC 0.125–1.0 mg/l) would not be picked up by this method. It is not certain how this problem can be solved, because most laboratories around the world (including the West) are dependent on disc testing and cannot test for MICs.

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Typhoid Prevention

Sanitation and hygiene are the critical measures that can be taken to prevent typhoid. Typhoid does not affect animals and therefore transmission is only from human to human.

Typhoid can only spread in environments where human feces or urine are able to come into contact with food or drinking water. Careful food preparation and washing of hands are crucial to preventing typhoid.

A vaccine against typhoid fever was developed during World War II by Ralph Walter Graystone Wyckoff.

There are two vaccines currently recommended by the World Health Organization for the prevention of typhoid: these are the live, oral Ty21a vaccine (sold as ''Vivotif Berna'') and the injectable Typhoid polysaccharide vaccine (sold as ''Typhim Vi'' by Sanofi Pasteur and ''Typherix'' by GlaxoSmithKline). Both are between 50% to 80% protective and are recommended for travelers to areas where typhoid is endemic. Boosters are recommended every 5 years for the oral vaccine and every 2 years for the injectable form.

There exists an older killed whole-cell vaccine that is still used in countries where the newer preparations are not available, but this vaccine is no longer recommended for use, because it has a higher rate of side effects (mainly pain and inflammation at the site of the injection).

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Typhoid Fever History

Around 430–424 BC, a devastating plague, which some believe to have been typhoid fever, killed one third of the population of Athens, including their leader Pericles. The balance of power shifted from Athens to Sparta, ending the Golden Age of Pericles that had marked Athenian dominance in the ancient world.

Ancient historian Thucydides also contracted the disease, but he survived to write about the plague. His writings are the primary source on this outbreak.

The cause of the plague has long been disputed, with modern academics and medical scientists considering epidemic typhus the most likely cause. However, a 2006 study detected DNA sequences similar to those of the bacterium responsible for typhoid fever.

Other scientists have disputed the findings, citing serious methodologic flaws in the dental pulp-derived DNA study.

The disease is most commonly transmitted through poor hygiene habits and public sanitation conditions; during the period in question, the whole population of Attica was besieged within the Long Walls and lived in tents.

In the late 19th century, typhoid fever mortality rate in Chicago averaged 65 per 100,000 people a year. The worst year was 1891, when the typhoid death rate was 174 per 100,000 people.

The most notorious carrier of typhoid fever—but by no means the most destructive—was Mary Mallon, also known as Typhoid Mary. In 1907, she became the first American carrier to be identified and traced. She was a cook in New York. She is closely associated with fifty-three cases and three deaths. Public health authorities told Mary to give up working as a cook or have her gall bladder removed. Mary quit her job but returned later under a false name. She was detained and quarantined after another typhoid outbreak. She died of pneumonia after 26 years in quarantine.

In 1897, Almroth Edward Wright developed an effective vaccine. In 1909, Frederick F. Russell, a U.S. Army physician, developed an American typhoid vaccine and two years later his vaccination program became the first in which an entire army was immunized. It eliminated typhoid as a significant cause of morbidity and mortality in the U.S. military.

Most developed countries saw declining rates of typhoid fever throughout the first half of the 20th century due to vaccinations and advances in public sanitation and hygiene.

Antibiotics were introduced in clinical practice in 1942, greatly reducing mortality. Today, incidence of typhoid fever in developed countries is around 5 cases per 1,000,000 people per year.

An outbreak in the Democratic Republic of Congo in 2004–05 recorded more than 42,000 cases and 214 deaths.

Typhoid fever was also known as ''suette milliaire'' in nineteenth-century France.

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