Salmonella enterica typhi
By David V. Pollack
Copyright Dennis Kunkel Microscopy, Inc.
Introduction
Worldwide, typhoid fever affects roughly 17 million people annually, causing nearly 600,000 deaths. The causative agent, Salmonella enterica typhi (referred to as Salmonella typhi from now on), is an obligate parasite that has no known natural reservoir outside of humans. Little is known about the historical emergence of human S. typhi infections, however it is thought to have caused the deaths of many famous figures such as British author and poet Rudyard Kipling, the inventor of the airplane, Wilbur Wright, and the Greek Empire’s Alexander the Great. The earliest recorded epidemic occurred in Jamestown, VA where it is thought that 6,000 people died of typhoid fever in the early 17th Century. This disease is rare in the United States and developed nations, but always poses the risk of emergence.
History
Originally isolated in 1880 by Karl J. Erberth, S. typhi is a multi-organ pathogen that inhabits the lympathic tissues of the small intestine, liver, spleen, and bloodstream of infected humans. It is not known to infect animals and is most common in developing countries with poor sanitary systems and lack of antibiotics, putting travelers to Asia, Latin America, and Africa in a high risk group. Of the 266 people infected in the United States in 2002, approximately 70% had traveled internationally within 6 weeks of the onset of disease.
Microbiological Characteristics
This gram-negative enteric bacillus belongs to the family Enterobacteriaceae. It is a motile, facultative anaerobe that is susceptible to various antibiotics. Currently, 107 strains of this organism have been isolated, many containing varying metabolic characteristics, levels of virulence, and multi-drug resistance genes that complicate treatment in areas that resistance is prevalent. Diagnostic identification can be attained by growth on MacConkey and EMB agars, and the bacteria is strictly non-lactose fermenting. It also produces no gas when grown in TSI media, which is used to differentiate it from other Enterobacteriaceae.
Image at right: Copyright Dennis Kunkel Microscopy, Inc.
Typhoid/ Enteric Fever
Infection of S. typhi leads to the development of typhoid, or enteric fever. This disease is characterized by the sudden onset of a sustained and systemic fever, severe headache, nausea, and loss of appetite. Other symptoms include constipation or diarrhea, enlargement of the spleen, possible development of meningitis, and/or general malaise. Untreated typhoid fever cases result in mortality rates ranging from 12-30% while treated cases allow for 99% survival.
Virulence Factors
S. typhi has a combination of characteristics that make it an effective pathogen. This species contains an endotoxin typical of Gram negative organisms, as well as the Vi antigen which is thought to increase virulence. It also produces and excretes a protein known as “invasin” that allows non-phagocytic cells to take up the bacterium, where it is able to live intracellularly. It is also able to inhibit the oxidative burst of leukocytes, making innate immune response ineffective.
Epidemiology
The encounter of humans to S. typhi is made via fecal-oral route from infected individuals to healthy ones. Poor hygiene of patients shedding the organism can lead to secondary infection, as well as consumption of shellfish from polluted bodies of water. The most common source of infection, however, is drinking water tainted by urine and feces of infected individuals. The estimated inoculum size necessary for infection is 100,000 bacteria. Typhoid fever also represents the second most commonly reported laboratory infection.
The entry of this bacterial species into the human body is most commonly achieved by ingestion, with the importance of aerosol transmission unknown. Once ingested, the organisms multiply in the small intestine over the period of 1-3 weeks, breech the intestinal wall, and spread to other organ systems and tissues. The innate host defenses do little to prevent infection due to the inhibition of oxidative lysis and the ability to grow intracellularly after uptake.
Transmission of S. typhi has only been shown to occur by fecal-oral route, often from asymptomatic individuals. 2-5% of previously infected individuals become chronic carriers who show no signs of disease, but actively shed viable organisms capable of infecting others. A famous example is “Typhoid” Mary Mallon, who was a food handler responsible for infecting at least 78 people, killing 5. These highly infectious carriers pose a great risk to public health due to their lack of disease-related symptoms.
The damage caused by typhoid fever is reversible and limited if treatment is started early in the infection. This leads to a mortality rate of less than 1% among treated individuals who have an antibiotic-susceptible strain of S. typhi, making the outcome and prognosis for patients a positive one.
Prevention
The key to avoiding infection by S. typhi is prevention of fecal contamination in drinking water and food supplies. Since the only source of this agent is infected humans, it is possible to control transmission by proper hygiene, waste management, water purification, and treatment of the sick. These measures are attained in developed societies, attributing to the low incidence. The United States has an average of around 400 infections annually, almost exclusively among people who have recently traveled to developing countries.
Prevention can also be aided by vaccination to the bacteria, however the effectiveness of this has been questionable. In addition, it is shown that large inoculum sizes can overwhelm the developed immunity and result in disease.
Typhoid fever has played a significant role in history. This pathogen thrives in developing societies or areas where disasters have compromised sanitation. Although the incidence in the United States is very low, outbreaks and substantial epidemics still remain possible due to worldwide travel and unknowing carriers of the disease. The development of antibiotic treatments and several vaccines have presented the possibility of worldwide eradication. Until this is achieved, however, S. typhi and its characteristic typhoid fever will remain a threat for future epidemics.
References Cited
Dennis Kunkel Microscopy, Inc.
Health Canada: MSDS of Infectious Substances
World Health Organization: Typhoid Fever Fact Sheet
Centers for Disease Control and Prevention: Typhoid Fever Disease Information
Wikipedia.org: Typhoid Fever
U. of Maryland Medical news: Typhoid Fever
Special thanks to Dr. Dennis Kunkel for use of S. typhi images.