Salmonella typhi (typhoid fever)
Definitions & Key takeaways
Salmonella is a rod-shaped, gram-negative bacteria of the Enterobacteriaceae family. This family includes Salmonella typhi (S. typhi), a strain of Salmonella that causes typhoid fever, which is a serious and sometimes life-threatening infection. This bacteria is primarily spread by ingestion of contaminated food or/and water, or through contact with an infected person.
Symptoms of typhoid fever include fever, abdominal pain, constipation followed by diarrhea, and rose or salmon-colored spots on the chest and abdomen. If left untreated, typhoid fever can lead to serious complications such as sepsis, intestine perforation, and organ failure. Prevention is by practicing good food safety, proper body hygiene, and getting the vaccination.
Salmonella is a bacterium belonging to the family Enterobacteriaceae. There are two main species: Salmonella bongori and Salmonella enterica, which itself has six subspecies.
One of the subspecies is enterica, which has over 2500 serotypes that can be divided into two main groups based on the clinical symptoms they cause typhoidal or non-typhoidal Salmonella.
The typhoidal group, which includes serotype Salmonella typhi (S. typhi), specifically infects humans and causes enteric fever, which is more commonly called typhoid fever.
If left untreated, it can be fatal and throughout history, has been the cause of death of aviator and engineer Wilbur Wright, one of the Wright brothers; Dr.
Hashimoto, the first to describe Hashimoto's thyroiditis; and several people in New York City infected by “Typhoid Mary” in the first documented asymptomatic carrier of the disease in the United States.
OK, but generally, Salmonella are encapsulated gram-negative, rod bacteria – meaning, they have a polysaccharide layer outside the cell envelope and look like little red or pink sticks on a gram stain.
They’re facultative intracellular pathogens, meaning they can live both outside or inside of its host’s cells. And have flagella, making them motile, but don’t form spores.
They’re also facultative anaerobes, so they can undergo respiratory and fermentative metabolism; and they can ferment glucose but not lactose; are oxidase negative; and produce hydrogen sulfide gas.
And while a variety of media can be used to selectively identify Salmonella, among them is Triple Sugar Iron agar which produces a black precipitate when hydrogen sulfide is produced.
Now, once Salmonella is ingested and reaches the distal ileum of the small intestine, it targets the epithelial layer of the mucosal lining.
Here, it uses surface appendages to adhere to microfold cells, or M-cells. And these M-cells eat, or phagocytose, the bacteria from the intestinal lumen and spit it out into the underlying Peyer’s patches - a type of mucosal immune tissue that extends into the submucosa.
And, well, S. typhi has a Vi capsular polysaccharide antigen virulence factor, which helps protect the bacteria from being tagged with antibodies that signal leukocytes like neutrophils to come in and phagocytose the bacteria.
Moreover, neutrophil recruitment is also suppressed. On the other hand, the recruitment of monocytes and macrophages is induced, making them the primary cells that respond to the infection.
And as they are recruited to the infection site, they cause hypertrophy and necrosis of the surrounding tissues; which can damage the epithelial lining, and potentially lead to ileal perforation, consequently, a secondary infection of the peritoneum.
Now, aside from that, macrophages also phagocytose S. typhi, so the bacteria is slowly engulfed by the cell membrane, which invaginates to form a sac on its inner side.
The sac then separates from the actual cell membrane forming what’s referred to a Salmonella-containing vacuoles. Normally, the vacuole would fuse with the host cell’s lysosomes, which are organelles filled with digestive enzymes that destroy the bacteria.
But, S. typhi uses needle-like protein appendage, called a Type III secretion system, to inject a variety of effector proteins across the vacuole membrane and into the host cell’s cytoplasm.
This leads to a remodeling of the vacuole that prevents fusion with the lysosome, so S. typhi survives and replicates within the vacuole.All the while, S.
typhi is using the host macrophage to hitch a ride to the nearby lymphatic vessels that drain into local mesenteric lymph nodes.
Once there, the macrophage can continue to flow through the thoracic duct and into systemic lymphatic circulation where they can enter reticuloendothelial tissues in the liver, spleen, bone marrow, gall bladder and additional lymph nodes.
At about this point, S. typhi can induce macrophage apoptosis, or cell death, so the bacteria is released into the bloodstream, called bacteremia.
Bacteremia can progress to sepsis, an acutely life-threatening condition characterized by systemic vasodilation and hypoperfusion of vital organs - which means the organs aren’t getting enough nutrient and oxygen-rich blood.
This includes people who have undergone a splenectomy, or spleen removal, or those with sickle cell disease, who have functional asplenia.
In these individuals, S. typhi can cause osteomyelitis, which is an acute infection of the bones.
On the other hand, some people can become chronically infected with S. typhi, and that means they are carriers for the bacteria for decades or a lifetime, even after symptoms have resolved.
In these cases, S. typhi typically remains in the gallbladder, and is periodically swept along with bile through the bile duct to the intestines, where it can be excreted in feces.
Now, S. typhi is uniquely adapted and restricted to only infect humans, who are also the only known reservoir; and its route of transmission is fecal to oral - even if the feces come from a currently asymptomatic host.
So, transmission is usually linked to any contact between contaminated hands or objects and the mouth, and also to poor sanitation and poor hygiene that leads to consuming contaminated water or food, especially if prepared with unwashed hands.
It also seems to be particularly endemic to Asia, Africa, Latin America, and the Caribbean. Finally, S.
typhi is sensitive to gastric acids, so half of the time, it takes a large inoculum, of around 100,000 microorganisms, to cause an infectionNow, symptoms of typhoid fever first appear about 1-2 weeks after initial infection, and can take 4-6 weeks to resolve.
Typically, there’s a high, sustained fever, abdominal pain, constipation followed by diarrhea, and rose or salmon-colored spots on the chest and abdomen.
Hepatomegaly and splenomegaly may also occur as the infection spreads. Dehydration, weakness, headaches, and an overall cloudy or confused mental state can occur, especially in advanced cases.
typhi, particularly in the first week of infection. For asymptomatic carriers, bile cultures are the most effective diagnostic tool because the bacteria can be absent from stool.
Treatment involves managing symptoms, particularly fluid and electrolyte replenishment for diarrhea and non-steroidal anti-inflammatory drugs for pain and fever.
Commonly, broad-spectrum antibiotics are used, like fluoroquinolones or cephalosporins, like ceftriaxone. Even though antibiotics can prolong the excretion of bacteria in feces.
For carriers, a combination of antibiotic therapy with fluoroquinolones and surgical removal of the gallbladder is the most effective form of treatment.
Finally, an important part of treatment is practicing good hygiene and sanitation to limit the spread to uninfected individuals.
Prophylaxis is available in the form of an inactivated intramuscular vaccine containing the Vi capsular polysaccharide, or a live oral vaccine.##Summary So, to recap: Salmonella is a rod-shaped, gram-negative bacteria of the Enterobacteriaceae family.
After ingestion, Salmonella tends to infect M-cells of the small intestine epithelial mucosa, which transfer the bacteria to the underlying Peyer’s patches.
Serotypes that are typhoidal evade and dampen the immune response, and use host macrophages to systematically spread through the lymphatic system and bloodstream.
Symptoms include a high fever with constipation followed by diarrhea, salmon-colored spots on the abdomen, and abdominal pain.
A carrier state exists in which the bacterium colonizes the gallbladders of people with the disease so they continue to excrete bacteria in their feces.
Treatment can include ceftriaxone or a fluoroquinolone, but antibiotics can prolong fecal excretion of the pathogen. Vaccines exist, with an oral, live attenuated vaccine, and an intramuscular vaccine containing Vi capsular polysaccharide.
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