TYPHOID FEVER IN SOUTH AFRICA

Salmonella typhi and Salmonella paratyphi are both aerobic gram negative rods³⁾⁾ . The rod shape is shown in Figure 1 and Figure 2.

These bacteria are both aerobic and need oxygen in order to survive and metabolize⁴⁾⁾ . Aerobic organisms use oxygen as the terminal electron acceptor at the end of the electron transport chain in order to maximize its metabolic energy production required for cell function.

Bacteria are grouped as either a gram negative or a gram positive based on their cell envelope structure. Both bacteria are gram negative. The outer membrane of gram negative bacteria has proteins and sugars integrated within it, sometimes extending outward. The outer membrane contains channels and proteins for transport of molecules and ions. It also contains lipopolysaccharides (LPS) which extend outward. These lipopolysaccharides serve as protection for the bacterium, but they can become toxic in some cases. The LPS consists of a lipid that anchors the entire structure to the membrane, a core polysaccharide, and an O-polysaccharide. The O-polysaccharide is specific and changes between bacterium based on the cell's needs. Lipoproteins anchor the outer membrane to the next layer, the peptidoglycan. The peptidoglycan is located in between periplasm of the cell envelope. The peptidoglycan consists of a polymer of linked amino acids and sugars that is mainly involved in maintenance of structure and protection of the cell⁵⁾ . Interior to the periplasm surrounding the peptidoglycan is the inner membrane of the cell envelope which contains various proteins as well.

Salmonella typhi is motile due to flagella that twist and whip in order to propel the bacterium⁶⁾ . This can be particularly troublesome for humans as bacteria that can move have a higher travel rate within the body, increasing chances for infection.

There are two types of antigens for Salmonella typhi- antigen O and antigen H⁷⁾ . Antigen O, or somatic antigen, is present on the bacterium's surface in the form of the O-polysaccharide mentioned above (part of the LPS)⁸⁾ . Antigen H is present and created on the flagella⁹⁾ . The presence of these antigens in the body produce an immune response in the form of the production of antibodies¹⁰⁾ . The body's response and production of these antibodies is what allows for lab tests to result in a typhoid fever diagnosis¹¹⁾ .

There are three serotypes of Salmonella paratyphi - A, B, and C¹²⁾ . Each are varying degrees of occurrence with serotype A being most common, and serotype C being rare¹³⁾ . Each serotype results in paratyphoid fever, but with varying symptoms¹⁴⁾ .

The numerous different serotypes for both Salmonella typhi and Salmonella paratyphi is what makes treatment somewhat difficult. Once the bacterium and serotype is known, a provider can more accurately perscribe an antibiotic that will better suite the infection for treatment¹⁵⁾ .

In the 1980's South Africa had an annual 17 cases for every 100,000 people within the population diagnosed with typhoid fever¹⁶⁾ . Annual cases has dropped since then. However, there was an outbreak in 2005 in which there was 0.4 cases per 100,000 in the population¹⁷⁾ , seen in Figure 4. Presently, there are only 0.1 cases for every 100,000 in the population of South Africa¹⁸⁾ . The incidence of paratyphoid fever has always been low¹⁹⁾ , seen in Figure 4. In 1993 there was a large typhoid fever outbreak within South Africa²⁰⁾ . Similarly, in 2005 there was an outbreak in which there was 600 diagnosed cases of typhoid fever²¹⁾ . Strains from both 1993 and 2015 were compared via pulsed-field electrophoresis and multi-locus tandem repeats, revealing that the two strains were related and shared commonality²²⁾ . This supports the movement to provide access and ensure safe running water and food preparations for the future, or the lack of these could lead to more outbreaks.

Figure 3: The incidence of typhoid fever distribution within the world²³⁾ .

Figure 4: Graph of the isolates of Salmonella typhi and the serotypes (A, B, and C) of Salmonella paratyphi ²⁴⁾ .

https://www.youtube.com/watch?v=ON6A9kueUjQ

Typhoid fever can be contracted by ingesting the bacteria Salmonella typhi (Figure 1) or Salmonella paratyphi (Figure 2) that lives in contaminated food. Humans are the preferred organism for these bacteria, being that they cannot thrive in other organisms like they do humans²⁵⁾ . The contaminated food could be due to lack of washing hands after using the restroom or people directly contaminating water.

Once entering the digestive tract of the body, the bacteria makes it way from the mouth through the esophagus to the stomach. The bacteria then enters the small intestine, where it is absorbed into the bloodstream and multiplies in the liver, bone marrow, and the spleen via white blood cell transportation . These bacteria can sense epithelial cells, which line the lumen of the intestines and other organs within the body²⁶⁾ . This sensing and preference for epithelial cells allows for an effective multiplication. Salmonella typhi has a type III secretion system in which it can inject its own protein into a host cell, changing to operation of the host cell to take in the bacteria²⁷⁾ . This uptake from the host cell allows for the bacteria to use the host cell's mechanics to multiply itself. Following multiplication, the bacteria re-enters the bloodstream and attacks the biliary system (bile ducts and gallbladder, specifically) and the bowel's lymphatic tissues²⁸⁾ . The bacteria then rapidly multiply and re-enter into the GI tract²⁹⁾ . The re-entrance into the GI tract allows for the bacteria to be tested for diagnosis.

Figure 5: Perforation of the intestine due to typhoid fever³⁰⁾ .

Many times typhoid fever can go untreated as it has symptoms similar to a common cold. Symptoms include: fever, headache, stomach pain, diarrhea, and cough³¹⁾ . Salmonella typhi and Salmonella paratyphi have similar symptoms, but Salmonella paratyphi is milder³²⁾ . Infection of Salmonella paratyphi results in more mild symptoms, however a leb (fecal, urine, or blood) test is needed in order to come to a definite diagnosis³³⁾ .

Is is important to note that typhoid fever, or more specifically Salmonella typhi, has an incubation period of 10-14 days³⁴⁾ . An incubation period is the period of time between the initial infection of the bacteria and the first sign of symptoms. Therefore, someone could be infected and have typhoid fever but may not know and could be infecting other people. Even if symptoms are not apparent, precautions of food and water safety should be taken to ensure health.

Figure 6: Development of a typhoid rash (rose spots)³⁵⁾ .

Typhoid fever is treated with antibiotics, however this can become troublesome with the increasing prevalence of antibiotic resistant bacteria³⁶⁾ . Many times the bacteria is tested in order to determine if the bacteria is antibiotic resistant . When taking antibiotics, the patient should take them for the entire time so that the infection doesn't stick around, seeming as if it is no longer present³⁷⁾ . If the antibiotics are not working, sometimes the gallbladder is removed in attempt to remove the original point of rapid multiplication of the bacteria³⁸⁾ . Treatment is becoming increasingly difficult with an increased resistance to antibiotics, specifically ciprofloxacin and azithromycin³⁹⁾ .

Treatment requires a lab test for correct diagnoses. The widal test is the diagnostic test in which typhoid fever is endemic⁴⁰⁾ , such as South Africa. The test allows for fast results, however it can sometimes lead to false positives⁴¹⁾ . The widal test consists of multiple tubes that are prepared with the bacteria: the H and O antigen of Salmonella typhi and the H antigen of Salmonella paratyphi respectively⁴²⁾ . Patients that have typhoid fever will have antibodies within their system. The mixture of the antibodies from the patient and the antigens result in the aggregation of the antigens, which is visible in both the tubes as well as test cards in which they are deposited after incubation in the tubes⁴³⁾ .

As is the case with other diseases, typhoid fever is not 100% preventable. However, there are some actions to take in order to be proactive about safety. Travelers should become aware of the areas in which typhoid fever is prevalent, such as: East Asia, Southeast Asia, Africa, the Caribbean, Central America, and South America⁴⁴⁾ . There are two different routes of precautions to take before traveling- a vaccination or an oral medication. The vaccination is an intramuscular injection. It should be given at least within two weeks of traveling in order to ensure its effectiveness⁴⁵⁾ . It is only a one time injection needed, but it is effective for two years, when a booster is needed⁴⁶⁾ . The oral medication should be completed at least one week prior to traveling to ensure its effectiveness⁴⁷⁾ . It is taken once a day, every other day, for a week but it is effective for five years when another dose is needed⁴⁸⁾ . The vaccination and medication are only for typhoid fever, they are not for prevention of paratyphoid fever in which there is no vaccination or medication⁴⁹⁾ . Antibiotics are used for treatment and not prevention. In addition to either vaccination or medication, travelers should avoid certain things, such as: food that is room temperature, new foods you aren't familiar with, or fresh foods that aren't prepped yourself⁵⁰⁾ . Bottled water is also suggested over tap water when traveling.

The steps that should be taken for prevention for typhoid fever however sometimes cannot be taken based on the location within South Africa. According to the RDP (Reconstruction and Development Program) 17% of South Africa are still without clean running water⁵¹⁾ . Therefore, travelers are still encouraged to use bottled water for their various needs.