CHAPTER ONE
INTRODUCTION
1.BACKGROUND OF STUDY
Typhoid fever, also known as enteric fever, is a potentially fatal multisystemic illness caused primarily by Salmonella enterica, subspecies enterica serovar typhi and, to a lesser extent, related serovars paratyphi A, B, and C.
The protean manifestations of typhoid fever make this disease a true diagnostic challenge. The classic presentation includes fever, malaise, diffuse abdominal pain, and constipation. Untreated, typhoid fever is a grueling illness that may progress to delirium, obtundation, intestinal hemorrhage, bowel perforation, and death within 1 month of onset. Survivors may be left with long-term or permanent neuropsychiatric complications.
S typhi has been a major human pathogen for thousands of years, thriving in conditions of poor sanitation, crowding, and social chaos. It may have responsible for the Great Plague of Athens at the end of the Pelopennesian War. [1] The name S typhi is derived from the ancient Greek typhos, an ethereal smoke or cloud that was believed to cause disease and madness. In the advanced stages of typhoid fever, the patient’s level of consciousness is truly clouded. Although antibiotics have markedly reduced the frequency of typhoid fever in the developed world, it remains endemic in developing countries. [2]
S paratyphi causes the same syndrome but appears to be a relative newcomer. It may be taking over the typhi niche, in part, because of immunological naivete among the population and incomplete coverage by vaccines that target typhi.
Note that some writers refer to the typhoid and paratyphoid fever as distinct syndromes caused by the typhi versus paratyphi serovars, while others use the term typhoid fever for a disease caused by either one. We use the latter terminology. We refer to these serovars collectively as typhoidalsalmonel
1.1 RISK FACTORS
Typhoidal salmonella have no nonhuman vectors. An inoculum as small as 100,000 organisms of typhi causes infection in more than 50% of healthy volunteers. [9]Paratyphi requires a much higher inoculum to infect, and it is less endemic in rural areas. Hence, the patterns of transmission are slightly different
The following are modes of transmission of typhoidal salmonella:
§ Oral transmission via food or beverages handled by an often asymptomatic individual—a carrier—who chronically sheds the bacteria through stool or, less commonly, urine
§ Hand-to-mouth transmission after using a contaminated toilet and neglecting hand hygiene
§ Oral transmission via sewage-contaminated water or shellfish (especially in the developing world). [10, 11, 12]
Paratyphi is more commonly transmitted in food from street vendors. It is believed that some such foods provide a friendly environment for the microbe.
Paratyphi is more common among newcomers to urban areas, probably because they tend to be immunologically naïve to it. Also, travellers get little or no protection against paratyphi from the current typhoid vaccines, all of which target typhi. [13, 14]
Typhoidal salmonella are able to survive a stomach pH as low as 1.5. Antacids, histamine-2 receptor antagonists (H2 blockers), proton pump inhibitors, gastrectomy, and achlorhydria decrease stomach acidity and facilitate S typhiinfection. [4]
HIV/AIDS is clearly associated with an increased risk of nontyphoidal Salmonellainfection; however, the data and opinions in the literature as to whether this is true for S typhi or paratyphi infection are conflicting. If an association exists, it is probably minor.
Other risk factors for typhoid fever include various genetic polymorphisms. These risk factors often also predispose to other intracellular pathogens. For instance, PARK2 and PACGR code for a protein aggregate that is essential for breaking down the bacterial signaling molecules that dampen the macrophage response. Polymorphisms in their shared regulatory region are found disproportionately in persons infected with Mycobacterium leprae and S typhi.
On the other hand, protective host mutations also exist. The fimbriae of S typhi bind in vitro to cystic fibrosis transmembrane conductance receptor (CFTR), which is expressed on the gut membrane. Two to 5% of white persons are heterozygous for the CFTR mutation F508del, which is associated with a decreased susceptibility to typhoid fever, as well as to cholera and tuberculosis. The homozygous F508del mutation in CFTR is associated with cystic fibrosis. Thus, typhoid fever may contribute to evolutionary pressure that maintains a steady occurrence of cystic fibrosis, just as malaria maintains sickle cell disease in Africa. [19, 20]
As the middle class in south Asia grows, some hospitals there are seeing a large number of typhoid fever cases among relatively well-off university students who live in group households with poor hygiene. [21] American clinicians should keep this in mind, as members of this cohort often come to the United States for advanced degrees. The diseases mainly affect those living in poorer regions of the world where sanitation and clean water are lacking. The World Health Organization (2000) estimates that typhoid fever affects 17 million people a year, causing approximately 600,000 deaths. Typhoid fever has a typical case fatality rate of 10%, but this can be reduced to as little as 1% with appropriate antimicrobial therapy. Paratyphoid fever is a similar illness but tends to be milder, with a lower case fatality rate.