Typhus Infantile Remittant Fever Biology Essay

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Typhoid fever, also known simply as typhoid MedlinePlus Encyclopedia is a common worldwide bacterial disease, transmitted by the ingestion of food or water contaminated with the feaces of an infected person, which contain the bacterium Salmonella typhi, serotype Typhi (Giannella RA (1996). The disease has received various names, such as gastric fever, abdominal

typhus, infantile remittant fever, slow fever, nervous fever or pythogenic fever. The name "typhoid" means "resembling typhus" and comes from the neuropsychiatric symptoms common to typhoid and typhus (Oxford English Dictionary, 2011). Despite this similarity of their names, typhoid fever and typhus are distinct diseases and are caused by different species of bacteria (Cunha, 2004). The impact of this disease fell sharply in the developed world with the application of 20th century sanitation techniques.

Classically, the course of untreated typhoid fever is divided into four individual stages, each lasting approximately one week. In the first week, the temperature rises slowly and fever fluctuations are seen 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 a decrease in the number of circulating white blood cells (leukopenia) with eosinopenia and relative lymphocytosis, a positive reaction and blood cultures are positive for Salmonella typhi or paratyphi. The 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 40 °C (104 °F) and bradycardia(sphygmothermic dissociation or Faget sign), 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 (Weinberg, 2008).

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, comparable to pea soup, with a characteristic smell. However, constipation is also frequent. The spleen and liver are enlarged (hepatosplenomegaly) and tender, and there is elevation of liver transaminases. The Widal test is strongly positive with antiO and antiH antibodies. Blood cultures are sometimes still positive at this stage. (The major symptom of this fever is that thefever 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.


Neuropsychiatric symptoms (described as "muttering delirium" or "coma vigil"), with picking at bedclothes or imaginary objects.

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 starts subsiding (defervescence). This carries on into the fourth and final week (Ryan and Ray, 2004).

The bacterium which causes typhoid fever may be spread through poor hygiene habits and public sanitation conditions, and sometimes also by flying insects feeding on feces. Public education campaigns encouraging people to wash their hands after defecating and before handling food are an important component in controlling spread of the disease. According to statistics from the United States Centers for Disease Control and Prevention (CDC), the chlorination of drinking water has led to dramatic decreases in the transmission of typhoid fever in the U.S.A. A person may become an asymptomatic carrier of typhoid fever, suffering no symptoms, but capable of infecting others.

According to the CDC approximately 5% of people who contract typhoid continue to carry the disease after they recover. The most famous asymptomatic carrier was Mary Mallon (commonly known as "Typhoid Mary"), a young cook who was responsible for infecting at least 53 people with typhoid, three of whom died from the disease (New York Times, 1938). Mallon was the first apparently perfectly healthy person known to be responsible for a Typhoid "epidemic". In the early 20th century, many carriers of typhoid were locked into an isolation ward never to be released to prevent further typhoid cases. These people often deteriorated mentally, driven mad by the conditions they lived in (BBC on Long Grove Hospital Surrey GB).

Typhoid fever remains a devastating disease in developing countries and is prevalent in areas with inadequate sanitation and poor hygiene (Singh and Mcfeters, 1992). The causative agent Salmonella enterica serovar typhi is pathogenic both to man and animals with associable inflammatory reaction in the intestinal tract. Like other enteric pathogens, S. enterica serovar Typhi is transmitted through food or water that has been contaminated with faeces from acutely infected person's persistent excretors (that is constant stooling or diarrhoea) or from chronic asymptomatic carriers (Rajiv et al. 2007). It is a serious systemic disease, spread via fecal-oral route. As per the survey conducted by WHO, there are annual global burden of typhoid of 22 million new cases, 5% of which are fatal (Ivanoff, 2003; Crump et al. 2004). Salmonella enterica subsp. enterica serovar Typhi is primarily but not exclusively the etiological agent of a systemic infection in humans known as enteric (typhoid) fever (Selander et al. 1990; Kidgell et al. 2002).

Salmonella enterica serovar Typhi continues to cause severe disease in many parts of the world, its most feared complication being perforation of ulcerated Peyer's patches within the small intestine, leading to peritonitis with associated mortality. The disease is characterized by prolonged fever, bacterial replication in the reticulo-endothelial system (RES) and significant inflammation of the lymphoid organs of the small intestine (Everest et al. 2001). In developing countries, typhoid fever causes at least 5% of all deaths, with markedly different rates where typhoid fever is endemic. The reasons for these differences in disease severity are not known but may be related to differences in health care facilities, host immune responses, genetic factors, and perhaps in the strains of Salmonella enterica serovar Typhi circulating in areas of endemicity (Zhu et al. 1996; Everest et al. 2001).

S. typhi has a combination of characteristics that make it an effective pathogen. The disease is initiated when Salmonella typhi enters gastrointestinal epithelial cells for submucosal translocation. The organism uses Cystic fibrosis transmembrane conductance regulator (CFTR) for entry into regulator proteins (Pier et al. 1998). This species contains an endotoxin typical of Gram negative organisms, as well as the Vi antigen which is thought to increase virulence. The Vi antigen of Salmonella typhi, is a capsular polysaccharide which is controlled by two widely separated loci, viaA and viaB. Salmonella typhi 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. Virulence genes of Gram negative and Gram-positive bacteria are very often organized in clusters known as "Pathogenicity Islands", located either on the bacterial chromosome or on large virulence-associated plasmids (Groisman and Ochman, 1996; Hacker et al. 1997). A DNA region of about 40 kb located at the centisome 63 of the Salmonella chromosome is required for the entry of the pathogen into host cells (Galan, 1994; Groisman, 1997; Mills et al. 1995) and is also involved in macrophage cytotoxicity (Chen et al. 1996). This region is designated as "Salmonella pathogenicity island 1" (SPI-1), and it bears the genetic information for a large number of proteins belonging to a type III secretion system (Mills et al. 1995). A second 40-kb pathogenicity island, designated SPI-2, has been also described in S.tyhimurium (Ochman et al. 1996; Hensel et al. 1997). Both SPI's are reported to be important for different stages of the infectious life cycle of Salmonella. Virulence genes encode products that assist the organisms in expressing its virulence in the host cells. Some genes are known to be involved in adhesion and invasion viz., sef, pef, spv or inv; others are associated with the survival in the host system- mgtC or in the actual manifestation of pathogenic processes viz., sop, stn, pip A, B, D (Murugkar et al. 2003).

Some of the antibiotics used for typhoid fever treatment are chloramphenicol, ampicillin and other B-lactams, sulphademidine, gentamicin and other aminoglycosides, nalidixic acid, ciprofloxacin and the fluoroquinolones (norfloxacin and ofloxacin) (Girgis et al. 1999; Kadhiravan et al. 2005). In the early 1990's, multidrug resistant (MDR) strain of S. enterica serovar typhi, that were resistant to the first three line drugs (chloramphenicol, amoxicillin and cotrimoxazole), then in use emerged and become endemic in developing countries. The spread of MDR to the conventionally used antibiotics for treatment of typhoid fever has caused therapeutic and public health problem in the African continent, South East Asia and Middle East since 1987 (Samuel et al. 2000; Well, 2003).

Until the mid-1970s chloramphenicol was the drug of choice for typhoid fever, and resulted in a marked reduction in mortality from 10% to <2% in developed countries. Unfortunately, a few sporadic isolations of chloramphenicol-resistant Salmonella enterica serotype Typhi were reported from Chile and Kuwait before 1970, and multi-drug resistant S.enterica Typhi emerged in the Indian subcontinent in 1987 (Rowe and Ward, 1997). After introduction of ciprofloxacin, it is used extensively for the treatment of typhoid both in the devel- oping and developed countries. Thus, recent emergence of S. enterica Typhi isolates with decreased susceptibility to ciprofloxacin has been gaining worldwide attention (Herikstad et al. 1997; Threlfall et al. 1999).

Enteric fever due to infection with multidrug resistant (MDR) Salmonella enterica serovar Typhi is a cause of great concern. The emergence and reemergence of MDR S. enterica serovar Typhi isolates was reported in the studies of Mandal et al. (2002). The emergence of MDR S. enterica serovar Typhi is due to indiscriminate use of antibiotics in the streatment of enteric fever. Under such selective pressure of antibiotics, the antibiotic-sensitive bacteria may acquire resistance traits from antibiotic-resistant strains belonging to the same or different genera, and thus become resistant to one or more antibiotics. The R-plasmid has clinical importance in the acquisition and spread of antibiotic resistance among bacteria. In Salmonella enterica serovar Typhi, R-plasmid-encoded resistance to ampicillin (A), chloramphenicol (C), cotrimoxazole (Co), and tetracycline (T) has been reported to be transferable (Jevanand et al. 1997). Plasmid-mediated transferable drug resistance has also been reported among E. coli isolates (Bauernfeind et al. 1987). Therefore, the surveillance of R-factor among bacterial isolates is essential to trace the source of infection. Further, identification and characterization of virulence factors will provide new insights into the evolution of bacterial pathogens which could lead to the development of novel therapeutic strategies.

Hence the present study entitled "Molecular characterization of multidrug resistant Salmonella species isolated from typhoid patients" was conducted with the following objectives:


To identify Salmonella species isolated from typhoid patients.

To access various risk factors associated with typhoid infection.

To determine the anitibiotic suceptibility pattern of the isolates.

To evaluate the multidrug resistant properties of the isoaltes at molecular level.