5,000 2,500

Topic Description




Salmonellae are Gram negative, short plump shaped rods, non-lactose fermenting and non-sporulating bacteria, belonging to the family Enterobacteriacea, that has more than 2501 serotypes characterized on the basis of their somatic (0) and flagella (H) antigens (Beers et al.,2004; Todar, 2005).  With the exception of Salmonella pullorum and Salmonella gallinarum, all Salmonellae are actively motile.  They are also non-capsulated with the exception of Salmonella typhi (Cheesbrough, 2002, Perilla, 2003).  The genus was named after Daniel Elmer Salmon, an American veterinary pathologist (FDA/CFSAN, 2009).

Salmonella can be divided into two major groups of clinical importance, group one includes members of the genus that are involved as aetiologic agent of typhoid fever (typhoidal Salmonellosis) S. typhi and S. paratyphi.  Group two includes members of the genus that are involved as aetiologic agents of food poisoning (non-typhoidal Salmonellosis). Salmonella typhimurium and more recently serotype DT 104, other members are Salmonella agona, Salmonella newport, Salmonella heidelberg, Salmonella enteritidis, Salmonella hada, and Salmonella dublin (Arora, 2001).  Typhoid fever caused by Salmonella enteric serotypes typhi commonly presents as a prolonged febrile illness with a paucity of physical signs. The spectrum of the disease varies from mild self-limiting febrile illness to severe disease associated with gastrointestinal bleeding, intestinal perforation, or mental confusion with shock.  It is a major cause of morbidity and mortality worldwide, causing an estimated 16 million new infections and 600,000 deaths each year (Buttler et al., 1991; Bhanu et al., 2011).

The incidence of typhoid fever has declined greatly with the provision of clean water and good sewage systems in Europe and USA since the early 20th century, but the disease remains a serious public health problem in developing countries (Bhanu et al., 2011).  In India, typhoid fever is highly endemic, with the southern provinces most heavily affected.  In a study conducted in Dong thap province in 1995 and 1996, the incidence of confirmed serotype typhi infection was 198 per 100,000 populations for all ages (Bhanu et al., 2011).  The incidence of typhoid fever was high (>100 cases per 100,000 populations per year), in South Central Asia, Southeast Asia, and possibly Southern Africa, Medium (10-100 cases per 100,000) in the rest of Asia, Africa, Latin America, and Oceania (Abdurrahman et al., 1979).

Isolation of serotype S. typhi from blood, urine or stool is the most reliable means of confirming an infection.  However, this requires laboratory equipments and technical training that are beyond the means of most primary health care facilities in developing world (Rubin et al., 1990).  Different techniques are used in diagnosis of typhoid fever, including blood culture, stool culture, rectal swab culture, urine culture, widal test, Elisa and immunofluoresence but widal test blood and stool cultures remains the only universally practiced diagnostic procedures because other methods are either invasive, have failed to prove their utility or are more expensive (Abdul et al., 1999; Beer et al., 2004).

In Nigeria, most of the typhoid cases are diagnosed on the basis of clinical symptoms and a single widal test performed in hospitals and private laboratories. Hence, the reliability of diagnosis based on widal test alone is often questionable (Onuigbo, 1998) widal test is abused in Nigeria and could be responsible for over diagnosis of typhoid fever thereby causing an epidemic scare.  Symptoms of malaria can mimic those of typhoid; again malaria can interfere in the diagnosis of typhoid fever, especially if a single widal test is used. (Annimashaun et al., 1990; Ohanu et al., 2003). Both typoid and malaria share social circumstances which are imperative to their transmission.  Therefore, a person living in a poor hygienic and unsanitized environment is at risk of contracting both these diseases either concurrently or an acute infection superimposed on a chronic one (Uneke, 2008).

Although the isolation of S. typhi on blood culture remains the gold standard for diagnosing typhoid fever, this may be problematic in endemic areas where adequate microbiological facilities are limited.  The widespread availability and use of antibiotics in the community makes it frequently difficult to isolate the organism on blood cultures and alternative methods such as bone marrow cultures may be required.  However, the latter are invasive and difficult to obtain routinely in pediatric patients (Choo et al., 1993; Zulfiqar and Naseem, 1999).  Stool isolation of S. typhi alone is insufficient for diagnosis and only marginally improves diagnosis by blood culture.  However, it is confirmatory for carrier detection (Gasem et al., 1995).  Most serotype typhi infections are diagnosed purely on clinical grounds and treated presumptively.  As a result, the diagnosis may be delayed or missed while other febrile illnesses are considered, and patients without typhoid fever may receive unnecessary and inappropriate antimicrobial therapy.  Emerging drug resistance among circulating serotype strains has complicated the treatment of typhoid fever and heightened the need for rapid accurate diagnosis and appropriate selective use of antimicrobial agents to which the organism has thus far remained susceptible (Rubin et al., 1990; Beers et al., 2004; Bhanu, et al., 2011).

Malaria on the other hand is caused by obligate intracellular parasites (Plasmodium) which lives in host erythrocytes and remodel these cells to provide optimally for their own needs.  It is a major public health problem in tropical and sub-tropical regions of the world, with 300 to 500 million cases and 2 to 3 million deaths per year (Uneke, 2008; Prasanna, 2011).  Young children, pregnant women, people who are immunosuppressed and the elderly are particularly at risk of severe diseases. Malaria, particularly Plasmodium falciparium, in non-immuned pregnant women increases the risk of maternal death, miscarriage, still birth and neonatal death (Richard and Kamini, 2002).  Conventional light microscopy of stained film and rapid diagnostic tests (RDTs) for malaria which use immunochromatographic methods to detect plasmodium specific antigens are commonly used in the diagnosis of malaria parasite (WHO, 2000; Prasanna, 2011).

  • Statement of Problem

In most developing countries, there have been repeated cases of over diagnosis of typhoid fever due to the use of a single widal test which has led to inappropriate and unnecessary administration of antimicrobial therapy to patients without typhoid fever. Also, the inappropriate use of antibiotics by these individuals can lead to antibiotic resistance. In Nigeria, there is paucity of reports on simultaneous screening of patients for malaria and enteric fever with bacteriological proof.

  • Aim

This study is aimed at comparing different almonella and malaria diagnostic methods and salmonella co-infection with malaria in Nsukka area.

  • Objectives

The specific objectives of the study are:

  1. To compare the effectiveness of different diagnostic techniques of Salmonellosis and malaria infection.
  2. To establish relationship between slide and tube agglutination in the diagnosis of typhoid fever.
  • To correlate the presence of significant titre with the rate of isolation of the organism.
  1. To establish the prevalence of malaria in salmonella seropositive individual.
  2. To determine the antimicrobial susceptibility profile of the Salmonella
    • Significance of the Study

It is hoped that this work will help reduce over diagnosis of typhoid fever and also reduce unnecessary and inappropriate administration of antimicrobial therapy



  • Literature Review
    • History of Salmonella

The story of the term salmonella starts with the discovery of the bacterium Salmonella enterica (Var. Choleraesuis) by medical research scientist Theobaldsmith.  At the time, Theobald was working as a research laboratory assistant in the veterinary division of the United States Department of Agriculture.  The department was under the administration of Daniel Elmer Salmon, a Veterinary pathologist, and that is for whom the salmonella was named. During the search for the cause of hog cholera, it was proposed that the causal agent be named salmonella.  While it happened eventually that salmonella did not cause the hog cholera,the actual pathogen was found out to be a virus. Eventually, Salmonella was alluded to as a source of infection in typhoid fever patients following the confirmation of typhoid transmission via the faecal-oral route by English physician, William Budd in 1873. William Budd described the contagious nature of the disease and incriminated faecally contaminated water sources in transmission. (Amyes et al., 2002; Koletzko and Osterrider, 2009).  At the beginning of the 19th century, typhoid was defined on the basis of clinical signs and symptoms and pathological (anatomical) changes.  However, at this time, all sorts of enteric fevers were characterized as “typhoid”.  In 1880s, the typhoid bacillus was first observed by Eberth in Spleen sections and mensenteric lymph nodes from a patient who died from typhoid.  Robert Koch confirmed a related finding by Gaffky and succeeded in cultivating the bacterium in 1881.  But due to the lack of differential characters, separation of the typhoid bacillus from other enteric fever was uncertain.  In 1896, it was demonstrated that the serum from an animal immunized with the typhoid bacillus agglutinated (Clumped) the typhoid bacterial cells, and it was shown that the serum of patient afflicted with typhoid likewise agglutinated the typhoid bacillus.  Sero diagnosis of typhoid was thus made possible by 1896 (Koletzko and Osterrider 2009).



  • Physiology and Structural Features of Salmonella

Around the cytoplasmic membrane lies a thin layer of peptidoglycans.  This so called murine layer consists of a long chains of repetitive disaccharide links.  Oligopeptide bridges connect the sugar chains. External to this second layer is a third layer, the outer membrane.  It consists of a phospholipids double layer in which complex lipopolysaccharides (LPS) are anchored.  These fatty sugars have the following components, seen from the inside out: a fatty part (Lipid A) anchored in the membrane, a core and an external sugar part consisting of repeating oligosaccharide chains.  Lipid A is very toxic (cendotoxin) and causes a broad spectrum of effects such as fever and shock during gram – negative septicaemia.  The vast majority of human isolates (>99.5%) are subspecies S. enterica.  These organisms are rod shaped and measures 2 – 3 µm long and 0.4 – 0.6 µm in diameter.  As with other Gram-negative bacilli, the cell envelope of salmonella contains a complex lipopotysaccharide structure that is liberated on lysis of cell and to some extent, during culture (Bledsoe et al., 2010).

  • Antigenic Features of Salmonella

There are numerous (over 2500) serovars, which are found in a disparate variety of environments and which are associated with many different diseases.  Salmonella isolates are commonly classified according to serology (Kauffman – white classification).  The main division is first by the somatic O antigen, then by flagellar H antigen and the capsular Vi antigen (Crump and Mintz, 2010).   


  1. O (Somatic) antigens

These somatic antigens represent the side chains of repeating sugar units projecting from the outer lipopolysaccharide layer of the bacteria cell wall. They are hydrophilic and enable the bacteria to form stable, homogenous suspensions in saline solution.  More than 60 different O-antigens have been identified (Crump and Mintz, 2010).

  1. H (Flagellar) antigens

These antigens represent the determinant groups in the flagellar protein. They are heat labile as well as alcohol labile and are well preserved in 0.04-0.2% formaldehyde.  Heating at 600C or above causes detachment of the flagella from the bacteria and is well achieved by heating at 1000C for 30 min.  The detached flagella remain immunogenic, but not the bacterium suspensions of such bacilli, which are freed from detached flagella by centrigugation and washing or by heating at 1000C for 2 – 5 h. The resultant bacilli can be used for the production of O – antisera (Crump and Mintz, 2010).

  • Vi-antigen

Almost all strains of S. typhi produce, the vi-antigen as a covering layer outside their cell wall.  It is an acid polysaccharide and when fully developed, it renders the bacteria agglutinable by Vi-antibody (Crump and Mintz, 2010).

  • Genome Structure of Salmonella

The genome for S. typhi has been completely sequenced. There are about 204 pseudogenes encoded in S. typhi.  The majority of these genes have been inactivated by a stop codon which shows the genes were recently modified due to evolutionary changes of the 204 genes; 27 are remnants of insert sequences and genes of bacteriophage origin.  Seventy five (75) are involved in housekeeping functions and 46 of the gene mutations have to do with host interaction.  There are two commonly used strains of S. typhi, CT18 and TY2.  Salmonella typhi CT18 has a large circular chromosome consisting of 4.8 Mb and two plasmids, PHCM1 and PHCM2, one of which has multiple drug resistance (PHCM1).  Salmonella typhi TY2 has one large chromosome that is 4.7 Mb and unlike CT18, it does not have plasmids and can be affected by antibiotics (Parkhill, 2001).

  • Cell Structure and Metabolism

Salmonella typhi has a complex regulatory system, which mediates its response to the changes in its external environment.  Sigma factors, which are global regulators that alter the specificity of RNA polymerase, are examples of such regulation.  Some sigma factors direct transcription to produce stress proteins, which increases the chances of the bacteria surviving environmental changes.  RNA polymerase 3 is produced in response to starvation and changes in pH and temperature.  It also regulates the expression of up to 50 other proteins and is also involved in the regulation of virulence plasmids  (Ojcius, 2007).  In order to survive in the intestinal organs of its hosts where there are low levels of oxygen, S. typhi has to be able to learn to use other sources other than oxygen as an electron acceptor.  Therefore, S. typhi has adapted to growth under both aerobic and anaerobic conditions.  Salmonella’s most common source of electron acceptor is nitrogen, examples of other election acceptors are nitrate, nitrite, fumerate, and dimethylsulphoxide.  Global and specific regulatory systems of anaerobic gene expression, like the ones mentioned above are implemented to make sure that the most energetically favourable metabolic process is used.  Evidence show that availability of oxygen is an environmental signal that controls Salmonella virulence (Contreras et al., 1997).

  • Mode of Transmission of Salmonella

Typhoid and paratyphoid are transmitted through contaminated water or food.  They can also be transmitted by the faecal oral route.  Water, ice, raw vegetables, salads and shellfish are important sources for travelers.  The disease commonly occurs in association with poor standards of hygiene in food preparation and handling (Su and Chiu, 2007).  The typhoid bacilli infect only humans, there is no animal reservoir, unlike the majority of the other Salmonella species.  Paratyphoid bacilli infect humans and rarely domestic animals.  It is communicable as long as typhoid or paratyphoid bacilli are present in excreta.  Everyone is susceptible to infection and some patients become permanent carriers. Immunity following clinical disease or immunization is insufficient to protect against a large infectious dose of organisms.  Incubation period differs for typhoid and paratyphoid fever.  Typhoid fever usually lasts for 8-14 days but this depends on the infective dose and can vary from three days to one month. For paratyphoid fever, it is usually one to ten days (Shrivastava et al., 2011).

  • Pathogenesis of Salmonella

Most salmonella enter the body when contaminated food is ingested. Person-to-person spread of salmonella also occurs.  To be fully pathogenic, salmonella must possess a variety of attributes called virulence factors.  These include (1) the ability to invade cells (2) a complete lipopolysaccharide coat, (3) the ability to replicate intracellularly, and (4) possibly the elaboration of toxin(s).  After ingestion the organisms colonizes the ileum and colon, invade the intestinal epithelium, and proliferate within the epithelium and lymphoid follicles.  The mechanism by which Salmonella invade the epithelium is partially understood and involves an initial binding to specific receptors on the epithelial cell surface followed by invasion.  Invasion occurs by the organism inducing the enterocyte membrane to undergo “ruffling” and thereby to stimulate pinocytosis of the organisms.  Invasion is dependent on rearrangement of the cell cytoskeleton and probably involves increases in cellular inositol phosphate and calcium.  Attachment and invasion are under distinct genetic control and involve multiple genes in both chromosomes and plasmid (Hohmann et al., 1978).

  • Invasion of Intestinal Mucosa by Salmonella

After invading the epithelium the organisms multiply intracellulary and then spread to mesenteric lymphnodes and throughout the body via the systemic circulation. They are then taken up by the reticuloendothelial cells. The retculoendothelial system confines and controls spread of the organism.  However, depending on the serotype and the effectiveness of the host defenses against the serotype, some organisms may infect the liver, spleen, gallbladder, bones, meninges, and other organs.  Fortunately, most serovars are killed promptly in extraintestinal sites, and the most common human Salmonella infection, gastroenteritis, remains confined to the intestine. Much is now known about the mechanisms of Salmonella gastroenteritis and diarrhea.  Only strains that penetrate the intestinal mucosa are associated with the appearance of an acute inflammatory reaction and diarrhea, the diarrhea is due to secretion of fluid and electrolytes by the small and large intestines.  Invasion of the intestinal mucosa is followed by activation of mucosal adenylate cyclase, the resultant increase in cyclic Adenosine monophosphate induces secretion.  The mechanism by which adenylate cyclase is stimulated is not understood, it may involve local production of prostaglandins or other components of the inflammatory reaction.  In addition, Salmonella strains elaborate one or more enterotoxin–like substances which may stimulate intestinal secretion (Fabrega and Vila, 2013).

  • Intestinal Epithelium Responses to Salmonella

The first specific interactions during natural infection between pathogenic salmonella and a host occur at the epithelial surface of organized patches of lymphoid tissue or follicles that are scattered throughout the small intestine.  This lymphoid tissue, also called payer’s patches, has a specialized epithelium and an underlying dome that contains mature lymphocytes as well as developing lymphocytes.  The primary function of this tissue is believed to be immune surveillance of the gut.  Invasive salmonella strains specifically target these peyer’s patches for the initial penetration of the host small intestine.  Early infection studies with mice demonstrated that virulent S. typhi administered by an oral route, associated almost exclusively with peyer’s patch tissue of the terminal ileum as quickly as 3 h post inoculation. M cells are specialized residents of the epithelium of lymphoid follicles and are interspersed within the epithelial layer of an intestinal lymphoid follicle at a ratio of approximately 1 per 10-20 enterocyte.  M cells have several distinctive characteristics that allow them to be identified easily.  These cells possess microvilli that are visibly shorter than those of enterocytes.  They also lack a rigid cytoskeleton that allows migratory lymphocytes to deform and distort their cytoplasm.  In addition, they have elevated pinocytic activity that facilitates the uptake of intestinal microorganisms and particles.  This suggests that a primary function of these cells is to transport and process luminal antigens to prime local intestinal immunity in the peyer’s patches (Jantsch et al., 2011). M cells also share similarities with epithelial cells in that they form tight junctions with adjacent enterocytes and align along the basal lamina surface (Fabrega and Vila, 2013).

  • Phagocytic Cell Responses and Interactions

Following passage through the intestinal epithelium of the peyer’s patch, invading organism quickly enter the lymphatic system where interactions with professional killing cells determine the ultimate fate of the infection.  These cells possess both oxygen dependent and independent killing mechanisms to kill internalized bacteria (Falknow et al., 1992).  The production of toxic oxygen molecules such as superoxide, hydrogen peroxide, and hydroxyl radicals that are pumped into the phagolysosome are the primary oxygen dependent killing molecules of macrophages.  The oxygen independent killing mechanisms of the macrophages include acidification of the phagolysosome as well as secretion of small bactericidal peptides into the compartment. Because the oxygen dependent killing mechanisms of macrophages appear to have little effect on pathogenic salmonella, the host is more dependent on oxygen independent killing mechanisms. However, experimental evidence suggests that salmonella has evolved mechanisms to circumvent or delay the killing activity of these mechanisms (Garcia-del et al., 1993).

  • Primary Host Defense against Salmonella

Host defense mechanism is very important for resistance to Salmonella. Multiple bacterial and host factors determine the outcome of Salmonella infections.  Normal gastric acidity (pH < 3.5) and intestinal motility is very important to reduce the infection of the bacteria.  The normal intestinal micro flora protects against salmonella, probably through anaerobes, which liberate short-chain fatty acids that are thought to be toxic to Salmonellae.  Alteration of the anaerobic intestinal flora by antibiotics renders the host more susceptible to Salmonellosis (Woods et al., 2008).  Secretary or mucosal antibodies also protect the intestine against Salmonellae. Animal strains genetically resistant to intestinal invasion by Salmonellae have been described (Guan and Holley, 2003).  In patients living with AIDS, Salmonella infection is common, frequently persistent and bacteremic and often resistant to even prolonged antibiotic treatment. Relapses are common.  The role of host defenses in salmonellosis is extremely important, and much remains to be learned.  Multiantibiotic resistant strains of Salmonella typhi offer a compelling argument for the development of next generation typhoid vaccination (Woods et al., 2008).   

  • Symptoms of Typhoid Fever

The symptoms of typhoid fever usually develop one or two weeks after a person becomes infected with Salmonella. Symptoms of typhoid and paratyphoid fever are similar although paratyphoid tends to be less severe than typhoid (Su and Chiu, 2007).  Primary symptoms include loss of appetite, fever (39 or 400C), headache, joint pain, sore throat, constipation (or less commonly, diarrhea), abdominal pain and tenderness.  As the illness progresses, fever remains high and the person may become delirious.  Sustained fever is often accompanied by a slow heartbeat and extreme exhaustion.  During the second week and last 2 to 5 days: 10% of infected people get clusters of small pink spots on the chest and abdomen.  Intestinal bleeding or perforation occurs in 3 to 5% of infected people. Pneumonia may develop, infection of the gallbladder and liver may also develop.  At the final stage, a blood infection (bacteremia) occasionally leads to infection of bones (osteomyelitis), heart valves (endocarditis), kidneys (Glomerulitis), the genitourinary tract and tissues covering the brain and spinal cord (Menigitis).  Infection of muscles may lead to abscesses (Bronze and Greenfield, 2005).

  • Epidemiology of Salmonella

Infection with salmonella enterica occur worldwide, however, certain diseases are more prevalent in different regions. Non-typhoidal salmonellosis is more common in industrialized countries whereas enteric fever is mostly found in developing countries (with most cases in Asia) (Chimalizeni et al., 2010).  There are about 1.3 million cases of non-typhoidal salmonellosis worldwide each year and World Health Organization (WHO) estimates that there are 17 million cases and over 500,000 deaths each year caused by typhoid fever.  The WHO identifies typhoid as a serious public health problem.  Its incidence is highest in children between 5 and 19 years old (Buttler et al., 1991).  In the developing world, salmonellosis contributes to childhood diarrhea morbidity and mortality. Epidemics of salmonellosis have been reported in institutions such as hospitals and nursing homes.  The incidence is linked to conditions of hygiene and to the risk of oral-fecal contamination (Bronze and Greenfield, 2005).

A recent epidemiologic study showed that south-east and south-central Asia are the regions of highest endemicity with rates greater than 100/100,000 cases per year. The rest of Asia, Africa, Latin America, the Caribbean and Oceania (except Australia and New Zealand) are the next highest with incidence rates of 10 – 100/100,000 per year. Europe, North America and the rest of the developed world have low rates of the disease. Typhoid represents the 4th most common cause of death in Pakistan (WHO, 2006). A number of studies in Nigeria has shown that Salmonella infections, especially the enteric fever (typhoid and paratyphoid), is endemic in many parts of the country (Abdurrahman and Joss, 1979; Ogunbiyi and Onabowale, 1997; Katung, 2000).

  • Prevention and Treatment for Typhoid Fever

The most cost effective strategy for reducing the incidence of typhoid fever is the institution of public health measures to ensure safe drinking water and sanitary disposal of excreta.  The effects of these measures are long-term and reduce the incidence of other enteric fever infections. In the absence of such strategy, mass immunization with typhoid vaccines at regular intervals also considerably reduces the incidence of infections. Careful food preparation and washing of hands are therefore crucial to preventing typhoid (Levine et al., 2007).  Healthcare workers caring for patients with typhoid fever should pay strict attention to adequate hand washing and safe disposal of feaces and urine.  Antibiotic therapy is essential and should begin empirically if the clinical evidence is strong.  Patients must receive adequate fluids, electrolytes, and nutrition.  Antimicrobials shorten the course of infection, reduce the rate of complications if began early and drastically reduce the case fatality rate (Whitaker et al.,2009).

Chloramphenical was introduced in 1948 and was once the mainstay of treatment.  By the 1970s, widespread resistance to the drug developed.  Ampicillin and cotrimoxazole became treatments of choice.  However, in the late 1980s, some S. typhi strains developed simultaneous plasmid-mediated resistance to all 3 drugs.  Fluoroquinolones and third generation – cephalosporins have filled the breach (Nagshetty et al., 2010).

  • Causes of Antimicrobial Resistance of Salmonellae

Microbes, such as bacteria, viruses, fungi and parasites, are living organisms that evolve over time.  There primary function is to reproduce, thrive and spread quickly and efficiently.  Therefore, microbes adapt to their environment and change in ways that ensure their survival.  If something stops their ability to spread, such as an antimicrobial, genetic changes can occur that enable the microbe to survive.  There are several ways this happen, e.g. mutation and gene transfer which are natural causes, selective pressure, society pressure, and inadequate diagnosis, inappropriate use of antibiotics by individuals, hospitals and in agriculture (Shrikals, 2004).

  • Problems Associated with Antibiotic Resistance of Salmonella typhi

A drug-resistant Salmonella typhimurium – subtype, associated with severe human illness, has emerged in the United States, known as S. typhimurium definitive type 104 (DT104), characterized by multiple antimicrobial resistance, has been present in the United Kingdom since 1984.  Studies in the United Kingdom showed that S. typhimurium is present in animals.  Some variant typhi have developed multidrug resistance as an integral part of the genetic materials of the organism.  The global increase in resistance to antimicrobial drugs, including the emergence of bacterial strains that are resistant to all available antibacterial agents, has created a public health problem of potential crisis proportion (Doughari et al., 2007).  Any time bacteria are exposed to an antibiotic, they are under selective pressure that allows only the resistant forms to survive and reproduce.  So the basic rule in slowing the evolution of resistance is reducing the unnecessary use of antibiotics.  There is increase in the occurrence of strains resistant to Ciprofloxacin. Reports of typhoidal salmonellae with increasing minimum inhibitory concentration (MIC) and resistance to newer quinolones raise the fear of potential treatment failures and necessitate the need for new alternative antimicrobials. For therapeutic purposes, intermediate susceptibility should be regarded as full resistance (Doughari et al., 2007). The emergence of broad spectrum β – lactamases in typhoidal salmonella constitutes a new challenge (Harish et al., 2011).

  • Prognosis of Typhoid Fever

The prognosis for recovery is good for most patients.  In the era before effective antibiotics were discovered, about 12% of all typhoid fever patients died of the infection.  Now, however, less than 1% of patients who received prompt antibiotic treatment will die.  The mortality rate is highest in the very young and very old, and in patients suffering from malnutrition.  The most ominous signs are changes in a patients state of consciousness, including stupor or coma (CDC, 2012).

  • Vaccination against Typhoid Fever

Three types of typhoid vaccines are currently available for use in United States:

  1. An oral live attenuated vaccine
  2. A parenteral heat – phenol – inactivated vaccine
  • A newly licensed capsular polysaccharide vaccine for parenteral use.
  1. Live Oral Vaccines: Although oral killed vaccines are without efficacy, vaccines using living avirulent bacteria have shown promise. The live oral typhoid vaccine should be given in four doses, 2 days apart, as needed for protection. It should not be given to children younger than 6 years of age. For those travelling from a less endemic to an endemic area, last dose of oral vaccine should be given at least one week before travel to allow the vaccine time to work.  A booster dose is needed every 2 years for people who remain at risk (Threlfall et al., 2006).
  2. The Parenteral Heat – Phenol – Inactivated Vaccine: It has been widely used for many years. In field trials involving a primary series of two doses of heat phenol – inactivated typhoid vaccine, efficacy over the 2 to 3 years follow up periods range from 51% to 77%.  Efficacy for the acetone inactivated parenteral vaccine, available only to the armed forces, ranges from 75% to 94%.  Since the inactivated vaccines contain the O antigen (endotoxin) local and general reactions occur.  The inactivated typhoid vaccines should not be given to children younger than 2 years of age.  One dose provides protection.  It should be given at least 2 weeks before travel to allow the vaccine time to work.  A booster dose is needed every 2 years for people who remain at risk.
  • The Parenteral Vaccine Vi capsular Polysacharide (ViCPS): It is composed of purified Vi (Virulence) antigen.  The capsular polysaccharide elaborated by typhi isolated from blood cultures, in recent studies, one 25-µg injection of purified ViCPS produced seroconversion (i.e. at least a fourfold rise in antibody titres) in 93% of healthy U.S. adults.  Two field trials in disease endemic areas have demonstrated the efficacy of ViCPS in preventing typhoid fever.  In one trial in Nepal, in which vaccine recipients were observed for 20 months, one dose of ViCPS among persons 4 – 5 years of age resulted in 74% reduction in fever cases of typhoid fever.  ViCPS has not been tested among children less than 1 year of age (Kenneth Todar, 2005).


  • Diagnosis of Typhoid Fever

Diagnosis is made by blood, bone marrow or stool cultures and with the widal test (demonstration of Salmonella antibodies against antigens O – Somatic and H – flagella).  The diagnosis however is confirmed by culture.  Cultures are the most accurate method of diagnosis.  The onset of symptoms of typhoid fever is associated with entrance of a bacterium. Blood cultures usually become positive in the first week of illness in 80% of patients who have not taken antibiotics. From the first week onwards, the frequency with which S. typhi can be isolated from the blood falls. Salmonellae can usually be isolated from the urine in about 25% of patients after the second week of infection. The bacteria may also be isolated from stool cultures but several specimens may need to be cultured before isolation because the bacteria are not excreted continuously. The diagnosis of typhoid is also possible by polymerase chain reaction using blood as sole source of S. typhi template DNA (Kumer et al., 2002).  The DNA hybridization method uses DNA probe specific to the Vi – polysaccharide antigen of S. typhi to detect the organism in the blood of patient with typhoid fever.  Patient with typhoid fever usually have less than 15 Salmonella typhi cells per ml of blood and probe cannot detect fewer than 500 bacteria thus, diagnosis may be missed in low infection (Wain and Hosoglu, 2008).

  • Clinical Specimens for the Isolation of Salmonellae

Knowledge of the natural history and pathophysiology of the infectious disease process is important in determining the optimal time for specimen collection.  From the 1st week of infection, the frequency with which S. typhi can be isolated from the blood falls.  By the end of the 3rd week it can be found in about half the cases, after the 4th week its isolation is infrequent.  Salmonella typhi is most easily isolated from faeces between 3rd and 5th week of the illness.  During the 1st week only 50% of faeces cultures will yield organisms on culture.  The number of organisms in faeces increases greatly from 1st to 3rd week of illness.  The bacteria do not disappear from the intestine so quickly or as completely as from blood.  Many patients excrete typhoid bacilli at a time when positive blood cultures can no longer be obtained.  During the 1st week in urine samples, about 20% of cases show the presence of antibodies, the curve then rises sharply, crossing the blood culture curve just before the end of the 2nd week, and still rising and attains a value of 90% or over by the 4th week. It remains at a high level for some weeks (Nsutebu et al., 2003).  Various clinical specimens are:

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