ENTERIC FEVER
1. Etiology
2. Pathogenesis
3. Key Clinical Features
4. Diagnostic Investigations
5. Treatment
6. Understanding Of Individual Risk Factors, Appropriately Counsel Patients About Preventing
Further Transmitted Through The Oral Route, Including Vaccination Strategies.
Etiology
Like other members of the Enterobacteriaceae family,
Salmonellae are Gram-Negative, Facultative Anaerobic Bacillae.
Salmonella comprises 2 main species, Salmonella enterica and Salmonella bongori (prev S
enterica subspecies V). S enterica, in turn, comprises 6 subspecies of which S.enterica subsp enterica has
the most serovars (or serotypes) and is the most important to human infection.This includes S Typhi
and S Paratyphi,
Unlike many other Salmonella species, S Typhi and S Paratyphi are exclusively human pathogens.
Other species within the genus Salmonella are collectively known as nontyphoidal salmonella (NTS),
many of which are pathogenic to humans or other animals. NTS infections are mainly limited to
gastroenteritis in humans, although invasive nontyphoidal serovars (iNTS) exist.
Previously classified by phage typing ,
With the advent of genetic techniques, enteric fever classification is increasingly based on genotypes for
research, surveillance, and clinical purposes, to identify and track outbreaks and antimicrobial resistance
and monitor for emerging antimicrobial resistance mechanisms. When combined with emerging clinical
antimicrobial susceptibility patterns, this provides additional guidance for empiric therapy.
Epidemiology
Transmission is primarily through the fecal-oral route, via consumption of food or water contaminated
with the feces of a convalescent or chronic asymptomatic carrier. S Typhi and S Paratyphi can exist in the
environment for a prolonged period in a nonculturable, nonreplicative state. This creates a persistent
environmental reservoir that can lead to infection and outbreaks, such as via contaminated crops.
Individual host factors
On average, the incidence of enteric fever peaks between the ages of 5 and 9. However, this masks
great variability in the age of onset in different locations, with a younger peak age incidence correlating
to a higher prevalence of enteric fever. In very high prevalence areas, peak incidence may occur in
infants due to increased exposures and the greater accumulated immunity acquired with repeat clinical,
subclinical, or asymptomatic infections as people age. Reinfections demonstrate that only a moderate
level of protection is conferred by clinical infection.
Typhoid fever is more severe in debilitated and immunocompromised patients or with altered
phagocyte function (eg, patients with malaria and sickle cell anemia).
, Salmonellae are most commonly acid-sensitive bacteria and are destroyed in the stomach by gastric acid
unless a large dose is ingested. Achlorhydria and intake of antacids and antihistamines increase
susceptibility to infection with smaller doses.
Normal flora of the gut is protective against the infection. The use of broad-spectrum antibiotics that
destroy the normal flora allows increased invasion.
Malnutrition decreases normal gut flora and also increases the susceptibility to infection.
( Human genetics likely plays a role in susceptibility to typhoid, with a marker mapping to the HLA class II
region strongly associated with enteric fever resistance)
PATHOGENESIS
Ingestion and Invasion
Following ingestion, food and beverages act as buffers against gastric acid, facilitating bacteria reaching
the small bowel. S Typhi and S Paratyphi then rapidly cross the gut epithelium. Invasion likely occurs via
several routes as with other Salmonellae: transcellular or by direct invasion of enterocytes and the M
cells that overlie Peyer patches. In contrast to noninvasive salmonella, invasion causes a minimal
inflammatory response. In S Typhi, this is mediated by a protein that downregulates flagellin (also
known as flagellar H antigen), which is associated with inflammation and upregulates Vi production.
Initial Dissemination
Intracellular dissemination occurs during the asymptomatic incubation period of enteric fever and is of
primary importance in its pathogenesis. Two-thirds of the S Typhi or S Paratyphi load during an infection
is estimated to be intracellular. Intracellular dissemination occurs via CD18 cells of the
reticuloendothelial system, including macrophages, dendritic cells, polymorphonuclear monocytes, and
phagocytes. Invasive Salmonellae can live intracellularly by forming a modified phagosome that does not
allow normal fusion with the cell's phagocyte oxidase complex. In S Typhi infection, the Vi antigen
capsule is thought to play a role. The intracellular nature of the bacteria safeguards against extracellular
antibiotics, limiting the available options for treatment.
A transient primary bacteremia, detectable by the presence of bacterial deoxyribonucleic acid, occurs
within the first 24 hours of ingestion, possibly coinciding with this bacterial dissemination. A systemic
cytokine response occurs, whether or not systemic illness ensues. The eosinophil count begins to drop 5
days before symptoms develop.
Clinical Illness
Increasing fever begins with the persistent secondary bacteremia of established infection. The
gallbladder is colonized through hematogenous or local spread, more commonly if gallstones or
structural abnormalities are present
Lymphoid tissue within Peyer patches is a site of primary infection, reinfection, and chronic infection,
becoming a secondary source for fecal excretion and transmission. The proliferation of lymphoid tissue
may cause constipation. Endotoxin-mediated necrosis may occur, resulting in intestinal bleeding,
perforation, or tertiary bacteremia with enteric microorganisms.
The total white count, lymphocytes, platelets, and neutrophils begin to drop with the onset of
symptoms. Immunoglobulin (Ig) IgG, IgM, and IgA antibodies develop against flagellin and
lipopolysaccharide in those who develop clinical disease , but not against Vi.
1. Etiology
2. Pathogenesis
3. Key Clinical Features
4. Diagnostic Investigations
5. Treatment
6. Understanding Of Individual Risk Factors, Appropriately Counsel Patients About Preventing
Further Transmitted Through The Oral Route, Including Vaccination Strategies.
Etiology
Like other members of the Enterobacteriaceae family,
Salmonellae are Gram-Negative, Facultative Anaerobic Bacillae.
Salmonella comprises 2 main species, Salmonella enterica and Salmonella bongori (prev S
enterica subspecies V). S enterica, in turn, comprises 6 subspecies of which S.enterica subsp enterica has
the most serovars (or serotypes) and is the most important to human infection.This includes S Typhi
and S Paratyphi,
Unlike many other Salmonella species, S Typhi and S Paratyphi are exclusively human pathogens.
Other species within the genus Salmonella are collectively known as nontyphoidal salmonella (NTS),
many of which are pathogenic to humans or other animals. NTS infections are mainly limited to
gastroenteritis in humans, although invasive nontyphoidal serovars (iNTS) exist.
Previously classified by phage typing ,
With the advent of genetic techniques, enteric fever classification is increasingly based on genotypes for
research, surveillance, and clinical purposes, to identify and track outbreaks and antimicrobial resistance
and monitor for emerging antimicrobial resistance mechanisms. When combined with emerging clinical
antimicrobial susceptibility patterns, this provides additional guidance for empiric therapy.
Epidemiology
Transmission is primarily through the fecal-oral route, via consumption of food or water contaminated
with the feces of a convalescent or chronic asymptomatic carrier. S Typhi and S Paratyphi can exist in the
environment for a prolonged period in a nonculturable, nonreplicative state. This creates a persistent
environmental reservoir that can lead to infection and outbreaks, such as via contaminated crops.
Individual host factors
On average, the incidence of enteric fever peaks between the ages of 5 and 9. However, this masks
great variability in the age of onset in different locations, with a younger peak age incidence correlating
to a higher prevalence of enteric fever. In very high prevalence areas, peak incidence may occur in
infants due to increased exposures and the greater accumulated immunity acquired with repeat clinical,
subclinical, or asymptomatic infections as people age. Reinfections demonstrate that only a moderate
level of protection is conferred by clinical infection.
Typhoid fever is more severe in debilitated and immunocompromised patients or with altered
phagocyte function (eg, patients with malaria and sickle cell anemia).
, Salmonellae are most commonly acid-sensitive bacteria and are destroyed in the stomach by gastric acid
unless a large dose is ingested. Achlorhydria and intake of antacids and antihistamines increase
susceptibility to infection with smaller doses.
Normal flora of the gut is protective against the infection. The use of broad-spectrum antibiotics that
destroy the normal flora allows increased invasion.
Malnutrition decreases normal gut flora and also increases the susceptibility to infection.
( Human genetics likely plays a role in susceptibility to typhoid, with a marker mapping to the HLA class II
region strongly associated with enteric fever resistance)
PATHOGENESIS
Ingestion and Invasion
Following ingestion, food and beverages act as buffers against gastric acid, facilitating bacteria reaching
the small bowel. S Typhi and S Paratyphi then rapidly cross the gut epithelium. Invasion likely occurs via
several routes as with other Salmonellae: transcellular or by direct invasion of enterocytes and the M
cells that overlie Peyer patches. In contrast to noninvasive salmonella, invasion causes a minimal
inflammatory response. In S Typhi, this is mediated by a protein that downregulates flagellin (also
known as flagellar H antigen), which is associated with inflammation and upregulates Vi production.
Initial Dissemination
Intracellular dissemination occurs during the asymptomatic incubation period of enteric fever and is of
primary importance in its pathogenesis. Two-thirds of the S Typhi or S Paratyphi load during an infection
is estimated to be intracellular. Intracellular dissemination occurs via CD18 cells of the
reticuloendothelial system, including macrophages, dendritic cells, polymorphonuclear monocytes, and
phagocytes. Invasive Salmonellae can live intracellularly by forming a modified phagosome that does not
allow normal fusion with the cell's phagocyte oxidase complex. In S Typhi infection, the Vi antigen
capsule is thought to play a role. The intracellular nature of the bacteria safeguards against extracellular
antibiotics, limiting the available options for treatment.
A transient primary bacteremia, detectable by the presence of bacterial deoxyribonucleic acid, occurs
within the first 24 hours of ingestion, possibly coinciding with this bacterial dissemination. A systemic
cytokine response occurs, whether or not systemic illness ensues. The eosinophil count begins to drop 5
days before symptoms develop.
Clinical Illness
Increasing fever begins with the persistent secondary bacteremia of established infection. The
gallbladder is colonized through hematogenous or local spread, more commonly if gallstones or
structural abnormalities are present
Lymphoid tissue within Peyer patches is a site of primary infection, reinfection, and chronic infection,
becoming a secondary source for fecal excretion and transmission. The proliferation of lymphoid tissue
may cause constipation. Endotoxin-mediated necrosis may occur, resulting in intestinal bleeding,
perforation, or tertiary bacteremia with enteric microorganisms.
The total white count, lymphocytes, platelets, and neutrophils begin to drop with the onset of
symptoms. Immunoglobulin (Ig) IgG, IgM, and IgA antibodies develop against flagellin and
lipopolysaccharide in those who develop clinical disease , but not against Vi.
