Transcript enteric fever

DR NCHIMBA
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Salmonella is a Gram-negative facultative rodshaped bacterium belonging to family
Enterobacteriaceae,
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Salmonellae live in the intestinal tracts of warm and
cold blooded animals. Some species are ubiquitous.
Other species are specifically adapted to a particular
host. Over 2400 serotypes.
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In humans, Salmonella are the cause of two
diseases:
 enteric fever, resulting from bacterial invasion of the
bloodstream, and
 acute gastroenteritis, resulting from a foodborne
infection/intoxication.
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ENTERIC FEVER – includes both typhoid and
paratyphoid fevers. Both are caused by
Salmonellae that are markedly more invasive
and pathogenic than those that cause food
poisoning
CAUSAL ORGANISMS – of typhoid fever is
Salmonella enterica serotype typhi. S
paratyphi A B and C cause paratyphoid fever.
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1800 – Typhoid bacillus first observed in spleen
sections and mesenteric lymph-nodes from a patient
who had died from typhoid
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1881 - Robert Koch cultured the bacterium in lab (but
differentiation from other enteric bacteria was
uncertain)
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1896 – sero-diagnosis made possible. Basis for Widal’s
test demonstrated
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Early 1900s – enter ‘TYPHOID MARY’ a food handler
responsible for infecting at least 78 people and
causing the death of 5
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strongly
endemic
Endemic
sporadic
S typhi and S paratyphi have no nonhuman vectors.
Modes of transmission:
 Oral transmission via food or beverages handled by an
individual who chronically sheds the bacteria through
stool or, less commonly, urine
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Hand-to-mouth transmission after using a
contaminated toilet and neglecting hand hygiene
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Oral transmission via sewage-contaminated water or
shellfish (especially in the developing world)
Ingestion of antacids, H2 blockers, proton-pump
inhibitors, gastrectomy
 Genetic polymorphisms
 Environmental/ behavioural
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Street vendors’ food
Household contact
Inadequate washing of hands
Drinking unpurified water
Home without a toilet
Students in hostels with poor hygiene
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Protective host mutations occur in cystic
fibrosis. Heterozygotes have a mutation
which is associated with a decreased
susceptibility to typhoid fever, cholera and TB
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All pathogenic Salmonella species are engulfed
by phagocytic cells, which then pass them
through the mucosa and present them to the
macrophages in the lamina propria.
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With nontyphoidal salmonellae macrophages
recognize pathogen-associated molecular
patterns (PAMPs) such as flagella and
lipopolysaccharides and then attract T cells and
neutrophils with interleukin 8 (IL-8), causing
inflammation and suppressing the infection.
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S typhi enters the host's system primarily
through the distal ileum.
It has specialized fimbriae that adhere to the
epithelium over clusters of lymphoid tissue in
the ileum (Peyer patches), the main relay point
for macrophages traveling from the gut into the
lymphatic system.
S typhi has a Vi capsular antigen that masks
PAMPs, avoiding neutrophil-based
inflammation. The bacteria then induce their
host macrophages to attract more
macrophages.
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S typhi co-opts the macrophages' cellular machinery
for its own reproduction as it is carried through the
mesenteric lymph nodes to the thoracic duct and the
lymphatics and then through to the
reticuloendothelial tissues of the liver, spleen, bone
marrow, and lymph nodes.
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Once there, the S typhi bacteria pause and continue to
multiply until some critical density is reached.
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Afterward, the bacteria induce macrophage
apoptosis, breaking out into the bloodstream to
invade the rest of the body
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The bacteria then infect the gallbladder via
either bacteremia or direct extension of S
typhi –infected bile.
Therefore the organism re-enters the GIT in
the bile and reinfects Peyer patches or is shed
in the stool and is then available to infect
other hosts.
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Factors that influence the severity and overall
clinical outcome of the infection:
 duration of illness before the initiation of appropriate
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therapy
choice of antimicrobial treatment
Age
previous exposure or vaccination history
virulence of the bacterial strain
quantity of inoculum ingested
several host factors affecting immune status.
 1st week – gradual onset. Fever, headache,
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vomiting. Constipation. Rose spots.
2nd week – distended abd, tympanic note.
Splenomegaly. Rales over the bases
3rd week – complication week
4th week – recovery/death
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GIT – haemorrhage, perforation
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CNS - Encephalopathy, cerebral edema, subdural empyema, cerebral abscess,
meningitis, transient parkinsonism, motor neuron disorders, ataxia, seizures,
GBS, psychosis
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CVS - Endocarditis, myocarditis, pericarditis, arteritis, CCF
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PULM - Pneumonia, empyema, bronchopleura fistula
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BONE/JOINT – osteomyelitis, septic arthritis
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HEPATOBILIARY - Cholecystitis, hepatitis, hepatic abscesses, splenic abscess,
peritonitis, paralytic ileus
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GUT - Urinary tract infection, renal abscess, pelvic infections, testicular abscess,
prostatitis, epididymitis
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SOFT TISSUE - Psoas abscess, gluteal abscess, cutaneous vasculitis
Diagnosis of typhoid fever by
culture and serology
Percent of Patients With Positive
Cultures
100
90
80
70
60
Blood
50
Stool
40
Urine
30
Serum agglutinins
20
10
0
Wk 1
Wk 2
Wk 3
Wk 4
Wk 5
Wk 6
Wk 7
Wk 8
Weeks of Illness
18
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Resistance to chloramphenicol well
documented
MDR typhoid have necessitated the the use
of Quinolones (drug of choice) and 3rd
generation cephalosporins
Supportive care (fluid/electrolyte balance,
fevers)
% Antibiotic Resistance for Salmonella Typhi
n=61 (UTH Lab 2012)
Antibiotic
No. Tested
%R
Ampicillin
10
100
Cefotaxime
38
7.9
Chloramphenicol
51
58.8
Ciprofloxacin
32
12.5
Azithromycin not tested
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Despite appropriate therapy, 2–4% of
infected children may relapse after initial
clinical response to treatment
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Individuals who excrete S. Typhi for ≥3 mo
after infection are regarded as chronic
carriers.
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Children with schistosomiasis can develop a
chronic urinary carrier state.
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CHALLENGES ON THE WARD
 Diagnostic challenges (blood culture bottles;
delay in getting results)
 ??Treatment and resistance
 Policy for screening for carriers after treatment
not effective
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Patients go back to the same environment;
continue getting exposed to the same
contaminated water and food
Water and sanitation crisis in Lusaka’s
residential areas
Practices do not change much
Do we have carriers in the community???
The human-to-human spread by chronic
carriers is important, and attempts should
therefore be made to target food handlers and
high-risk groups for S. Typhi carriage screening.
Once identified, chronic carriers must be
counseled as to the risk for disease
transmission and given advice on handwashing
and preventive strategies.
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Traditionally, 2 vaccines. An oral, live-attenuated
preparation of the Ty21a strain of S. Typhi has
been shown to have good efficacy (67–82%) for
up to 5 years.
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The Vi capsular polysaccharide can be used in
people ≥2 yr of age. It is given as a single
intramuscular dose, with a booster every 2 yr
and has a protective efficacy of 70–80%.
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The vaccines are currently recommended for
traveling into endemic areas.
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Vi-polysaccharide conjugate typhoid vaccine (TCV): It is a Vicapsular polysaccharide conjugate typhoid vaccine conjugated
with tetanus toxoid
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The vaccine has been licensed by the Drug Controller General of
India (DCGI) in August, 2013 for clinical use in India
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This vaccine has been approved for use in children below 1 years of
age. Seroconversion rates of 98.05% have been reported with this
vaccine.
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The Indian Academy of Pediatrics recommends that the TCV can
be given below one year of age, preferably between 9-12 months