Enteric fever, Current diagnostics & Treatment approach. International vs MMIDS Pakistan recommendations

1. Dr. Badar Ahmad Jamal
PGR Internal Medicine

2. 
 A collective term for the multisystemic illness caused by Salmonella Enterica serovars
that include Salmonella typhi and Salmonella paratyphi A, B and C
 It’s a clinical syndrome that manifests with constitutional symptomatology such as
fever, malaise, leathargy together with abdominal complaints ie pain abdomen with or
without diarrhoea or constipation.
 Although the clinical picture for all Salmonella serotypes is almost indistinguishable
yet, the most invasive clinical course has been observed with ailment secondary to
infection with serotype typhi , that is termed as typhoid fever.
 If no complications occur, symptoms gradually improves over7-10 days.
INTRODUCTION

3. 
 Responsible for significant disease burden worldwide
 It has been estimated that 33 million cases and 500,000 deaths occur annually
throughout the developing world due to typhoid fever with a worldwide incidence of
365 /100,000 and 540 /100,000 (0.5%) in the
developing world
 Transmission takes place via feco-oral route
 Bears a long and variable incubation period ranging from 6 to 30 days
 Duration of sickness ranges from 14-35 days with a mean of 28 days
 Complications occur in 30% of the untreated cases and account for 75% of the deaths
 Frequency of relapse in 5% of the cases
 Carrier rate is 3% on average
 With emergence of XDR S.typhi especially in Middle East Asia and Pakistan, its
management has now become a challenge.
EPIDEMIOLOGY

4. 
 Infection begins with the organism invading the mucosal epithelial barrier of small gut.
 Subsequently, The agents invade and replicate in the macrophages of Peyer patches,
mesenteric lymph nodes and spleen.
 Bacteremia occurs, and infection dwells predominantly in Peyer patches
 Proliferation ensues via recruitment of lymphocytes and macrophages in the Peyer
patches secondary to bacterial invasion, which may ultimately ulcerate that may lead
to dangerous hemorrhage and intestinal perforation.
 Nontyphoidal Salmonella strains usually do not cause invasive disease owing to lack of
human specific virulence factors (typhoid toxin, Vi antigen etc)
PATHOPHYSIOLOGY

5. 
 Remittent fever, that begins low then rises gradually reaching as high as 104.9 degrees,
usually rises over the course of each day, dropping by subsequent morning. Takes
plateau after abuot 7-10 days. Sphygmothermal dissociation may occur
 Dull frontal headache, more pronounced in younger age group
 Coated tongue
 Myalgias
 Anorexia, upper GI upset
 Diffuse abdominal pain and tenderness with or without constipation / diarrhoea. Pea
soup (foul smelling green colored) diarrhoea may also develop.
 Salmon colored, blanching maculopapular rash on trunk, lesions are 1-4 cm wide and
usually less than 5 in number. Generally resolve within 2-5 days.
 By the third week, apathy, confusion and psychosis may ensue (said typhoid state)
 Intestinal perforation, secondary peritonitis and toxemia can take place
SIGNS & SYMPTOMS

6. 
 Blood culture is the investigation of choice, that is positive in 80 % of the patients
within the first week of illness. Rate of usefullness declines thereafter. Still positive in
25 percent of the cases by the 3rd week.
 Bone marrow cultures may be occasionally positive when blood cultures are not, and
can be carried out. Stool cultures are however unreliable
 Serological testing is also used but is obsolete and unreliable.
 Full blood count typically reveals leucopenia, may reveal anemia and/or
thrombocytopenia, may also reveal elevated ESR.
 Elevation of serum bilirubin and aminotransferases to twice the upper limit of normal
 Mild hyponatremia / hypokalemia could also be there.
LABORATORY INVESTIGATIONS

7. 
 Might be rational in patients who’s symptoms do not resolve by the third week,
or who have severe constipation or in any way are suspects for intestinal
perforation.
 Include X-RAY abdomen erect and supine and CT scan with IV Contrast.
SONOGRAPHIC IMAGING

8. 
Notables include (but not limited to)
 Acute appendicitis
 Malaria
 Dengue
 Hepatic abcess
 SBP/ Secondary bacterial peritonitis
 Brucellosis
DIFFERENTIAL DIAGNOSES

9. 
 Intestinal Hemorrhage
 Intestinal perforation
 Secondary peritonitis
 Psychosis
 Myocarditis
 Cholecystitis
COMPLICAIONS

10. 
 Treatment is aimed at shortening the due course of illness, relieving the
symptoms and preventing the complications.
 Good nursing care should be offered
 Vital signs, intake and output monitoring and according management
 Fluid and electrolyte replacement as per customized scenario, adequate oral
intake
 Antipyretics for fever
 Symptomatic treatment such as anti emetics for nausea/vomiting, analgesics
for headache and myalgias
 Antibiotics – empiric vs organism specific.
 According management of complications if any.
MANAGEMENT

11. 
General Considerations
 Once enteric fever is suspected on clinical grounds, empiric antibiotic therapy
better be initiated on empiric basis. This is known to limit the complications
and shorten the course of illness.
 Fluoroquinolones and third generation Cephalosporins , in general are the
antibiotics of choice against salmonella infections.
 For suspected enteric fever, levofloxacin 500 mg once daily or Ciprofloxacin 750
mg twice daily for 5-7 days are quite effective.
 Ceftriaxone 1-2 mg twice daily is also effective
 Alternatively, using macrolide ie azithromycin 500 mg once daily for 5-7 days
is also effective
ANTIMICROBIAL THERAPY

12. 
Geographical Considerations in Anti-biotic Selection
 Resistance is being faced by ampicillin, co-trimoxazole and chloramphenicol in
treatment of typhoid globally
 Strains have become increasingly resistant to quinolones in Middle East Asia
including Pakistan.
 XDR strain of S typhi was isolated in Pakistan in 2016, that is resistant to
ceftriaxone but continues to maintain sensitivity to Azithromycin.
 International sources recommend usage of carbapenepms (eg meropenem 1G
thrice daily) for complicated salmonella infections acquired in Pakistan,
ceftraxone 1-2 gram twice daily outside Pakistan and a quinolone (levofloxacin
500 mg once daily) outside South Asia, on empiric basis.
 Certain antibiotic combinations eg cefixime-ofloxacin have shown better results
in background of increasing antibiotic resistance, especially in Asia.
CONTINUED..

13. 
Guidelines by MMIDSP
 The Medical Microbiology & Infectious Diseases Society of Pakistan 2019
Guidelines recommend empiric therapy with monoantibiotic which should be
as follows.
 Cefixime 400 mg orally twice daily that could be changed to IV therapy if no
improvement is there for 5 days or there is emergence of complications
OR
 Ceftriaxone intravenous in 1 gram twice daily dosage.
 Once culture/sensitivity report is available, antibiotic should be adjusted
accordingly
CONTINUED..

14. 
 A chronic carrier is the one who continues to secrete S typhi in stool for more
than 1 year are considered carriers.
 Ciprofloxacin 750 mg twice daily for 10-14 days is effective
TREATMENT FOR CARRIERS

15. 
 Despite of all the treatments, mortality rate is 2% in treated cases
 Elderly pts with a number of co-morbids are likely to are likely to do worse
PROGNOSIS

16. 
 Maintaining good hygeine
 Proper hand wash
 Appropriate waste disposal
 Vaccination should be considered for close contacts of typhoid patients
PREVENTION

17. 
 Current Medical Diagnosis and Treatment 2021
 Center of Disease Control & Prevention- Typhoid fever & Paratyphoid fever >
symptoms and treatment
Available from Symptoms and Treatment | Typhoid Fever | CDC
 Typhoid Management Guidelines – 2019 by MMIDS Pakistan. Available from
Typhoid Management Guidelines – 2019 – MMIDSP
 Online sources – open access
References

18. THANK YOU