ENTERIC FEVER IN MUMBAI

CLINICAL PROFILE,

SESITIVITY PATTERNS AND RESPONSE TO

ANTIMICROBIALS.

--Dr.VENKAT NARAYANA GOUTHAM.V

INTRODUCTION Enteric fever is a systemic disease

which includes Typhoid fever caused by S.typhi, and Paratyphoid fever caused by S,paratyphi A and B.

In India,the disease is endemic with an incidence ranging from 102 to 2219 per 100,000 population.

In the early 1800s, typhoid fever was clearly defined pathologically as a unique illness on the basis of its association with enlarged Peyer's patches and mesenteric lymph nodes.

PATHOGENESIS

All Salmonella infections begin with ingestion of organisms, most commonly in contaminated food or water.

Once S. typhi and S. paratyphi reach the small intestine, they penetrate the mucus layer of the gut and traverse the intestinal layer through phagocytic microfold (M) cells that reside within Peyer's patches.

After crossing the epithelial layer of the small intestine, S. typhi and S. paratyphi, which cause enteric (typhoid) fever, are phagocytosed by macrophages.

These salmonellae survive the antimicrobial environment of the macrophage by sensing environmental signals that trigger alterations in regulatory systems of the phagocytosed bacteria.

Once phagocytosed, typhoidal salmonellae disseminate throughout the body in macrophages via the lymphatics and colonize reticuloendothelial tissues (liver, spleen, lymph nodes, and bone marrow).

Signs and symptoms, including fever and abdominal pain etc, result from secretion of cytokines by macrophages and epithelial cells in response to bacterial products that are recognized by innate immune receptors.

Over time, the development of hepatosplenomegaly , marked enlargement and necrosis of the Peyer's patches.

S.Typhi.

stomach

Lower ileum

peyer's patches &mesenteric lymph nodes

thoracic

duct

1st bacteremia(Incubation stage)

10-14d

(mononuclear phagocytes )

2nd bacteremia

liver、 spleen、 gall、BM ,ect

early stage&acme stage(1-3W）

LN Proliferate,swell necrosis

defervescence stage

（ 3-4w）

Bac. In gall

Bac. In feces

S.Typhi eliminatedconvalvescence stage

(4-5w)

Enterorrhagia,intestinal

perforation

CLINICAL COURSE The incubation period ranges from 3–21 days. prolonged fever (38.8°–40.5°C; 101.8°–

104.9°F), which can continue for up to 4 weeks if untreated.

Abdominal pain headache (80%), chills (35–45%), cough

(30%), sweating (20–25%), myalgias (20%), malaise (10%), and arthralgia (2–4%). Gastrointestinal symptoms included anorexia (55%), abdominal pain (30–40%), nausea (18–24%), vomiting (18%), and diarrhea (22–28%) more commonly than constipation (13–16%). Physical findings included coated tongue (51–56%), splenomegaly (5–6%).

Early physical findings of enteric fever include rash ("rose spots"; 30%), hepatosplenomegaly (3–6%), epistaxis, and relative bradycardia at the peak of high fever (<50%).

Complications include toxaemia,dehydration,PCF,DIC,intestinal perforation&haemorrhage,delirium,psychosis,coma,meningitis,encephalopathy,myocarditis,endocarditis,pericarditis,pyelonephritis,glomerulonephritis,arthritis,pneumonia,hepatitis,thrombophlebitis.

DIAGNOSIS Diagnosis is made by

blood, bone marrow, or stool.

The Widal test is commonly used to diagnose Typhoid.Looks for salmonella

antibodies against antigens O-somatic and H-flagellar)

EXAMS AND TESTS

Leucopenia with relative lymphocytosis.

A blood culture the shows the bacteria

A stool culture An ELISA test to show

the Vi antigen A platelet count (low

platelet count) A fluorescent antibody

study and molecular methods like PCR

CARRIERS OF TYPHOID 3%-5% of people who

have been infected become carriers of the disease.

Carriers are treated with prolonged antibiotics.

Removal of the gallbladder(cholecystectomy) or the site of the infection will usually cure the patient.

Typhoid Carrier undergoes treatment

AIMS AND OBJECTIVES OF STUDY

To study the…

Sensitivity patterns of S. enteritica and response to antimicrobial therapy.

The clinical and laboratory profile of patients suffering with enteric fever.

MATERIAL AND METHODS

This was a retrospective chart review of all cases of enteric fever carried out at a tertiary care private hospital in Mumbai, India.

The records of all patients discharged from our hospital with a diagnosis of enteric fever(typhoid fever or paratyphoid fever) were assessed for suitability for inclusion in our study.

SEVENTY-FOUR OF THE 119 STUDY PATIENTS WERE MALE AND 45 WERE FEMALE. THE AGE RANGED FROM 7 MONTHS TO 66 YEARS, THE MEAN AGE BEING 21.7 YEARS.ALL PATIENTS HAD FEVER PRIOR TO ADMISSION; THE MEDIAN DURATION OF FEVER PRIOR TO ADMISSION WAS 7 DAYS, THE RANGE BEING 2 TO 90 DAYS.

SYMPTOM PERCENTAGE

HIGH GRADE FEVER 66.3

chills 57.9

VOMITING 42

ABDOMINAL PAIN 33.6

LOOSE STOOLS 31

HEPATOMEGALY 15.9

SPLEENOMEGALY 7.5

HEPATOSPLEENOMEGALY 12.6

OTHERS

DIAGNOSTIC TEST PERCENTAGE

WBC COUNT NORMAL 85

LEUCOPENIA 11.4

LYMPHOCYTOSIS 4 PATIENTS

ABSOLUTE EOSINOPENIA 76.9

THROMBOCYTOPENIA 25.9

HYPERBILIRUBINEMIA 28.7

CULTURE POSITIVE 73 PATIENTS

WIDAL TEST 64 PATIENTS

Ceftriaxone was the most common antibiotic used to treat patients in hospital 74 of 119 patients (62.1%).

A combination of ceftriaxone (2 gm bd IV) and azithromycin (500 mg od PO) was used in 16 patients (13.4%).

Rest of the patients (25%) received various other antibiotics singly or in combination.

The mean duration of receipt of antimicrobials after hospitalization was 11 days.

The overall mean time to defervescence when ceftriaxone alone was used as therapy was 4.2 days.

The mean time to defervescence in those patients who received a combination of ceftriaxone and azithromycin was 5.1 days and did not differ significantly from those who received ceftriaxone alone.

CONCLUSION As many as 46.2% patients in our study

received antibiotics either single or in combination for as long as 10 days before being admitted to the hospital. Despite this they were still culture positive.

There is high prevalence of nalidixic acid resistance and return of sensitivity to chloramphenicol,ampicillin and cotrimoxazole. We did not observe any resistance to third generation cephalosporins.

The mean fever clearance time with ceftriaxone used as single therapy observed in our study was 4.2 days as against 6.1 days in literature.

Results of our study however suggest that combination therapy may not be superior to single drug therapy, as we did not observe any significant difference in the time to defervescence in those patients who received ceftriaxone alone or in combination with azithromycin.

Importance of absolute eosinopenia as a diagnostic marker of typhoid.

High culture positivity despite receipt of prior antibiotics, high prevalence of nalidixic acid resistance (79%), return of susceptibility to chloramphenicol (96%), 100% sensitivity to ceftriaxone and non superiority of combination therapy versus single agent therapy.

INTERESTING FACTS

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HISTORY OF TYPHOID FEVER. Antonius Musa :

A Roman physician who achieved fame by treating the Emperor Augustus 2,000 year ago, with cold baths when he fell ill with typhoid.

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HISTORY OF TYPHOID FEVER.

Thomas Willis:who is credited

with the first description of

epidemic typhoid in

1659 .

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HISTORY OF THE TYPHOID FEVERS

William Wood Gerhar :who was the first

to differentiate clearly

between typhus & typhoid

in 1837.

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HISTORY OF TYPHOID FEVER.

Carl Joseph Eberth

who discovered the typhoid

bacillus in 1880.

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HISTORY OF TYPHOID FEVER.

Georges Widal:who describes

‘Widal agglutination

reaction’ in 1896.

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IN DEVELOPING COUNTRIES, MANY PATIENTS WITH TYPHOID FEVER ATTEND FOR TREATMENT LATE.

The Diazo test had a sensitivity of 81% and specificity 90% .

No other studies have attempted to highlight the usefulness of this test. It is often not possible in clinical practice to submit blood for culture in the first week of a febrile illness before starting antibiotics. Besides, blood culture is not routinely available everywhere.

Diazo test became positive from day 5 of fever and remained positive till day 31 of fever.

The average duration of test positivity was 6-16 days of fever.

We believe that this is a simple bedside test which can be used to diagnose typhoid fever where facilities for blood culture and Widal test are not available.

INTERNATIONAL HISTORY OF TYPHOID FEVER Around 430-426 B.C. it is

believed that Typhoid Fever killed 1/3 of the population in Athens.

This was long disputed but after a DNA discovery in 2006, it was determined that it was the Typhoid Fever bacterium.

Between 2004-2005 an outbreak in the Dominican Republic occurred with 42,000 cases and 214 deaths.

In the late 19th century, a typhoid fever outbreak in Chicago occurred killing 65 per 100,000 people.

In 1891, the worst mortality rates were 174 per 100,000 people.

In 1907, the first American carrier was discovered - Mary Mallon aka Typhoid Mary.

CARRIERS OF TYPHOID FEVER

A carrier is usually a healthy person who survived the disease but in whom the bacteria are able to survive without causing further symptoms.

Carriers continue to spread the disease through their excrement without realizing it.

TYPHOID MARY She infected 47 people and killed 3

She constantly changed her employment but the members of the household always got sick.

She was forced into containment for two years and then released under the conditions that she could no longer be a cook.

She assumed a false name and began cooking again and of course, infecting numerous people.

She was forced into life-time containment where she died 26 years later of pneumonia.

HOW CAN TYPHOID BE AVOIDED? Avoid risky foods or

drinks Get vaccinated Use only clean water Ask for drinks without ice

unless you know where it’s coming from

Only eat foods that have been thoroughly cooked

Avoid raw fruits and vegetables

Avoid food and drinks from street vendors