Enteric Fever

Dr Paul Collini

TYPHOID
tufoV = smoke i.e. stupor or clouding of mind unfortunatley ricketssial disease also does this and is called typhus We are concerned with Enteric fever Typhoid or paratyphoid

Organisms
Salmonella gram negative bacillus flagellated Antigens somatic o antigen flagella H antigen Surface Vi antigen

Types of Salmonella
Salmonella typhi Salmonella paratyphi A,B,(sometimes C) remember other forms of salmonella nontyphopidal salmonellae or NTS
salmonella typhimurium, salmonella enteritidis cause diarrhoeal illness but not severe enteric fever (except in immunocompromised)

Epidemiology
typhoid salmonellae bacteria are endemic in all parts of the 'developing' world tend to be found in the tropics only because those are the same areas with poor sanitation. incidence higher in dry season or times of flood 12-20 M cases annually worldwide, India especially Annual incidence 0.5-1% population in endemic area Children and Young Adults predominantly MR 5-20% NTS more prevelant as cause of enteric fever in areas of high HIV prevalence

reservoir of infection
only in man are asymptomatic human carriers. bacteria continue a low level infection in the gall bladder, and with bile are excreted into the faeces. water supply contaminated by faeces low standfard of self hygiene extra problem if carrier is food worker / handler

Infection
is via ingestion of bacteria bacteria are either in water supply or contaminate food food kept at the right temperature (i.e. not refrigerated) allows for multiplication of bacteria infecting dose is impotrtant
10^3 organisms rarely cause disaese 10^5 organisms 25% attack rate 10^9 organisms 95% attack rate

gastric acid can neutralise the bacteria to some extent, thus those on PPI / H2 blockers may be at more risk

Pathophysiology
ingestion bacilli attach to and penetrate mucosa of small intestine enter lymphatics and taken to mesenteric glands here multiplication of bacteria occurs drainage from lymphatic system to blood stream via thoracic duct lead to a first, transient bacteraemia

Pathophysiology
infection travels to liver, gall bladder, spleen and bone marrow further multiplication in the spleen and liver second bacteraemia as organisms re-enter blood this coincides with start of symptoms i.e. the end of the incubation period Bile is infected and excreted into the lumen of the intestine resulting in a secondary invasion of the bowel mucosa (if pre existing Gall Bladder disease - e.g. stones there is a greatly increased risk of chronic carriage)

Pathophysiology
The bacilli avoid immune system largely because they infect but don't kill macrophages.
The organism multiplies within the macrophage during jopurney through lymphatics and blood, while evading phagocytosis further multiplication occurs in the lymphoreticular system as the immune system responds foci of inflammation are seen. these foci of infection/inflammation are called typhoid nodules

Peyer's Patches
focus of inflammation in gut lymphoid tissue if no resolution, by 7-10 days necrosis occurs and subsequent ulceration these intestinal ulcers are responsible for GI bleeding and at times gut perforation

Ulcerated Peyers Patches due to Enteric S typhi

Ulceration in S typhi

Pathophysiology
Effects on other organs are mediated by a non specific toxin
heart muscle central nervous system

Clincal: Enteric fever

Incubation period 7 -21 days, usually 14 untreated course of illness isusually 3 weeks but may continue for months few signs or symtpoms are consistently seen other than Fever and Headache most common = 90%

Fever in typhoid
first week stepwise increase second week remittant third week falling again can be high i.e. 40 degrees often the patient has a relative bradycardia

others symptoms:
abdominal pain constipation diarrhoea deafness cough psychiatric: psychosis or depression

Signs
Fever relative bradycardia abdominal distension common hepatomegaly, splenomegaly 25-50% mental change: confusion, ataxia, tremors, apathy rose spots (from day 7), red macules that blanch deafness, meningism SHOCK if severe e.g. perforation

Presentation
early: fairly well patient, alert not dehydrated late: toxic, confused and very dehydrated any system can be involved, so presentation can vary very widely: always suspect

Complications
Perforation
5% most likely in 3rd week

Haemorrhage
from ulcerated Peyers patches

Metastatic infection
abscess or bone infection, poss years later

Carriage
flukes / stones encourage Carcinoma of GB late complication

Diagnosis
Culture Serology Other tests

Culture
Blood Culture 40 - 70% sensitivity
best option to yield result in first week can be positive at any point in illness lysis centrifugation )macrophage fraction) more sensitive

Bone Marrow Culture 95% sensitivity (even if antibiotics) Stool Culture

can be positive in first four days after infection (i.e. during incubation period when patient asymptomatic) and if diarrhoea present (usually second week) sensitivity can be increased to 86% using a string capsule

Rose spot Aspirate, CSF culture, Pus from abscess

Serology
WIDAL TEST
measures antibodies to the somatic 'O' antigen + flagellar 'H' antigen

it is largely useless, especially in an endemic setting

it is NON SPECIFIC other salmonella infection (even asymptomatic) will give high titres

titres will be high from previous exposure or immunisation

four fold increase between illness and convalescence is unhelpful:
titres rise greatly during incubation period and not much thereafter the diagnosis is made after the illness has finished how many patients will return and pay for a second widal when better

some culture proven typhoid patients have a 'negative' widal.

antigen based tests are still in development

Other
WBC
is often normal but both leucocytosis and classic leucopaenia are seen. if WBC is raised tend to be lymphocytosis may have thrombocytopenia

Chemistry
no specific findings but can get raised transaminases and bilirubin

Management
supportive
nursing care is paramount to ensure fluid intake, sanitation (barrier nurse) and pressure area care

fluid and electrolyte balance are critical Antibiotics Specific interventions

Antimicrobial Therapy
CHLORAMPHENICOL AMOXYCILLIN SMP-TMX 'SEPTRIN' CIPROFLOXACIN CEPHALOSPORINS AZITHROMYCIN

first line agents

Chloramphenicol, amoxycillin and cotrimoxazole
rapid improvement in symptoms defervessence in 3-5 days chloramphenicol : 500mg 4 hourly then 6 hourly after defervessence: 14 days total Co-trimoxazole : 960mg bd useful for empirical treatment available and affordable resistance in Asia, has been seen in Kenya but little solid data elsewhere

Ciprofloxacin
highly effective
defervessence 3-5 days lower rate of carriage and rare relapse 500mg bd x 14 very good oral absorption (only IV required if vomiting or diarrhoea is present)

not recommended in children and pregnancy resistance emerging already more costly, not always available

Cephalosporins 3rd gen

as effective all IV and all expensive but share resistance with first line

Azithromycin
Very good tissue penetration and oral preparation works as well as all others effective in resistant cases no problem for children but expensive

specific issues
perforation / haemorrhage
full iv resuscitation +/- blood cover for G-ve and anaerobic EARLY surgery

typhoid shock
high dose steroids early

relapse
not due to resistance but recrudescence from GB

carriers
up to a month of cipropfloxacin