Approach to fever

Prof.S.Shivakumar.MD.,
HOD & Professor ofMedicine
ofMedicine,,
Stanley medical college

Etiology

Infections
Bacterial

Viral

Protozoal

Collagen vascular disease

SLE, rheumatoid arthritis, etc.

Malignancy

Leukemia, lymphoma

Infectious causes

Malaria
common cause

P.falciparum causes increased mortality/ morbidity.

leptospirosis

occurs during monsoon

contaminated environment.

TB
Pulmonary

Extra pulmonarypulmonary- lymph node, meningeal, abdominal
etc.

CONTD
CONTD

Enteric fever

Viral fever

Dengue can occur in epidemics

HIV

Resistance to drugs

Emerging infectious disease

Sepsis community acquired & nosocomial

Commonly due to pneumonia

UTI

Approach to fever

Fever

Duration of fever

Organ dysfunction

Cause of fever

Duration of fever

Fever < 1 week

Viral fever

Fever > 1week

Malaria

Leptospirosis

Enteric

Pyleonephritis (UTI)

Fever > 2 weeks

TB

HIV

Organ dysfunction

Jaundice

Renal failure

Pneumonia/ ARDS

Meningitis/ encephalitis

Malaria/ sepsis/ leptospirosis

Pulmonary

Malaria/ leptospirosis/ sepsis

TB/ Cerebral malaria

Bleeding diathesis

Dengue/ leptospirosis

Malaria
Clinical presentation

Uncomplicated

Complicated

Malaria - Uncomplicated

Clinical features

Initial symptomssymptoms- non specific resembling viral inf.,

Fever / headache/ myalgia

Hepatosplenomegaly

Wt. loss

Fever with no obvious respiratory or abdominal

symptoms-- suspect malaria
symptoms

Uncompli

Relapse 50%

P. vivax & p. ovaleovale- relapse after resolution of

primary infection

Distinguish from primary infectioninfection- incomplete trt.

Recrudescence ( p. falciparum)falciparum)- after 2 to 4 wks

Relapse months or weeks after plasmodium

infection ( 33-6wks / 9 months)

Complicated Malaria ( WHO)

WHO)

Cerebral malaria

Shock

Severe anemia

Spontaneous bleeding

Renal failure

Hypoglycemia

ARDS

Acidemia

Repeated generalized
convulsions

Macroscopic
hemoglobinuria

Cerebral malaria

Unarousable coma should persist for 30 mins. After

generalized convulsions

Renal failure
S.Creatinine > 3mg %

Urine output <400ml in 24 hrs in adults

< 12ml/kg in children

Spontaneous bleeding

More likely due to DIC

Severe anemia
Normocytic anemia with Hct < 15% or Hb < 5g%
in presence of parasitemia > 10,000/mcl

Presentation

Acute cardiac failure, respiratory distress

Chronic asymptomatic

Shock
Pts with severe malaria develop sudden
hypotension Algid malaria
hypotension

Sepsis / dehydration

Acidemia

Hypoglycemia

PH <7.25, Hco3 <15meq/ L

Blood sugar < 40 mg%

Convulsions

> 2 episodes / 24hrs despite cooling

Macroscopic hemoglobinuria

Associated with acute malarial infection not the

result of oxidant antimalarial drugs

Pulmonary edema & ARDS

Common in pregnancy

Rare in children

D.D
D.D-- Metabolic acidosis, aspiration pneumonia

Other manifestations of severe

Malaria ( not in WHO)
WHO)

Impairment of consciousness less marked than

Unarousable coma

Jaundice

S.Bilirubin > 3mg%

Hemolytic , Hepatitic, Cholestatic components

Hyperpyrexia temperature > 40 deg.C

Hyperparasitemia -- > 10%

Clinical features
features Indian studies

Jaundice 60 %

ARF -- 6%

Anemia 26%

ARDS 5%

Spontaneous bleed -25%

Hypoglycemia 1.5%

Cerebral malaria -- 10%

Shock-Shock
-- 10%

MODS ( Jaundice + RF)

-- 22 %
Thrombocytopenia -70%

Study of 150 cases smch (2005)

Total cases of malaria for 6months (may(may-dec 05)

P.vivax- 122
P.vivax
P.falciparum -26

Mixed -2

Jaundice- 28 cases

Mild (biliurbin 1.5
1.5--3)
3)-- 14

Severe (>3) -14

Renal failure -18

Mild ( creatinine 1.5
1.5--3) -12

Severe
Severe--(>3) -6

Treatment of uncomplicated
falciparum malaria

Artemesinin based combination

therapy(oral)

3 days short course treatment

artemether

+ lumefantrine,
lumefantrine,

artesunate + amodiaquine,
amodiaquine,

artesunate + mefloquine,
mefloquine,

artesunate + sulfadoxine
sulfadoxine
pyrimethamine.

Drug dosage for adults

artemether + lumefantrine

1tab = 20mg A + 120mg L .

4 tab/dose at 0,8,24,36,48,60(hr) to be taken with food
artesunate + amodiaquine
amodiaquine

50 mg AS Tab + 153 mg AQ Tab

4 tab AS OD for 3 days + 4 tab AQ OD for 3 days
artesunate + mefloquine
mefloquine

50 mg AS Tab & 250 mg MQ.

4 tab AS OD for 3 days + no MQ on day 1 , 3 tab on day 2 , 2 tab on
day 3.
artesunate + sulfadoxine
sulfadoxinepyrimethamine

50 mg AS Tab + 500 mg sulpha + 25 mg pyri/tab

4 tab AS OD for 3 days + 3 tab SP once on day 1

Uncomplicated Vivax Malaria

Chloroquine sensitive P.v

Chloroquine 10 mg/kg stat, 5mg/kg at 6,24 & 48
hrs with

Primaquine 5mg/kg for 14 days.

Chloroquine resistant P.v

Amodiaquine 10mg/kg OD for 3 days with

primaquine 5mg/kg for 14 days..

Treatment of severe falciparum and

vivax malaria

1. Artesunate2.4
Artesunate2.4 mg/kg body weight (2vials) IV at 0 hr, 12 hrs and 24 hrs
and then daily till the patient can take orally. Then AS 2 mg/kg body
weight per day (100 mg/day) to complete 7 days course.
2. Artemether 3.2 mg/kg body weight (2 amp) IM on admission then 1.6
mg/kg body weight (lamp) IM daily till patient can take orally. Then (40
mg caps) 2 caps daily orally to complete 7 day course.
3. Quininine Loading dose of 20 mg salt/kg in 1 pint 5% Dextrose Saline
in 4 hrs time, then10 mg salt/kg body weight (maximum 600 mg) to be
repeated 8 hourly. When the patient will be able to take orally give
Quinine 10 mg/kg body weight (maximum 600 mg) 8 hourly orally to
complete 7 days course.
*Doxycycline 3.5 mg/kg/day/Tetracycline/Clindamycin (Children and
Pregnancy) should be added when patient takes orally for 7 days with either
of 3 drugs mentioned above.

Leptospirosis

Introduction

Most common,
common, underreported and underdiagnosed zoonosis

India - Cases reported from Kerala , Tamil Nadu, Karnataka,

Maharashtra, Gujarat & Andamans.

Source Animals ( rodents and domestic animals )

Epidemiological factors

Contaminated environment

Rainfall

High risk groups

Epidemiology

Rainfall
Contaminated environment

Poor Sanitation & inadequate drainage facilities

Presence of Rodents, cattle& stray dogs

Walking bare foot.

Any person can get infected, if exposed to

contaminated environment

Epidemiology..

Risk groups
Farmers Rice, Sugarcane, Vegetables, Cattle,
Pigs

Sewerage workers

Abattoirs, Butchers

Vetenarians , Lab staff

Miners

Fishermen Inland

Soldiers

Transmission
Rodents (Urine)
Contaminated environment

Domestic animals

Humans

Clinical Features

Anicteric

Icteric (Weils Syndrome)

Hemorrhagic fever with renal syndrome

Atypical pneumonia syndrome

Myocarditis

Aseptic Meningoencephalitis

Ocular Manifestations

Anicteric (>90%)
Leptospiremic Phase
Fever
Myalgia
Conj.suffusion
Headache
Epistaxis
Abdominal pain

Immune Phase
Fever
Meningitis
Uveitis

Anicteric - Mild / Severe

Incubation Period - 7 -14 days (2 21 days)

Icteric Leptospirosis
LIVER

Jaundice - Occurs 44-6 days (2 - 9 days)

Sr.Biliruubin Markedly (20

(20--40 mg/dl)

SGOT / SGPT - Mild elevation

Hepatocellular necrosis / Intra hepatic cholestasis

Death - Not due to Liver Disease

Renal failure mild/severe

Pre
Pre--renal azotemia

ATN/ AIN

Oliguric/ NonNon-oliguric

Urinalaysis-- proteinuria/ pyuria/hematuria

Urinalaysis

Haemorrhagic Fever with

Renal Syndrome

Vascular injury
Occurs form Respiratory, Alimentary, Renal &
Genital tracts .

More common in Icteric & with Renal Failure

Atypical Pneumonia Syndrome

Hemorrhagic Pneumonitis

Haemoptysis / Respiratory failure

CXR : Single/ Multiple ill defined opacities/

Consolidation

Occurs 2nd week (As early as 2424-48 hrs)

Cardiac

Hemorrhagic Myocarditis

Arrhythmias / Cardiac failure

Hypotension / Death

Arrhythmias

Atrial fibrillation / Conduction defects

Aseptic MeningoEncephalitis

Feve,, headache, neck rigidity

Feve

Occurs in the Immune phase

CSF proteins , lymphocytes

Ocular

Conjunctival suffusion / hemorrhage

Late complication

Anterior uveal tract inflammation

Iritis / Iridocyclitis / chorioretinitis

occurs 2 weeks 1 yr (6 months)

LABARATORY CRITERIA FOR DIAGNOSIS OF

CURRENT LEPTOSPIROSIS

CULTURE : Positive

MAT :
Seroconversion / 4 fold rise in the titre

High titre.

ELISA / MSAT : positive.

Problems In Diagnosis

Early Diagnosis (First Week)

No Reliable test

Culture Delayed results (weeks / month)

PCR Valuable

Serologic tests

Genus specific - SAT / ELISA (>5days)

Serovar specific - MAT.

Serological Tests

SAT & ELISA

Simple, Reliable & sensitive for diagnosis of current

inf.

MAT
Gold Standard

Complicated, DFM required

titres occur late, but persist longer

 valuable in serosero-epidemiologic studies

less sensitive for current diagnosis

Interpretation of Tests

MAT Titres ( IgM & IgG antibodies)

>1/80 or >1/400

Possibilities
 Rising

titres of Current infection

 Declining
 To

titres of Past infection

confirm, second sample essential

ELISA/ SAT (IgM antibodies)

Valuable for diagnosis of Current infection

Interpretation of Tests
ELISA/SAT

MAT

INTERPRETATION

+
+
NA

+
+
Rising titres

Current Infection
Current Infection
Past infection
Current Infection

0 1 week
ELISA/SAT
MAT

1 month

2 months 1 yr

5 yrs

Approach to Diagnosis of Leptospirosis

Clinical features suggestive of current Leptospirosis

Leptospiremic phase < 7days

Blood culture

PCR

Immune phase > 7 days

ELISA / MSAT
Confirm
( if available )

Negative

Repeat ( > 3 days )

Positive

MAT

Approach ..
MAT

Positive

Repeat (if low titre)

High titre

Rising titre

Negative

Repeat

Seroconversion

Treatment

Mild Leptospirosis

Doxycycline 100 mg bd X 7 10 days

Amoxycillin 500 mg qid

Ampicillin 500 750 mg qid

Severe Leptospirosis

Penicillin 1.5 million units IV qid

Ampicillin 1 gm IV qid

Supportive Treatment

IV

Fluids

Analgesics

Dialysis

Mortality

Renal

failure

Cardiovascular

Bleeding

complications

A study leptospirosisleptospirosis-80 cases at

Smch(2004--05)
Smch(2004

Anicteric cases - 81.75%

Jaundice - 18.75%
Renal failure - 8.75%
Rainfall - 48.75%
Contaminated environment - 95%
Animal contact - 95%

Dengue fever

Clinical manifestations
Dengue fever

Fever / Headache /
Myalgia

Dengue
Hemorrhagic
fever

Above +
Thrombocytopenia +
Spontaneous Bleeding +
Plasma leakage
Above + shock

Dengue Shock
syndrome

Grading of severity

DF Headache, retroorbital pain, Myalgia

DHF I Above signs + positive tourniquet test
DHF II Above signs + Spontaneous bleeding
DHF III Above Signs + Circ
Circ.. Failure
DSS
DHF IV Profound shock
Lab.. DHF Thrombocytopenia, Hct 20
Lab
20%
%

Disease course
Febrile phase 22-7 days

Afebrile phase 22-3 days
(critical phase)

Convalescent phase

Pathogenesis of DHF

capillary leak
Thrombocytopenia
DIC

Investigations

Confirm diagnosis of DF

Thrombocytopenia (< 100

100,,000
000/c
/c..mm)

Evidence of plasma leakage due to

increased capillary permeability




> 20
20%
% rise in Hct
> 20
20%
% drop in Hct following treatment
Signs of plasma leakage pleural effusion,
ascites, hypoproteinemia

Evidence of blood loss Hct Hb

Treatment of DF/ DHF

Febrile phase






Bed rest
Paracetamol 4times/day
Avoid Aspirin & Brufen
Avoid antibiotics
Oral Rehydration therapy fluid loss due to
vomiting / high temp. (2.5(2.5-4 litres /day)

Afebrile phase - observe

DHF (Grade I & II)

Febrile phase
as for dengue fever

Afebrile phase
Initiate IV fluid therapy (6ml/kg/Hr)
Crystalloid solution (GNS/RL) 1 - 2 hrs

Improvement
Reduce fluid therapy (3ml/kg/Hr) 6 -12 hrs discontinue
after 24 Hrs

Contd..
No Improvement
Increase fluid therapy crystalloids (10ml/kg/Hr)
for 2 Hrs
Improvement
reduce fluids 10ml 6ml 3ml/kg/Hr
discontinue after 24 -48 hrs.

No improvement/ unstable vitals

Hct - IV colloids (Dextran 40) or plasma
10 ml/kg/hr

Hct - Blood Transfusion (10ml/kg/hr)

Platelets < 5000cu.mm - platelet transfusion

Improvement crystalloid as above

DHF
CRYSTALLOIDS
(RL/DNS)

6ml/kg/hr

Improvement

3ml/kg/hr

Discontinue after
6-12 hrs
CRYSTALLOIDS

6ml/kg/hr No Improvement 10ml/kg/hr

No
improvement
Plasma (Hct)
Blood (Hct)

discontinue

improvement
Crystalloids
10-6-3ml

Dengue shock syndrome



AFEBRILE PHASE shock / Oliguria

Immediate rapid volume replacement
 Crystalloid solution 10
10--20
20ml/kg/Hr
ml/kg/Hr


 Improvement

Reduce fluid 20
20--10
10ml/kg
ml/kg , 10
10--6ml/kg 6-3ml/kg
 Discontinue 24
24--48 hrs later


Contd
 No

improvement - Oxygen therapy

Hct - IV Colloid (Dextran ) or Plasma

10
10ml/kg/HR
ml/kg/HR as IV bolus
 HCt Blood transfusion(
transfusion(10
10ml/kg/Hr)
ml/kg/Hr)


 Improvement

- crystalloid as above

DSS
CRYSTALLOIDS
(10-20 ml/kg/hr)

Improvement

CRYSTALLOIDS No Improvement

Reduce
10-6-3ml/kg/hr

Blood (Hct )
Plasma (Hct )

CRYSTALLOID
10-6-3ml
discontinue

Summary of treatment of DHF

Cases of DHF should be observed every hour

Serial platelet & Hematocrit determination necessary, drop

in platelets & rise in HCt are essential for diagnosis of DHF

Timely IV therapy crystalloid solution can prevent shock

and/or lessen its severity

If the patients condition worsen after giving 20

20ml/kg/HR
ml/kg/HR
for one hour, replace crystalloid solution with colloid
solution such as dextran or plasma
plasma.. As soon as
improvement occurs replace with crystalloid.
crystalloid.

Cont

If improvement occurs, reduce the speed from 20

20ml
ml to
10
10ml,
ml, then to 6ml & finally to 3 ml/kg.
ml/kg.

If Hct falls, give blood transfusion

transfusion10
10/ml/kg
/ml/kg & then give
crystalloid fluid at the rate of 10
10ml/kg/Hr
ml/kg/Hr..For severe
bleeding give 20
20ml/kg
ml/kg for two hours.
hours.

In case of shock, give oxygen

For correction of acidosis, use sodium bicarbonate

Do not use antibiotics, aspirin, brufen & steroids

Change of fluid therapy should not be drastic

Sepsis

Definitions

Septicemia presence of microbes or their toxins in

blood.

SIRS (systemic inflammatory response syndrome) Two

or more of the following conditions

Fever -oral temp > 38 c or <36c

RR >24 breaths/min
HR> 90 /min
WBC >12000/mcl or <4000/mcl
May have noninfectious etiology

Sepsis SIRS with proven or suspected microbiological

etiology

Defini

Severe sepsissepsis- sepsis with 1 or more signs of

organ dysfunction
CVS

Renal

Jaundice

CNS

Acute renal failure

Hepatic

Shock tissue hypo perfusion lactic acidosis

Altered sensorium

RS

ARDS

Defini..

Septic shock

Sepsis with hypotension (SBP <90 mmHg) for at least 1 hr
despite adequate fluid therapy OR

Need for vasopressors to maintain systolic BP >90mmHg

Refractory septic shock

Shock that lasts for > 1hr and does not respond to IVF or
vasopressors

MODS ( multi organ dysfunction syndrome)

Dysfunction of more than 1 organ, requiring intervention
to maintain homeostasis

Sepsis sourcesource- community acquired & nosocomial

Pneumonia
UTI
Cellulitis

Predisposing factors

Diabetes
Cirrhosis liver
Burns
Indwelling catheter
Neutropenia

Cholecystitis
Meningitis
Abscess

Organ dysfunction

CVS

Renal

Jaundice

CNS

Acute renal failure

Hepatic

Shock tissue hypo perfusion lactic acidosis

Altered sensorium

RS

ARDS

Lab findings

Leukocytosis or leucopenia
Thrombocytopenia
Hyperbilirubinemia
Proteinuria
Low fibrinogen
Metabolic acidosis
Fibrin degradation products
D- dimers
cultures

Management

Elimination of source
Broad spectrum antibiotics

Ceftriaxone or ticaricillinticaricillin-clavulanate +
gentamicin

Ciprofloxacin + clindamycin

Vancomycin added if MRSA infections
Fluid resuscitation
Steroids
Activated protein C
Ventilator and ICU care for MODS and shock

Investigations

Blood
Complete hemogramhemogram- Hb/TC/DC/ESR/ Platelet/
peripheral smear

Blood sugar

LFT

S.Bilirubin, SGOT, SGPT, T.proteins, alb/globulin

RFT
S.Creatinine

Bl.urea

Contd..

Chest XX-ray

Ultrasound-- abdomen
Ultrasound

ECG

ABG

Urine analysis

Culture & sensitivity

Blood
urine

Investigation-- specific
Investigation

Malaria QBC/ peripheral smear

Leptospirosis ELISA/ MSAT/ MAT

Enteric fever blood culture/ widal

Dengue fever ELISA IgM

TB

Pulmonary -CxR, Sputum AFB

Extra pulmonary -lymph node & tissue biopsy

UTI Urine culture

Algorithmic approach

Fever

Organ dysfunction

No Organ dysfunction

Jaundice

Renal failure

ARDS

Shock

DIC/
Low platelet

Conclusion

Evaluate cause of fever

Assess organ failure

Start treatment aggressively

Empiric therapytherapy- very valuable

Organ dysfunctiondysfunction- refer to specialist