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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