MORTALITY CASE

PRESENTATION
A RARE CASE OF CO-INFECTION
THAT DID NOT END WELL

Dr. Arnavjyoti Das

Senior Resident
Division of Critical Care Medicine,
Deptt. of Anaesthesiology,
IMS-BHU
PATIENT PROFILE
20 year old female
Hindu by religion
Student
Resident of Gazipur, UP
MRD 4265815
Came to EOPD, SSH on 17th August at 12:30 pm.
HISTORY
CHIEF COMPLAINTS
As obtained from the patient attendant in EOPD on 18th August at 6 pm by ICU Team:
1. Fever for 15 days
2. Yellowish discoloration of eyes for 10 days
3. Vomiting for 7 days
4. Altered sensorium for 5 days, and
5. Shortness of breath for 2 days.
HISTORY OF PRESENT ILLNESS
Patient had low grade continuous fever for 15 days, which was
o never recorded,
o remitting on paracetamol intake,
o associated with chills,
o but no diurnal variations,
o associated with occasional dry cough and malaise,
o but not associated with headache, chest pain with respiration or loose stool.
HISTORY OF PRESENT ILLNESS
Patient developed yellowish discoloration of eyes noted 4 days after the onset of fever,
o with passage of high coloured urine,
o was insidious in onset,
o gradually progressive, and
o not associated with clay coloured stool or pruritus
o associated with occasional diffuse pain abdomen and decreased appetite.
HISTORY OF PRESENT ILLNESS
Patient had bouts of vomiting 4-5 times a day, for 7 days, which was
onon projectile,
onon-bilious,
ousually associated with bad taste in mouth and lethargy.

Patient became less active, starting 5 days back, and

ogradually became less apprehensive about the surroundings, and
ostarted to have suboptimal diet, poor self care and became confined to bed
ostopped responding verbally 1 day back.
HISTORY OF PRESENT ILLNESS
Patient also had developed shortness of breath for 2 days which was
oacute in onset,
oprogressive in nature,
osaturation never recorded,
onot associated with exertion,
odid not aggravate on lying down,
oassociated with coughing, and
odid not relieve on bronchodilator medications.
TREATMENT HISTORY
The patient was taken to a local hospital a week after the onset of symptoms, where she
received conservative, mostly symptomatic managements with oral medications and underwent
investigations. But she did not show any signs of improvement, following which she was brought
to SSH EOPD on 17th August.
PAST HISTORY
There was no history of Hypertension, DM, IHD, Tuberculosis, COPD, Asthma, Rheumatoid
Arthritis, psychiatric illnesses.

No history of prior major trauma, medical or surgical diseases. No prior hospital admissions. No
ongoing chronic medications.

No h/o contact to COVID patients. No travel history in 6 months.

No h/o blood transfusion.
MENSTRUAL HISTORY
Unmarried
LMP - 08/08/21
Normal cycle and flow
No history of contraceptive use or conceptions.
FAMILY HISTORY
No significant family history.
PERSONAL HISTORY
Unmarried.
10+2 completed. Used to help in household choirs.
Belonged to a low socioeconomic family.
Mixed diet.
No h/o addiction or allergy.
No problems in bowel and bladder habits, sleep or appetite prior to illness.
PHYSICAL EXAMINATION
Patient was examined in the EOPD, with the help of a female nursing staff, with proper
precautions and privacy to the patient.
GENERAL EXAMINATION
General condition poor.

Drowsy, but arousable.

Not oriented to time, place and person.

Average built.

Height 152 cm, weight 50 kg, BMI 21.6 kg/m2.

GENERAL EXAMINATION
Pulse rate 140 bpm, regular, normovolemic, with no radioradial and radiofemoral delay.

BP 84/42 mmHg measured in the right arm in supine position.

RR 26/min, regular.

SpO2 97% @5 L/min O2 flow.

Febrile to touch, axillary temperature 101 degree F.

GENERAL EXAMMINATION
No pallor, cyanosis, clubbing, lymphadenopathy.
Icterus +
Bilateral pitting edema +.
No visible neck vein.
No neck rigidity
No gross skin, hair or nail lesions.
Thyroid was not palpable.
Tongue appeared moist and oral cavity was normal.
qSOFA score: 3
SYSTEMIC EXAMINATION
ABDOMEN EXAMINATION
A. Inspection:
i. Abdomen was distended.
ii. Flanks appeared full
iii. No venous prominences, scar marks, localized swelling or hernia
iv. Umbilicus was in midline, inverted
v. Abdominal skin appeared normal.
ABDOMEN EXAMINATION
B. Superficial Palpation:
i. Temperature was raised.
ii. RUQ tenderness could be elicited.
iii. Abdomen was soft in consistency, no rigidity.
iv. Fluid thrill was negative.
c. Deep Palpation:
i. Liver and spleen were not palpable
ii. Deep Tender Point are non tender
iii. Rebound tenderness was absent
iv. Urinary bladder and uterus were not palpable.
ABDOMEN EXAMINATION
D. Percussion:
i. Tympanic note is present in general with dull notes in flanks.
ii. Liver dullness present
iii. Shifting dullness +
E. Auscultation: bowel sounds present.
CNS EXAMINATION
A. Higher Functions:
i. Patient was drowsy but arousable. Not oriented to time, place and person.
ii. GCS E4V2M5
iii. Memory, intelligence and speech could not be assessed.
B. Cranium and Spine: appeared WNL.
C. Signs of Meningeal Irritation: Neck rigidity absent. Kernig’s sign absent.
D. Cranial nerves: limited assessment as patient was not cooperative.
i. Pupils are of normal size and reactive to light. (III)
ii. Corneal reflex present B/L (V)
iii. No drooling of saliva. (VII)
iv. Gag reflex present (IX, X)
CNS EXAMINATION
E. Motor Functions: Tone was normal. Power could not be assessed. No involuntary
movements.
F. Sensory Functions: Patient could localize pain. But sensory levels could not be assessed.
G. Reflexes: all superficial and deep reflexes appeared to be intact.
H. Cerebellar Functions, Autonomic functions and Gait could not be assessed.
RESPIRATORY SYSTEM
EXAMINATION
Upper Respiratory Tract: Appeared normal.
Lower Respiratory Tract:
A. Inspection of chest:
i. RR is 26/min, regular, with accessory muscle use
ii. Shape is WNL, chest moving equally with respiration.
iii. No venous prominence or scars seen.
iv. Skin over chest appeared normal. Nipples are in the same level.
RESPIRATORY SYSTEM
EXAMINATION
B. Palpation:
i. Surface temperature was raised.
ii. No tenderness. No subcutaneous emphysema.
iii. Chest symmetrical, moves normally. No spinal deformity.
iv. Trachea was in midline. Apex beat was in position.
v. Vocal fremitus could not be assessed.
vi. Cough reflex was poor.
C. Percussion: reveals resonant sounds B/L in all quadrants.
D. Auscultation: Air entry equal B/L, Coarse crepts + B/L.
CVS EXAMINATION
A. Pulse: 140 bpm, regular, normal volume, no delays, felt in all peripheral pulses.
B. BP: 84/42, measured in supine position, in right arm.
C. Examination of Neck Veins: not visible.
D. Examination of Heart:
i. Precordium appeared normal.
ii. Auscultation revealed S1, S2 +. No murmur.
DIFFERENTIAL DIAGNOSIS
1. Tropical fever 2. Acute hepatitis
a. Dengue a. Hepatitis A
b. Severe Malaria b. Hepatitis E
c. Leptospirosis c. Autoimmune Hepatitis
d. Scrub typhus 3. Liver abscess
e. Typhoid and Paratyphoid 4. Acute cholangitis
OUTSIDE REPORTS
TESTS 10/08/21 13/08/21 15/08/21
Hb 13.9 11.1 12.7
TLC/DC 5000 N68L23E7 5500 N60L32E3 5100 N60L30E3
PLC 115 70 105
SGPT/OT 164/75 1560/1200 1046/810
INR 1.23
ALKP 127 416 396
Bil T/D 3.8/1.4 5.1/3.5 4.5/3.9
Alb 4.4 2.8 3.0
U/Cr 25/0.7 33/0.7
Na/K 140/4.5
RBS 89 117
 OUTSIDE REPORTS
OTHER BLOOD TESTS ABG (14/8/21) USG W/A
(11/08/21)
HBsAg: NR Parameters Values
1. Liver, spleen normal size and
HBsAg: NR
Anti-HCV: NR echotexture.
Anti-HCV: NR
HIV pH 7.55 2. Kidneys are normal in size
HIV1,1,2:2:NRNR
and echotexture and CMD
present.
pO2 130 3. Uterus and ovaries normal.
Blood
BloodGroup:
Group:B Positive
B Positive
4. GB Lumen shows biliary
pCO2 41 sludge.
10/08/21 5. Free fluid seen in Cul de Sac.
(10/08/21)
WidalTest:
Widal Test: Negative
Negetive HCO3 36.5 Impression: GB sludge with PID
MPDA: Negative
MPDA: Negetive (?)
OUTSIDE CXR (17/08)
ABG IN EOPD (18/08; 5 pm)
Parameters Values
pH 7.529
pO2 63.6
pCO2 30
HCO3 24.4
AG 20
BE 2.8
AaDO2 48.6
P/F 158.8
Osm 276
Na 136.7
K 2.1
Cl 94.2
PROVISIONAL DIAGNOSIS
A 20 year old unmarried female presented to the EOPD with fever for 15 days, jaundice for 10
days, altered mental state for 5 days and dyspnea for 2 days, is provisionally diagnosed with
Acute Hepatitis of unknown etiology, possibly of infective origin, with Hepatic Encephalopathy,
Distributive Shock and Pneumonitis.
SHIFTING TO ICU
Patient was shifted to SSH ICU on 18th August at 8 pm.
Upon arrival, her vital signs were:
GCS: E4 V2 M5
HR: 156/min
BP: 97/41 mmHg
Spo2: 92% (@5 L/min O2 flow)
RR 28 breaths/min
Temperature 102 degree F
INITIAL RESUSCITATION
ABC approach of resuscitation was followed immediately after ICU admission.

She was put on Face Mask with Reservoir Bag to treat hypoxia. Her saturation increased to 95%.

To treat her hypotension, normal saline infusion was started and POCUS was performed, which revealed:
1. IVC: dilated with <18% collapsibility
2. EF: good (approximately >50%) with RV normal size and no RWMA
3. B profile: >3 in all quadrants, with pleural breaks+ in Rt side
4. B/L mild pleural effusion+ with ascites+
5. ONSD: Rt- 5.8 mm, Lt- 5.7 mm
6. DVT scan: Negative
 INITIAL RESUSCITATION
Depending on the POCUS result, patient was started on Noradrenaline infusion, after placement of a central
venous line, and restricted fluid intake.

Inj. Paracetamol 1 gm IV bolus over 20 mins given to treat fever.

All cultures sent, ABG done and Lactate showed to be 6.7 mmol/L.

Baseline Sr. PCT was found to be 14.7 ng/dL.

Patient was started on broad spectrum antibiotics (Meropenem and Doxycyclin).

Patient remained hypotensive, tachycardic and febrile despite Noradrenaline and PCM infusion, hence
prognosticated gravely.
ABG AT ICU ADMISSION
Parameters Values
pH 7.525
pO2 54.4
pCO2 27.5
HCO3 22.2
AG 23.6
BE 1.0
AaDO2 476.5
P/F 68
Osm 272
Na 135.9
K 3.3
Cl 93.4
INVESTIGATIONS ORDERED
1. Routine investigations (CBC, LFT, RFT, RBS, Urine R/M, CXR, ECG),
2. Hepatitis profile [Hepatitis A and E IgM, PT/aPTT/INR, Serum Ammonia].
3. Ultrasound abdomen was requested.

4. Complete fever profile was sent [Covid RT-PCR, Leptospira IgM/IgG, Scrub Typhus IgM/IgG,
Typhidot, MP, MPDA, Dengue IgM/IgG].

Lumbar puncture was not performed due to possible raised ICT as evident by ONSD.
INITIALLY ADVISED TREATMENT
1. Broad spectrum antibiotic (Meropenem, Doxycyclin)

2. Hepatic encephalopathy coverage was given (Lactulose with stool target, Rifaximine)

3. Stress Ulcer prophylaxis given.

4. Tab. Ursodeoxycholic acid was advised as well.

CLINICAL PROGRESSION
• Patient remained febrile despite starting on antibiotics, PCM and intermittent cold sponging,
cold gastric lavage and cold saline bladder wash.
1h

• Hemodynamically deteriorating, noradrenaline dose increased.

• Patient became drowsy (GCS<10) and desaturating.
2h
• Trachea was intubated and patient was put on MV with 1.0 FiO2.
• Persistent fever, tachycardia and hypotension.
3h • ETT culture was sent.
ABG @4 & 6 Hour th th
Parameters 4th Hour 6th Hour
pH 7.497 7.363
pO2 51.2 133.2
pCO2 23.7 27.6
HCO3 18.0 15.3
AG 26.0 24.3
BE -3.2 -8.4
AaDO2 343.5 539.0
P/F 51.2 133.2
Osm 288 263
Na 142.6 131.3
K 2.18 2.7
Cl 100.7 94.3
Lactate 10.69 Out of Range
CLINICAL PROGRESSION
• Continuous hemodynamic deterioration and persistent fever, tachycardia.
6h • Inf. KCl started.

• Patient was put on Vasopressin as the 2nd vasopressor.

10 h • Patient maintained U/O @>1 ml/kg/hr.

• Vasopressor requirement kept increasing. Fever, tachycardia persisted.

16 h • Inj. Hydrocortisone was added as intermittent boluses.
ABG @16th & 20th Hour
Parameters 16th Hour 20th Hour
pH 7.392 7.324
pO2 114.9 110.7
pCO2 29.6 28.6
HCO3 17.6 14.6
AG 25.4 24.4
BE -5.8 -9.9
AaDO2 554.6 560.7
P/F 114.9 110.7
Osm 280 297
Na 140.9 150.6
K 3.6 3.18
Cl 100.5 114.1
Lactate 9.93 10.86
REFERRALS
1. Gastroenterology ref. additionally advised for Autoimmune Liver profile (ANA, anti-Sm Ab,
anti-LKm1 and S. IgG4), Sr. Copper and Pl. Ceruloplasmin and injection of LOLA, on top of
advised treatments.

2. Cardiology ref. included bedside 2D Echocardiography which was normal.

3. Radiology ref. for USG W/A revealed normal liver/spleen size and echotexture, bilateral kidney
showed altered echogenicity and “Sweat sign” which is s/o AKI. IVC diameter was 1.36 mm and
portal vein diameter was 1.01 mm; moderate ascites and bilateral mild pleural effusion was
present.
CLINICAL PROGRESSION
24 h

Inj. Teicoplanin was added.

Patient is started on intermittent IV Vecuronium
boluses to counter ventilator asynchrony.
Inf. Phenylephrine started as 3rd vasopressor.
Hypernatremia correction started.
APACHE II score after 24 h ICU stay: 26
SOFA score: initial 14, highest 17.
ABG @24 Hour th
Parameters 24th Hour
pH 7.244
pO2 49.4
pCO2 38.9
HCO3 16.5
AG 23.1
BE -10.2
AaDO2 610.9
P/F 49.4
Osm 293
Na 147.6
K 3.77
Cl 111.8
Lactate 7.47
 INVESTIGATIONS RESULT
Tests 19/08/21 Tests 19/08/21
Hb 10.9 Covid RT PCR Negative
TLC/DC 3170 N76L18E3 Dengue NS1 Positive
PLC 69
Dengue IgM Positive
SGPT/OT 457/99
Dengue IgG Negative
INR 1.3
Leptospira IgM Positive
ALKP 179
Bil T/D 6.6/5.3 Leptospira IgG Positive
Alb 2.1 HAV IgM Positive
U/Cr 38.5/1.0 HEV IgM Negative
Na/K 147/2.3 Scrub Typhus IgM/IgG Negative
Sr. Amylase/Lipase 15/26 Ceruloplasmin 26.8 (WNL)
Ascitic tap Transudative
Sr. Copper 109 (WNL)
Sr. Ammonia 21 (WNL)
FINAL DIAGNOSIS
The patient is diagnosed with Acute liver failure from Dengue Shock Syndrome, Leptospirosis and
Hepatitis A, with Pneumonitis.
CLINICAL PROGRESSION
• Albumin was started in view of low albumin.
• Vasopressors and MV are continued in full support, still patient is hypotensive, tachycardic
30 h and desaturating (SpO2 82% in 1.0 FiO2)

•POCUS findings are unchanged.

•Ventilator Mode readjusted from PCV to PRVC..

• U/O decreased drastically. Sodium bicarbonate is started in infusion. CRRT started.

• 25%Dextrose infusion is started to counter new onset recurrent hypoglycemia.
ABG @ 30th, 36th & 40th Hour
Parameters 30th Hour 36th Hour 40th Hour
pH 7.144 7.156 6.892
pO2 72.6 74.4 49.8
pCO2 34.2 38.8 46.2
HCO3 11.8 13.4 8.2
AG 25.8 25.5 28.3
BE -14.8 -14.6 -17.4
AaDO2 534.7 587.1 489.7
P/F 72.6 74.4 49.8
Osm 293 284 287
Na 146.1 142.5 148.2
K 5.8 6.03 7.12
Cl 108.5 107.7 114.2
Lactate 11.73 11.08 Out of Range
CARDIAC ARREST AND DEATH
Approximately after 40 hours of ICU admission, despite maximum vasopressors and mechanical
ventilation support, patient went into cardiac arrest, and CPR started as per ACLS protocol.

Even after 30 minutes of CPR, ROSC could not be achieved.

Patient is declared to be dead at 3:30 pm, on 20th August, 2021

CASE SUMMARY
A 20 year old unmarried female, presented to the EOPD on 17th August, with fever for 15 days,
jaundice for 10 days, altered mental status for 5 days and dyspnea for 2 days, was diagnosed
with Acute Liver Failure from Dengue Shock Syndrome, Leptospirosis and Hepatitis A, with
pneumonitis, septic shock and AKI, succumbed to death 40 hours after ICU admission despite
maximum treatment.
 Metabolic acidosis and
Hyperkalemia 10 hours

AKI 10 hours

Acute Liver Failure, Septic

40 hours
shock and Pneumonitis

Dengue Shock Syndrome,

40 hours
Leptospirosis and Hepatitis A
DISCUSSION
WHY WAS THIS CASE CHOSEN?
There is no reported case of Co-infection with Dengue, Hepatitis A and Leptospirosis.
These three diseases share the common risk factors, which are frequent travel, inappropriate
hygiene, poorly developed drainage system, inadequate vector control and low socioeconomic
condition.1
Data has shown, that the chance of infection with Leptospira, and subsequent chance of shock
and mortailty is increased in a patient who is already infected with Dengue virus serotype 1.2
Multiple regression analysis data had shown, that presence of shock and male sex can predict a
co-infection of Leptospira and Dengue.2
PATHOGENESIS OF CO-INFECTION 3
SEVERITY OF ILLNESS
All these three diseases separately are known to cause hepatitis. However, the illness severity and
clinical outcome of this ‘triple infection’, has not been studied yet as previously there is no case
reported.

The rapidly progressive course of ‘triple infection’ in our patient suggested a possible worse
outcome than individual diseases.

So, this case opens up a possibility to initiate a prospective study in that direction, which would aid
us in treating patients, without mistakenly ruling out any of them based on one positive report.
LIMITATIONS WE FACED
1. Delayed presentation
2. Non availability of definitive tests, e.g. RT PCR for Dengue, HAV and MAT for Leptospirosis.
SCOPE OF IMPROVEMENT
1. A dedicated ‘Resuscitation Team’ in EOPD
2. Better point of care testing in EOPD
REFERENCE
1. Concurrent infection of dengue fever and hepatitis A infection: A case report; Zaki et al;
IJCCM 2011 Oct-Dec Vol 15 Issue 4.

2. Clinical predictors of dengue fever co-infected with leptospirosis among patients admitted
for dengue fever – a pilot study; Suppiah et al; J Biomed Sci. 2017; 24: 40.

3. Comparison between three rare cases of co-infection with dengue, leptospira and hepatitis
E: is early endothelial involvement the culprit in mortality?; Singh et al; Ann Med Health Sci
Res. 2014 Mar-Apr; 4(Suppl 1): S32-S34.
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