Morbidity and Mortality Conference

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Morbidity and Mortality Conference

• Jay V. Dy M.D.
• Medical Resident

2

• Good Morning!

3
Learning Objective

• To present a case of Severe Leptospirosis and
  discuss its diagnosis, pathogenesis,
  complications and mode of treatment.

4
Identifying Data

• D.D.
• 25 year old female
• Filipino
• single
• Chief Complaint Fever

5
History of Present Illness

• 4 days PTA- undocumented intermittent fever
  () body malaise, () dry cough ()
  sorethroat, (-) colds, rashes
• self-medicated with paracetamol affording
  temporary relief.

6
History of Present Illness

• Few hrs PTA - persistence of symptoms ()
  diarrhea, 2x () crampy epigastric pain.
  () nausea
• (-) vomiting
• Admission

7
Review of systems

• (-) headache
• (-) dizziness
• (-) difficulty of breathing
• (-) orthopnea
• (-) paroxysmal nocturnal dyspnea

• (-) palpitations
• (-) dysuria
• (-) urinary frequency
• (-) joint pains

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Past Medical History

• Diagnosed w/ Leptospirosis 7 yrs ago
• Unrecalled work up
• Admitted St Pauls Hospital for several days
• Given unrecalled IV antibotics
• Non hypertensive
• Non diabetic
• Non asthmatic
• No known allergies
• No previous operation

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Family History

• () Hypertension- father
• () DM- mother
• (-) Bronchial asthma
• (-) PTB
• (-) Cancer

10
Personal/ Social History

• Non smoker
• Non alcoholic beverage drinker
• Works in the office

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Physical Examination

• General survey conscious, coherent not in
  respiratory distress
• Vital signs BP 110/70, HR 98 RR 20, T 38c
• Skin No rashes, no jaundice
• HEENT pinkish palpebral conjunctivae, anicteric
  sclerae, no nasoaural discharge, no
  tonsillopharyngeal congestion, dry lips and
  tongue, no cervical lymphadenopathy, flat
  neck veins

12
Physical Examination

• Chest/Lungs equal chest expansion, no
  retraction, clear breath sounds
• Heart Adynamic precordium, normal
  rate, regular rhythym, S1 louder than S2 at the
  apex, S2 louder than S1 at the base, PMI at
  5th ICS, LMCL, no murmur
• Abdomen flabby, normoactive bowel sounds, soft,
  no tenderness, no palpable mass, no
  hepatosplenomegaly
• Extremities no gross deformities, no
  edema, no cyanosis, full and equal pulses

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Salient features

• 25 y.o, F, single
• cc fever x 5 days
• body malaise, dry cough, sore throat
• () 2 episodes of diarrhea
• () crampy epigastric pain
• () nausea
• P.E. Temp 38c
• Flat neck veins
• Dry lips and tongue

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At the E.R.
15
Day of Admission
16
Initial Impression

• Acute gastroenteritis with some signs of
  dehydration
• T/C Dengue fever

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Course in the Wards 1st hospital day (8/3)

• intermittent fever (D6) (Tmax - 39.5 c)
• bloatedness
• crampy epigastric pain
• diarrhea, 8x
• vomiting, 1x
• Secnidazole 500mg/tab. 4 tabs as single dose
• Metoclopramide 10 mg Iv push q8
• Loperamide 2 tabs x 1 dose
• IVF rate increased to 166 cc/hr.

18
Course in the Wards 1st hospital day (8/3)

• PTT - 49.6 (n.v. 25.1-33.9 secs)
• PT was normal
• plt ct 69,000 from 109,000
• gt Monitoring of platelet ct q 12 hrs.
• gtStand by 4 units of FFP

19
2nd hospital day (8/4)

• on and off fever (D7) (37.0- 39.5 c)
• bloatedness
• crampy epigastric pain
• 7 episodes of LBM
• 3 episodes of vomiting
• direct epigastric tenderness
• Plain film of the abdomen no localizing signs
• hydration/meds were continued
• additional dose of Loperamide and Eldicet
• started Vamin glucose

20
2ND Hosp day
21
Course in the Wards 2nd hospital day (8/4)

• Lab test
• K - 2.3
• BUN - 23
• creatinine - 3.1

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Course in the Wards 2nd hospital day (8/4)

• Problem () Difficulty of breathing
• Respiratory rate 26
• Flat neck veins
• Clear breath sounds
• ABG uncompensated metabolic acidosis.
  pO296.9, pH7.28, Pco220.1, HCO39.3, O2
  sat96.8, B.E.-14.9, Total CO29.9, RR26, Rm
  air
• given NaHCO3 IV

23
2nd hosp day (aug4)
24
Course in the Wards 2nd hospital day (8/4)

• CBC Hgb 8.2, hct 23.6, seg 8,320, seg 77, lym
  17 and plt ct 71,000
• gtReserved 2 u prbc
• gtrepeat CBC w/ plt ct in am
• gtBlood culture done
• gtReferred to Nephrology Infectious disease
  service

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3rd hospital day (8/5)

• () fever (D8) (Tmax39.6 c)
• () Epigastric tenderness
• () decreased BM (semi-formed to soft)
• (-) vomiting
• Rpt CBC Hgb 8.4, hct 24.4, plt ct 84,000
  from71,000
• Transfused 1 of 2 unit Prbc
• Increased omeprazole to 1 cap BID

26
Course in the Wards 3rd hospital day (8/5)

• PTT- 49.6
• PT Activity 66.4 INR 1.2
• Vitamin K given
• Urinalysis showed proteinuria 2, Blood 3, elev
  RBC 572.2, elev WBC 14.4
• Urine CS requested

27
3rd hospital day

• Problem () dyspnea
• () distended neck veins
• () bibasal crackles
• () bipedal edema
• Lasix 40mg IV given
• IVF rate was decreased to 40cc/hr
• Central line inserted (13-14 cmH2O)

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2nd hosp day 3rd hosp day
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3rd hospital day (8/5)

• Stat ABG Po2 52.3, Ph 7.27, Pco2 32.3,
  HCO3 14.7, O2 sat 83,B.E.
• -10.9, TCO2 15.7, RR 28 (O2 2LPM via Nasal
  cannula).
• gt Nasal cannula was shifted to MVM
• gt stand by intubation
• gt scheduled for stat Hemodialysis

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Course in the Wards 3rd hospital day (8/5)

• Spec (pre HD)
• K 2.7, Ca 1.5, total protein 4.6 and Albumin
  1.6
• bun 23, crea 3.1, SGOT 336, SGPT 78 and
  T. Bili 1.4.
• Given K, Ca, and albumin correction

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Course in the Wards 3rd hospital day (8/5)

• During dialysis transfused w/ 4 units FFP
  (150cc/unit/bag)600cc
• 1 unit Prbc (250cc)
• 550cc flushing/ meds
• Na HCO3 drip _at_ 40 cc/hr x 4 hrs 160cc
• Ca Gluconate drip _at_ 80 cc/hr x 4 hrs 320cc
• Kcl drip 10 40meqs x 4 hrs 100cc
• UF Volume (output)4,000 cc
• HD total Input 1,980 cc

32
3RD hosp day (Aug 5)
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Course in the Wards 3rd hospital day (8/5)

• gt scheduled for another hemodialysis.
• gt Total Input3,910 cc vs
• Total output4,340 cc (urine 340 HD 4,000cc)

34

• Leptospira antigen test() IgM
• gt Penicillin G 2 million units IV q 4 given.

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4th hospital day (8/6)

• Problem dyspnea
• BP 110/60 CR 120s RR40s
• decreased urine output (7-8 cc/hr)
• () bloody secretions/sputum.
• CVP 15 cmH2O
• ABG Po2 39, ph 7.41, Pco2 32.9, HCO3 20.6, O2
  sat 75.1, B.E. -3.0, TCO2 21.6, RR 60 MVM 0.4
• reffered to a pulmonologist

36
Course in the Wards 4th hospital day (8/6)

• immediately intubated
• hooked to a mechanical ventilator (settings AC
  mode, FiO2 100, RR 20, TV 300, PEEP 5).

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post intubation
38

• ABG 1 hr post intubation still showed hypoxemia
  (pO2 58, O2 sat 91.7 5)
• Atrovent neb given
• PEEP was increased to 7.5
• Patient immediately underwent (2nd)hemodialysis

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Course in the Wards 4th hospital day (8/6)

• Pre HD Labs
• decreased serum K (2.4 from 2.7), Ca 1.9,
  Phosphorus 2.3 and Mg 1.6 (2.5-4.9).
• Serum creatinine further increased (4.6 from 3.1)
• Patient was given K, Ca, Mg and phosphorus
  correction

40
Course in the Wards 4th hospital day (8/6)

• During dialysis
• 100cc flushing/ meds
• PNSS 40 cc/hr x 4 hrs 160cc
• Vamin glucose 40 cc/hr x 4 hrs 160cc
• Albumin 50cc
• HD total Input 470 cc
• UF Volume (output)3,000 cc

41
Course in the Wards 5th hospital day (8/7)

• afebrile
• () tachycardia (100-118)
• () decreased urine output (4-5cc/hr)
• JVP 13cmH2O
• Lasix was continued

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Post Intubation 5th Hosp day
43
Course in the Wards 5th hospital day (8/7)

• Patient underwent 3rd hemodialysis.
• During dialysis
• 50cc flushing/ meds
• K Phos 40mmol in PNSS 100ccx 4hrs 100cc
• Ca Gluc 5 g in 450cc pnss x 20cc/hr x 480cc
• MgSO4 5 g in 500cc PNSS X 20cc/hr x 480cc
• total Input 470 cc
• UF Volume (output)2,000 cc

44
Course in the Wards 5th hospital day (8/7)

• Pulmonary service was able to bring down FiO2 to
  0.6 but had desaturation
• eventually placed back to 100 FiO2
• More bloody secretions coming out/ suctioned from
  ET
• Frequent/ prn suctioning of secretions.
• PEEP was increased to 10.

45
Course in the Wards 5th hospital day (8/7)

• CBC Hgb 12.1, hct 35.1, wbc (15, 760 from
  6,850), seg 74, plt ct 135,000 fro 128,000).
• Pen G was discontinued
• Piperacillin Tazobactam 2.25 IV q8 was started.
• Total Input 2,298cc
• Total Output 2,107cc
• (Urine 107 cc HD 2,000cc)

46
Course in the Wards 6th hospital day (8/8)

• afebrile (D2)
• lesser bloody secretions from ET.
• Persistent oliguria (4-5 cc/hr)
• Lasix was continued
• patient had another dialysis (4th)

47
Course in the Wards 6th hospital day (8/8)

• During dialysis
• 50cc flushing
• 100cc OF
• Ca Gluc 5 g in 450cc pnss x 20cc/hr x 480cc
• Dialysis terminated due to BP 94/63 (3rd hr)
• Bp went up 110/70 after
• total Input 230 cc
• UF Volume (output)1,700 cc

48
Course in the Wards 6th hospital day (8/8)

• chest xray post HD clearing of bilateral lung
  infiltrates.
• FiO2 was titrated down to 30.

49
S/P 4th dialysis
50
Course in the Wards 6th hospital day (8/8)

• Problem desaturation (02 sat 50).
• Fi0 was increased to 100
• suctioning of secretions
• ambubagging
• BP noted to be 0, HR 0.
• hooked to a cardiac monitor flat line.
• CPR done
• Given epinephrine 1 dose

51
Course in the Wards 6th hospital day (8/8)

• revived after 3 minutes
• Dopamine drip was started.
• Bp went up to 110/70 from 50 pallpatory
• ABG mixed (slight) metabolic and respiratory
  acidosis with PO2 496 at FiO2 1.
• Patient became fully awake and responsive

52
Course in the Wards 6th hospital day (8/8)

• 30 mins after referred again (O2 desaturation
  80)
• suctioned secretions
• BP0, HR0, flat line on cardiac monitor
• CPR was done but after 15 minutes, relatives
  ordered to discontinue CPR
• Patient was then declared expired.

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Problem 1 Fever/Diarrhea

• Sgt DOA () Fever, () diarrhea ()
  myalgia () nausea/ vomiting/ epigastric
  pain () dec platelet ct. 69,000 from
  109,000
• Ogt Temp 38c flat neck veins Dry lips
  and tongue

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Problem 1 Fever/Diarrhea

• Agt T/C Dengue fever gt Acute gastroenteritis
  with some signs of dehydration gt R/O
  Typhoid fever
• Pgt Plasil 10 mg IV q 8 for vomiting Loperamide
  tab Ciprofloxacin 500mg tab
  bid Secnidazole tab 4 tabs x 1 dos Hydration
  IVF platelet ct monitoring q12
• Blood CS

55
Problem 1 Persistent fever

• Sgt 3rd hospital day
• () fever (D8) () wading in floodwater
  3wks
• () Myalgia before onset of fever
• () nausea
• () decreased urine output/ elevated crea 3.1
• () elevated SGOT 336
• Ogt temp 38.5c
• Agt T/C Leptospirosis
• Pgt Leptospira Igm ()
• Penicillin G 2 million units IV q4

56
Problem 1 Persistent feverT/C Typhoid fever

• Points for
• Prolonged fever (75)
• Abdominal pain (20-40)
• Diarrhea (30-50)
• Non specific symptom (myalgia, nausea)

• Points against
• gtNo rash (rose spots)
• (30)
• gtNo response to Ciprofloxacin despite 3 days tx
• gtNegative Blood Culture (60-90 yield)

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Problem 1 Persistent feverMalaria

• Points for
• gtFever spikes

• Points Against
• No history of travel to endemic areas
• Prominent diarrhea and abdominal pain suggests
  another dx
• gtnon specific symptoms (no headache, chills)

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Fever pattern
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Problem 2 Decreased urine output
Oral/ OF Parenteral Total Input Urine Crea BM Dialysis Total output
DOA 1,660 1,640 3,300 9x 9x
1st HD 3,325 3,300 6,625 13x 8x
2ndHD 2,260 4,620 6,880 9x 3.1 7x
3rdHD 1,090 2,820 3,910 340 3.1 2x 4,000 4,340
4thHD 810 1008 2,933 78 4.6 1x 3,000 3,078
5thHD 673 1625 2,298 107 3.8 1x 2,000 2,107
6thHD 460 568 1,028 33 2x 1,700 1,733
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Problem 2 Decreased urine output

• Ogt JVP 6-7cm H2O ------gt JVP 12-13 cm H2O Clear
  breath sounds----gtBibasal crackles (-)
  edema--------gtgrade 2 bipedal edema
• Agt Acute renal failure probably pre renal 2 to
  dehydration (GI fluid loss) and/or Intrinsic
  renal failure secondary to leptospirosis
• Pgt accurate I O monitoring monitor bun,
  crea, electrolytes
• hydrationlt--------gthemodialysis

61
2nd HD 3RD HD 4TH HD 5TH HD
Na 135-145 mmol/L 135 140 132 135
K 3.5-5.5 mmol/L 2.3 2.7 2.4 2.9
BUN 2.5-6.5 mmol/L 23 (8.3) 23 (8.3) 37 (13.2) 31 (11)
Crea 53-88 Umol/L 3.1 (274) 3.1 (274) 4.6 (406.6) 3.8 (335)
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Problem 3 Difficulty of Breathing

• Sgt () Difficulty of breathing
• ()bloody secretions
• urine output 340cc/24 hrs(14cc/hr)
• total input4,490cc/24 hrs(187cc/hr
• Ogt RR40s
• () distended neck veins () bibasal
  crackles () bipedal edema

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Problem 3 Difficulty of Breathing

• Agt Acute Respiratory failure 2 to Pulmonary
  congestion probably secondary to Acute renal
  failure

64

• 2nd hosp day

Day of Adm
65

• 3rd hosp day

3rd hosp day
66
4th Hosp day
5th Hosp day
67
6th Hosp day Post dialysis

• 5th Hosp day

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(No Transcript)
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Problem 3 Difficulty of Breathing

• Pgt Nasal cannula was shifted to MVM
• gt stand by intubation--?Intubated
• gt Hemodialysis
• gt NaHCO3 IV
• gt CVP monitoring
• gt Accurate I O

70
Problem 4 Hypokalemia

• Sgt () diarrhea x several episodes
• () vomiting x several episodes
• Agt Hypokalemia probably 2 to GI loss (diarrhea)
• Pgt Na, k, crea monitoring
• KCL drip

71
Problem 5 ANEMIA

• Sgt () bloody/frothy secretions suctioned per ET
• (-) black stools/ bloody stools
• Ogt pale palpebral conjunctivae
• (-) Petechiae
• (-) bruises

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DOA 1st HD 2ndHD 3rdHD AM 3RDHD PM 5THHD 6THHD
Hgb 12.1 10.5 8.2 8.4 14.8 12.1 10.4
Hct 35.5 30.8 23.6 24.4 42.3 35.1 30.2
RBC 4.3 3.8 2.9 3 5.3 4.4 3.8
WBC 13,470 7,960 8,320 6,850 15,650 15,760 16,580
Seg 91 80 77 79 76 74 75
Lym 6 18 18 17 17 15 14
Mon 3 2 4 4 6 9 10
Plt ct 109,000 69,000 71,000 84,000 128,000 135,000 180,000
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Problem 5 ANEMIA

• Agt Anemia probably secondary to acute blood loss
• (T/C Alveolar /Interstitial hemmorhage)
• T/C Anemia secondary to renal failure
• T/C Anemia secondary to Sepsis
• Pgt CBC monitoring
• Blood transfusion(2 u prbc)
• PT/PTT- prolonged PTT (49.6)
• Peripheral smear
• rbc normocytic, normochromic,
• pletelets decreased

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DIAGNOSIS

• 1 Severe Sepsis (Leptosprosis)
• 2 Acute renal failure probably Intrinsic and pre
  renal secondary to leptospirosis and dehydration
  (GI fluid loss)
• 3 Acute respiratory failure 2 to 2
• 4 Anemia probably secondary to alveolar
  hemorrhage, renal failure and Sepsis
• 5 Hypokalemia secondary to GI loss (diarrhea)

75
Cause of Death ?

• Mucus Plug
• Septic Shock
• Arrhythmia
• Hypokalemia
• Pulmonary Embolism

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Cause of Death ?
Points For Points Against
Mucus plug Sudden dyspnea Sudden O2 desaturation () mucus plugs/ big blood clots on the tip and inside the lumen of the Endotracheal tube upon removal
Septic Shock Elevated WBC count 16,580 from as low as 6,850 Tachycardia () Leptospira IgM Had O2 desaturation first before BP went down
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Cause of Death ?
Points For Points Against
Arryhthmia/ Hypokalemia K 2.9 Cardiac monitor showed no arrythmia Improving K level (2.9 from 2.4) w/ ongoing correction
Pulmonary Embolism Sudden onset dyspnea, O2 desaturation, tachycardia, Patient is relatively immobile (intubated) pO2 400
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CASE DISCUSSION Leptospirosis
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Leptospirosis

• zoonosis with protean manifestations
• caused by the spirochete, Leptospira interrogans

80

• Infection in small rodents (carrier animals)
  usually occurs during infancy
• animals shed the organism in their urine
  intermittently or continuously throughout life
  resulting in contamination of the environment,
  particularly water.
• Organisms may remain viable for days to months
  in soil and water with a neutral pH.

81

• Portals of entry include cuts or abraded skin,
  mucous membranes or conjunctiva. The infection is
  rarely acquired by ingestion of food contaminated
  with urine or via aerosols.
• Controversy exists as to whether Leptospira can
  penetrate the intact skin.

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Risk factors for infection

• Occupational exposure farmers, ranchers,
  abattoir workers, trappers, veterinarians,
  loggers, sewer workers, rice field workers,
  military personnel, laboratory workers
• Recreational activities fresh water swimming,
  canoeing, kayaking, trail biking

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• Household exposure pet dogs, domesticated
  livestock, rainwater catchment systems, and
  infestation by infected rodents.
• Other Skin lesions, contact with wild rodents

84

• The spirochetes enter the host through abraded
  skin or intact mucous membranes and travel to the
  liver where they reproduce.
• After an incubation period of 2 to 30 days
  (usually 5 to 14 days), leptospiremia occurs,
  spreading organisms to all parts of the body
  including the meninges

85
LEPTOSPIROSIS

• 2 general patterns occur
• 1 anicteric leptospirosis (90)
• 2 icteric leptospirosis or Weil disease (10)

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CLINICAL MANIFESTATIONS

• fever (75 to 100)
• Myalgias (50-80)
• headache (15-30)
• nonproductive cough (25 to 35)
• nausea, vomiting and diarrhea (50)

87

• less common symptoms
• arthralgias
• bone pain
• sore throat
• abdominal pain

88

• Physical examination
• conjunctival suffusion- (40-70)
• muscle tenderness (30-40)
• Jaundice (50-80 in severe form)
• Splenomegaly
• Lymphadenopathy
• Pharyngitis
• Hepatomegaly
• skin rash

89

• Liver failure is generally reversible and not a
  cause of death in leptospirosis.
• Dyspnea, oliguria, WBC counts above 12,900/mm3
• Alveolar infiltrates on chest radiography have
  been associated with adverse outcomes.

90

• Complications While most cases of leptospirosis
  are mild to moderate, the course may be
  complicated by renal failure, uveitis,
  hemorrhage, acute respiratory distress syndrome,
  myocarditis and rhabdomyolysis

91

• The potential severity of leptospirosis was
  illustrated in a retrospective study of 60
  patients with leptospirosis requiring ICU
  admission in India .
• Multiorgan failure developed in 46 patients (77
  percent)
• the mortality for patients with leptospirosis
  requiring ICU admission was 52 percent.

92

• Severe pulmonary disease may be underdiagnosed in
  regions of high endemicity.
• Among 321 patients with serologic and clinical
  evidence of leptospirosis in Peru, seven (3.7
  percent) had severe pulmonary manifestations,
  including hemoptysis in six
• 5 of the 7 patients died, 4 from pulmonary
  hemorrhage and 1 from acute respiratory distress
  syndrome and multiorgan failure

93

• LABORATORY FINDINGS Leptospirosis is a
  nonspecific clinical illness, and routine
  laboratory tests are similarly nondiagnostic.
• White blood cell (WBC) counts are generally less
  than 10,000/mm3 but may range between 3,000 and
  26,000/µL
• Urinalysis frequently shows proteinuria, pyuria,
  granular casts and occasionally microscopic
  hematuria
• Elevated creatine kinase is found in
  approximately 50 percent of patients and may be a
  useful clue for the diagnosis

94

• Approximately 40 percent of patients have minimal
  to moderate elevations of hepatic transaminases
  (usually lt200 IU/L). Hyponatremia is common in
  severe leptospirosis.

95

• Thrombocytopenia is uncommon, but a poorly
  understood hemorrhagic diathesis may occur in the
  absence of demonstrable coagulation defects or
  severe thrombocytopenia. Pancytopenia has been
  reported as the presenting manifestation in case
  reports with complete resolution following
  treatment with penicillin 29. The CSF may show
  a neutrophilic or lymphocytic pleocytosis with
  minimal to moderately elevated protein
  concentrations and normal glucose. A low CSF
  glucose concentration is rarely seen 30.

96

• Imaging Chest radiographs may show small
  nodular densities, which can progress to
  confluent consolidation or a ground glass
  appearance Pathologically, these infiltrates may
  represent alveolar hemorrhage, ARDS, or pulmonary
  edema

97

• DIAGNOSIS Because the clinical features and
  routine laboratory findings of leptospirosis are
  not specific, a high index of suspicion must be
  maintained for the diagnosis. The organism can be
  cultured, but the diagnosis is more frequently
  made by serologic testing.

98

• Culture As noted above, leptospirosis can be
  confirmed by culture of the organism from
  clinical specimens in appropriate media. B
• Blood and CSF specimens are positive during the
  first 10 days of the illness. I
• Isolation of the organism from the blood is
  successful in approximately 50 percent of cases.
• Urine cultures become positive during the second
  week of the illness and remain so for up to 30
  days after the resolution of symptoms

99

• Serology Because some clinical microbiology
  laboratories do not offer culture for the
  diagnosis of leptospirosis, serological tests are
  most often used for confirmation.
• A number of serologic tests are employed or are
  under development, including the microscopic
  agglutination test (MAT), macroscopic
  agglutination test, indirect hemagglutination,
  and ELISA

100

• While all of these assays are useful in
  establishing the diagnosis, the gold standard is
  considered to be the MAT Unfortunately, this test
  requires live organisms, considerable expertise,
  and is performed only by reference laboratories
  such as the CDC.
• Like other serologic tests, the MAT is most
  specific when a fourfold or greater rise in titer
  is detected between acute and convalescent serum
  specimens. However, a single titer of gt1800 is
  strong evidence of current or recent infection
  with leptospira.

101

• Cross reactive antibodies have been associated
  with syphilis, relapsing fever, Lyme disease, and
  legionellosis 1. The level of the antibody
  titers as found in the MAT cannot be used to
  predict the serovar that infects the individual
  patient

102

• Since the MAT is not readily available, another
  assay typically is performed first in suspected
  cases of leptospirosis.
• Two commercially available rapid tests, the
  microplate IgM ELISA and an IgM dot-ELISA
  dipstick test, performed well in studies
  conducted in the United States and Thailand that
  used MAT as the comparator
• If one of these assays is positive, sera for MAT
  can then be sent to the CDC

103

• LEPTOCHECK (Rapid test for antibodies to
  Leptospira)
• Sensitivity 100 (only 90 in a study made in
  India by Maskey et at)
• Specificity 92 (Maskey et at)

104

• TREATMENT The vast majority of infections with
  leptospira are self-limiting.
• Although penicillins, tetracyclines,
  chloramphenicol, and erythromycin have anti
  leptospiral activity in vitro and in animal
  models, it remains controversial whether
  antimicrobials produce a beneficial effect in
  mild human leptospirosis since the illness has a
  variable natural history.

105

• Nevertheless, if the illness is severe enough to
  result in a physician visit and the diagnosis is
  recognized, antibiotic therapy should be given.

106

• Efficacy Two small, randomized,
  placebo-controlled trials have shown a benefit
  from antimicrobial therapy. In one in which
  doxycycline (100 mg PO twice daily) was compared
  to placebo, doxycycline shortened the illness by
  an average of two days and prevented shedding of
  the organism in the urine 1.

107

• In the second trial, patients with severe
  leptospirosis who were treated with penicillin (6
  million units daily) had fewer days of fever,
  more rapid resolution of serum creatinine
  elevations, and a shorter hospital stay
  penicillin therapy also prevented urinary shedding

108

• Supportive care with dialysis, ventilatory
  support, and blood products may be necessary in
  severe cases of leptospirosis.
• Antimicrobial treatment Human leptospirosis is
  often self-limited and requires no antibiotic
  treatment.
• Symptomatic patients presenting for medical care
  should be treated to shorten the illness and
  decrease shedding of the organism in the urine.
  We suggest the following approach that varies
  with the clinical presentation

109

• We suggest treatment with oral doxycycline for
  outpatients because it is also effective for
  rickettsial disease, which can be confused with
  leptospirosis (100 mg orally twice daily in
  adults 2 mg/kg per day in two equally divided
  doses in children 8 years of age to a maximum
  dose of 200 mg daily).

110

• The exceptions are children 8 years or pregnant
  women, in whom we suggest treatment with
  amoxicillin (25 to 50 mg/kg in three equally
  divided doses).

111

• For hospitalized adults with severe disease, we
  suggest intravenous therapy with penicillin (6
  million units daily), doxycycline (100 mg twice
  daily), ceftriaxone (1 g every 24 hours), or
  cefotaxime (1 g every six hours).

112

• PROGNOSIS Mortality rates in hospitalized
  patients with leptospirosis have ranged from 4 to
  50 percent.
• Pulmonary hemorrhage (30-70) A retrospective
  review of 282 cases of leptospirosis during a
  2002 outbreak in India identified risk factors
  for mortality

113

• Most authorities agree that if antibiotics are
  not started early in the disease (up to the
  fourth day), they do not change the course of the
  illness (50-80motality)

114

• PREVENTION Vaccination of domestic animals
  against leptospirosis provides substantial
  protection, but is not effective in 100 percent
  of animals. Some immunized animals become
  infected and excrete leptospires in their urine.

115

• The major control measure available for humans is
  to avoid potential sources of infection such as
  stagnant water, water derived from run off from
  animal farms, rodent control, and protection of
  food from animal contamination.

116

• Thank you