MEDICINE (Dr.

Cerrada)

INFECTIOUS DSE: LEPTOSPIROSIS

17 AUGUST 2017

z liver histopathology: focal necrosis, foci of inflammation, and

LEPTOSPIROSIS
plugging of bile canaliculi.
Etiologic Agent: LEPTOSPIRA z No widespread hepatocellular necrosis
z Coiled, thin, highly motile organism z Petechiae hge.
z Have hooked ends and 2 periplasmic flagella
motility IMMUNITY:
z Stain poorly but can be seen microscopically by depends on the production of circulating antibodies to serovar-
dark- filed exams and after silver impregnation specific LPS.
z Takes weeks- months for cultures to become Activation of TLR- 2 and TLR- 4 are also demonstrated
positive
Epidemiology: CLINICAL MANIFESTATIONS:
z m.c. in tropics and sub- tropics Bleeding and multi- organ failure- clinical hallmarks of the
z m.c. in men disease (when the dse is severe)
z peaks during summer and fall and during rainy season in Mild presentations occur as a sudden onset of febrile illness
tropics Incubation period: 1- 2 weeks but can range 1- 30 days
z high risk occupations: veterinarians, agri. workers, sewage It is biphasic:
workers, slaughterhouse employees and in fishing industry a. Acute leptospiremic phase- fever of 3- 10 days and
z risk factors: direct or indirect contact with animals, exposure organism can be cultured from blood
to water and soil contaminated with animal urine b. Immune phase- antibodies appear in the blood, but
z in the Phils: endemic during the rainy months of June- Aug. leptospires disappear, therefore culture of organism is
Transmission taken from the urine sample.
nd
1. direct contact with urine, blood or tissue from an infected z Milder cases- do not include the 2 phase
animal or exposure to environmental conditions. z Severe cases- are usually monophasic
2. Human- human (controversial) Acute febrile illness for at least 2 days + either residing in a flooded
z Water is an impt. vehicle for transmission. area or high risk exposure + presenting at least 2 of the ff:
z Outbreaks: are due to exposure to flood waters contaminated by o myalgia, calf tenderness, conjunctival suffusion, chills, abdnal
urine from infected animals pain, h/a, jaundice or oliguria SHOULD BE CONSIDERED A
SUSPECTED LEPTOSPSIROSIS CASE (grade A)
PATHOGENESIS
Mild Severe
Entry flu-like illness of sudden rapidly progressive and is
(through cuts, abraded skin or mucous memb.) onset, with fever, chills, associated with a case
headache, nausea, fatality rate ranging from 1
vomiting, abdominal pain, to 50%.
conjunctival suffusion Higher mortality rates are
Leptospiremic phase (redness without exudate), associated with an age >40,
Organisms proliferate and disseminate and myalgia altered mental status, acute
hematogenously Muscle pain is intense and renal failure, respiratory
Initial incubation where leptospires can be especially affects the insufficiency, hypotension,
isolated from bloodstream (2- 28 days) calves, back, and abdomen. and arrhythmias
The headache is intense, classic presentation, often
localized to the frontal or referred to as Weil's
retroorbital region syndrome, encompasses the
Organisms survives and evade the complement (resembling that occurring triad of hemorrhage,
killing by binding factor H in dengue), and sometimes jaundice, and acute kidney
a strong inhibitor of complement accompanied by injury or (fever, jaundice
system photophobia and renal failure in the
Lepstospires resist ingestion and killing by Aseptic meningitis (more handouts)
neutrophils, monocytes and macrophages common with children)
PE findings: fever,
conjunctival suffusion,
pharyngeal injection,
IMMUNE PHASE muscle tenderness,
Appearance of antibodies but disappearance of lymphadenopathy, rash,
leptospires in the blood meningismus,
Bacteria persist in various organs including liver, hepatomegaly, and
lung, kidney, heart and brain. splenomegaly.
natural course of mild
PATHOLOGY: leptospirosis usually
Renal: involves spontaneous
z Acute tubular damage and interstitial nephritis interstitial resolution within 710
edema and acute tubular necrosis days,
z deregulation of the expression of several transporters along the
nephron, including the proximal sodium-hydrogen exchanger 3
(NHE3), aquaporins 1 and 2 (AQP1 and AQP2), Na+-K+ ATPase,
and the Na-K-2Cl cotransporter NKCC2, tubular potassium
wasting, hypokalemia, and polyuria

1
DIAGNOSTICS:
Direct Detection
z culture and isolation z Microagglutination
GOLD standard
Time consuming and
labor intensive
6- 8 weeks result
needs dark- field
microscopy
low dx yield
can identify serovar
but insensitive
z PCR
Adv: early
confirmation of the
dse esp. during the
acute phase of the
illness before the
appearance of
antibodies z Specific IgM Rapdi
z Non- specific rapid
PROPHYLAXIS
Indirect Detection Pre- exposure
Test Doxycycline 200mg once weekly, to being 1-2 days before
(MAT) exposure and continued throughout the period of exposure.
o 4- fold increase in titer Post- exposure
from acute to Doxycycline 200mg, duration depends on the degree of
convalescent is exposure and the presence of wounds.
confirmatory a. Low-risk exposure: Doxycycline 200mg single dose
o adv: highly sensitive within 24-72 hours from exposure. [Grade B]
and specific b. Moderate-risk exposure: Doxycycline 200mg once
o disadv: time- daily for 3-5 days to be started immediately within
consuming and 24-72 hours from exposure. [Grade C]
hazardous to perform, c. High-risk exposure: Doxycyline 200mg once weekly
cross reactions may until the end of exposure. [Grade B]
occur
o in the Phils, single titer
of at least 1:1600 in
symptomatic px is
INDICATIVE
Diagnostic Test
(LeptoDapstick), Leptospira
IgM ELISA (PanBIO), MCAT
and DriDot
o Serologic tests for
quick detection
o In early stage of the
dse, prone to false
negative results
Diagnostic Test
o Detects antibody
through an
agglutination reaction
o Used as screening test
but NOT sensitive

Other Laboratory Tests:

PROGNOSIS:
CBC- leukocytosis with neutrophilia, thrombocytopenia
Most pxs recover
U/A- proteinuria, pyuria and often hematuria, hyaline and granular
Post- leptospirosis sxs: depression- like nature
casts
Leptospirosis during pregnancy is associated with high fetal
Serum Creatinine- can be normal but can increase along the process
mortality rates.
CPK- MM- elevated in pxs w/ severe myalgia
Liver fxn tests- slight increase bilirubin, ALT, AST and alkaline
phosphatase
Bleeding parameters- prolonged PT and PTT

MANAGEMENT:
MILD
Doxycycline is the drug of choice.
Alternative drugs: Amoxicillin and Azithromycin dihydrate.
MODERATE TO SEVERE
Penicillin G remains the drug of choice.
Alternative drugs: Ampicillin, 3rd generation cephalosporin
(Cefotaxime, Ceftriaxone), and parenteral Azithromycin
dihydrate.
Antibiotic therapy should be completed for 7 days, except for
Azithromycin dihydrate which could be given for 3 days.
Indications for dialysis
Uremic symptoms nausea, vomiting, altered mental status,
seizure, coma
Serum creatinine > 3mg/dL
Serum Potassium > 5meq/L in an oliguric patient
ARDS, pulmonary hemorrhage
pH < 7.2
Fluid overload
Oliguria despite measures following the algorithm