Leptospirosis Flashcards
A globally important zoonotic disease, reemerging globally, caused by pathogenic Leptospira species
Leptospirosis
What are the symptoms of mild leptospirosis?
Nonspecific symptoms like fever, headache, and myalgia
Weil’s syndrome
Jaundice, renal dysfunction, hemorrhagic diathesis
What is an important presentation of severe leptospirosis?
Severe pulmonary hemorrhage, with or without jaundice.
What are the characteristics of Leptospires?
Coiled, thin, highly motile, with hooked ends and two periplasmic flagella. 6–20 μm long, ~0.1 μm in diameter.
How can Leptospires be observed?
Stain poorly but visible by dark-field examination and after silver impregnation staining of tissues.
The most important reservoirs for leptospirosis?
Rodents, especially rats, though other wild and domestic animals can also harbor these microorganisms.
How do leptospires persist in hosts?
Establish symbiotic relationship
How is leptospirosis transmitted?
Direct contact with urine, blood, or tissue of infected animals, or environmental contamination
What is the severity of most human leptospirosis infections?
Mild
Which occupational groups are at high risk for leptospirosis?
Veterinarians, agricultural workers, sewage workers, slaughter-house employees, fishing industry workers.
Leptospires can be isolated from the bloodstream
Leptospiremic phase
Appearance of antibodies coincides with the disappearance of leptospires from the blood
Immune phase
What is the incubation period for leptospirosis?
Usually 1–2 weeks, but ranges from 2 to 30 days
Fever of 3–10 days, organism can be cultured from blood and detected by PCR.
Leptospiremic phase
Resolution of symptoms may coincide with the appearance of antibodies, leptospires can be cultured from urine
Immune phase
What is the characteristic muscle pain in mild leptospirosis?
Intense muscle pain, particularly affecting calves, back, and abdomen.
How is the headache in mild leptospirosis described?
Intense, frontal or retroorbital, sometimes with photophobia, resembling dengue
What is the natural course of mild leptospirosis?
Spontaneous resolution within 7–10 days, but persistent symptoms can occur.
What factors are associated with higher mortality in severe leptospirosis?
Age >40 years, altered mental status, acute renal failure, respiratory insufficiency, hypotension, arrhythmias.
Typical electrolyte abnormalities in severe leptospirosis
hypokalemia
hyponatremia
Loss of ___ in the urine is uniquely associated with leptospiral nephropathy
Magnesium
What cardiac findings are considered poor prognostic factors
Repolarization abnormalities and arrythmias
What radiographic abnormalities are observed in severe leptospirosis?
Patchy bilateral alveolar pattern, pleura-based densities, diffuse ground-glass attenuation typical of ARDS.
What does CSF examination reveal in leptospirosis with meningitis symptoms?
CSF shows pleocytosis that can range from a few cells to >1000 cells/μL, with a predominance of lymphocytes
What is required for a definitive diagnosis of leptospirosis?
Isolation of the organism
positive PCR result
seroconversion, or
a rise in antibody titer.
What antibody titer indicates leptospirosis in the MAT?
A single antibody titer of 1:200–1:800 in the MAT, depending on endemic area, or a fourfold rise in titer between acute- and convalescent-phase serum specimens.
When do antibodies typically become detectable in leptospirosis?
Usually not until the second week of illness.
What are the standard serologic procedures for leptospirosis?
microscopic agglutination test (MAT)
enzyme-linked immunosorbent assay (ELISA).
What is the limitation of serologic testing in early acute leptospirosis?
Lacks sensitivity in the early acute phase (up to day 5)
What is the advantage of PCR in diagnosing leptospirosis?
PCR, especially real-time PCR, can confirm diagnosis with high accuracy during the first 5 days of illness.
What is the recommended initial treatment for severe leptospirosis?
What is the recommended oral treatment for mild leptospirosis?
Doxycycline, azithromycin, ampicillin, or amoxicillin.
What should be considered with regards to treatment in regions with coendemic rickettsial diseases?
Doxycycline or azithromycin as the drug of choice.
What rare reaction may develop after starting antimicrobial therapy?
Jarisch-Herxheimer reaction
What is crucial in the supportive care for leptospirosis with nonoliguric renal dysfunction
Aggressive fluid and electrolyte resuscitation
What is crucial in the supportive care for leptospirosis with oliguric renal failure
peritoneal dialysis or hemodialysis
What is the ventilation strategy for patients with pulmonary hemorrhage?
Patients with pulmonary hemorrhage may have reduced pulmonary compliance (as seen in ARDS) and may benefit from mechanical ventilation with low tidal volumes to avoid high ventilation pressures
What is the impact of leptospirosis on pregnancy?
high fetal mortality rates
Which patients have the highest mortality rates in leptospirosis?
Elderly patients
those with severe disease (pulmonary hemorrhage, Weil’s syndrome).
chemoprophylaxis in pregnant women and children
Azithromycin
[CPG] Increased Mortality Risk Factors
Altered mental status
respiratory insufficiency
hemoptysis
oliguric hyperkalemic acute renal failure
cardiac involvement.
[CPG ] Prognostic Factors from Studies
> Dyspnea, oliguria, WBC >12,900/cu mm, repolarization abnormalities on EKG, alveolar infiltrates on chest radiograph.
Age > 40 years, development of oliguria, platelet count <70,000/uL, creatinine > 3mg/dl, pulmonary >involvement.
Altered mental status as the strongest predictor of death; other significant predictors include age > 37 years, renal and respiratory insufficiency.
[CPG] Locally Observed Poor Prognosis Factors:
> Severe jaundice, acute renal failure, bleeding diatheses.
Comorbid illnesses, advanced age.
Leukocytosis (WBC >10,000), thrombocytopenia (platelet count <100,000/uL), evidence of bleeding, oliguria, delay in consultation (>6 days after disease onset).
[CPG ] Weil’s Disease
Fever
Jaundice
Renal failure
[CPG] Gold standard in diagnosis of leptospirosis
Culture and isolation
[CPG] Early diagnosis advantage, especially during acute leptospiremic phase (first week).
PCR
Microscopy of blood is of value only during the _______ of the acute illness during leptospiremia
first 7-10 days
[CPG] EKG associated with mortality
Repolarization abnormalities
[CPG] What other laboratory examinations are recommended in leptospirosis and usual findings?
cbc- peripheral leukocytosis with neutrophilia, thrombocytopenia,
ua- proteinuria, pyuria, hematuria, hyaline and granular casts during the first week of illness
crea-normal then elevates
cpk-mm- severe myalgia
bilirubin,alt, ast elevated
alp
pt ptt- prolonged
[CPG] What findings in a Complete Blood Count (CBC) with platelet count may indicate severe leptospirosis?
Leukocytosis (WBC > 12,000 cells/cumm) with neutrophilia
Thrombocytopenia (< 100,000 cells/cu mm)
[CPG] Platelet count ____ is a risk factor for bleeding and pulmonary hemorrhage.
< 100,000/cu mm
[CPG] What serum creatinine and BUN levels suggest severe leptospirosis?
Serum creatinine > 3 mg/dL (or Creatinine Clearance (CrCl) < 20 ml/min)
BUN > 23 mg/dL
[CPG] What liver function test values are markers of severe leptospirosis?
AST/ALT ratio > 4x
Bilirubin > 190 umol/L
[CPG] What arterial blood gas (ABG) findings suggest severe leptospirosis?
Severe metabolic acidosis:
pH < 7.2
HCO3 < 10
Hypoxemia:
PaO2 < 60 mmHg
SaO2 < 90%
PF ratio < 250
[CPG] Which bleeding parameter is associated with severe leptospirosis?
Prolonged prothrombin time (PT) < 85%
[CPG] What serum potassium level is an indicator of severe leptospirosis?
Serum potassium > 4 mmol/L
[CPG] What chest radiograph finding may indicate severe leptospirosis?
Extensive alveolar infiltrates
[CPG] What electrocardiogram (ECG) findings are associated with severe leptospirosis?
Signs of heart block
Myocarditis
Repolarization abnormalities
[CPG] The only coagulation marker associated with mortality
Prolongation of prothrombin time
[CPG] The drug of choice for mild leptospirosis
Doxycyline
[CPG] Drug of choice for moderate to severe leptospirosis
Pen G
[CPG] Duration of Antibiotic Therapy
7 days
azith 3 days
Reported in patients treated with penicillin for leptospirosis.
Result from the activation of the cytokine cascade during spirochete degeneration.
Patients on penicillin should be monitored for this reaction.
Jarisch-Herxheimer Reactions
[CPG] Classic leptospirosis phases
Septicemic (leptospiremic) phase
Immune phase
[CPG] Most effective preventive measure
Avoidance of high-risk exposure (e.g., wading in floods, contact with contaminated water, animal body fluids).
Pre-exposure Antibiotic Prophylaxis is
NOT ROUTINELY RECOMMENDED T/F
T
Pre-exposure Antibiotic Prophylaxis is considered for
Individuals visiting highly endemic areas likely to get exposed (e.g., travelers, soldiers, water-related recreational/occupational activities) [Grade B]
Recommended pre exposure antibiotic pro regimen for non-pregnant, non-lactating adults:
Doxycycline (hydrochloride and hyclate) 200 mg once weekly
Start 1 to 2 days before exposure and continue throughout exposure period [Grade B]
[CPG] What is the recommended post-exposure prophylaxis for leptospirosis?
[CPG] Rises earlier in acute tubular necrosis (ATN) than serum creatinine by at least two days and helps differentiate ATN from pre-renal azotemia.
Urine or serum NGAL (neutrophil gelatinase-associated lipocalin)
[CPG] What are the symptoms and signs of hypovolemia?
Thirst
Dry mucosal membranes and axillae
Poor skin turgor, especially over the sternum
[CPG] What are the indications for acute renal replacement therapy or dialysis?
Uremic symptoms: Nausea, vomiting, altered mental status, seizure, coma
Serum creatinine > 3 mg/dL
Serum K > 5 meq/L in an oliguric patient
ARDS, pulmonary hemorrhage
pH < 7.2
Fluid overload
Oliguria despite measures following the algorithm
Uremic symptoms are an absolute indication for dialysis
[CPG] How should a leptospirosis patient with oliguria be managed?
[CPG] How frequent should the dialysis be?
Daily dialysis is recommended for critically ill patients, especially those with pulmonary involvement. [Grade B]
[CPG] The first sign of pulmonary involvement in most cases
Tachypnea (Respiratory Rate > 30/min)
What are the predictors for the development of pulmonary complications in leptospirosis?
delayed antibiotic treatment
thrombocytopenia at the onset of the disease
Independent factors associated with mortality in patients with pulmonary involvement are
hemodynamic disturbance
serum creatinine level > 265.2 μmol/L
serum potassium level > 4.0 mmol/L
[CPG] Most common serotype in patients with pulmonary involvement
Leptospira interrogens bataviae
[CPG] What are the pulmonary complications that can develop in leptospirosis?
Pulmonary hemorrhage
Acute Respiratory Distress Syndrome (ARDS)
[CPG] Methylprednisolone given within the first ____ of respiratory involvement is life-saving, especially in severe disease.
12 hours
[CPG] How should corticosteroids be given?
IV bolus Methylprednisolone at 1 gm/day for 3 days.
Followed by oral Prednisolone at 1 mg/kg/day for 7 days.
Recommended initial mechanical ventilator settings:
Assist/control mode
Low tidal volume at 6 ml/kg body weight
Positive End-Expiratory Pressure (PEEP) of 5 cm H2O
FiO2 of 100%
Respiratory rate of 25/min
Adjust FiO2 and PEEP to maintain SaO2 ≥ 90%.
If available, maintain plateau pressure ≤ 30 cm H2O.
Adjust the respiratory rate to avoid asynchrony.
[CPG] Intubation should be strongly considered
CXR bilateral infiltrates PaO2/FiO2 is <200 or SaO2 is less than 90%
A 45-year-old male presents to the hospital with a 4-day history of fever, myalgia, and cough. He has a history of wading in floodwaters during a recent heavy rain. On examination, his respiratory rate is 32 breaths per minute, and he has bilateral crackles on lung auscultation. Chest x-ray shows bilateral pulmonary infiltrates. His PaO2/FiO2 ratio is 180. What is the most appropriate next step in management?
A) Start oral doxycycline and monitor in the general ward
B) Admit to the ICU for close monitoring and consider invasive ventilation
C) Initiate corticosteroids only if hemoptysis develops
D) Discharge home with a follow-up chest x-ray in 48 hours
B
A 50-year-old woman is admitted with suspected leptospirosis and presents with hemoptysis, dyspnea, and fever. Her chest x-ray shows diffuse, bilateral pulmonary infiltrates, and her PaO2/FiO2 ratio is 160. Which of the following statements regarding corticosteroid therapy in this patient is correct?
A) Corticosteroids are contraindicated due to the risk of secondary infections
B) Corticosteroids should be initiated only if mechanical ventilation is required
C) High-dose methylprednisolone should be started within 12 hours of onset of dyspnea
D) Oral prednisolone should be started immediately without IV corticosteroids
C
A patient with confirmed leptospirosis is being managed in the ICU for pulmonary involvement. He has developed hypoxemia with a PaO2/FiO2 ratio of 180 and shows signs of tachypnea. Which of the following mechanical ventilation settings is appropriate as an initial approach?
A) Tidal volume of 10 ml/kg body weight and PEEP of 0 cm H2O
B) Assist/control mode with tidal volume 6 ml/kg, PEEP of 5 cm H2O, and FiO2 of 100%
C) Spontaneous mode with a tidal volume of 8 ml/kg and FiO2 of 40%
D) Pressure support mode with no PEEP and FiO2 of 21%
B
A 55-year-old man with confirmed leptospirosis is admitted with oliguria, creatinine of 3.5 mg/dL, and serum potassium of 5.8 mmol/L. Which of the following is the most appropriate next step in management?
A) Increase oral fluid intake and monitor urine output
B) Start oral antibiotics and repeat kidney function tests in 48 hours
C) Initiate hemodialysis due to hyperkalemia and rising creatinine
D) Administer IV diuretics to increase urine output
C
A 60-year-old female presents with fever, vomiting, and decreased urine output. Her creatinine is 3.8 mg/dL, and she is diagnosed with leptospirosis-associated AKI. Which of the following markers could indicate the early onset of acute tubular necrosis (ATN) before serum creatinine rises?
A) Elevated serum albumin
B) Urinary or serum neutrophil gelatinase-associated lipocalin (NGAL)
C) Elevated serum uric acid
D) Increased blood urea nitrogen/creatinine ratio
B