Low serum total nitrite and nitrate levels in severe leptospirosis

BACKGROUND: The relationship between inducible nitric oxide synthatase activity and disease severity in leptospirosis is unclear. Nitric oxide is converted to nitrites and nitrates, thus nitrite and nitrate levels (NO(x)) in serum are considered surrogate markers for nitric oxide. NO(x) are excreted through the kidneys, and elimination is diminished in renal impairment. We assessed the correlation of NO(x) with disease severity in patients with leptospirosis, compared with healthy controls and non-leptospirosis fever patients. METHODS: All patients admitted over a two-month period to the National Hospital, Colombo, Sri Lanka with a clinical picture suggestive of leptospirosis were included. Leptospirosis was confirmed by the microscopic agglutination test (titre≥400). Severe leptospirosis was defined by the presence of two or more of the following criteria: jaundice (bilirubin> 51.3 μmol/l), oliguria (urine output < 400 ml/day), serum creatinine> 133 μmol/l or blood urea > 25.5 mmol/l, or the presence of organ dysfunction. Non-leptospirosis fever patients and healthy volunteers were used as control groups. NO(x) levels were measured using a modified Griess reaction. RESULTS: Forty patients were confirmed as having leptospirosis and 26 of them had severe disease. NO(x) levels were significantly higher in confirmed leptospirosis patients compared to healthy controls, MAT equivocal patients and non-leptospirosis fever patients (p<0.001). NO(x) concentrations were also significantly higher in patients with severe compared to mild leptospirosis (p<0.001). Once NO(x) levels were corrected for renal function, by using the ratio NO(x)/creatinine, NO(x) levels were actually significantly lower in patients with severe disease compared to other patients, and values were similar to those of healthy controls. CONCLUSIONS: We postulate that high NOx levels may be protective against severe leptospirosis, and that finding low NOx levels (when corrected for renal function) in patients with leptospirosis may predict the development of severe disease and organ dysfunction.