Low serum total nitrite and nitrate levels in severe leptospirosis

Thilini Kalugalage,Senaka Rajapakse,Shiroma Handunnetti,Thamal Vithanage,Pranitha Somaratne,Chaturaka Rodrigo,H Janaka De Silva

doi:10.1186/1471-2334-13-206

Thilini Kalugalage, Senaka Rajapakse + Show 5 more

Open Access

https://doi.org/10.1186/1471-2334-13-206

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Abstract

BackgroundThe 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 (NOx) in serum are considered surrogate markers for nitric oxide. NOx are excreted through the kidneys, and elimination is diminished in renal impairment. We assessed the correlation of NOx with disease severity in patients with leptospirosis, compared with healthy controls and non-leptospirosis fever patients.MethodsAll 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. NOx levels were measured using a modified Griess reaction.ResultsForty patients were confirmed as having leptospirosis and 26 of them had severe disease. NOx levels were significantly higher in confirmed leptospirosis patients compared to healthy controls, MAT equivocal patients and non-leptospirosis fever patients (p<0.001). NOx concentrations were also significantly higher in patients with severe compared to mild leptospirosis (p<0.001). Once NOx levels were corrected for renal function, by using the ratio NOx/creatinine, NOx levels were actually significantly lower in patients with severe disease compared to other patients, and values were similar to those of healthy controls.ConclusionsWe 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.

Highlights

The relationship between inducible nitric oxide synthatase activity and disease severity in leptospirosis is unclear
Elevation of serum Total nitrites and nitrates (NOx) levels during acute infections such as dengue, malaria and leptospirosis has been shown in previous studies, the main criticism of these studies has been the lack of correction of NOx concentrations for renal function
We postulate that this indicates that a blunted inducible nitric oxide synthatase (iNOS) response is seen in severe leptospirosis; whether this is the result of the inflammatory response that occurs, or whether a diminished iNOS response plays a role in the genesis of severe leptospirosis and organ dysfunction remains to be elucidated

Summary

Introduction

The relationship between inducible nitric oxide synthatase activity and disease severity in leptospirosis is unclear. NOx are excreted through the kidneys, and elimination is diminished in renal impairment. Leptospirosis is a zoonotic illness that has a high morbidity and mortality in the tropics [1]. It is caused by a spirochaete of the genus Leptospira, which is found to have at least nine pathogenic species and over 250 serovars. Severe leptospirosis is associated with adult respiratory distress syndrome (ARDS), pulmonary haemorrhage, acute kidney injury, liver impairment, and multi-organ dysfunction syndrome (MODS) [3,4]. The case fatality in severe leptospirosis (Weil’s disease) can be as high as 40% [5]

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