A Simple Scoring System to Differentiate between Relapse and Re-Infection in Patients with Recurrent Melioidosis

Melioidosis is a serious infectious disease caused by the Gram-negative bacterium, Burkholderia pseudomallei. This organism is present in the environment in areas where melioidosis is endemic (most notably East Asia and Northern Australia), and infection is acquired following bacterial inoculation or inhalation. Despite prolonged oral eradicative treatment, recurrent melioidosis occurs in approximately 10% of survivors of acute melioidosis. Recurrent melioidosis can be caused by relapse (failure of initial eradicative treatment) or re-infection with a new infection. The aim of this study was to develop a simple scoring system to distinguish between re-infection and relapse, since this has implications for antimicrobial treatment of the recurrent episode, but telling the two apart normally requires bacterial genotyping. A prospective study of melioidosis patients in NE Thailand conducted between 1986 and 2005 identified 141 patients with recurrent melioidosis. Of these, 92 patients had relapse and 49 patients had re-infection as confirmed by genotyping techniques. We found that relapse was associated with previous inadequate treatment and shorter time to clinical features of recurrence, while re-infection was associated with renal insufficiency and presentation during the rainy season. A simple scoring index to help distinguish between relapse and re-infection was developed to provide important bedside information where rapid bacterial genotyping is unavailable. Guidelines are provided on how this scoring system could be implemented

Simultaneous Infection with More than One Strain of Burkholderia pseudomallei Is Uncommon in Human Melioidosis▿

A prospective study was performed to determine the rate at which patients with melioidosis are infected with more than one strain of Burkholderia pseudomallei. Genotyping of 2,058 bacterial colonies isolated from 215 samples taken from 133 patients demonstrated that mixed infection is uncommon (2/133 cases [1.5%; 95% confidence interval, 0.2 to 5.3%])

Four predictors of re-infection and relapse for patients with recurrent melioidosis.

<p>Points can be determined for each of the predictors using the figure. Factors associated with re-infection give a positive score, while factors associated with relapse give a negative score. The total score is reached by adding the points together for these four variables. A total score of more than or equal to 5 is predictive for re-infection as the probable cause of recurrent melioidosis, while a total score of less than 5 is predictive for relapse.</p

Multivariable predictors of re-infection among patients with recurrent melioidosis.

<p>Abbreviations: CI, confidence interval; OR, odds ratio.</p>*<p>The OR is for a week increase of treatment with effective oral treatment regimens, including TMP-SMX and doxycycline based regimens and amoxicillin-clavulanic acid regimen.</p>†<p>The OR is for a 10 mL/min per 1.73 m² increase.</p>‡<p>Model Chi-square = 42.10; <i>df</i> = 4; <i>P</i><0.001; area under ROC curve = 0.81 (95% CI: 0.74–0.89); Hosmer-Lemeshow statistics = 9.24, <i>df</i> = 8, <i>P</i> = 0.32.</p

Predictive ability of the risk index model for relapse and re-infection of a total score within the range <−15, −15 to <−5, −5 to <5, 5 to <15, 15 to <25, and ≥25, respectively.

<p>Predictive ability of the risk index model for relapse and re-infection of a total score within the range <−15, −15 to <−5, −5 to <5, 5 to <15, 15 to <25, and ≥25, respectively.</p

Comparison between patients with relapse and re-infection in relation to: (A) calendar month of presentation and (B) interval between primary episode and recurrent infection.

<p>Dotted line in <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0000327#pntd-0000327-g001" target="_blank">Figure 1B</a> shows the proportion of patients with relapse presenting within each interval (right Y axis).</p

Demographic characteristics.

<p>Abbreviations: GFR, glomerular filtration rate; Q1–Q3, 25^th percentile and 75^th percentile; ^* mL/min per 1.73 m², ^† Trimethoprim-sulfamethoxazole and doxycycline, ^‡ Trimethoprim-sulfamethoxazole, doxycycline, and chloramphenicol, ^§ Fluoroquinolone-based regimen, doxycycline alone, and trimethoprim-sulfamethoxazole alone.</p