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Published on: October 15, 2013
Clinical features that affect indirect-hemagglutination-assay responses to Burkholderia pseudomallei
Patrick N A Harris1, Natkunam Ketheesan, Leigh Owens
1Pathology Queensland, Townsville Hospital, Queensland, Australia 4811.
Abstract:
Melioidosis, a disease endemic to northern Australia and Southeast Asia, is caused by the soil saprophyte Burkholderia pseudomallei. The indirect hemagglutination assay (IHA) is the most frequently used serological test to help confirm exposure to the causative organism. However, despite culture-confirmed disease, patients often have a negative IHA result at presentation and occasionally fail to seroconvert in serial testing. We retrospectively examined results for all patients with culture-confirmed melioidosis from our laboratory between January 1996 and August 2008. One hundred forty patients had a recorded IHA titer at presentation, 71 of which were positive at a titer of 1:40 or greater. Fifty-three patients went on to have subsequent IHAs 1 month or more after presentation. The relationships between IHA responses and clinical features were examined. The presence of bacteremia was significantly associated with a negative IHA at presentation. The coexistence of diabetes was associated with the presence of a positive IHA at presentation. In total, 14 patients (26%) demonstrated persistently negative IHA titers upon serial testing. No clinical factors were found to be significantly associated with this phenomenon. Supplementary testing using melioidosis-specific immunoglobulin G by EIA demonstrated different effects, with only Aboriginal or Torres Straits Islander ethnicity being significantly associated with a positive EIA at presentation. Reasons for these findings are examined, and directions for future research are discussed.
Insights
Melioidosis serology using indirect hemagglutination assay (IHA) can be negative, even with confirmed Burkholderia pseudomallei infection. Bacteremia is linked to negative IHA, while diabetes correlates with positive results.
Area of Science:
- Medical Microbiology
- Infectious Diseases
- Immunology
Background:
- Melioidosis, caused by Burkholderia pseudomallei, is endemic in tropical regions.
- The indirect hemagglutination assay (IHA) is a common serological test for melioidosis.
- Negative IHA results and lack of seroconversion occur despite culture-confirmed disease.
Purpose of the Study:
- To investigate the diagnostic utility of IHA in culture-confirmed melioidosis.
- To identify clinical factors associated with IHA results in melioidosis patients.
- To explore discrepancies between IHA and enzyme immunoassay (EIA) in serological testing.
Main Methods:
- Retrospective analysis of 140 patients with culture-confirmed melioidosis (1996-2008).
- Examination of IHA titers at presentation and serial testing (≥1 month).
- Correlation of IHA results with clinical features, including bacteremia and diabetes. Supplementary testing with melioidosis-specific IgG by EIA.
Main Results:
- 71 of 140 patients had a positive IHA (titer ≥1:40) at presentation.
- Bacteremia was associated with negative IHA at presentation.
- Diabetes was associated with positive IHA at presentation.
- 14 patients (26%) showed persistently negative IHA titers on serial testing, with no associated clinical factors.
- Aboriginal or Torres Strait Islander ethnicity was linked to positive EIA results.
Conclusions:
- IHA may yield false-negative results in melioidosis, particularly in patients with bacteremia.
- Clinical factors like diabetes influence IHA positivity.
- Further research is needed to understand persistently negative IHA and explore alternative serological methods like EIA.
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