Clinical characteristics, genotyping and molecular detection of burkholderia pseudomallei

Zueter, Abdel Rahman Mohammad Abdallah (2016) Clinical characteristics, genotyping and molecular detection of burkholderia pseudomallei. PhD thesis, Universiti Sains Malaysia.

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Burkholderia pseudomallei is a saprophytic Gram-negative bacterium that infects human body through inhalation, ingestion or percutaneous inoculation and causes melioidosis. The pathophysiology and clinical presentations of melioidosis are influenced by B. pseudomallei load on exposure, route of infection and human risk factors. Laboratory methods for B. pseudomallei include various procedures applied for diagnosis, molecular epidemiology and pathogenicity studies using conventional, immunological and molecular techniques. In this study, the clinical characteristics and risk factors of melioidosis were explored. Genotyping using multilocus sequence typing (MLST) was performed on clinical B. pseudomallei isolates to explore the degree of their genotypic diversity in the area of the study and to correlate the identified genotypes with clinical presentations and outcomes. In order to improve the laboratory detection of B. pseudomallei, a PCR-based assay targeting sctq gene of the TTS1 cluster has been developed. In this study, which involved 158 cases, the principal clinical presentations reported were lung infection in 65 (41.1%), skin infection in 44 (27.8%), septic arthritis/osteomyelitis in 20 (12.7%) and liver infection in 19 (12.0%). Bacteremic melioidosis was seen in most cases (n=121, 76.6%). Focal melioidosis was seen in124 (78.5%) of patients and multi-focal melioidosis was reported in 45 (28.5%) cases, while melioidosis with no evident focus was reported in 34 (21.5%) patients. Internal organ abscesses and secondary foci in lungs and/or soft tissue were common in this study. Sixty seven (41%) patients were admitted during the monsoonal wet season. Death due to melioidosis was reported in 52 (32.9%) of patients, while recurrent infections occurred in 4 (2.5%) patients. Twelve fatal melioidosis cases directly attributed to the absence of prompt acute-phase treatment were seen in this study. Predisposing risk factors were reported in 133(84.2%) patients, which included diabetes (74.7%), immune disturbances (9.5%), cancer (4.4%) and chronic kidney disease (11.4%). On multivariate analysis, the independent predictors of mortality were the presence of at least one co-morbid factor (OR 3.0; 95% CI 1.1– 8.4), the occurrence of septic shock (OR 16.5; 95% CI 6.1–44.9) and age >40 years (OR 6.47; 95% CI 1.7–23.8). Multilocus sequence typing of 83 B. pseudomallei isolates has revealed 32 different sequence types, of which 13 (40%) were novel, namely: ST1317, ST1318, ST1319, ST1320, ST1321, ST1322, ST1323, ST1324, ST1325, ST1326, ST1327, ST1358 and ST1359. All retrieved sequence types were deposited in MLST database. The frequencies of sequence types among the 83 isolates ranged from 1-12 observations with predomination of ST54, ST371 and ST289. All non-novel sequence types identified in this study were not exclusive for Malaysia; they were identified in other regional countries with different frequencies. However, some of these sequence types were firstly identified in Malaysia such as ST371, ST164, ST47, ST306, ST55, ST376, ST402, ST507, ST368, ST369, ST10 and ST168. This study has provided major review for melioidosis and its causative agent, Burkholderia pseudomallei among selected population clusters residing in the Northeastern part of Peninsular Malaysia. Clinical presentations and risk factors of melioidosis were not unique for Malaysia and B. pseudomallei genotypes showed wide diversity that was correlated with the distribution of different strains in the environment. Novel sequence types indicated the genetic activity and instability of the bacteria which predicted the emergence of new strains that may harbor different virulence effect. This work kept on previous assumption that host and environmental factors were behind the diversity for clinical presentation of the disease. For molecular diagnosis, further upgrading and evaluation are needed to improve the performance of the assay.

Item Type: Thesis (PhD)
Uncontrolled Keywords: Melioidosis
Subjects: R Medicine > RA Public aspects of medicine
Divisions: Kampus Kesihatan (Health Campus) > Pusat Pengajian Sains Perubatan (School of Medical Sciences) > Thesis
Depositing User: Mr Abdul Hadi Mohammad
Date Deposited: 15 Aug 2018 01:54
Last Modified: 12 Apr 2019 05:25

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