Biomedical subjects
Publications and source records attributed to Allen C Cheng.
Clinical cases of melioidosis caused by the saprophyte Burkholderia pseudomallei were first noted in the Lao People's Democratic Republic (PDR) in 1999. In this study, 36% of 110 soil samples in northern Lao PDR were positive for B. pseudomallei, providing further evidence for the presence of melioidosis in this country.
Melioidosis is associated with significant mortality in countries in which it is endemic. Previous studies have demonstrated that quantitative Burkholderia pseudomallei counts in blood are predictive of mortality. Here we examine the relationship between outcomes and quantitative B. pseudomallei counts in urine. A total of 755 patients presenting to Sappasithiprasong Hospital, Ubon Ratchathani, northeast Thailand (in the northeast part of the country), with melioidosis between July 1993 and October 2003 had quantitative urine cultures performed within 72 h of admission. Urine culture results were divided into the following groups: (i) no growth of B. pseudomallei from a neat sample or pellet, (ii) positive result from a centrifuged pellet only (< 10(3) CFU/ml), (iii) detection of between 10(3) CFU/ml and 10(5) CFU/ml from a neat sample, or (iv) detection of > or = 10(5) CFU/ml from a neat sample. The overall in-hospital mortality rate was 45%. Patients with negative urine cultures had the lowest death rate (39%). Mortality rates rose with increasing B. pseudomallei counts in urine, from 58% for those with positive spun pellets only to 61% for those with between 10(3) CFU/ml and 10(5) CFU/ml and 71% for those with > or = 10(5) CFU/ml. This was independent of age, presence of bacteremia, known risk factors for melioidosis such as diabetes, and the prior administration of antibiotics. The presence of B. pseudomallei in urine during systemic infection is associated with a poor prognosis.
The indirect hemagglutination assay routinely used to detect antibodies to Burkholderia pseudomallei was modified to detect cross-reactivity of antibodies to B. pseudomallei, B. mallei, and B. thailandensis antigens. We demonstrate a lack of cross-reactivity between B. pseudomallei and B. thailandensis but marked cross-reactivity between B. pseudomallei and B. mallei.
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Pneumonia is a common manifestation of melioidosis, the disease caused by Burkholderia pseudomallei. In this study, we defined the prognostic significance of a positive sputum culture. A total of 712 patients presenting to Sappasithiprasong Hospital, Ubon Ratchathani, Thailand, with melioidosis between January 1992 and December 2002 had a sputum culture performed during admission, which was positive for B. pseudomallei in 444 patients (62%). The median duration of sputum positivity was 9 days (range, 1 to 49 days). Sputum cultures were negative in 32% of patients with radiologic changes suggestive of pulmonary involvement. Overall in-hospital mortality was 48%. A positive sputum culture was associated with mortality (adjusted OR 2.8, 95% CI: 1.9, 4.0; P < 0.001). This was independent of renal disease, a prior history of melioidosis, positive blood cultures, and other potential confounders. The presence of B. pseudomallei in the sputum of patients with melioidosis is associated with a poorer prognosis.
The diagnostic potential of a Burkholderia pseudomallei type three secretion system (TTS1) polymerase chain reaction (PCR) was examined on clinical specimens from 27 patients with sepsis in the Northern Territory of Australia, a region endemic for melioidosis. The TTS1 PCR was conducted on DNA extracted from a range of clinical specimens (blood, sputum, urine, joint, pericardial and pleural fluid, and swabs from skin lesions, throat, nose, and rectum). The PCR sensitivity in culture-positive clinical specimens from the nine confirmed patients with melioidosis was 65% and the specificity was 100%, with no PCR-positive results in specimens from 18 patients without melioidosis. The PCR based on the B. pseudomallei TTS1 has the potential to substantially improve the timeliness of diagnosis of melioidosis.
This study examined whether coinfection with HIV and Burkholderia pseudomallei leads to altered disease severity or outcome associated with melioidosis. Coinfection was detected in only 8 of 524 (1.5%) adults with melioidosis in northeast Thailand. Clinical presentation and acute outcome were similar in HIV-positive and HIV-negative patients.
Melioidosis, the infection due to Burkholderia pseudomallei, may present with a spectrum of severity and may affect any site in the body. Differential strain virulence and tropism suggested by previous studies would have implications for virulence and vaccine work. We explored clinical correlations using pulsed-field gel electrophoresis (PFGE) typing in a well-characterised clinical collection. Two methods of analysis were used based on band-based similarity values: first, a conventional cluster analysis formed by the unweighted paired group mean analysis, and second, an analysis of the distribution of the "within-group" and "between-group" Dice coefficient. Clinical isolates from 114 cases of melioidosis occurring in the Northern Territory, Australia were studied; 71 strain types were defined with a Simpson's index of 0.91. No correlation was found between strain type and disease severity or site of melioidosis on presentation, with no differences in similarity values found when comparing within and between-groups. In particular, isolates from patients with neurological melioidosis were not clustered. There was evidence of geographical localisation. This study suggests that the variation in strain type may not be as important as host and environmental factors in determining the pattern of disease.
Clinical management of infective endocarditis (IE) is expected to become more difficult with the emergence of Staphylococcus aureus with reduced susceptibility to vancomycin (SARV) in the United States and worldwide. We report the strain characterization and treatment of a patient with SARV IE.
Improving safety is important, but in many regions antivenoms are not available.
OBJECTIVES: The aims of this study were to describe the epidemiology of melioidosis in tropical northern Australia and to assess the importance of defined risk factors. METHODS: The data were taken from a 14-year prospective study of 364 cases of melioidosis in the 'Top End' of the Northern Territory. A whole-population logistic regression model was used to estimate the crude and adjusted relative risk (RR) for the defined risk factors. RESULTS: The mean age of the study population was 46.8 years, 264 (72.5%) were male, 178 (49%) were aboriginal Australians and 59 (16.2%) died from melioidosis. Average annual incidence was 19.6 cases per 100 000 population, with an estimated rate of 260 cases per 100,000 diabetics per year. Using a whole-population logistic regression model, the estimated crude and adjusted RR [95% confidence intervals (CI)] for melioidosis were 6.3 (5.1-7.8) and 4.0 (3.2-5.1) for those aged > or = 45 years, 2.3 (1.8-2.9) and 2.4 (1.9-3.0) for males, 2.9 (2.3-3.5) and 3.0 (2.3-4.0) for aboriginal Australians, 21.2 (17.1-26.3) and 13.1 (9.4-18.1) for diabetics, 2.7 (2.2-3.4) and 2.1 (1.6-2.6) for those with excess alcohol consumption, 6.8 (5.4-8.6) and 4.3 (3.4-5.5) for chronic lung disease and 6.7 (4.7-9.6) and 3.2 (2.2-4.8) for chronic renal disease, respectively. CONCLUSIONS: Diabetes, excess alcohol intake, chronic renal disease and chronic lung disease are each independent risk factors for melioidosis. In tropical northern Australia, male sex, aboriginal ethnicity and age of > or = 45 years are also independent predictors for melioidosis. Impaired polymorph function may be critical in the predisposition to melioidosis.
Melioidosis, an infection due to Burkholderia pseudomallei, is endemic in southeast Asia and northern Australia. We reviewed our experience with meropenem in the treatment of severe melioidosis in 63 patients over a 6-year period. Outcomes were similar to those of ceftazidime-treated patients (n = 153) despite a deliberate selection bias to more-unwell patients receiving meropenem. The mortality among meropenem-treated patients was 19%. One patient had a possible drug fever associated with the use of meropenem. We conclude that meropenem (1 g or 25 mg/kg every 8 h intravenously for >/=14 days) is an alternative to ceftazidime and imipenem in the treatment of melioidosis. The use of meropenem may be associated with improved outcomes in patients with severe sepsis associated with melioidosis.
Melioidosis is the disease caused by the saprophytic organism Burkholderia pseudomallei. Previous studies have suggested some strain tropism and differential virulence. In this study, we defined strains by multilocus sequence typing (MLST) of isolates taken from the Top End of Australia's Northern Territory and compared the results with those of other strains typed worldwide. We specifically sought clinical and geographical correlates of strain types. Among 87 Australian isolates, 48 sequence types were defined. None of the sequence types in this study has been found elsewhere in the world. Strains were distributed widely throughout the region, and the different presentations of disease, including neurological and prostatic infection, were associated with many different strains. There was excellent congruence between pulsed-field gel electrophoresis and MLST, and the two typing methods had a similar level of strain discrimination. The work suggests that host and environmental factors may be more important in determining disease presentation than infecting strain type. It is possible that the distinct but diverse strain types found in this study reflect Australia's geographical isolation over many millions of years.
Immunochromatographic test (ICT) kits for the rapid detection of immunoglobulin G (IgG) and IgM antibodies to Burkholderia pseudomallei were compared to the indirect hemagglutination (IHA) assay. In 138 culture-confirmed melioidosis cases, sensitivities were 80, 77, and 88% for IHA, ICT IgG, and ICT IgM, respectively. In a prospective study of 160 consecutive sera samples sent for melioidosis serology, respective specificities were 91, 90, and 69, positive predictive values were 41, 32, and 18, and negative predictive values were 99, 98, and 100%. ICT IgM kits are unreliable for diagnosis of melioidosis, but ICT IgG kits may be useful for diagnosing travelers presenting with possible melioidosis who return from regions where melioidosis is endemic.
An enzyme-linked immunosorbent assay-based rapid cassette immunoglobulin G (IgG) and IgM immunochromogenic test kit was compared to the indirect hemagglutination test (IHA) for the diagnosis of acute melioidosis in northeastern Thailand. Admission sera from 70 culture-confirmed septicemic melioidosis patients and 30 patients with localized infections were tested. As a control group, 80 patients with other acute febrile illnesses (other bacterial infections, leptospirosis, or scrub typhus) and 119 healthy individuals were tested. The diagnostic sensitivity of the IgG and IgM tests and the IHA test were 79, 67, and 72%, respectively, with corresponding specificities of 90, 80, and 68%. This kit represents an improvement over IHA for the diagnosis of melioidosis an area of endemicity although, as with other serological tests, it has reduced diagnostic utility in a population with high background seropositivity.
Previous work suggested that C-reactive protein (CRP) may be a useful test in the diagnosis of melioidosis, the infection caused by Burkholderia pseudomallei. We reviewed patients with culture-confirmed melioidosis to define the role of this inflammatory marker in the diagnosis of melioidosis. In 175 patients, we found that the admission CRP level may be normal or only mildly elevated, including patients with severe sepsis, fatal cases, and in relapsed melioidosis. In a multivariate analysis, sepsis and bacteremia were more strongly associated with mortality than CRP. Admission levels of CRP are not a sensitive marker for the presence of melioidosis and a normal level cannot be used to exclude acute, chronic, or relapsed melioidosis in febrile patients in or from endemic regions.
Melioidosis, caused by the intracellular pathogen Burkholderia pseudomallei, is endemic in northern Australia and Southeast Asia. Risk factors for this infection have also been associated with functional neutrophil defects. Because of this, granulocyte colony-stimulating factor (G-CSF) was adopted for use in patients with septic shock due to melioidosis in December 1998. We compared the mortality rates from before and after the introduction of G-CSF therapy at the Royal Darwin Hospital (Darwin, Australia) during the period of 1989-2002. The mortality rate decreased from 95% to 10% after the introduction of G-CSF. Risk factors, the duration of illness before presentation, and the severity of illness were similar in both groups. A smaller decrease in mortality among patients in the intensive care unit who did not have melioidosis was observed, suggesting that other changes in management did not account for the magnitude of the benefit seen. We conclude that G-CSF may have contributed to the reduction in the mortality rate among patients with septic shock due to melioidosis.