AbstractThe Darwin Prospective Melioidosis Study (DPMS) commenced on October 1st, 1989. Over 30 years to September 30th, 2019, there were 1148 individuals with Burkholderia pseudomallei culture-positive melioidosis, of whom 133 (12%) died. Median age was 50 years (IQR 38–60), 48 (4%) study participants were children younger than 15 years of age, 721 (63%) were male individuals, and 600 (52%) First Nations Australians. All but 186 (16%) had clinical risk factors, 513 (45%) had diabetes, and 455 (40%) hazardous alcohol use. Only three (2%) of 133 fatalities had no identified clinical risk factor. Of 1148 primary
melioidosis presentations, 1013 (88%) were acute (with an incubation period of 1–21 days, median 4 days, IQR 3–7 days), 106 (9%) were chronic (defined as symptoms for ≥ 2months), and 29 (3%) were considered to be infection activations from latency. 60 (5%) individuals had one or more recurrences of melioidosis, of whom 44 individuals had a relapse and 20 individuals had a new infection, making a total of 1212 episodes of melioidosis over the 30 years. Pneumonia was the most common presentation occurring in 595 (52%) patients. Bacteraemia occurred in 633 (56%) of 1135 patients, septic shock in 240 (21%) patients, and 180 (16%) patients required mechanical ventilation. Cases correlated with rainfall, with 80% of infections occurring during the wet season (November to April). Median annual incidence was 20·5 cases per 100,000 people; the highest annual incidence in First Nations Australians was 103·6 per 100,000 in 2011–12. Over the 30 years, annual incidences increased, as did the proportion of patients with diabetes, although mortality decreased to 17 (6%) of 278 patients over the last 5 years.
Genotyping of B. pseudomallei at Menzies School of Health Research evolved from ribotyping in the early days, to pulsed–field gel electrophoresis and BOX–PCR. With the advent of direct genome sequencing, Menzies embraced multilocus sequence typing (MLST) and more recently analysis of whole genome sequencing of B. pseudomallei DNA. Menzies curates the open access global B. pseudomallei MLST website; https://pubmlst.org/organisms/burkholderia-pseudomallei and this, together with shared leadership of the International Melioidosis Network (https://groups.google.com/g/melioidosis) has facilitated long term global collaborations which have informed the emerging understanding of the origins and dynamic global dispersal of B. pseudomallei, both over millennia and in recent years.
Of the 1148 primary presentations, we have stored B. pseudomallei isolates and MLST results from 1108 (97%). There were 349 distinct B. pseudomallei sequence types (STs), of which 243 were found only in a single patient. The large diversity of sequence types was especially evident in rural and remote Top End regions. In urban Darwin there was a dynamic situation of persistence throughout the 30 years of common STs 36, 109 and 132, while ST 553 was rare in early years but increased to become the commonest ST in Darwin in the last 5 years. The proliferation of ST 553 is linked to a period of intense urban construction. An evolving story is the likely point source introduction into Darwin of an Asian genotype ST 562, which continues to spread. How this introduction occurred and specifically where from remain to be established.
Genotyping has provided important insights into the epidemiology of melioidosis, enabling linking of B. pseudomallei from individual cases to environmental B. pseudomallei recovered from specific potential exposure sites. One notable example is matching a B. pseudomallei genotype from air sampling during stormy weather to the genotype from an individual with presumptive inhalational melioidosis. Case clusters linked to contaminated water supplies have also been confirmed by genotyping.
Therapy guidelines for melioidosis have evolved in Darwin over the 3 decades of the DPMS, with local experience informed by a series of randomised comparative antimicrobial trials from Thailand. The revised 2020 Darwin Melioidosis Treatment Guideline is now used nationally and internationally.
One conclusion of the DPMS is that melioidosis can be considered analogous to an opportunistic infection. It is very unlikely to kill a healthy person, provided the infection is diagnosed early and resources are available to provide appropriate antibiotics and critical care where required. However, the reality remains that such resources are just not available or are extremely limited in many of the world’s regions where melioidosis is endemic.
|Date of Award||2022|
|Supervisor||Nicholas Anstey (Supervisor)|