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Melioidosis is caused by the environmental pathogen Burkholderia pseudomallei. Among 1,331 patients with melioidosis during 1989–2023 in the Darwin Prospective Melioidosis Study in Australia, we identified 6 locally acquired cases caused by B. pseudomallei sequence type 46. Because of global transmission and expansion of endemicity, clinicians should increase awareness of melioidosis.

Trimethoprim/sulfamethoxazole is the first-line agent for oral eradication therapy for melioidosis but has been associated with toxicity in this context. This study aimed to quantify adverse drug reactions (ADRs) to trimethoprim/sulfamethoxazole when used for treatment of melioidosis, and assess risk factors for ADR development. A retrospective review of antimicrobial associated ADRs was performed in all patients treated for melioidosis in the Northern Territory of Australia from January 2017-September 2022. Over this time, 268 treatment episodes from 256 individuals were included. The frequency of clinician-attributed ADRs to trimethoprim/sulfamethoxazole (51% of exposed) was higher than for other antimicrobials used (ceftazidime 12%, meropenem 8%, and doxycycline 12% of those exposed; P < 0.0001). 44% of those treated with trimethoprim/sulfamethoxazole required drug cessation or dose reduction and 5 individuals (2%) had a severe cutaneous adverse reaction, with one fatality. Acute kidney injury was the most frequent ADR (25% of those exposed), with age and pre-existing renal disease independently associated with its development. Here we report very high rates of ADRs attributed to trimethoprim/sulfamethoxazole resulting in frequent discontinuation of this drug as part of oral eradication therapy for melioidosis. Further work is needed to balance the necessity and toxicity of this drug in this clinical context.

Melioidosis, an infection with the bacterium Burkholderia pseudomallei, is highly endemic in the Top End of the Northern Territory of Australia. The indirect haemagglutination assay (IHA) is the most widely used serology test globally, but it is not standardised among the limited number of laboratories that perform it. While concerns have been raised about the sensitivity of IHA early in melioidosis infections, the advantage of IHA over more recently developed ELISAs is that testing serial dilutions allows a titre to be recorded. While in Australia a titre of 1:40 or higher is considered positive, the specificity at these low positive titres remains uncertain. However, a high titre is considered to represent recent or past true infection with B. pseudomallei, rather than cross-rection with other environmental Burkholderia species. Also, the natural history of IHA titres over time, in both asymptomatic infection and melioidosis has been little studied. We have assessed the clinical status and serology time courses of all 534 patients who had an IHA titre of 1:640 or higher, over a 20-year period. Of these, 324 (60.7%) were diagnosed with culture-confirmed melioidosis, with varying time courses of diagnosis of melioidosis in relation to the high serology. Of the 210 without confirmed melioidosis, 22 (10.5%) were considered highly likely to be melioidosis despite being culture-negative, and these were all treated as melioidosis. In the remainder, titres mostly gradually decreased over time, but the majority remained seropositive. A small number who had not been treated for melioidosis continued to have high IHA titres over years and activation from latency with a new diagnosis of melioidosis was occasionally documented. This study highlights the importance of a full clinical workup in those found to have high titre melioidosis serology as well as subsequent close clinical surveillance and where resources allow, yearly IHA in those not confirmed or treated as melioidosis.

Burkholderia pseudomallei, the causative agent of melioidosis, is a gram-negative soil bacterium well recognized in Southeast Asia and northern Australia. However, wider and expanding global distribution of B. pseudomallei has been elucidated. Early diagnosis is critical for commencing the specific therapy required to optimize outcome. Serological testing using the indirect hemagglutination (IHA) antibody assay has long been used to augment diagnosis of melioidosis and to monitor progress. However, cross reactivity and prior exposure may complicate the diagnosis of current clinical disease (melioidosis). The goal of our study was to develop and initially evaluate a serology assay (BurkPx) that capitalized upon host response to multiple antigens. Antigens were selected from previous studies for expression/purification and conjugation to microspheres for multiantigen analysis. Selected serum samples from non-melioidosis controls and serial samples from culture-confirmed melioidosis patients were used to characterize the diagnostic power of individual and combined antigens at two times post admission. Multiple variable models were developed to evaluate multivariate antigen reactivity, identify important antigens, and determine sensitivity and specificity for the diagnosis of melioidosis. The final multiplex assay had a diagnostic sensitivity of 90% and specificity of 93%, which was superior to any single antigen in side-by-side comparisons. The sensitivity of the assay started at >85% for the initial serum sample after admission and increased to 94% 21 days later. Weighting antigen contribution to each model indicated that certain antigen contributed to diagnosis more than others, which suggests that the number of antigens in the assay can be decreased. In summation, the BurkPx assay can facilitate the diagnosis of melioidosis and potentially improve on currently available serology assays. Further evaluation is now required in both melioidosis-endemic and non-endemic settings. Author summary Melioidosis has a wide diversity of symptoms, making laboratory diagnosis essential. The diagnosis of melioidosis is primarily by culture of the causative bacterium, Burkholderia pseudomallei, which is problematic for locations with limited laboratory resources and for laboratories inexperienced in handling B. pseudomallei. Early diagnosis of melioidosis facilitates the specific antimicrobial therapy that optimizes outcomes and substantially lowers mortality. We have developed and evaluated a multiple antigen-antibody serology assay using serial samples from culture confirmed melioidosis patients including the first sample after patient admission, together with non-melioidosis serum controls. Multiantigen reactivity was compared to single antigens and to the indirect hemagglutination (IHA) antibody assay data collected from routine patient testing. The results from testing patients with culture-confirmed melioidosis suggest that using multiple individual antigen assays coupled with models can improve the sensitivity and specificity of serological diagnosis using the same antigens evaluated individually. In addition, all evaluated antigens may not be needed to improve assay performance. Further antigen down selection and evaluation of the utility of this assay is now required in both melioidosis-endemic and non-endemic settings.

Melioidosis is endemic in the remote Katherine region of northern Australia. In a population with high rates of chronic disease, social inequities, and extreme remoteness, the impact of melioidosis is exacerbated by severe weather events and disproportionately affects First Nations Australians. All culture-confirmed melioidosis cases in the Katherine region of the Australian Top End between 1989-2021 were included in the study, and the clinical features and epidemiology were described. The diversity of Burkholderia pseudomallei strains in the region was investigated using genomic sequencing. From 1989-2021 there were 128 patients with melioidosis in the Katherine region. 96/128 (75%) patients were First Nations Australians, 72/128 (56%) were from a very remote region, 68/128 (53%) had diabetes, 57/128 (44%) had a history of hazardous alcohol consumption, and 11/128 (9%) died from melioidosis. There were 9 melioidosis cases attributable to the flooding of the Katherine River in January 1998; 7/9 flood-associated cases had cutaneous melioidosis, five of whom recalled an inoculating event injury sustained wading through flood waters or cleaning up after the flood. The 126 first-episode clinical B. pseudomallei isolates that underwent genomic sequencing belonged to 107 different sequence types and were highly diverse, reflecting the vast geographic area of the study region. In conclusion, melioidosis in the Katherine region disproportionately affects First Nations Australians with risk factors and is exacerbated by severe weather events. Diabetes management, public health intervention for hazardous alcohol consumption, provision of housing to address homelessness, and patient education on melioidosis prevention in First Nations languages should be prioritised.