Melioidosis, Singapore, 2003–2014

In contrast with northern Australia and Thailand, in Singapore the incidence of melioidosis and co-incidence of melioidosis and pneumonia have declined. Burkholderia pseudomallei deep abscesses increased 20.4% during 2003–2014. These trends could not be explained by the environmental and climatic factors conventionally ascribed to melioidosis.

binomial generalized linear model with identity link was used to quantify temporal changes in the absolute proportion of melioidosis cases having each co-morbidity. We conducted a binomial test of whether the prevalence of comorbidities equaled that of the general population; the latter was derived from the last published National Health Survey 2010 (http://www.moh.gov.sg/content/ moh_web/home/Publications/Reports/2011/national_ health_survey2010.html) for persons 50−59 years of age (for diabetes and hypertension) and 40−54 years of age (for renal impairment). Analyses were performed with R Statistical Software version 3.3.1 (https://www. r-project.org/).
This study, comprising one of the largest melioidosis patient cohorts thus far, yielded some unanticipated disease trends from Singapore. Foremost was the decreasing melioidosis incidence, in the context of declining B. pseudomallei bacteremia cases and, more significantly, the steady decrease in pneumonia.
By contrast in Australia and Thailand, melioidosis numbers stayed constant or increased (6). Pneumonia continued to feature prominently in 50% of the cases in these countries (7). It would be reasonable to theorize that pneumonia would be the predominant feature following inhalation of aerosolized B. pseudomallei after rainfall (8). Several groups have reported the association between rainfall, humidity, and water exposure with melioidosis (9,10). In equatorial Singapore, however, rainfall patterns have not changed recently. In addition, our analysis of rainfall and humidity during the corresponding study period found these climatic variables to be constant on   a yearly scale (rainfall, p = 0.846; humidity, p = 0.815). Hence, climate is unlikely to be related to the decline in disease incidence.
Soil, in particular anthrosol and acrisol soil, encountered in irrigated agriculture, has been suggested as a likely reservoir for B. pseudomallei (10). Consequently, urbanization leading to reduction of agricultural or rural land areas ought to align with a lower incidence of melioidosis. However, the developed island state of Singapore already had reached 100% urbanization by the early 1990s (11); thus, urbanization could not have been the primary factor for this decreasing incidence after 2003.
Conversely, water sanitization, storm/rainwater drainage, and flood reduction have remained a major focus of ongoing infrastructural improvements of the Singapore government through the 2000s to now. The national water strategy entails a complex system encompassing optimized drainage and collection, followed by water treatment intended for consumption and use. Flood risk is managed through design and implementation of stateof-the-art water drainage systems and flood-protection measures for public infrastructures (12). Together with a national flood alert response plan, these measures potentially minimize direct rain or contaminated water exposure and aerosol inhalation risk; thus, they are plausible factors to account for the overall melioidosis and pneumonia case reductions, but further study is needed to investigate this possibility. We did not anticipate the 20.4% increase of B. pseudomallei deep organ abscesses during the study period. We theorized that it might partly be explained by compromised host immunity to B. pseudomallei, attributable to the progressively higher prevalence of diabetes in Singapore (than in Australia and Thailand) (13). Specifically in the context of abscess development, diabetic tissue macrophages impair B. pseudomallei killing capacity and an impaired interleukin IL12-interferon-γ response had been implicated (14). Conversely, melioidosis-associated deaths in patients with diabetes had decreased by 10.8% during our study period. This improvement in outcome might have found its roots in the drive for optimization of diabetes care at the public health level in Singapore in recent years (15).

Conclusions
The overall death rate from melioidosis in Singapore was 18.4%, similar to that in the Northern Territory of Australia (14%). In both locations, these rates were attained on the background of similar standards and accessibility to healthcare and a low threshold for institution of treatment for melioidosis in accordance with recommendations (1). As efforts continue to further optimize clinical outcomes in acute melioidosis, our experience from Singapore for 2003-2014 suggests that acquisition of melioidosis and pneumonia may be curtailed through enhanced environmental and water management incorporating countrywide infrastructural improvements. In addition, enhanced management of the at-risk cohort of persons with diabetes also might prove pivotal in reducing disease. L.Y.A.C. has received grant support and has been advisor/ consultant for Pfizer and Merck Sharp and Dohme, Gilead, and Astellas.
Mr. Pang is a biostatistician at the Saw Swee Hock School of Public Health, National University of Singapore. His primary research interests include infectious diseases epidemiology and modeling.