Case Report: Risk Factors Associated with Mortality in Adults with Burkholderia Pseudomallei Bacteremia: A Retrospective Case Series of Melioidosis in Cambodia

Andrea R. Pacheco International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia;

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Sophana Chea International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia;

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Helena Saunders Department of Psychology, Colorado College, Colorado Springs, Colorado;

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Sokna Ly International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia;

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Ratanak Sath International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia;

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Rathna Tim International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia;

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Sreyngim Lay International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia;
National Center of Parasitology, Entomology, and Malaria Control, Phnom Penh, Cambodia;

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Mengheng Oum International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia;

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Gechlang Tang International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia;

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Lyhourng Long International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia;

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Sovann Ly Communicable Disease Control Department, Ministry of Health, Phnom Penh, Cambodia;

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Heng Seng Communicable Disease Control Department, Ministry of Health, Phnom Penh, Cambodia;

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Sidonn Krang Communicable Disease Control Department, Ministry of Health, Phnom Penh, Cambodia;

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Chhouv Chhuon Takeo Provincial Referral Hospital, Takeo, Cambodia;

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Vantha Te Takeo Provincial Referral Hospital, Takeo, Cambodia;

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Sosorphea Seang Takeo Provincial Referral Hospital, Takeo, Cambodia;

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Chanthap Lon International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia;

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Christina Yek Department of Critical Care Medicine, National Institutes of Health Clinical Center, Bethesda, Maryland;
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, Maryland

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Jessica E. Manning International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia;
Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, Maryland

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ABSTRACT.

In resource-scarce settings, melioidosis is associated with up to 80% mortality. Studies of melioidosis in Cambodia report primarily on pediatric populations with localized infection; however, literature describing Cambodian adults with severe melioidosis is lacking. We present a case series of 35 adults with sequence-confirmed Burkholderia pseudomallei bacteremia presenting to a provincial referral hospital in rural Cambodia. More than 90% of the patients had diabetes, an important risk factor for developing melioidosis. Inappropriate antimicrobial therapy was significantly associated with lower odds of survival. Improved diagnostic testing and greater access to first-line antibiotics for acute melioidosis treatment present potential targets for intervention to reduce mortality associated with this disease in resource-limited settings.

INTRODUCTION

Melioidosis, caused by the gram-negative environmental bacterium Burkholderia pseudomallei, is responsible for an estimated 4.64 million disability-adjusted life-years annually and poses a growing global threat.1 Sixty countries have confirmed endemicity, but the true burden may be underappreciated; crude models project an additional 22 countries where melioidosis has not yet been reported.2,3 In nonendemic areas, infected travelers or wildlife import the bacteria.4 Mortality rates range from 6% to 80%, with worse outcomes in resource-scarce settings.36 High-risk populations include adults with diabetes, chronic lung or renal disease, excessive alcohol use, and high occupational exposure (e.g., rice farmers).4,5,7

Despite recent efforts to recognize melioidosis as a neglected tropical disease,1 B. pseudomallei has received little attention outside the hyperendemic regions of Southeast Asia and northern Australia. Clinical data from melioidosis patients derive mostly from Australia, where timely diagnosis and appropriate treatment have brought mortality rates below 10%.5 In contrast, recent studies from Southeast Asia have estimated 60% mortality.3 In Cambodia, clinical appreciation has been relatively recent, and diagnostic capacity remains scattered.8 Published Cambodian reports have been largely limited to pediatric patients, reflecting overrepresentation from select pediatric hospitals with well-established microbiology laboratories.4,610 One small case series of seven adult patients reported mortality surpassing 50%.11 Rates of appropriate antibiotic treatment of melioidosis in Cambodia range from 33% to 66%, as hospital supplies are often insufficient or, in the case of carbapenems, nonexistent.611

Here, we describe clinical presentations and outcomes of systemic melioidosis in an adult cohort in rural Cambodia. Understanding key features leading to poor outcomes will add to improved management of B. pseudomallei bacteremia in the future.

MATERIALS AND METHODS

The study protocol was approved by the Cambodian National Ethics Committee for Health Research as part of the antimicrobial resistance surveillance network. Cases were identified from patients presenting to Takeo Provincial Referral Hospital, a 250-bed government hospital serving approximately 900,000 people in southern Cambodia.11 Cases were defined as growth of B. pseudomallei from blood cultures drawn at the hospital and analyzed by the hospital’s microbiology laboratory between January 1, 2021 and June 15, 2022.

At the Takeo Hospital microbiology laboratory, blood cultures were processed in nonautomated systems. Laboratory technicians visually checked cultures for signs of bacterial growth every 24 hours, then performed Gram stain on positive cultures. If organisms morphologically suggestive of B. pseudomallei were seen, samples were directly plated using the three-antibiotic disk method for rapid identification.8 All other positive cultures were subcultured on sheep blood and/or MacConkey agar before further biochemical and antibiotic susceptibility testing for isolate differentiation and characterization.

Once B. pseudomallei infection was confirmed, deidentified patient chart data were entered into a standardized case report form, with primary site of infection assigned based on presenting symptoms, discharge diagnosis, and available imaging and comorbid conditions (e.g., chronic alcohol use, diabetes) obtained from physician documentation. Ceftazidime and carbapenems were considered appropriate antibiotics for acute treatment.5 Isolate identification was confirmed by sequencing at the National Institute for Allergy and Infectious Diseases/International Center of Excellence in Research in Phnom Penh using methods previously described.12

The primary outcome was in-hospital mortality (“death”) or discharge to hospice. Patients discharged with “no improvement” or “hopeless” documented in notes were classified as discharged to hospice given the local cultural tradition of dying at home, particularly where in-hospital care is unaffordable.7 Covariates were demographics (age, sex), comorbid diseases (diabetes, chronic alcohol use), infection site, and treatment details (time to presentation, time to positive culture, receipt of appropriate antibiotic therapy).

Normally and non-normally distributed data were reported using mean (SD) or median (interquartile range [IQR]), respectively. Univariate analyses were performed using Fisher’s exact test for categorical variables and t-test or Wilcoxon rank-sum/matched-pairs signed-rank tests for continuous variables with parametric and nonparametric distributions, respectively. Analyses were performed using GraphPad Prism v. 9.2.0 (332) (LaJolla, CA).

RESULTS

Patient population.

Of 178 blood cultures collected during the study period, 82 (46%) were Enterobacterales and 55 (31%) were initially identified as B. pseudomallei (Supplemental Table 1). Sequencing revealed that one isolate was misidentified Klebsiella pneumoniae and another Achromobacter xylosoxidans. Antimicrobial susceptibility testing revealed sensitivity to ceftazidime, amoxicillin-clavulanic acid, meropenem, and trimethoprim/sulfamethoxazole and resistance to gentamicin in all isolates.

Of the 53 sequencing-confirmed cases of B. pseudomallei, 35 had available patient records. Most patients were male (26/35), and the mean (SD) age was 56.1 (13.3) years (Table 1). Almost all patients (32/35) had diabetes. Twenty-three percent of patients (8/35) reported chronic alcohol use. Most cases (69%; 24/35) presented with primary pneumonia, 14% (5/35) with skin or soft-tissue infection, 14% (5/35) with intraabdominal infection, and 3% (1/35) with urinary tract infection. Symptom duration before admission was 4 days (IQR: 2.0–10.0), ranging from 1 day of fever and dyspnea for pneumonia to 90 days of epigastric pain for visceral abscesses. Eleven percent of patients initially sought treatment at an ancillary facility, of whom 27% (3/11) survived compared with 54% (13/24) of patients presenting initially to the referral hospital.

Table 1

Demographics, clinical features, and outcomes of 35 patients with bacteremic melioidosis

Variables All Patients (N = 35)

n (%)
Improved (n = 16)

n (%)
Died or Discharged to Hospice (n = 19)

n (%)
P-Value and OR (95% CI)
Demographics
 Age, Mean (SD) 56.1 (13.3) 56.2 (15.4) 55.9 (11.8) P = 0.7746
 Sex
  Male 26 (74) 11 (69) 15 (79)
  Female 9 (26) 5 (31) 4 (21) 0.6 (0.2–2.8)
P = 0.7003
 Diabetes* 32 (91) 16 (100) 16 (84)
 Hypoglycemic Use in Diabetic Patients (N = 31)
  Oral and/or Insulin 25 (78) 15 (94) 10 (63)
  None 6 (19) 1 (6) 5 (31) 7.5 (1.0–93.2)
P = 0.0829
 Chronic Alcohol Use*
  No 27 (77) 13 (81) 14 (74)
  Yes 8 (23) 3 (19) 5 (26) 1.5 (0.3–6.7)
P = 0.7003
 First Treated at Ancillary Facility
  No 24 (69) 13 (81) 11 (58)
  Yes 11 (31) 3 (19) 8 (16) 3.2 (0.7–12.7)
P = 0.1667
Clinical Presentation
 Days of Symptom Duration before Admission, Median (IQR) 4.0 (2.0–10.0) 8.0 (3.8–11.3) 2.5 (2.0–10.0) P = 0.0379
 Primary Site of Infection
  Respiratory 24 (69) 9 (56) 15 (79)
  Skin/Soft Tissue 5 (14) 2 (13) 3 (16) 0.9 (0.2–5.8)
P >0.9999
  Intraabdominal 5 (14) 5 (31) 0
  Urinary 1 (3) 0 1 (5)
Clinical Course
 Days Hospitalized, Median (IQR) 4.0 (2.0–16.0) 17.5 (13.8–21.3) 2.0 (1.0–3.5) P <0.0001
 Days from Admission to Positive Culture, Median (IQR) 4.0 (2.5–6.0) 4.5 (3.0–5.3) 3.0 (2.0–6.0) P = 0.5791
 Appropriate Antibiotics Received§
  Ever 13 (37) 11 (69) 2 (11)
  Never 18 (51) 3 (19) 15 (79) 27.5 (4.1–148.2)
P = 0.0003

IQR = interquartile range; OR = odds ratio. Statistically significant (P <0.05) differences (quantitative data) and ORs (qualitative data) are shown in bold.

Comorbid conditions were obtained from physician documentation.

Oral hypoglycemic use was typically metformin, but four patients received glyburide alone or in combination with metformin; hypoglycemic data were incomplete for one patient (died/discharged to hospice) and excluded for three nondiabetic patients.

For acute treatment, appropriate antibiotics included ceftazidime and carbapenems.

Medication data were incomplete for four patients (two improved; two died/discharged to hospice).

Factors impacting mortality.

There were 10 deaths and nine discharges to hospice, accounting for an overall likely case-fatality rate of 54%. Deaths and discharges occurred a median of 7.0 (2.5–17.5) days after symptom onset and 2.0 (1.0–3.5) days after presentation to the hospital. In survivors, the duration of symptoms prior to presentation was 8.0 (3.8–11.3) days, and the length of hospitalization was 17.5 (13.8–21.3) days. Most patients (32/35) had blood cultures drawn within 24 hours of presentation and confirmed as B. pseudomallei 3.5 (2.0–5.0) days after admission. Survivors received positive results 4.5 (3.0–5.3) days after admission. Nonsurvivors died or were discharged to hospice within a median of 2.5 days from admission, but cultures did not return results until at least 3 days from admission (deaths: 2.0 (1–2.8) versus 3.5 (2.0–6.8), P = 0.0117; discharges to hospice: 2.0 (1.0–4.0) versus 3.0 (3.0–5.0), P = 0.0430) (Supplemental Table 2). For patients with complete drug administration logs (31/35), approximately 40% received appropriate antibiotics over the course of hospitalization (13/31). Fifteen patients died or were discharged to hospice without receiving appropriate antibiotic therapy, including two who received culture results before death or discharge. Patients who did not receive appropriate antibiotics had significantly higher odds of death than those who did (odds ration [OR]: 27.5, 95% CI: 4.1–148.2, P = .0003). When patients who were discharged to hospice were excluded, the odds of death remained significantly higher for those who did not receive appropriate antibiotics (OR: 14.67, 95% CI: 1.9–84.1, P = .0111).

DISCUSSION

Burkholderia pseudomallei is a pathogen of increasing global relevance as suitable environments and at-risk populations grow. In this cohort, we demonstrated that administration of appropriate antibiotics was strongly associated with survival of patients with bacteremic melioidosis. Developing rapid diagnostics, providing access to first-line therapies, and honing empiric treatment algorithms are therefore critical to reducing mortality associated with the disease.

Rapid diagnostics can help ensure that appropriate antibiotics are administered quickly. Recent efforts to standardize and optimize diagnostic testing have been followed by increases in culture-confirmed melioidosis cases in Cambodia, but unavailability and inefficient use of laboratory resources (e.g., Ashdown selective media) have impeded widespread efforts, resulting in nonsystematic sampling of disease and incomplete surveillance on a national level.8

Cambodian microbiology laboratories depend primarily on blood cultures with basic biochemical panels (occasionally via bioMérieux API 20NE strips; Marcy-l′Étoile, France), more frequently manual testing for taxonomic identification. Three-disc tests, in which isolates are cultured on plates with discs containing an antibiotic (here, gentamicin, colistin and amoxicillin-clavulanate), are used to determine susceptibility.8 These methods require at a minimum 48–72 hours to return actionable results; we and others have found that most deaths occur within 72 hours of admission.7,10 One promising serology-based point-of-care test provides results in 15 minutes, after which patients with positive results for B. pseudomallei could present directly to regional hospitals rather than first seeking care at less-equipped community health centers.13 Such community-based screening methods implemented in high-risk populations could quickly identify potential cases and accelerate access to gold standard diagnostic testing.14

Although early diagnosis is the cornerstone of timely therapy, access to appropriate antibiotics is also key to reducing disease morbidity and mortality. In this case series, we noted that some patients did not receive appropriate antibiotics even after receiving a culture diagnosis. Many Cambodian hospitals report a lack of first-line antibiotics, leading to suboptimal therapy with ceftriaxone, co-trimoxazole, or shortened courses of ceftazidime before de-escalation to “eradication” therapy.8,11 Prioritizing availability of meropenem, for instance, may bolster empiric treatment given that nearly one-third of all pathogens isolated from blood cultures at Takeo Hospital during the study period were resistant to third-generation cephalosporins.

Ninety-one percent of the cases described here were diabetic, among the largest proportions in published melioidosis case series. Although diabetes has been well-described as a risk factor for bacteremia, there may have been additional unappreciated predisposing risks in this population (e.g., occupational hazards of rice farming) not present in other country reports.5 Patient charts were considered in their entirety, and other conditions significantly associated with bacteremia were infrequent or absent (i.e., chronic lung and kidney disease, immunosuppression, and malignancy).5 Globally, 50% or more of melioidosis patients have diabetes, which increases the risk of developing melioidosis at least 12-fold.4 In Cambodia, an estimated 596,000 adults aged 20–79 years have diabetes.15 Of these, 56.1% remain undiagnosed, a rate higher than that in 90% of the countries in the western Pacific region.15 Providers caring for patients with diabetes in B. pseudomallei–endemic regions should maintain heightened awareness of their risk for infection and consider early initiation of and/or rapid escalation to ceftazidime or carbapenems in patients presenting with syndromes consistent with melioidosis. However, the myriad presentations of patients with both diabetes and melioidosis, as highlighted above, may challenge such empiric treatment algorithms. Ultimately, more data are needed from disease-endemic, low-resource areas with a high prevalence of melioidosis and uncontrolled diabetes to help understand potential synergies in diagnostic and management strategies of these two highly morbid diseases.

The study’s principal limitation is its narrow population of bacteremic patients, who compose up to 75% of melioidosis cases reported elsewhere.46 Including less-severe presentations is important to inform comprehensive treatment guidelines; however, these nonsevere cases are rarely recognized and captured in Cambodia. When considering our 54% likely case-fatality rate, it is important to note that bacteremia has been significantly associated with worse outcomes and mortality rates upwards of 75%.6,7,9,10 Given that the estimated global mortality rate is also 54%, the true rate for all melioidosis cases in Cambodia is likely lower.3 Furthermore, exclusion of the one-third of patients for whom charts were unavailable may have introduced unforeseen bias.

Seasonal differences were sought in date of admission, length of hospitalization, appropriate treatment, site of infection, and outcomes, among other variables, but showed no significant correlations. However, the 1.5-year study period may have been too limited to appreciate seasonality or variations in access to melioidosis therapy that might explain inconsistent treatment across confirmed cases. Because this study was retrospective, we were unable to work with prescriber and laboratory stakeholders to change practices during the study period. We hope that by sharing results now, we raise awareness of the disease and associated morbidity and inform empiric prescribing for appropriate target populations. Future studies capturing potential exposure events, barriers to care, and adherence to antimicrobial therapy will further contribute to optimization of melioidosis diagnosis and treatment in Cambodia.

Supplemental Materials

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ACKNOWLEDGMENT

We thank the study participants and nurses at Takeo Provincial Referral Hospital.

REFERENCES

  • 1.

    Birnie E , Virk HS , Savelkoel J , Spijker R , Bertherat E , Dance DAB , Limmathurotsakul D , Devleesschauwer B , Haagsma JA , Wiersinga WJ , 2019. Global burden of melioidosis, 2015: A systematic review and data synthesis. Lancet Infect Dis 19: 892902.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Meumann EM , Limmathurotsakul D , Dunachie SJ , Wiersinga WJ , Currie BJ , Burkholderia pseudomallei and melioidosis. Nat Rev Microbiol 22: 155169.

  • 3.

    Limmathurotsakul D et al., 2016. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol 1: 15008.

  • 4.

    Wiersinga WJ , Virk HS , Torres AG , Currie BJ , Peacock SJ , Dance DAB , Limmathurotsakul D , 2018. Melioidosis. Nat Rev Dis Primers 4: 17107.

  • 5.

    Currie BJ et al., 2021. The Darwin Prospective Melioidosis Study: A 30-year prospective, observational investigation. Lancet Infect Dis 21: 17371746.

  • 6.

    Vlieghe E , Kruy L , De Smet B , Kham C , Veng CH , Phe T , Koole O , Thai S , Lynen L , Jacobs J , 2011. Melioidosis, Phnom Penh, Cambodia. Emerg Infect Dis 17: 12891292.

  • 7.

    Rammaert B et al., 2011. Pulmonary melioidosis in Cambodia: A prospective study. BMC Infect Dis 11: 126.

  • 8.

    Bory S et al., 2018. A report from the Cambodia Training Event for Awareness of Melioidosis (C-TEAM), October 2017. Trop Med Infect Dis 3: 23.

  • 9.

    Pagnarith Y , Kumar V , Thaipadungpanit J , Wuthiekanun V , Amornchai P , Sin L , Day NP , Peacock SJ , 2010. Emergence of pediatric melioidosis in Siem Reap, Cambodia. Am J Trop Med Hyg 82: 11061112.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Chandna A , Bonhoeffer M , Miliya T , Suy K , Sao S , Turner P , 2021. Improving treatment and outcomes for melioidosis in children, northern Cambodia, 2009–2018. Emerg Infect Dis 27: 11691172.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Schully KL et al., 2017. Melioidosis in lower provincial Cambodia: A case series from a prospective study of sepsis in Takeo Province. PLoS Negl Trop Dis 11: e0005923.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Bohl JA et al., 2022. Discovering disease-causing pathogens in resource-scarce Southeast Asia using a global metagenomic pathogen monitoring system. Proc Natl Acad Sci USA 119: e2115285119.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Phokrai P et al., 2018. A rapid immunochromatography test based on Hcp1 is a potential point-of-care test for serological diagnosis of melioidosis. J Clin Microbiol 56: e00346-18.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Paz-Soldan VA et al., 2019. Potential use of community-based rapid diagnostic tests for febrile illnesses: Formative research in Peru and Cambodia. PLoS Negl Trop Dis 13: e0007773.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    International Diabetes Federation , 2021. IDF Diabetes Atlas. Available at: https://www.diabetesatlas.org. Accessed January 13, 2024.

    • PubMed
    • Export Citation

Author Notes

Financial support: This work was supported by the Division of Intramural Research at the National Institute of Allergy and Infectious Diseases at the National Institutes of Health and the Bill and Melinda Gates Foundation (grant no. INV-028123 to J. E. Manning).

Disclosure: Anonymized clinical data and bacterial genomic data are available upon request.

Authors’ contributions: C. Yek, C. Lon, and J. E. Manning designed the study. C. Chhuon, V. Te, and S. Seang oversaw patient management and microbiology testing. S. Ly, R. Sath, and R. Tim collected patient data. S. Chea, S. Lay, M. Oum, G. Tang, and L. Long sequenced blood culture isolates. The study was supervised by C. Lon and J. E. Manning and coordinated by S. V. Ly, H. Seng, and S. Krang. Data extraction and curation were done by A. R. Pacheco, H. Saunders, S. Chea, C. Yek, and C. Lon. A. R. Pacheco analyzed the data. A. R. Pacheco, C. Yek, and J. E. Manning prepared the original draft. All authors reviewed and edited the manuscript before submission.

Current contact information: Andrea R. Pacheco, University of Miami Leonard M. Miller School of Medicine, Miami, FL, E-mail: arp2170@columbia.edu. Sophana Chea, Sokna Ly, Ratanak Sath, Rathna Tim, Mengheng Oum, Gechlang Tang, Lyhourng Long, and Chanthap Lon, International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia, E-mails: cheas@icercambodia.org, lys@icercambodia.org, sratanak@icercambodia.org, rathnat@icercambodia.org, hengo@icercambodia.org, gechlangt@icercambodia.org, lyhournglong@icercambodia.org, and lonc@icercambodia.org. Helena Saunders, Department of Psychology, Colorado College, Colorado Springs, CO, E-mail: l_saunders@coloradocollege.edu. Sreyngim Lay, International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia, and National Center of Parasitology, Entomology, and Malaria Control, Phnom Penh, Cambodia, E-mail: lays@icercambodia.org. Sovann Ly, Heng Seng, and Sidonn Krang, Communicable Disease Control Department, Ministry of Health, Phnom Penh, Cambodia, E-mails: sovann_ly@yahoo.com, hengcdc@gmail.com, and sidonnkrang@yahoo.com. Chhouv Chhuon, Takeo Provincial Referral Hospital, Takeo, Cambodia, E-mail: chhouvchhuon@yahoo.com. Vantha Te and Sosorphea Seang, Takeo Provincial Referral Hospital, Takeo, Cambodia, E-mails: pediatrh@yahoo.com and sosorpheaseang@gmail.com. Christina Yek, Department of Critical Care Medicine, National Institutes of Health Clinical Center, Bethesda, MD, and Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, MD, E-mail: christina.yek@nih.gov. Jessica E. Manning, Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, Rockville, MD, and International Center of Excellence in Research, National Institute of Allergy and Infectious Diseases, Phnom Penh, Cambodia, E-mail: jessica.manning@nih.gov.

Address correspondence to Christina Yek, 1 Christopher Howes Place, Phnom Penh, Cambodia 120211. E-mail: christina.yek@nih.gov
  • 1.

    Birnie E , Virk HS , Savelkoel J , Spijker R , Bertherat E , Dance DAB , Limmathurotsakul D , Devleesschauwer B , Haagsma JA , Wiersinga WJ , 2019. Global burden of melioidosis, 2015: A systematic review and data synthesis. Lancet Infect Dis 19: 892902.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Meumann EM , Limmathurotsakul D , Dunachie SJ , Wiersinga WJ , Currie BJ , Burkholderia pseudomallei and melioidosis. Nat Rev Microbiol 22: 155169.

  • 3.

    Limmathurotsakul D et al., 2016. Predicted global distribution of Burkholderia pseudomallei and burden of melioidosis. Nat Microbiol 1: 15008.

  • 4.

    Wiersinga WJ , Virk HS , Torres AG , Currie BJ , Peacock SJ , Dance DAB , Limmathurotsakul D , 2018. Melioidosis. Nat Rev Dis Primers 4: 17107.

  • 5.

    Currie BJ et al., 2021. The Darwin Prospective Melioidosis Study: A 30-year prospective, observational investigation. Lancet Infect Dis 21: 17371746.

  • 6.

    Vlieghe E , Kruy L , De Smet B , Kham C , Veng CH , Phe T , Koole O , Thai S , Lynen L , Jacobs J , 2011. Melioidosis, Phnom Penh, Cambodia. Emerg Infect Dis 17: 12891292.

  • 7.

    Rammaert B et al., 2011. Pulmonary melioidosis in Cambodia: A prospective study. BMC Infect Dis 11: 126.

  • 8.

    Bory S et al., 2018. A report from the Cambodia Training Event for Awareness of Melioidosis (C-TEAM), October 2017. Trop Med Infect Dis 3: 23.

  • 9.

    Pagnarith Y , Kumar V , Thaipadungpanit J , Wuthiekanun V , Amornchai P , Sin L , Day NP , Peacock SJ , 2010. Emergence of pediatric melioidosis in Siem Reap, Cambodia. Am J Trop Med Hyg 82: 11061112.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    Chandna A , Bonhoeffer M , Miliya T , Suy K , Sao S , Turner P , 2021. Improving treatment and outcomes for melioidosis in children, northern Cambodia, 2009–2018. Emerg Infect Dis 27: 11691172.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Schully KL et al., 2017. Melioidosis in lower provincial Cambodia: A case series from a prospective study of sepsis in Takeo Province. PLoS Negl Trop Dis 11: e0005923.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Bohl JA et al., 2022. Discovering disease-causing pathogens in resource-scarce Southeast Asia using a global metagenomic pathogen monitoring system. Proc Natl Acad Sci USA 119: e2115285119.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Phokrai P et al., 2018. A rapid immunochromatography test based on Hcp1 is a potential point-of-care test for serological diagnosis of melioidosis. J Clin Microbiol 56: e00346-18.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 14.

    Paz-Soldan VA et al., 2019. Potential use of community-based rapid diagnostic tests for febrile illnesses: Formative research in Peru and Cambodia. PLoS Negl Trop Dis 13: e0007773.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    International Diabetes Federation , 2021. IDF Diabetes Atlas. Available at: https://www.diabetesatlas.org. Accessed January 13, 2024.

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