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[A case of melioidosis in a Japanese soldier in Malaya]

SAKIHARA H

Jpn. J. Med. Sci. Biol., 1952 Dec;5(6):425-32.
PMID: 13069136
Matched MeSH terms: Melioidosis*
Fulltext Whole-genome comparative analysis of Malaysian Burkholderia pseudomallei clinical isolates

Ghazali AK, Eng SA, Khoo JS, Teoh S, Hoh CC, Nathan S

Microb Genom, 2021 02;7(2).
PMID: 33565959 DOI: 10.1099/mgen.0.000527

Burkholderia pseudomallei, a soil-dwelling Gram-negative bacterium, is the causative agent of the endemic tropical disease melioidosis. Clinical manifestations of B. pseudomallei infection range from acute or chronic localized infection in a single organ to fulminant septicaemia in multiple organs. The diverse clinical manifestations are attributed to various factors, including the genome plasticity across B. pseudomallei strains. We previously characterized B. pseudomallei strains isolated in Malaysia and noted different levels of virulence in model hosts. We hypothesized that the difference in virulence might be a result of variance at the genome level. In this study, we sequenced and assembled four Malaysian clinical B. pseudomallei isolates, UKMR15, UKMPMC2000, UKMD286 and UKMH10. Phylogenomic analysis showed that Malaysian subclades emerged from the Asian subclade, suggesting that the Malaysian strains originated from the Asian region. Interestingly, the low-virulence strain, UKMH10, was the most distantly related compared to the other Malaysian isolates. Genomic island (GI) prediction analysis identified a new island of 23 kb, GI9c, which is present in B. pseudomallei and Burkholderia mallei, but not Burkholderia thailandensis. Genes encoding known B. pseudomallei virulence factors were present across all four genomes, but comparative analysis of the total gene content across the Malaysian strains identified 104 genes that are absent in UKMH10. We propose that these genes may encode novel virulence factors, which may explain the reduced virulence of this strain. Further investigation on the identity and role of these 104 proteins may aid in understanding B. pseudomallei pathogenicity to guide the design of new therapeutics for treating melioidosis.

Matched MeSH terms: Melioidosis/microbiology*
Fulltext Variations in ceftazidime and amoxicillin-clavulanate susceptibilities within a clonal infection of Burkholderia pseudomallei

Sam IC, See KH, Puthucheary SD

J Clin Microbiol, 2009 May;47(5):1556-8.
PMID: 19297597 DOI: 10.1128/JCM.01657-08

A patient with a clonal infection of Burkholderia pseudomallei had subpopulations with ceftazidime and amoxicillin-clavulanate susceptibilities that differed among the clinical specimens. Resistance was associated with a novel Cys69Tyr substitution in the Ambler class A beta-lactamase. Susceptibility testing of multiple colony variants from different sites should be performed for patients with culture-confirmed melioidosis.

Matched MeSH terms: Melioidosis/microbiology*
Fulltext Utilization of Point-of-Care Ultrasound to Detect Splenic Microabscesses in Pediatric Melioidosis

Sakulchit T, Ngu L, Chor YK, Ong GY

Cureus, 2021 Mar 08;13(3):e13760.
PMID: 33842136 DOI: 10.7759/cureus.13760

Melioidosis is an infectious disease most commonly found in places with tropical climates. Definitive diagnosis can be confirmed by culture or pathological results of blood or infected organ. However, imaging study is helpful in providing early provisional diagnosis and guiding therapy. Point-of-care ultrasound can be currently performed bedside by non-radiological staff such as emergency physicians or intensivists. We present the case of a pediatric patient who got diagnosed with melioidosis after detection of multiple splenic and hepatic abscesses by point-of-care ultrasound, leading to early diagnosis and appropriate empirical antibiotic selection, resulting in good treatment outcome.

Matched MeSH terms: Melioidosis
Fulltext Urogenital melioidosis: a review of clinical presentations, characteristic and outcomes

Chong Vh VH, Sharif F, Bickle I

Med J Malaysia, 2014 Dec;69(6):257-60.
PMID: 25934955 MyJurnal

INTRODUCTION: Melioidosis is endemic to the tropical regions, in particular Thailand and Northern Australia. Any organ can be affected by melioidosis. Involvement of the urogenital system is common in Northern Australia, but is less common in other regions. This study assesses the characteristics of melioidosis affecting the urogenital system treated in a tertiary referral centre in Brunei Darussalam.

MATERIAL AND METHODS: All patients treated for melioidosis of the urogenital system were identified and retrospectively reviewed.

RESULTS: There were 9 patients with 11 episodes of urogenital infections treated over 13 years. The median age at diagnosis was 38 years old (range 29 - 63) with men predominantly affected. The major risk factor was underlying diabetes mellitus (n=9), including three patients diagnosed at the time of diagnosis of melioidosis. The median glycosylated haemoglobin (HbA1c) was 12.8% (range 6.4 to 16.6%). One patient's risk factor was only moderate alcohol consumption. Common symptoms included; fever, lethargy, rigor and anorexia. Dysuria was reported by two patients. The median duration of symptoms before presentation was 7 days (range 2 to 21 days) and the median number of sites involved were 3 (range of 2 to 6). Urogenital involvement included prostate (n=6), kidney (n=8), seminal vesicles (n=1) and testis (n=1). Radiological imaging showed that large prostate abscesses (>4.5cm) were common, and in some patients, the kidney abscess had the 'honeycomb' previously described as typical for melioidosis liver abscess. All patients were successfully treated for melioidosis and at a median follow up of 34 months (range 1 - 97), there was one death from complications of diabetes mellitus.

CONCLUSION: Urogenital melioidosis only accounted for a small proportion of all melioidosis involvement, with prostate and kidney most commonly affected. Concomitant involvement of other sites were common. The major risk factor was poorly controlled diabetes mellitus.

Matched MeSH terms: Melioidosis
Unrecognised infection in a cystic fibrosis patient

Asiah K, Hanifah YA, Norzila MZ, Hasniah L, Rusanida A

J Paediatr Child Health, 2006 Apr;42(4):217-8.
PMID: 16630326

We report a 17-year-old Malay boy with cystic fibrosis who over a 14-month period experienced worsening respiratory symptoms and deteriorating lung function. Burkholderia pseudomallei was eventually isolated from his sputum. He improved clinically following treatment for meliodosis and his lung function returned to normal.

Matched MeSH terms: Melioidosis/diagnosis*; Melioidosis/drug therapy; Melioidosis/microbiology
Tropical pulmonary diseases

Bovornkitti S

Respirology, 1996 Mar;1(1):11-21.
PMID: 9432400

The term 'tropical' refers to the region of the Earth lying between the Tropic of Cancer and the Tropic of Capricorn. Located between these equatorial parallels demarcating the Torrid Zone are several underdeveloped and developing countries: Thailand, the Philippines, Malaysia, Singapore, Indonesia, southern India, Sri Lanka, Brazil, Cuba, Ethiopia, Sudan and Nigeria, to name but a few considered to be 'tropical'. The climate in most of these countries is characterized by high temperatures and high humidity. The tropical climate and general state of socio-economic underdevelopment in such countries provide an ideal environment for pathogenic organisms, their vectors and intermediate hosts to flourish. Furthermore, the cultural habits and educational background of the people living in such countries expose them to pathogens and, when these people become infected, they readily become reservoirs for, or carriers of, those organisms. Ultimately, the adverse socioeconomic conditions of underdeveloped countries impede attempts to eradicate or control tropical diseases.

Matched MeSH terms: Melioidosis
Transcriptome analysis of Burkholderia pseudomallei T6SS identifies Hcp1 as a potential serodiagnostic marker

Chieng S, Mohamed R, Nathan S

Microb Pathog, 2015 Feb;79:47-56.
PMID: 25616255 DOI: 10.1016/j.micpath.2015.01.006

Burkholderia pseudomallei, the causative agent of melioidosis, is able to survive extreme environments and utilizes various virulence factors for survival and pathogenicity. To compete and survive within these different ecological niches, B. pseudomallei has evolved specialized pathways, including the Type VI secretion systems (T6SSs), that have a role in pathogenesis as well as interbacterial interactions. We examined the expression profile of B. pseudomallei T6SS six gene clusters during infection of U937 macrophage cells. T6SS-5 was robustly transcribed while the other five clusters were not significantly regulated proposing the utility of T6SS-5 as a potential biomarker of exposure to B. pseudomallei. Transcription of T6SS regulators VirAG and BprB was also not significant during infection when compared to bacteria grown in culture. Guided by these findings, three highly expressed T6SS genes, tssJ-4, hcp1 and tssE-5, were expressed as recombinant proteins and screened against melioidosis patient sera by western analysis and ELISA. Only Hcp1 was reactive by both types of analysis. The recombinant Hcp1 protein was further evaluated against a cohort of melioidosis patients (n = 32) and non-melioidosis individuals (n = 20) sera and the data clearly indicates a higher sensitivity (93.7%) and specificity (100%) for Hcp1 compared to bacterial lysate. The detection of anti-Hcp1 antibodies in patients' sera indicating the presence of B. pseudomallei highlights the potential of Hcp1 to be further developed as a serodiagnostic marker for melioidosis.

Matched MeSH terms: Melioidosis/diagnosis*
Fulltext The relationship between bacterial sources and genotype to the antimicrobial resistance pattern of Burkholderia pseudomallei

Sadiq MA, Hassan L, Aziz SA, Zakaria Z, Musa HI, Amin MM

Vet World, 2018 Nov;11(10):1404-1408.
PMID: 30532493 DOI: 10.14202/vetworld.2018.1404-1408

Background: Melioidosis is a fatal emerging infectious disease of both man and animal caused by bacteria Burkholderia pseudomallei. Variations were suggested to have existed among the different B. pseudomallei clinical strains/genotypes which may implicate bacterial susceptibility and resistance toward antibiotics.
Aim: This study was designed to determine whether the phenotypic antibiotic resistance pattern of B. pseudomallei is associated with the source of isolates and the genotype.
Materials and Methods: A collection of 111 B. pseudomallei isolates from veterinary cases of melioidosis and the environments (soil and water) were obtained from stock cultures of previous studies and were phylogenetically characterized by multilocus sequence typing (ST). The susceptibility to five antibiotics, namely meropenem (MEM), imipenem, ceftazidime (CAZ), cotrimoxazole (SXT), and co-amoxiclav (AMC), recommended in both acute and eradication phases of melioidosis treatment were tested using minimum inhibitory concentration antibiotics susceptibility test.
Results: Majority of isolates were susceptible to all antibiotics tested while few resistant strains to MEM, SXT, CAZ, and AMC were observed. Statistically significant association was found between resistance to MEM and the veterinary clinical isolates (p<0.05). The likelihood of resistance to MEM was significantly higher among the novel ST 1130 isolates found in veterinary cases as compared to others.
Conclusion: The resistance to MEM and SXT appeared to be higher among veterinary isolates, and the novel ST 1130 was more likely to be resistant to MEM as compared to others.

Matched MeSH terms: Melioidosis
Fulltext The man with the boggy head: cranial melioidosis

Kuan YC, How SH, Ng TH, Fauzi AR

Singapore Med J, 2010 Feb;51(2):e43-5.
PMID: 20358143

Melioidosis is known to cause abscesses in various organs, including the cranium, though less commonly. We present a patient with scalp abscess and subdural empyema that was visible on computed tomography of the brain. The neurosurgical drainage grew Burkholderia pseudomallei. Despite our best effort to treat the patient using parenteral antibiotics and surgical drainage, the patient did not survive.

Matched MeSH terms: Melioidosis/drug therapy; Melioidosis/radiography*
The histopathology of human melioidosis

Wong KT, Puthucheary SD, Vadivelu J

Histopathology, 1995 Jan;26(1):51-5.
PMID: 7713483

We examined human tissues infected by Burkholderia (Pseudomonas) pseudomallei which is endemic in Malaysia to study the types of inflammation invoked, and to look for histopathological clues to its diagnosis. The lesions which varied from acute to chronic granulomatous inflammation were not tissue-specific. In five autopsy cases, the inflammation was usually a focal or diffuse, acute necrotising inflammation with varying numbers of neutrophils, macrophages, lymphocytes and 'giant cells'. The 'giant cells' probably represent giant macrophages with phagocytosed leukocytes. There were numerous gram-negative, non-acid-fast, intra- and extracellular bacilli, occurring either singly or in chains. Intracellular bacteria within macrophages and 'giant cells' were so numerous as to resemble globi. This feature has not been previously reported and may be a useful diagnostic clue in melioidosis. In 14 surgical cases biopsies showed acute inflammatory lesions that appeared no different from acute inflammation due to other causes. In many biopsies, however, the inflammation was either an acute-on-chronic inflammation with a focal granulomatous component, or was purely granulomatous in character. Bacilli were difficult to demonstrate in surgical biopsies even with the gram strain.

Matched MeSH terms: Melioidosis/pathology*
Fulltext The epidemiology and clinical spectrum of melioidosis in a teaching hospital in a North-Eastern state of Malaysia: a fifteen-year review

Zueter A, Yean CY, Abumarzouq M, Rahman ZA, Deris ZZ, Harun A

BMC Infect Dis, 2016;16:333.
PMID: 27423906 DOI: 10.1186/s12879-016-1583-2

Over the last two decades, many epidemiological studies were performed to describe risks and clinical presentations of melioidosis in endemic countries.

Study site: Hospital Universiti Sains Malaysia (HUSM)

Matched MeSH terms: Melioidosis
Fulltext The bug and the big heart --melioidotic pericardial effusion

Yew KL, Ng TH, How SH, Kuan YC

Med J Malaysia, 2011 Mar;66(1):71-2.
PMID: 23765151 MyJurnal

Melioidosis is an infection caused by Gram negative bacterium Burkholderia pseudomallei leading to abscesses in lungs, liver, spleen, musculoskeletal system, prostate and sepsis. We present a rare case of purulent pericardial effusion caused by melioidosis with concomitant pneumonia and splenic abscesses. The patient underwent pericardiocentesis and successfully recovered from cardiogenic and septic shock.

Matched MeSH terms: Melioidosis
Fulltext The Trend of Direct Medical Cost of Meliodiosis Patients in Kedah: A Retrospective Study from 2014 to 2017

Mardhiah K, Wan-Arfah N, Naing NN, Abu Hassan MR, Chan HK, Hasan H

Clinicoecon Outcomes Res, 2021;13:155-162.
PMID: 33732004 DOI: 10.2147/CEOR.S286283

Purpose: This study was conducted to determine the direct medical cost of treating melioidosis patients. The calculation was made according to the variables extracted from medical records.
Materials and Methods: Data collection was performed retrospectively on a total of 293 cases from Hospital Sultanah Bahiyah, Kedah, Malaysia. The data consisted of personal information, treatment history, and investigation findings, including blood results, USG abdomen results, and CT scan results. The site of culture and sensitivity were also obtained. The total direct medical cost was based on the antibiotics/treatments received by the patients, diagnostic test and investigations performed. The trend analysis used to see the pattern of costs from 2014 to 2017. All the costs were compared based on patients' status and duration of stay at the hospital using the independent t-test.
Results: The overall mean of direct medical cost for melioidosis amounted to US $233.61 (RM931.33). Overall, the finding confirms a huge reduction (44.7%) of direct medical cost from 2014 to 2017 (P = 0.001). From 2015 to 2016, there was a 19.1% reduction of direct medical cost (P>0.95), followed by a 38.8% reduction in costs from 2016 to 2017 (P = 0.019). In the case of the duration of stay, the mean of total direct medical cost among patients with ≥14 duration of stay was higher compared to those with <14 duration of stay (p < 0.001). There was no significant mean difference of direct medical cost between patients who were cured and died.
Conclusion: Despite the higher mortality of melioidosis cases compared to other infectious diseases, there is a limitation in the amount of published data on the management cost of melioidosis. The importance of cost in managing this disease should be underlined to perform a fully prepared management toward the disease.

Matched MeSH terms: Melioidosis
Fulltext The Cox model of predicting mortality among melioidosis patients in Northern Malaysia: A retrospective study

Mardhiah K, Wan-Arfah N, Naing NN, Hassan MRA, Chan HK

Medicine (Baltimore), 2021 Jun 25;100(25):e26160.
PMID: 34160382 DOI: 10.1097/MD.0000000000026160

Melioidosis is an infectious disease that is initiated by a bacteria recognized as Burkholderia pseudomallei. Despite the high fatality rate from melioidosis, there is a minimal published study about the disease in Malaysia.This study aimed to identify the prognostic factors of mortality among melioidosis patients in northern Malaysia.All inpatient patients who were admitted to Hospital Sultanah Bahiyah, Kedah and Hospital Tuanku Fauziah, Perlis with culture-confirmed melioidosis during the period 2014 to 2017 were included in the study. The study retrospectively collected 510 melioidosis patients from the Melioidosis Registry. Hazard ratio (HR) used in advanced multiple Cox regression was used to obtain the final model of prognostic factors of melioidosis. The analysis was performed using STATA/SE 14.0 for Windows software.From the results, among the admitted patients, 50.1% died at the hospital. The mean age for those who died was 55 years old, and they were mostly male. The most common underlying disease was diabetes mellitus (69.8%), followed by hypertension (32.7%). The majority of cases (86.8%) were bacteremic. The final Cox model identified 5 prognostic factors of mortality among melioidosis patients. The factors were diabetes mellitus, type of melioidosis, platelet count, white blood cell count, and urea value. The results showed that bacteremic melioidosis increased the risk of dying by 3.47 (HR: 3.47, 95% confidence intervals [CI]: 1.67-7.23, P = .001) compared to non-bacteremic melioidosis. Based on the blood investigations, the adjusted HRs from the final model showed that all 3 blood investigations were included as the prognostic factors for the disease (low platelet: HR = 1.76, 95% CI: 1.22-2.54, P = .003; high white blood cell: HR = 1.49, 95% CI 1.06-2.11, P = .023; high urea: HR = 2.92, 95% CI: 1.76-4.85, P

Matched MeSH terms: Melioidosis/blood; Melioidosis/drug therapy; Melioidosis/microbiology; Melioidosis/mortality*
Fulltext Thalassemia major is a major risk factor for pediatric melioidosis in Kota Kinabalu, Sabah, Malaysia

Fong SM, Wong KJ, Fukushima M, Yeo TW

Clin Infect Dis, 2015 Jun 15;60(12):1802-7.
PMID: 25767257 DOI: 10.1093/cid/civ189

Melioidosis is an important cause of community-acquired infection in Southeast Asia and northern Australia. Studies from endemic countries have demonstrated differences in the epidemiology and clinical features among children diagnosed with melioidosis. This suggests that local data are needed to determine the risk factors and outcome in specific areas.

Matched MeSH terms: Melioidosis/complications*; Melioidosis/drug therapy; Melioidosis/mortality; Melioidosis/epidemiology*
Fulltext Systemic lupus erythematosus and melioidosis

Che Rahim MJ, Mohammad N, Kamaruddin MI, Wan Ghazali WS

BMJ Case Rep, 2019 Jul 01;12(7).
PMID: 31266760 DOI: 10.1136/bcr-2019-229974

We reported a case of a young female patient presented with sepsis and diagnosed with melioidosis and systemic lupus erythematosus (SLE) within the same admission. She presented with 1-week history of productive cough, progressive dyspnoea together with prolonged fever, arthralgia, rashes and oral ulcers. She had septicemic shock, respiratory failure requiring intubation and ventilation in intensive care unit and subsequently developed acute renal failure requiring haemodialysis. Antibiotics and immunosuppressive treatment including low-dose intravenous cyclophosphamide were commenced. She had a remarkable recovery and was discharged after 6 weeks. There was no evidence of active SLE or relapse of melioidosis during clinic follow-ups.

Matched MeSH terms: Melioidosis/complications*; Melioidosis/diagnosis*; Melioidosis/drug therapy
Fulltext Survival and Intra-Nuclear Trafficking of Burkholderia pseudomallei: Strategies of Evasion from Immune Surveillance?

Vadivelu J, Vellasamy KM, Thimma J, Mariappan V, Kang WT, Choh LC, et al.

PLoS Negl Trop Dis, 2017 01;11(1):e0005241.
PMID: 28045926 DOI: 10.1371/journal.pntd.0005241

BACKGROUND: During infection, successful bacterial clearance is achieved via the host immune system acting in conjunction with appropriate antibiotic therapy. However, it still remains a tip of the iceberg as to where persistent pathogens namely, Burkholderia pseudomallei (B. pseudomallei) reside/hide to escape from host immune sensors and antimicrobial pressure.
METHODS: We used transmission electron microscopy (TEM) to investigate post-mortem tissue sections of patients with clinical melioidosis to identify the localisation of a recently identified gut microbiome, B. pseudomallei within host cells. The intranuclear presence of B. pseudomallei was confirmed using transmission electron microscopy (TEM) of experimentally infected guinea pig spleen tissues and Live Z-stack, and ImageJ analysis of fluorescence microscopy analysis of in vitro infection of A549 human lung epithelial cells.
RESULTS: TEM investigations revealed intranuclear localization of B. pseudomallei in cells of infected human lung and guinea pig spleen tissues. We also found that B. pseudomallei induced actin polymerization following infection of A549 human lung epithelial cells. Infected A549 lung epithelial cells using 3D-Laser scanning confocal microscopy (LSCM) and immunofluorescence microscopy confirmed the intranuclear localization of B. pseudomallei.
CONCLUSION: B. pseudomallei was found within the nuclear compartment of host cells. The nucleus may play a role as an occult or transient niche for persistence of intracellular pathogens, potentially leading to recurrrent episodes or recrudescence of infection.

Matched MeSH terms: Melioidosis/metabolism; Melioidosis/microbiology*
Successful surgical management of a case of pulmonary and pericardial melioidosis

Majid AA

Aust N Z J Surg, 1990 Feb;60(2):139-41.
PMID: 2327916

A 35 year old diabetic presented with features of septicaemia and developed cardiac tamponade. He was found to have pulmonary, acute septicaemic and pericardial melioidosis. Some initial improvement was achieved with medical therapy but only with surgical intervention was a successful outcome achieved.

Matched MeSH terms: Melioidosis/radiography; Melioidosis/surgery*
Stability of strain genotypes of Burkholderia pseudomallei from patients with single and recurrent episodes of melioidosis

Vadivelu J, Puthucheary SD, Drasar BS, Dance DA, Pitt TL

Trop Med Int Health, 1998 Jul;3(7):518-21.
PMID: 9705184

The constancy of strain genotypes of multiple isolates of Burkholderia pseudomallei from 13 patients with melioidosis was examined by BamHI ribotyping and pulsed-field gel electrophoresis (PFGE) of XbaI digests of DNA. Seven of 8 patients with single episodes of melioidosis each yielded genetically identical isolates and only one of five patients with recurrent episodes was infected with a new strain clearly distinct from the original primary strain. Variation was observed in PFGE patterns of primary and relapse isolates of another patient but this was insufficient to define genetically distinct strains. We conclude that most patients with single or multiple episodes of melioidosis retain a single strain.

Matched MeSH terms: Melioidosis/microbiology*

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