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PubMed1986

Application of indirect hemagglutination test and indirect fluorescent antibody test for IgM antibody for diagnosis of melioidosis in Thailand.

In hyperendemic areas such as Thailand, rapid diagnosis of melioidosis depends upon both bacteriological culture and serological methods. However, interpretation of indirect hemagglutination (IHA) for melioidosis which is the only test available, is seriously hampered by increased IHA titers present in one-third to one-half of the population. In order to get the best results from the available tests, IHA and indirect fluorescent antibody for IgM (IFA-IgM) were evaluated in controls and patients in Thailand. IHA titers of greater than or equal to 1:40 were considered remote or recent exposure to P. pseudomallei. IHA titers of this level were found in 47.1% of 227 blood donors and 29.5% of 210 sera submitted for other tests, while IFA-IgM was positive in only one donor who had an IHA titer of 1:1,280. IHA was positive in eight out of nine patients with melioidosis with IHA titers of less than 1:20 to 1:2,560. IFA-IgM was positive in six out of seven melioidosis patients whose sera were available for this test including a serum with IHA titer of less than 1:20. Six patients were predisposed by diabetes mellitus. Among sera serologically tested for melioidosis, 33 had IHA titers of 1:80-1:1,280, 10 of which were positive for IFA-IgM. This study demonstrates high background IHA titers among IHA titers among Thai people which greatly limits its use for serodiagnosis of melioidosis. In sharp contrast, serodiagnosis by IFA-IgM was more successful. Positive IFA-IgM among healthy Thais did exist indicating that serologic tests for melioidosis at best are only supplementary to bacteriological culture and clinical awareness.

Animals↗
PubMed1988

Childhood melioidosis in northeastern Thailand.

Eighteen cases of childhood melioidosis in Northeastern Thailand were reviewed. The mean age was 6.8 years with a range from eight months to 15 years. Twelve cases (66.7%) had localized melioidosis, six of which had pneumonia. Three patients were diagnosed as pharyngocervical melioidosis, the newly recognized syndrome. Nine cases (50.0%) had associated diseases including dengue hemorrhagic fever (DHF) in five cases. In all five cases, melioidosis was diagnosed during the convalescent stage as a cause of pyrexia with or without pneumonia. Pseudomonas pseudomallei strains isolated from 12 patients were all sensitive to chloramphenicol, cotrimoxazole and kanamycin. Ceftazidime, cefotaxime and ceftriaxone were also active against all six isolates tested. Three cases died, all were diagnosed as disseminated septicaemic melioidosis at postmortem. The overall mortality rate was 16.7%. The septicaemic form of melioidosis can resemble many diseases such as septicaemia due to Staphylococcus aureus or gram-negative organisms other than P. pseudomallei while the localized from may mimic pulmonary tuberculosis. A high index of clinical suspicion is required in making a diagnosis of melioidosis, particularly in areas where the disease is endemic.

Child↗
PubMed1995

Musculoskeletal melioidosis: clinical and imaging features.

OBJECTIVE: Melioidosis is a tropical infection caused by a gram-negative bacillus, Pseudomonas pseudomallei. The disease manifests initially as localized suppurative lesions and can progress to acute disseminated septicemia with 65-90% mortality if inadequately treated. Musculoskeletal involvement is common. The purpose of this study was to describe the clinical features and imaging appearances of musculoskeletal melioidosis. DESIGN: We retrospectively analyzed the clinical profiles and images of 26 patients diagnosed over a 6-year period as suffering from melioidosis. PATIENTS: The study group comprised 11 patients with musculoskeletal melioidosis and 15 patients with nonmusculoskeletal melioidosis. RESULTS AND CONCLUSIONS: We found that musculoskeletal melioidosis mimicks other infections both clinically and radiologically. Clinical awareness is therefore crucial, as diagnosis can only be established by bacteriological and immunological studies. Prompt treatment with long-term combination antibiotics in high dosages and surgical drainage of abscesses improves survival.

Adult↗
PubMedDate not supplied

The use of bone marrow culture for the diagnosis of melioidosis.

We have evaluated prospectively the contribution of bone marrow culture to the diagnosis of melioidosis. Bone marrow (BMC) and blood cultures (BC) were collected concurrently from 105 patients with suspected acute, severe melioidosis. 67 patients were subsequently proved to have the disease whilst other significant organisms were isolated from these specimens in 5 cases. Overall, 67.2% of BC and 64.2% of BMC from melioidosis patients grew Pseudomonas pseudomallei. Time to positivity did not differ significantly in paired BC and BMC specimens. These results do not support the routine use of BMC in the diagnosis of acute, severe melioidosis. In one patient with pulmonary melioidosis, however, blood cultures were repeatedly negative, whilst bone marrow grew P. pseudomallei, and this preceded the development of a distant focus of infection. This suggests that culture of bone-marrow may be of value in certain blood culture-negative patients with melioidosis.

Acute Disease↗
PubMed2000

Animal melioidosis in Australia.

Melioidosis was first diagnosed in Australia in sheep in 1949. While it has been considered endemic in tropical Australia, there have been animal outbreaks in southwest Western Australia and southern Queensland. Infection occurs in many species, with both latency and a wide range of clinical manifestations. Some species may develop melioidosis only if immunocompromised. Sheep and goats are particularly susceptible, resulting in the requirement for pasteurisation of tropical commercial goat's milk. Nine out of 43 (21%) goats had aortic lesions at autopsy and seven died from aortic aneurysm rupture. Transplacental transmission in goats has also been documented. Asymptomatic organ abscesses are common in pigs but bovine melioidosis is very rare. Camels moved north and an alpaca brought to Darwin have died from melioidosis. It also occurs in wildlife, including birds, crocodiles and kangaroos. Zoonotic transmission to humans is extremely unusual, but there are many similar epidemiological and clinical features of melioidosis in animals and humans. There have been three possible zoonotic cases in Australia. Molecular typing has found identical Burkholderia pseudomallei organisms from animals, humans and soil. The study of melioidosis in animals, especially the use of molecular genetic techniques for organism identification and typing, will continue to unravel aspects of the disease that remain unclear in humans.

Animals↗
PubMed2001

Paediatric melioidosis in the Northern Territory of Australia: an expanding clinical spectrum.

OBJECTIVE: The objective of this study was to present the laboratory and clinical features of the six cases of paediatric melioidosis diagnosed from 1997-2000. METHODOLOGY: All cases of melioidosis confirmed by the pathology department of Royal Darwin Hospital were prospectively identified by culture and/or serology. RESULTS: Four children were Aboriginal and all six cases presented during the rainy season (November-April) in rural areas in the tropical Top End of the Northern Territory. Delay in diagnosis ranged from 5 and 11 days. Two cases had localized melioidosis, two cases had underlying disease and were likely to be colonized with Burkholderia pseudomallei (B. pseudomallei). Two cases had neurological melioidosis with major residual disability. No deaths occurred. CONCLUSIONS: Melioidosis remains an unusual disease in children in the tropical Northern Territory. The average annual incidence since 1997 is 5.48 per 100 000. This series demonstrates that children in Australia can have serious neurological complications from B. pseudomallei infection. All children living in or visiting tropical Australia are at risk, especially those residing in rural areas in the rainy season. Melioidosis remains a difficult disease to manage, and expert opinion should be sought if B. pseudomallei is cultured from any site.

Child↗
PubMed2005

Melioidosis in 6 tsunami survivors in southern Thailand.

BACKGROUND: Six cases of melioidosis were identified in survivors of the 26 December 2004 tsunami who were admitted to Takuapa General Hospital in Phangnga, a region in southern Thailand where melioidosis is not endemic. All 6 cases were associated with aspiration, and 4 were also associated with laceration. METHODS: We compared the clinical, laboratory, and radiographic findings and the outcomes for these 6 patients with those for 22 patients with aspiration-related melioidosis acquired during 1987-2003 in a melioidosis-endemic region in northeast Thailand. Results of tests for detection of Burkholderia pseudomallei in soil specimens from Phangnga and from northeast Thailand were compared. RESULTS: The 6 patients (age range, 25-65 years) presented with signs and symptoms of pneumonia 3-38 days (median duration, 6.5 days) after the tsunami. Chest radiograph findings at the onset of pneumonia were abnormal in all cases; 1 patient developed a lung abscess. B. pseudomallei was grown in blood cultures in 3 cases and in cultures of respiratory secretions in 4 cases. Two patients required ventilation and inotropes; 1 patient died. Compared with tsunami survivors, patients with aspiration-related melioidosis in northeast Thailand had a shorter interval (median duration, 1 day) between aspiration and onset of pneumonia; were more likely to exhibit shock, respiratory failure, renal failure, and/or altered consciousness (P=.03); and had a higher in-hospital mortality (64% [14 of 22 patients]; P=.07). These differences may be related to the severity of the near-drowning episode, the inhalation of sea water versus fresh water, the size of bacterial inoculum, and the possible acquisition (among tsunami survivors) of B. pseudomallei via laceration. Only 3 (0.8%) of 360 soil samples from Phangnga were positive for B. pseudomallei, compared with 26 (20%) of 133 samples from northeast Thailand (P<.0001). CONCLUSIONS: Tsunami survivors are at increased risk of melioidosis if they are injured in an environment containing B. pseudomallei.

Adult↗
PubMedDate not supplied

Tropical disease in the immunocompromised host: melioidosis and pythiosis.

Melioidosis is an infection of humans and animals caused by a gram-negative motile bacillus, Pseudomonas pseudomallei. Forty-nine patients with melioidosis complicating diabetes mellitus, collagen vascular disorders, leukemia/lymphoma, and other hematologic malignancies are described. Twenty-nine of these patients had disseminated/septicemic infection, two developed toxic shock syndrome, and one with AIDS experienced recrudescent melioidosis. Patients with disseminated melioidosis often have a variety of defects in cellular immunity both in vitro and in vivo. In humans with recrudescent melioidosis, cellular immunity can be transferred by a transfer factor and by levamisole, a cellular immunopotentiating agent. The results of the treatment of our patients with disseminated/septicemic melioidosis with antimicrobial agents in combination have been successful. In recent years, four cases of fungal arteritis due to Pythium species and one case of keratitis due to Pythium were seen. Almost all patients with fungal arteritis had thalassemia; all presented with pain in the lower extremities and gangrenous lesions of the toes. Pythium species, an aquatic Phycomycetes, was identified in these cases as a human pathogen on the basis of clinical features, pathologic findings, and--of greatest importance--the isolation of the etiologic fungi. These five cases with remarkably similar presentations exhibited certain similarities with and differences from cases of mucormycosis, entomophthoromycosis, and peniciliosis.

Adolescent↗
PubMed1992

Multicenter prospective randomized trial comparing ceftazidime plus co-trimoxazole with chloramphenicol plus doxycycline and co-trimoxazole for treatment of severe melioidosis.

A prospective randomized trial was conducted at Srinagarind and Khon Kaen hospitals. Ceftazidime (100 mg/kg of body weight per day) and co-trimoxazole (trimethoprim, 8 mg/kg/day; sulfamethoxazole, 40 mg/kg/day) therapy was compared with conventional therapy (chloramphenicol, 100 mg/kg/day; doxycycline, 4 mg/kg/day; trimethoprim, 8 mg/kg/day; sulfamethoxazole, 40 mg/kg/day) in the treatment of 64 patients with bacteriologically confirmed cases of severe melioidosis who were admitted during September 1986 to January 1989. Of 61 evaluable patients (3 were excluded because of severe drug allergies), 42 were septicemic, and 31 of these patients had the most severe form, disseminated septicemic melioidosis. Their cumulative mortalities on day 7 were compared. There were significantly lower overall mortalities from melioidosis, septicemic melioidosis, and disseminated septicemic melioidosis in the group receiving the new treatment compared with those in the group receiving the conventional treatment (47 versus 18.5% [P = 0.039], 57.7 versus 25% [P = 0.039], and 82.3 versus 30.7% [P = 0.006], respectively); but the differences could have been influenced by the greater severity of illness, e.g., shock at initial presentation, in the patients who received the conventional treatment. Among patients with disseminated septicemia and initial shock, there was no significant difference in mortality between the regimens. Both regimens effectively eradicated bacteria from the circulation within 24 h (97 versus 96%, respectively). We recommend ceftazidime and co-trimoxazole as the drugs of choice for treatment of severe melioidosis, especially in those patients with disseminated septicemia.

Adult↗
PubMed2003

Septicaemic melioidosis in a tertiary care hospital in south India.

BACKGROUND & OBJECTIVES: Melioidosis and the causative organism Burkholderia pseudomallei are being recognized gradually in various centres in India. In the septicaemic form, melioidosis is a serious and life threatening condition which requires early detection and specific treatment to avoid case fatality. A review of patients with septicaemic melioidosis at a tertiary care hospital in south India was carried out with a view to define the clinical features, predisposing conditions, if any, and the outcome. METHODS: A total of 28 patients with culture proven septicaemic melioidosis during December 1993 to December 2002 were included. Information on clinical details and outcome was obtained and antibiotic susceptibility of the isolates studied. RESULTS: Of the 28 patients of blood culture proven septicaemic melioidosis, the organism was also isolated from pus in two patients. The presenting clinical features were varied, most presenting as pyrexia of unknown origin or visceral abscesses, or septic arthiritis. Associated/predisposing conditions were present in 50 per cent of the patients, and diabetes mellitus was the commonest one. mortality was 58 per cent in our series. INTERPRETATION & CONCLUSION: Melioidosis is an emerging infection in India. The magnitude of the problem can only be assessed by increasing awareness, both of its existence in the clinical setting and its identification in the laboratory.

Adolescent↗
PubMed2004

C-reactive protein in the diagnosis of melioidosis.

Previous work suggested that C-reactive protein (CRP) may be a useful test in the diagnosis of melioidosis, the infection caused by Burkholderia pseudomallei. We reviewed patients with culture-confirmed melioidosis to define the role of this inflammatory marker in the diagnosis of melioidosis. In 175 patients, we found that the admission CRP level may be normal or only mildly elevated, including patients with severe sepsis, fatal cases, and in relapsed melioidosis. In a multivariate analysis, sepsis and bacteremia were more strongly associated with mortality than CRP. Admission levels of CRP are not a sensitive marker for the presence of melioidosis and a normal level cannot be used to exclude acute, chronic, or relapsed melioidosis in febrile patients in or from endemic regions.

C-Reactive Protein↗
PubMed2006

Dural sinus thrombosis in melioidosis: the first case report.

Melioidosis which is infection with Burkholderia pseudomallei, is an important cause of sepsis in India, southeast Asia and northern Australia. Mortality is high and treatment is problematic. Neurological melioidosis is unusual but meningoencephalitis, encephalomyelitis and brain microabscess can occur Dural sinus thrombosis is not an uncommon cerebrovascular disorder with various etiologies. Hypercoagulable state, pregnancy, dehydration, certain blood dyscrasia and contraceptive pills are common causes however meningitis and local head & neck infections may lead to this condition. Dural sinus thrombosis complicating septicemic melioidosis has never been reported. The authors report a 42-year-old Thai man suffering from septicemic melioidosis with dural sinus thrombosis. He had high fever, headache, left hemiparesis, focal seizure and increased intracranial pressure. Diabetes and mild alcoholic cirrhosis were diagnosed in this admission. CT scan, MRI brain and MRV revealed superior saggital sinus thrombosis with complicating venous infarction over right posterior parietal lobe. Hemoculture demonstrated Burkholderia pseudomallei and CSF was acellular Investigations for causes of dural sinus thrombosis were all negative. This patient gradually improved after treatment with ceftazidime, antiepileptic drug and heparin without clinical recurrence. Neuromelioidosis is a rare syndrome that may present as brain abscess, encephalitis or meningoencephalitis. The authors report dural sinus thrombosis associated with septicemic melioidosis. The authors' hypothesis of venous thrombosis in the presented case is sepsis induced hypercoagulable state. Physicians should be aware of cerebral venous thrombosis in case of suspicious melioidosis with neurological involvement. Prompt treatment with intravenous heparin and antibiotic is potentially effective.

Adult↗
PubMed2006

Comparison by electron microscopy of intracellular events and survival of Burkholderia pseudomallei in monocytes from normal subjects and patients with melioidosis.

INTRODUCTION: Burkholderia pseudomallei (B. pseudomallei) has been shown to persist intracellularly in patients with melioidosis, until reactivated by decreasing immunocompetence. We have previously demonstrated by transmission electron microscopy, the internalisation of B. pseudomallei by human macrophages and the occurrence of phagosome-lysosome fusion. METHODS: Phagocytosis and electron microscopy were used to compare the rate of phagosome-lysosome fusion and the intracellular survival of B. pseudomallei using monocytes obtained from five patients with melioidosis and five normal healthy adults. RESULTS: Ingested bacilli were seen in various stages of degradation, with a few remaining viable within phagolysosomes, and the proliferation of these viable bacteria was observed. Phagocytosis of B. pseudomallei by normal macrophages was two-fold higher than uptake by the melioidosis macrophages (p-value is less than 0.001). Three times more phagolysosomes were present in the normal macrophages, indicating that fusion occurred slowly and inefficiently in the melioidosis macrophages (p-value is less than 0.001), resulting in higher number of organisms within the melioidosis macrophages (p-value is less than 0.001). Both variables were inversely related to each other. CONCLUSION: Our observations suggest that phagolysosome fusion occurred slowly and inefficiently in monocytes of patients with melioidosis, leading to an increased number of intracellular organisms compared to monocytes obtained from healthy donors.

Burkholderia Infections↗
PubMed2004

Adaptive immunity in melioidosis: a possible role for T cells in determining outcome of infection with Burkholderia pseudomallei.

Melioidosis is a potentially fatal disease caused by the bacterium Burkholderia pseudomallei. Individuals with subclinical melioidosis have no apparent clinical signs or symptoms, and are identified only by positive serology. The present study is the first to investigate cell-mediated immune (CMI) responses following in vitro stimulation with B. pseudomallei antigens in peripheral blood mononuclear cells (PBMC), collected under field conditions in Papua New Guinea (PNG) from individuals with exposure to B. pseudomallei (n = 13). While five had a clinical history of melioidosis (C(+)), the remaining individuals (n = 8) were seropositive, yet healthy with no clinical history of melioidosis (S(+)/C(-)). Proliferation and IFN-gamma production were significantly greater in lymphocyte cultures from S(+)/C(-) individuals compared to C(+) individuals (P < 0.001 and P < 0.05, respectively). These findings demonstrate that compared to C(+) patients, individuals with subclinical melioidosis have a stronger CMI response to B. pseudomallei antigens in vitro. Such a response may be essential for protection against disease progression.

Adolescent↗
PubMed2004

Bacteraemic melioidosis pneumonia: impact on outcome, clinical and radiological features.

OBJECTIVES: Melioidosis is an endemic disease in South-east (SE) Asia and bacteraemia in melioidosis is associated with high mortality. We describe some clinical and radiological features of bacteraemic pneumonia due to Burkholderia pseudomallei as well as a comparison with bacteraemic patients without pneumonia. METHODS: Patients with positive blood cultures for B. pseudomallei from October 1997 to November 2001 were included. Patients were grouped as 'Pneumonia' and 'Non-pneumonia' according to clinical and radiological features. RESULTS: Eighteen (60%) out of total 30 patients were in the pneumonia group. There was no significant difference in age, WBC count, platelet counts and bilirubin levels between the groups. However the 'Pneumonia' group had higher incidences of hyponatraemia, acidosis, diabetes with poor control, renal impairment and shorter length of stay. Twelve (66%) of 18 patients in the pneumonia group required ICU admission compared to none in the non-pneumonia group; all required mechanical ventilation. Only 13/30 (43%) patients had initial empiric antibiotic therapy that is appropriate for melioidosis. The pneumonia group also had significantly higher mortality (13/18, 72%) rate than the non-pneumonia group (3/12, 25%, P=0.03). Chest radiographs were non-specific. 7/18 (38%) had unilobar involvement of the lung, mostly left sided; the rest had multilobar or bilateral involvement. Six (33%) had pleural effusion. No patient had cavitary lung disease. Visceral abscesses (spleen, liver and prostate) were also common in ultrasound and CT scans in both groups. CONCLUSION: (1) Bacteraemic melioidosis with pneumonia carries high mortality with most patients dying early. (2) Radiological features of melioidosis pneumonia are non-specific. (3) Clinicians who treat patients from SE Asia need to be aware of this condition to institute early and appropriate antibiotic therapy.

Anti-Bacterial Agents↗
PubMed2003

Melioidosis.

Melioidosis, which is infection with the gram-negative bacterium Burkholderia pseudomallei, is an important cause of sepsis in east Asia and northern Australia. In northeastern Thailand, melioidosis accounts for 20% of all community-acquired septicaemias, and causes death in 40% of treated patients. B pseudomallei is an environmental saprophyte found in wet soils. It mostly infects adults with an underlying predisposing condition, mainly diabetes mellitus. Melioidosis is characterised by formation of abscesses, especially in the lungs, liver, spleen, skeletal muscle, and prostate. In a third of paediatric cases in southeast Asia, the disease presents as parotid abscess. In northern Australia, 4% of patients present with brain stem encephalitis. Ceftazidime is the treatment of choice for severe melioidosis, but response to high dose parenteral treatment is slow (median time to abatement of fever 9 days). Maintenance antibiotic treatment is with a four-drug regimen of chloramphenicol, doxycycline, and trimethoprim-sulfamethoxazole, or with amoxicillin-clavulanate in children and pregnant women. However, even with 20 weeks' antibiotic treatment, 10% of patients relapse. With improvements in health care and diagnostic microbiology in endemic areas of Asia, and increased travel, melioidosis will probably be recognised increasingly during the next decade.

Administration, Oral↗
PubMed1996

An immunohistochemical method for the diagnosis of melioidosis.

In order to assess the usefulness of immunohistochemistry in the diagnosis of melioidosis, an infection by Burkholderia pseudomallei, polyclonal antibodies were applied to tissues from known cases of melioidosis and to other infected tissues. Formalin-fixed, paraffin-embedded tissues were stained by a modified immunoperoxidase technique. In autopsy tissues with inflammatory lesions of melioidosis, the cytoplasm of phagocytes and intact bacilli, both intra- and extracellular, were stained very strongly positive. Relatively more focal positive staining was observed in some but not all surgical biopsies from proven cases of melioidosis. In granulomas staining was mainly found in the central necrotic areas, with little staining of peripheral phagocytes. All control materials stained negative. Immunohistochemistry appears to be a useful diagnostic tool in melioidosis.

Adolescent↗
PubMed2005

Two randomized controlled trials of ceftazidime alone versus ceftazidime in combination with trimethoprim-sulfamethoxazole for the treatment of severe melioidosis.

BACKGROUND: Two antibiotic regimens are used commonly in Thailand for the initial treatment of severe melioidosis: ceftazidime in combination with trimethoprim-sulfamethoxazole (TMP-SMX) and ceftazidime monotherapy. It is not known whether TMP-SMX provides an additional benefit. METHODS: Two prospective, randomized trials that compared these regimens for patients presenting with acute severe melioidosis were started independently at tertiary care hospitals in Ubon Ratchathani and Khon Kaen (in northeastern Thailand), and the results were analyzed together as a prospective, individual-patient data meta-analysis. The primary end point was in-hospital mortality rate. RESULTS: The in-hospital mortality rate among all enrolled patients (n=449) was not significantly different between those randomized to ceftazidime alone (25.1%; 56 of 223 subjects) and those randomized to ceftazidime with TMP-SMX (26.6%; 60 of 226 subjects; odds ratio [OR], 1.08; 95% confidence interval [CI], 0.7-1.7; stratified P=.73). Of the 241 patients with culture-confirmed melioidosis, 51 (21.2%) died. Of these 241 patients, 31 (12.9%) died > or =48 h after the time of study entry. Among patients with melioidosis, there was no difference in death rate between the 2 treatment groups for either all deaths (OR, 0.88; 95% CI, 0.48-1.6; stratified P=.70) or for deaths that occurred > or =48 h after hospital admission (OR, 0.88; 95% CI, 0.41-1.9; stratified P=.73). Conditional logistic regression analysis revealed that bacteremia, respiratory failure, and renal failure were independently associated with death and treatment failure. Drug regimens were not associated with death or treatment failure in this model. CONCLUSION: We conclude that the addition of TMP-SMX to ceftazidime therapy during initial treatment of severe melioidosis does not reduce the acute mortality rate.

Adult↗