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Melioidosis in children from Kuala Lumpur, Malaysia.

There are few data on paediatric melioidosis in endemic areas outside rural north-eastern Thailand and northern Australia. This study reports 16 culture-confirmed cases of melioidosis in children aged < or = 15 years seen between 1976 and 2005 at an urban teaching hospital in Kuala Lumpur, Malaysia. Seven (43.8%) patients had septicaemic melioidosis (with three known deaths) and nine (56.2%) had localised disease (one death). Eleven (68.8%) patients had underlying diseases, including five with haematological malignancies. Skin, soft tissue and lymph nodes were most commonly affected. There were no cases of parotitis or pharyngocervical disease (seen in Thailand), or encephalomyelitis (seen in Australia). The differences in disease seen in this study compared with the mostly rural patients described in previous studies might be owing to a different patient population in an urban environment. Septicaemic melioidosis has a high mortality, but localised disease has a good prognosis, and selected cases may be cured without the full recommended treatment regimen.

Adolescent↗

Clinical guideline for diagnosis and management of melioidosis.

Melioidosis is an emerging infection in Brazil and neighbouring South American countries. The wide range of clinical presentations include severe community-acquired pneumonia, septicaemia, central nervous system infection and less severe soft tissue infection. Diagnosis depends heavily on the clinical microbiology laboratory for culture. Burkholderia pseudomallei, the bacterial cause of melioidosis, is easily cultured from blood, sputum and other clinical samples. However, B. pseudomallei can be difficult to identify reliably, and can be confused with closely related bacteria, some of which may be dismissed as insignificant culture contaminants. Serological tests can help to support a diagnosis of melioidosis, but by themselves do not provide a definitive diagnosis. The use of a laboratory discovery pathway can help reduce the risk of missing atypical B. pseudomallei isolates. Recommended antibiotic treatment for severe infection is either intravenous Ceftazidime or Meropenem for several weeks, followed by up to 20 weeks oral treatment with a combination of trimethoprim-sulphamethoxazole and doxycycline. Consistent use of diagnostic microbiology to confirm the diagnosis, and rigorous treatment of severe infection with the correct antibiotics in two stages; acute and eradication, will contribute to a reduction in mortality from melioidosis.

Anti-Bacterial Agents↗

Musculoskeletal melioidosis.

During a four-year period, twenty-one patients were found to have melioidosis of the musculoskeletal system caused by Pseudomonas pseudomallei. The melioidotic patients were matched with thirty-nine patients who had a musculoskeletal infection due to some other organism, and the two groups were compared with regard to the presence of concurrent disease. The indirect hemagglutination test for melioidosis was positive for all of the melioidotic patients; in thirteen, cultures also were positive. For the patients who did not have melioidosis, the diagnosis was made on the basis of positive cultures of other organisms or histological sections. In most of the non-melioidotic patients, the infection was due to Staphylococcus aureus (twenty-four patients) or to Mycobacterium tuberculosis (twelve patients). The most common concurrent diseases in the melioidotic patients were diabetes and thalassemia. The odds that melioidosis was the cause of the infection in a patient who had a concurrent disease were twelve to one. All melioidotic patients were managed with operative débridement and a combination of drugs--usually, trimethoprim and sulfamethoxazole, doxycycline, and kanamycin or chloramphenicol--for six months. The mean duration of follow-up was one and one-half years. Of the twenty-one patients, eighteen had an excellent or good result in terms of motion of the joint and absence of relapse.

Adult↗

Two patients with recurrent melioidosis after prolonged antibiotic therapy.

Melioidosis is a tropical infectious disease caused by Burkholderia (Pseudomonas) pseudomalleï. Clinically manifest melioidosis occurs mostly in people with underlying disorders. Melioidosis is a disease with protein manifestations and a high rate of relapse. Two patients with infection due to Burkholderia pseudomalleï after a visit to Thailand are described. Both patients presented with sepsis and appropriate therapy was initiated and continued for several months. Despite such long-term antimicrobial treatment, both patients had a relapse after cessation of therapy. It is unclear if recurrent melioidosis can be prevented by prolonging the treatment even further.

Anti-Bacterial Agents↗

Case report: recovery from persistent septicemic melioidosis.

Septicemic melioidosis is often fatal despite treatment with antibiotics such as ceftazidime to which Burkholderia pseudomallei, the causal pathogen, is sensitive in vitro. We report a near-fatal case of septicemic melioidosis with persistent B. pseudomallei bacteremia despite intravenous ceftazidime in which combination therapy with meropenem and ciprofloxacin, splenectomy and correction of metabolic acidosis allowed for hospital discharge. The choice of antibiotic agents was supported by intracellular minimum inhibitory concentration analysis using B. pseudomallei co-culture in Acanthamoeba trophozoites. The patient's B. pseudomallei isolates were indistinguishable by pulsed-field gel electrophoresis from clinical and environmental isolates previously analyzed during investigation of a Western Australian melioidosis outbreak. A combination of antibiotics known to possess intracellular activity against B. pseudomallei, surgery and supportive critical care may provide a means of improving the probability of survival in persistent septicemic melioidosis.

Adult↗

[The efficacy and outlook for the study of live vaccines for the prevention of melioidosis].

The effect of immunization with Burkholderia pseudomallei, (Pur- and Ts), heterologous vaccines and the recombinant culture of Francisella tularensis RM2, carrying a plasmid with fragments of B. pseudomallei chromosome, was studied on four species of experimental animals, essentially differing by their sensitivity to melioidosis. B. pseudomallei mutants formed the statistically significant level of protection in subcutaneously challenged animals, moderately sensitive to melioidosis, but were not effective when tested, under the same conditions, in animals, highly sensitive to melioidosis. The effect produced by the experimental vaccines under study in animals of all species, subjected to aerogenic challenge, was leveled. The study showed good prospects for the use of tularemia vaccine with a view to create heterologous immunity to melioidosis and the possibility of its use as the basis of bivalent gene engineering vaccine.

Animals↗

Protein and energy metabolism in chronic bacterial infection: studies in melioidosis.

Chronic infection is often accompanied by a wasting process, the metabolic basis of which is not fully understood. The aims of the present study were to measure protein and energy metabolism in patients with melioidosis (a serious and antibiotic-refractory Gram-negative bacterial infection which is endemic in South-East Asia) in order to define the metabolic abnormalities that might contribute to wasting. Whole-body protein turnover was measured using the [(13)C]leucine technique, both in the fasted state and while consuming a high-energy meal. Resting energy expenditure was measured by indirect calorimetry, and total energy expenditure by the bicarbonate/urea method. Results were normalized for fat-free mass, as estimated from skinfold thickness. Protein turnover was increased in melioidosis patients compared with healthy controls during fasting (170.9 compared with 124.1 micromol x kg(-1) x h(-1); P=0.04), but the net rate of catabolism (22.2 compared with 20.5 micromol x kg(-1) x h(-1); P=0.77) and the anabolic response to feeding were similar in the two groups. Resting energy expenditure was higher in melioidosis patients compared with controls (191.4 and 157.3 kJ x kg(-1) x day(-1) respectively; P=0.04), but total energy expenditure (measured in a separate group of eight patients with melioidosis) was low (192.1 kJ x kg(-1) x day(-1)). In conclusion, this study found no evidence of metabolic causative factors, such as accelerated net protein catabolism during fasting, a blunted anabolic response to feeding or increased daily energy expenditure, and therefore suggests that reduced energy intake is the prime cause of wasting. The observed normal response to feeding should encourage nutritional approaches to prevent wasting.

Adult↗

Melioidosis of the head and neck.

Melioidosis is a potentially deadly infection that can affect any organ system. Reports of melioidosis of the ENT/head and neck region are relatively uncommon. Four cases are presented: (i) parotid abscess evolving into necrotising fasciitis, (ii) acute sinusitis and parapharyngeal cellulitis resulting in upper airway obstruction, (iii) acute suppurative lymphadenitis (iv) and chronic suppurative otitis media causing meningoencephalitis. Three of the four cases are believed to be unique, as a literature review of melioidosis in ENT/head and neck is also presented. Some practical issues of management are also discussed. Not suspecting melioidosis does not change contemporary empirical broadspectrum antibiotic therapy. The value of suspicion or on confirmation of diagnosis lies in anticipating and planning for rapid change.

Adult↗

Use of endotoxin antigens in enzyme-linked immunosorbent assay for the diagnosis of P. pseudomallei infections (melioidosis).

An enzyme-linked immunosorbent assay (ELISA) with endotoxin preparations of P. pseudomallei as antigen was developed for detection of IgG antibodies specific to melioidosis. Forty-seven sera of bacteriologically confirmed melioidosis patients, 55 non-melioidosis sera and 50 sera of healthy blood donors from non-endemic areas were subjected to this assay in comparison with indirect hemagglutination assay (IHA). The data were treated by receiver operating characteristics analysis. The sensitivity, specificity and accuracy in this ELISA were 95.7%, 94.2%, and 94.7%, respectively, with cut-off value of OD = 0.312 at 490 nm. Meanwhile, those in IHA were 81.0%, 91.4%, and 88.1%, respectively, with a cut-off value of > or = 1:160. From these results, the ELISA was judged to be more reliable than IHA as the seroassay for diagnosis of melioidosis.

Antibodies, Bacterial↗

Melioidosis; the remarkable imitator: recent perspectives.

Melioidosis is an important public health problem in some regions of the world. It is endemic in South East Asia. The clinical spectrum of melioidosis is extremely broad, and melioidosis requires awareness on the part of the clinician and the existence of a laboratory capable of isolating and identifying Burkholderia pseudomallei, the etiological agent of melioidosis. Beta-lactams such as ceftazidime is currently the treatment of choice. There is no vaccine licensed for human use. There is an urgent need for rapid diagnostic techniques and effective treatments that are affordable in countries where the disease is endemic.

Burkholderia pseudomallei↗

Melioidosis: an emerging infectious disease.

Infectious diseases account for a third of all the deaths in the developing world. Achievements in understanding the basic microbiology, pathogenesis, host defenses and expanded epidemiology of infectious diseases have resulted in better management and reduced mortality. However, an emerging infectious disease, melioidosis, is becoming endemic in the tropical regions of the world and is spreading to non-endemic areas. This article highlights the current understanding of melioidosis including advances in diagnosis, treatment and prevention. Better understanding of melioidosis is essential, as it is life-threatening and if untreated, patients can succumb to it. Our sources include a literature review, information from international consensus meetings on melioidosis and ongoing discussions within the medical and scientific community.

Anti-Bacterial Agents↗

The role and significance of sputum cultures in the diagnosis of melioidosis.

Pneumonia is a common manifestation of melioidosis, the disease caused by Burkholderia pseudomallei. In this study, we defined the prognostic significance of a positive sputum culture. A total of 712 patients presenting to Sappasithiprasong Hospital, Ubon Ratchathani, Thailand, with melioidosis between January 1992 and December 2002 had a sputum culture performed during admission, which was positive for B. pseudomallei in 444 patients (62%). The median duration of sputum positivity was 9 days (range, 1 to 49 days). Sputum cultures were negative in 32% of patients with radiologic changes suggestive of pulmonary involvement. Overall in-hospital mortality was 48%. A positive sputum culture was associated with mortality (adjusted OR 2.8, 95% CI: 1.9, 4.0; P < 0.001). This was independent of renal disease, a prior history of melioidosis, positive blood cultures, and other potential confounders. The presence of B. pseudomallei in the sputum of patients with melioidosis is associated with a poorer prognosis.

Adult↗

Short report: application of a polymerase chain reaction to detect Burkholderia pseudomallei in clinical specimens from patients with suspected melioidosis.

The diagnostic potential of a Burkholderia pseudomallei type three secretion system (TTS1) polymerase chain reaction (PCR) was examined on clinical specimens from 27 patients with sepsis in the Northern Territory of Australia, a region endemic for melioidosis. The TTS1 PCR was conducted on DNA extracted from a range of clinical specimens (blood, sputum, urine, joint, pericardial and pleural fluid, and swabs from skin lesions, throat, nose, and rectum). The PCR sensitivity in culture-positive clinical specimens from the nine confirmed patients with melioidosis was 65% and the specificity was 100%, with no PCR-positive results in specimens from 18 patients without melioidosis. The PCR based on the B. pseudomallei TTS1 has the potential to substantially improve the timeliness of diagnosis of melioidosis.

Burkholderia pseudomallei↗

Isolated articular melioidosis.

Melioidosis is an infection caused by a gram-negative bacilli, Pseudomonas pseudomallei. This organism can cause fatal infection in domestic animals and are probably transmitted to humans by soil contamination of skin abrasions, ingestion, and inhalation. Melioidosis is being increasingly diagnosed in Western countries in other than its endemic areas of tropical and subtropical zones. In the past, only a few single case reports of articular melioidosis were published in English journals, and almost all were secondary to melioidosis of another organ. Accurate diagnosis of this infection is important because a high mortality rate is usually associated with the septicemic form. Nine cases of isolated articular involvement were diagnosed between 1984 and 1988 in Northeast Thailand. Symptoms were subtle and diagnosis required a high degree of suspicion. Diagnosis depended on bacteriologic methods including Gram's stain, pus and blood cultures, and on an indirect hemagglutination titer of over 1:40. In addition to general measures for septic arthritis, antibiotic therapy using a combination of intravenous cotrimoxazole, doxycycline, and chloramphenicol was generally satisfactory. Second line drugs (i.e., more effective but also more expensive drugs that the authors administered when patients failed to respond to the first line drugs cotrimoxazole, doxycycline, and chloramphenicol) comprising intravenous ceftazidime and cotrimoxazole were administered in cases with an underlying disease. Comparison of the disease course before and during hospitalization as well as the total days of treatment between two small groups of patients with and without underlying disease revealed no statistically significant difference.

Anti-Bacterial Agents↗

The 1990-1991 outbreak of melioidosis in the Northern Territory of Australia: epidemiology and environmental studies.

From November 1990 to June 1991 33 acute cases of melioidosis occurred in the Northern Territory, Australia; 25 cases were reported in the capital city, Darwin. We carried out an epidemiological investigation to exclude a common source outbreak, describe the risk factors for disease, and develop and institute appropriate control measures. We compared population based attack rates among various risk groups using logistic regression, and the demographic, medical and behavioral risk factors for melioidosis by a matched case-control study. Environmental Health Officers collected soil, surface water and cooling tower water specimens for Pseudomonas pseudomallei culture. The crude attack rate of melioidosis during the outbreak was 52 per 100,000. Age, gender, race, diabetes and alcohol abuse were independent risk factors for disease. The relative risk of disease in diabetic patients was 12.9 (95% CI 5.1-32.7; p < 0.001) and 6.7 in alcoholic patients (95% CI 2.9-15.2; p < 0.001). We found no significant difference between cases and controls in matched pair analysis for any of several exposure factors studied. We isolated Pseudomonas pseudomallei from 4% of soil samples and 9% of surface water samples. Our study confirms the importance of host factors in the development of melioidosis, and attempts to quantify the risk of disease during the Darwin epidemic. Pseudomonas pseudomallei is widespread in the soil of urban Darwin.

Acute Disease↗

[Laboratory control of effectiveness of chemotherapy in melioidosis].

An undoubtable role of the melioidosis germ persistence in the form of L-variants with the development of DTH in the relapses of the disease was stated. Serological reactions such as CFT and PHAR were shown to be of the diagnostic value but it was by far lower than the allergotest. No correlation between the antibody titers in the tested sera and the isolation of the bacterial or L-variants of the melioidosis germ was observed. The criteria of the recovery from melioidosis were: stable normalization of the patient temperature, positive time course of the body weight changes, negative tests for the type and morphologically changed forms of the melioidosis germ and no allergic reactions.

Animals↗

Relapse in melioidosis: incidence and risk factors.

From 1986 to 1991, 602 patients with melioidosis were seen in Sappasitprasong Hospital, Ubon Ratchatani, Thailand. The in-hospital mortality was 42%. Of 118 adult patients followed long-term, 27 (23%) had culture-proven relapses of melioidosis (3 relapsed twice), a relapse rate of 15% (95% confidence interval [CI], 11-22) per year. The median time from discharge to relapse was 21 weeks (range, 1-290). In 44% of patients, relapses included septicemia, and 27% died. Patients with severe disease (multiple foci of infection or septicemia) relapsed 4.7 times (95% CI, 1.6-14.1) more frequently than patients with localized melioidosis. Underlying disease was not a risk factor, but initial parenteral treatment with ceftazidime reduced the risk of relapse 2-fold (95% CI, 1.1-3.4). Relapses were 3.3 (95% CI, 1.4-9.0) times more frequent following short-course (< or = 8 weeks) oral coamoxiclav than after the oral combination regimen of chloramphenicol, doxycycline, and cotrimoxazole. Longer oral treatment with either reduced relapse 1.6-fold (95% CI, 1.2-1.9). The optimum choice and duration of antibiotic treatment to prevent relapse in melioidosis remain to be determined.

Adolescent↗

Melioidosis In India: the tip of the iceberg?

Diagnosis of melioidosis by the isolation of Burkholderia pseudomallei from one or more body fluid/tissue specimens of 6 Indian subjects, 5 of whom had not travelled outside India, is reported. The places of residence of these 6 and one patient previously reported, namely Tripura (2), Kerala (2), Orissa (1), Tamil Nadu (1) and Maharashtra (1) are therefore potentially endemic for melioidosis. B.pseudomallei closely resembles common contaminant Pseudomonas sp. and are easily mis-identified in microbiology laboratories. We surmise that melioidosis is underdiagnosed and underreported in India and we alert clinicians, microbiologists and public health professionals to the possibility of melioidosis being far more common than previously recognised.

Adolescent↗