Melioidosis

PURPOSE OF REVIEW: Melioidosis is increasingly recognized around the world. Despite several decades of clinical research, the mortality rate for melioidosis remains high. This review focuses on studies that relate to patient management, including risk factors, diagnosis, treatment and prediction of the outcome. A brief summary of studies relating to genomics and genotyping, immunology and pathogenesis is provided. RECENT FINDINGS: Involvement in the tsunami of December 2004 is a risk factor for melioidosis, and risk may extend to individuals who were uninjured bystanders. Several standard microbiological techniques used to culture and identify Burkholderia pseudomallei have been evaluated. Polymerase chain reaction has been developed for bacterial identification, although limited evaluation has been performed in the clinical setting. Two trials of antimicrobial therapy provide evidence with which to refine existing treatment protocols. Inexpensive clinical and laboratory predictors for poor outcome have been described. Several putative vaccine candidates have been proposed and studied in animals, but no vaccine is on the immediate horizon. SUMMARY: None of the studies reviewed here report strategies that reduce mortality. A key area for future research is the identification of affordable interventions that lower the death rate, and are applicable to low-resource settings.     

Melioidosis

Melioidosis is an important public health problem in some regions, and a potential bioweapon. Recent reports confirm that it is endemic in China, Taiwan and Laos, but the true incidence in most countries is unknown, and the ecology poorly understood. Potable water was the source of two recent outbreaks. The epidemiology and clinical manifestations of the disease in Australia are similar to those in Thailand, although prostatic abscesses and neurological manifestations are more common and parotid abscesses less so. Mycotic aneurysms are not uncommon. Patients with cystic fibrosis are at risk of pulmonary melioidosis. Comparison with the avirulent Burkholderia thailandensis has identified capsular polysaccharide as an important virulence determinant in Burkholderia pseudomallei. Diagnosis still relies on culture, and a throat swab is a worthwhile sample. Several beta-lactams, such as meropenem, reduce the mortality, and long courses of cotrimoxazole-containing regimes are needed to prevent relapse. The value of adjunctive treatments, such as granulocyte colony-stimulating factor, warrants further evaluation.     

Melioidosis

Melioidosis is an infection with the gram-negative bacillus Burkholdria pseudomallei, previous known as Pseudomonas pseudomallei. We present a case report of a man with Non-Hodgkin's Lymphoma, who after visiting Indonesia presented himself with a urosepsis, with positive cultures to B. pseudomallei. Melioidosis is endemic in areas of southeast Asia and the northern part of Australia. Infection with the B. pseudomallei has a high mortality rate. Diagnosis can be made on the basis of cultures, the bacteria grow on standard media. Treatment should be based up on sensitivity studies. The optimum duration of therapy and choice of antibiotics remain to be determined. Due to the increase in travel, the infection will be seen more frequently in other parts of the world.     

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.     

Neurologic Melioidosis

Melioidosis is an important cause of morbidity and mortality in northern Australia and Southeast Asia. Diagnosis is best made by isolation of Burkholderia pseudomallei from clinical specimens. A variety of clinical presentations are described, including neurologic disease. The aim of this study was to review admissions with confirmed neurologic melioidosis to a regional hospital in a region to which melioidosis is endemic during 1995–2011. There were 12 culture-confirmed cases of neurologic melioidosis, of which two were detected by analysis of cerebrospinal fluid. Four of these cases were in children. Significant clinical features were fever, headache, and ataxia. Common changes on magnetic resonance imaging T2-weighted scans included ring-enhancing lesions and leptomeningeal enhancement. There were four deaths and an additional four patients had significant long-term neurologic sequelae. When considering the etiology of undifferentiated neurologic disease, an awareness of the possibility of neurologic melioidosis is important in disease-endemic regions.     

Fatal dengue hemorrhagic fever imported into Germany

Dengue virus (DENV) is an arthropod-borne virus (family Flaviviridae) causing dengue fever or dengue hemorrhagic fever. Here, we report the first fatal DENV infection imported into Germany. A female traveler was hospitalized with fever and abdominal pain after returning from Ecuador. Due to a suspected acute acalculous cholecystitis, cholecystectomy was performed. After cholecystectomy, severe spontaneous bleeding from the abdominal wound occurred and the patient died. Postmortem analysis of transudate and tissue demonstrated a DENV secondary infection of the patient and a gallbladder wall thickening (GBWT) due to an extensive edema.     

Zinc metallothionein imported into liver mitochondria modulates respiration

Metallothionein (MT) localizes in the intermembrane space of liver mitochondria as well as in the cytosol and nucleus. Incubation of intact liver mitochondria with physiological, micromolar concentrations of MT leads to the import of MT into the mitochondria where it inhibits respiration. This activity is caused by the N-terminal beta-domain of MT; in this system, the isolated C-terminal alpha-domain is inactive. Free zinc inhibits respiration at concentrations commensurate with the zinc content of either MT or the isolated beta-domain, indicating that MT inhibition involves zinc delivery to mitochondria. Respiratory inhibition of uncoupled mitochondria identifies the electron transfer chain as the primary site of inhibition. The apoform of MT, thionein, is an endogenous chelating agent and activates zinc-inhibited respiration with a 1:1 stoichiometry ([zinc binding sites]/[zinc]). Carbamoylation of the lysines of MT significantly attenuates the inhibitory effect, suggesting that these residues are critical for the passage of MT through the outer mitochondrial membrane. Such an import pathway has been proposed for other proteins that also lack a mitochondrial targeting sequence, e.g., apocytochrome c, and possibly Cox17, a mitochondrial copper chaperone that is the only protein known so far to exhibit significant primary sequence homology to MT. The presence and respiratory inhibition of MT in liver, but not heart, mitochondria suggest a hitherto unknown biological modulating activity of MT in cellular respiration and energy metabolism in a tissue-specific manner.     

Malaria imported into the United Kingdom in 1996

Virtually all malaria infections seen in the United Kingdom (UK) in recent years have been contracted overseas and imported into the UK, apart from two cases in 1976 due to imported infected mosquitoes and occasional cases of congenital or of transfusion     

Melioidosis: a reminder

Recrudescent pulmonary melioidosis developed in two patients 12 and 16 years after their last travels to an endemic area. In one, a clinically silent prostatic abscess may have been the focus; and in both, the diagnosis was difficult to make even when the laboratory was notified of the possibility of infection with Pseudomonas pseudomallei. Recrudescent melioidosis should be considered in febrile patients who have been in endemic areas regardless of the interval from last exposure to the development of disease.     

Clinical Definitions of Melioidosis

Clinical definitions of melioidosis and inhalation-acquired melioidosis (Burkholderia pseudomallei infection) are described together with the evidence used to develop these definitions. Such definitions support accurate public health reporting, preparedness planning for deliberate B. pseudomallei release, design of experimental models, and categorization of naturally acquired melioidosis.     

Melioidosis research in China

Research on melioidosis and its pathogen has been ongoing in China for more than two decades. It has been demonstrated that the natural foci are located predominantly in Hainan, Guangdong and Guangxi province, where there is a good correlation between soil isolation and the serum prevalence of antibodies to Burkholderia pseudomallei. The cases of melioidosis reported up to now are concentrated in the Hainan and Zhanjiang peninsula. Investigations on serotype, virulence, ecology, antibiotic susceptibility, whole cell analysis by gas chromatography, and genetics have led to a new understanding of the pathology of the disease. Immunological cross reactions between Burkholderia mallei and B. pseudomallei and the difference between melioidosis and glanders in horses is discussed.     

Melioidosis in the Americas

Melioidosis is a potentially severe bacterial infection caused by Burkholderia pseudomallei. There has been growing awareness of the disease in the Americas, particularly since the Vietnam conflict when it was diagnosed in returning service personnel. Accidental laboratory exposure indicates the difficulty making a culture-based diagnosis when melioidosis has not been considered in the differential diagnosis. Melioidosis is most likely underdiagnosed in tropical Central and South America where conditions are more suited to persistence of B. pseudomallei in the environment. Recent melioidosis case clusters in northeastern Brazil highlight the threat posed to rural populations located far from specialist services. Increased clinical awareness of the disease and improvements in laboratory diagnostic methods are likely to bring wider recognition of melioidosis in the Americas.     

Sri Lankan National Melioidosis Surveillance Program Uncovers a Nationwide Distribution of Invasive Melioidosis

The epidemiologic status of melioidosis in Sri Lanka was unclear from the few previous case reports. We established laboratory support for a case definition and started a nationwide case-finding study. Suspected Burkholderia pseudomallei isolates were collated, identified by polymerase chain reaction assay, referred for Matrix Assisted Laser Desorption Ionization-Time of Flight analysis and multilocus sequence typing (MLST), and named according to the international MLST database. Between 2006 and early 2014, there were 32 patients with culture-confirmed melioidosis with an increasing annual total and a falling fatality rate. Patients were predominantly from rural communities, diabetic, and male. The major clinical presentations were sepsis, pneumonia, soft tissue and joint infections, and other focal infection. Burkholderia pseudomallei isolates came from all parts of Sri Lanka except the Sabaragamuwa Province, the south central hill country, and parts of northern Sri Lanka. Bacterial isolates belonged to 18 multilocus sequence types, one of which (ST 1137) was associated with septicemia and a single-organ focus (Fisher''s exact, P = 0.004). Melioidosis is an established endemic infection throughout Sri Lanka, and is caused by multiple genotypes of B. pseudomallei, which form a distinct geographic group based upon related sequence types (BURST) cluster at the junction of the southeast Asian and Australasian clades.     

Melioidosis complicated by pericarditis

Melioidosis is a bacterial infection caused by the Gram-negative bacillus Burkholderia pseudomallei. We report an unusual case of melioidosis that presented as a pyrexia of unknown origin complicated by pericardial effusion. Our patient received a 6-week course of intravenous antibiotics, followed by 8 months of oral antibiotics, and made a complete recovery. This report illustrates the diagnostic and therapeutic challenge that clinicians may encounter when faced with this potentially fatal infection.     

Melioidosis: review and update

Melioidosis prevails in Southeast Asia and northern Australia. Sporadic cases have been increasingly reported from countries located between 20 degrees north latitude and 20 degrees south latitude as well as in travelers and in soldiers who have resided in these areas. The organisms are commonly found in water and soil and are usually transmitted to humans by cutaneous or respiratory routes. Clinical manifestations range from subclinical infection to overwhelming septicemia that resembles disseminated or localized suppurative infection due to various pathogens. A rapid and accurate diagnosis can be made by demonstration of small, few, and frequently bipolar-stained gram-negative bacilli in exudate or pus. The indirect hemagglutination test is of diagnostic value in cases with involvement of the internal organs or pyrexia of unknown origin. Chloramphenicol, doxycycline, trimethoprim-sulfamethoxazole, and kanamycin constitute conventional and effective chemotherapy. Newer antimicrobial agents such as piperacillin, amoxillin-clavulanic acid, ceftazidime, imipenem, and carumonam are active in susceptibility tests against the causative microorganism, Pseudomonas pseudomallei. Clinical trials for demonstration of the effectiveness of the latter agents in overwhelming septicemic melioidosis are ongoing in endemic areas.