Synonyms: Pseudomonas pseudomallei, Loefflerella pseudomallei, Malleomyces pseudomallei, Bacterium whitmori, Bacillus pseudomallei Burkholderia pseudomallei The genus Burkholderia was created by Yabuuchi et al. to accommodate the former rRNA group II pseudomonads, excluding Pseudomonas pickettii and Pseudomonas solanacearum, which were transferred to the genus Ralstonia. Traditionally, Burkholderia species are known as plant pathogens and soil bacteria with two important exceptions, B. mallei and B. pseudomallei, which are primary pathogens for humans and animals. The bacterium is a motile, aerobic, non-spore-forming, gram-negative bacillus. Melioidosis is an infectious disease of humans and animals caused by Burkholderia pseudomallei. It was first described under the name Bacillus pseudomallei by Whitmore and Krishnaswami (1912) following its isolation in Rangoon, Myanmar (Burma) more than 90 years ago. Subsequent reports described the causative agent under a variety of names, including Bacillus whitmori, Pfeifferella whitmori, Pfeifferella pseudomallei, Actinobacillus pseudomallei, Loefferella whitmori, Malleomyces pseudomallei and Pseudomonas pseudomallei. Melioidosis has to be considered an emerging disease with high impact on animal and man. In the past century, it has spread from East Asia to many parts of the world previously not affected. Burkholderia siamensis Burkholderia pseudomallei (Ara+ biotype) Two distinct biotypes of B. pseudomallei strains have been defined recently by their differential ability to assimilate L-arabinose, their virulence in animal models and nucleotide variations in the 16S rRNA gene. The arabinose-positive biotype (ara+) is avirulent and has been found almost exclusively in environmental samples. In contrast, isolates from clinical disease fail to utilise arabinose (ara-), are highly virulent and are also found in the environment. Recently it has been proposed that ara+ isolates should be grouped together to form a new species, Burkholderia thailandensis, on the basis of differences in 16S rRNA sequence. We have recently identified an organism closely resembling the pathogen B. pseudomallei in soil samples from northeast Thailand. Although the morphology, antigenicity, and antimicrobial susceptibility of this organism are similar to those of the bacteria isolated from patients with melioidosis, this organism has a number of biochemical differences, exemplified by the ability to utilize L-arabinose (Ara +). Burkholderia pseudomallei (Ara- biotype) In northeast Thailand, where melioidosis is common, 75% of soil isolates cannot utilize L-arabinose (Ara-), whereas in the central region, where melioidosis is uncommon, nearly all soil isolates have the Ara+ phenotype. Since 1986, we have studied more than 1,200 patients with melioidosis, and in every case the organism isolated had the Ara- biotype. Furthermore, in routine culture and subculture of these isolates, conversion to the Ara+ biotype was never observed, suggesting that the Ara- biotype is stably linked to the virulence of B. pseudomallei. The results of our study of experimental melioidosis show a striking difference between the virulence of the Ara+ and Ara- strains of B. pseudomallei for mice. Ara- strains are highly virulent, whereas Ara+ strains are essentially nonvirulent. Both biochemical types have antigenic similarities; both give positive reactions in the latex agglutination test, in which a polyclonal antibody raised to an Ara- clinical strain of B. pseudomallei is used, and both give similar result in indirect hemagglutination assays for melioidosis. Thus, despite the similarity of their morphologies, culture characteristics, antibiotic susceptibility profiles, and antigenicities, one biotype causes melioidosis and the other does not. Burkholderia pseudomallei 1106a Burkholderia pseudomallei strain 1106a. This is an unknown strain that will be used for comparative genomics. Burkholderia pseudomallei 1106b Burkholderia pseudomallei strain 1106b. This is an unknown strain that will be used for comparative genomics. Burkholderia pseudomallei 1655 Burkholderia pseudomallei strain 1655. This strain will be used for comparative genomics. Burkholderia pseudomallei 1710a Burkholderia pseudomallei strain 1710a. This strain will be used for comparative genomics. Burkholderia pseudomallei 1710b Burkholderia pseudomallei strain 1710b. This strain will be used for comparative genomics. Burkholderia pseudomallei 668 Burkholderia pseudomallei strain 668. This strain will be used for comparative genomics. Burkholderia pseudomallei K96243 Burkholderia pseudomallei strain K96243. This strain was a clinical isolate from Thailand. B. pseudomallei strain K96243 was isolated in 1996 from a 34-year-old female diabetic patient in Khon Kaen hospital in Thailand. Burkholderia pseudomallei Pasteur Burkholderia pseudomallei strain Pasteur. This strain will be used for comparative genomics. Burkholderia pseudomallei S13 Burkholderia pseudomallei strain S13. This strain will be used for comparative genomics. The bacteria are small (0.8 x 1.5 um). B. pseudomallei is visualized as a gram-negative bacillus with bipolar staining and is vacuolated and slender and has rounded ends; it is often described as having a "safety pin" appearance. It is oxidase positive and can be distinguished from the closely related but less pathogenic B. thailandensis by its ability to assimilate arabinose. The cells of the species of genus Burkholderia are Gram-negative, non-fermentitive straight rods, that have either a single polar flagellum or a tuft of polar flagella. Burkholderia pseudomallei is a saprophytic organism that routinely can be isolated from environmental niches like water, moist soil and rice paddies. Burkholderia pseudomallei is a natural saprophyte that can be isolated from soil and muddy water in endemic areas. It lives in the rhizosphere and is believed to play an important role in denitrification. The agent can be found in soil and clay layers from the surface but more often and regularly in deeper layers from 25 to 120 cm. B. pseudomallei can multiply in soil at a pH from 4 to 8, at a minimal humidity of 10-15% and at temperatures from 4 to 42C but not in estuarine or salt water. It has been noted that the isolation rate was high in places used by animals to rest in the shade. Aerotaxis may account for the bacteria moving actively from deeper layers to the surface soil if it is moistened, e.g. by rain or agricultural practices. The type of soil seems not to be a major factor. The minimum isotherm for a steady establishment in a new geographic area seems to be 11C. Humans and animals are infected by exposure to B. pseudomallei present in soil and surface water in endemic locations. The complete genome of B. pseudomallei strain K96243 consists of two circular replicons (European Molecular Biology Laboratory accession nos. BX571965 [GenBank] and BX571966 [GenBank] ) of 4.07 Mb and 3.17 Mb each that have been designated chromosome 1 and chromosome 2 and encode 3,460 and 2,395 coding sequences (CDS), respectively. 4074542 bp 3529 genes, 3399 proteins This strain was a clinical isolate from Thailand. The genome of this organism carries many genomic islands as compared to the related organism B. mallei, suggesting extensive horizontal transfer. Three different type III secretion systems (TTSS) are encoded on the chromosomes of this organism, two of which are similar to plant pathogenic TTSSs, while the third is similar to the Salmonella pathogenicity island, all of which may contribute to pathogenicity. Other virulence determinants include multidrug efflux pumps, secreted toxins and proteases, and various adhesins. Capsular polysaccharide may protect the organism from host defense mechanisms. This organism also carries a number of small sequence repeats which may promote antigenic variation, similar to what was found with the B. mallei genome. Chromosome 1 contains a higher proportion of CDSs involved in core functions, such as macromolecule biosynthesis, amino acid metabolism, cofactor and carrier synthesis, nucleotide and protein biosynthesis, chemotaxis, and mobility. 3173005 bp 2406 genes, 2329 proteins Chromosome 2 has a weaker G+C deviation pattern, and the predicted origin of replication contains features similar to those associated with plasmid replication, such as parA and parB homologues. Identification of CDSs on chromosome 2 that are involved in central metabolism and essential functions has led us to designate this component of the genome as a chromosome rather than a megaplasmid. Chromosome 2 contains a greater proportion of CDS encoding accessory functions: adaptation to atypical conditions, osmotic protection and iron acquisition, secondary metabolism, regulation, and laterally acquired DNA. In addition, chromosome 2 contains a greater proportion of CDSs with matches to hypothetical proteins or proteins that have no database matches at all. Comparison of the two chromosomes reveals that there is very little similarity, except in the regions of the rRNA clusters. This partitioning of core and accessory functions is reminiscent of the arrangement in the actinomycete soil-dwelling bacterium, Streptomyces coelicolor strain A3. 7211125 bp 5451 genes, 5451 proteins Burkholderia pseudomallei 1106a, unfinished sequence, whole genome shotgun sequence. NIH-NIAID has funded this genome project to sequence nine phenotypically characterized strains of B. pseudomallei, as well as 25 B. pseudomallei bacteriophage genomes isolated from 48 different B. pseudomallei strains from various geographic and clinical sources. Variable horizontal gene acquisition by B. pseudomallei is an important feature of recent genetic evolution, and has resulted in a genetically diverse bacterial species. The goal of this project is to identify the specific nucleotide sequences and/or single nucleotide polymorphisms that are correlated with expression of virulence and disease via comparative genomic analysis between B. pseudomallei strains as well as between various bacteriophages harbored within B. pseudomallei. 7187243 bp 5461 genes, 5461 proteins Burkholderia pseudomallei 1106b, unfinished sequence, whole genome shotgun sequence. 7029452 bp 5410 genes, 5410 proteins Burkholderia pseudomallei 1655, unfinished sequence, whole genome shotgun sequence. 7319487 bp 5502 genes, 5502 proteins Burkholderia pseudomallei 1710a, unfinished sequence, whole genome shotgun sequence 4126292 bp 3799 genes, 3736 proteins Burkholderia pseudomallei 1710b chromosome I, complete sequence. 3181762 bp 2621 genes, 2611 proteins Burkholderia pseudomallei 1710b chromosome II, complete sequence 7071938 bp 5433 genes, 5433 proteins Burkholderia pseudomallei 668, unfinished sequence, whole genome shotgun sequencing project 7346573 bp 5595 genes, 5595 proteins Burkholderia pseudomallei Pasteur, unfinished sequence, whole genome shotgun sequencing project 7388320 bp 5715 genes, 5715 proteins Burkholderia pseudomallei S13, unfinished sequence, whole genome shotgun sequence The two locations where melioidosis is arguably the most important single bacterial pathogen for humans are some northeast provinces in Thailand and the Top End of the Northern Territory of Australia. In northeast Thailand, 20% of community-acquired septicemic cases are caused by melioidosis, which accounts for 39% of fatal septicemias and 36% of fatal community-acquired pneumonias. In the Top End of the Northern Territory, melioidosis has been the commonest cause of fatal community-acquired bacteremic pneumonia. Melioidosis is endemic in south-east Asia and tropical Australia, and has been reported sporadically elsewhere. However, it is difficult to diagnose without relatively sophisticated laboratory facilities, and the true incidence of the disease in most countries remains unknown. Recent reviews have summarized the clinical experience with melioidosis in China, where cases have been acquired in Hainan Island, Guangdong and Guangxi provinces, and in Taiwan, where 11 indigenous cases have been diagnosed since 1982. A report of two cases in Laos, which is adjacent to the highly endemic areas of Thailand, comes as no surprise, although the authors pointed out the dilemma posed by diagnosing melioidosis in countries that cannot afford to treat it. Three human cases of melioidosis, each confirmed by independent Reference Laboratories, have been reported in the past 4 years. These originated from Martinique, Guadeloupe and Puerto Rico. The Caribbean must thus be regarded as endemic for melioidosis, although further work is needed to determine just how common the disease is there and how widely it is distributed. Northern Territory, Australia. Nine cases of melioidosis with four deaths occurred over a 28-month period in members of a small remote Aboriginal community in the top end of the Northern Territory of Australia. Typing by pulsed-field gel electrophoresis showed isolates of Burkholderia pseudomallei from six of the cases to be clonal and also identical to an isolate from the community water supply, but not to soil isolates. The clonality of the isolates found in this cluster contrasts with the marked genetic diversity of human and environmental isolates found in this region which is hyperendemic for B. pseudomallei. It is possible that the clonal bacteria persisted and were propagated in biofilm in the water supply system. While the exact mode of transmission to humans and the reasons for cessation of the outbreak remain uncertain, contamination of the unchlorinated community water supply is a likely explanation. Western Australia. An unusual clustering of culture-confirmed cases of acute melioidosis in a remote coastal community during the dry season prompted an urgent outbreak investigation. The population of the affected community fluctuates between about 200 and 300 persons. No record has been found of any cases of melioidosis in the community before 1997. In a typical year there would be around 3-5 cases of melioidosis confirmed in Western Australia. The seven patients had an age range of 34-57 years, four were female and three were male. All had at least one of the following chronic disease or co-morbidity risk factors: diabetes, high-risk alcohol consumption, chronic renal failure or rheumatic heart disease. The seventh case presented in August 1998 and gave a history of a brief febrile illness in December 1997, followed by multiple soft tissue lesions and finally culture-positive septicaemic melioidosis in August 1998. B. pseudomallei was isolated from all seven patients. B. pseudomallei was also isolated from water dripping from a back yard tap and from the 51 pre-chlorination bore water sample. No other environmental specimens (including 14 soil specimens from sites around homes of cases, 16 other soils, 4 water specimens from sites around homes of cases, 9 other surface water samples, 10x5L water specimens [4 from capped bores], 2 samples of rammed earth block and 1 water pipe) contained detectable B. pseudomallei. Brazil. Outbreak 1 comprised 4 previously healthy children from the Municipality of Tejussuoca; the children were admitted to the hospital with clinical features of systemic infection over the course of 10 days (February 28-March 7, 2003). Three of the children died because of multiple organ systems failure. Patient 1 died shortly after admission to a local hospital, before any diagnostic microbiology tests could be arranged. Gram-negative bacilli were isolated by blood culture from 2 children, patient 2 and patient 3. For patient 2, the isolate did not survive preliminary laboratory analysis, but findings at autopsy were consistent with melioidosis. In patient 3, the isolate was presumptively identified as B. pseudomallei. Bacterial identification and susceptibility results came too late to guide the treatment of patient 3, who also died, but did lead to changes in antimicrobial drug therapy of patient 4, who was admitted to the hospital later than the other 3 patients, survived, and remains healthy. In her case, melioidosis was demonstrated by laboratory evidence of late seroconversion, detected by indirect hemagglutination assay. Preliminary epidemiologic investigations indicated that the children were probably infected when diving into an irrigation reservoir that filled shortly after the onset of the summer rains. Just over 1 year later, in 2004, several suspected cases of septicemic melioidosis occurred in another location in the State of Ceara (outbreak 2). The B. pseudomallei isolate from 1 such patient and 2 B. pseudomallei isolates from soil and water samples in the corresponding environmental study were sent for confirmation and molecular typing, as before. The patient was from the Municipality of Banabuiu, approximately 400 km from the location of outbreak 1. She used to wash clothing while sitting in a nearby river. She first complained of a perineal abscess, which persisted for 2 weeks before she was admitted to the hospital with septicemia. B. pseudomallei was isolated by blood culture after she died. The B. pseudomallei environmental isolates were from river water taken near where she washed clothes and from soil from the compacted earth floor under the tub she bathed in at home. France. In France, in the 1970s, cases of melioidosis occurred in animals in a Paris zoo and then spread to other zoos and equestrian clubs in France. As well as fatal animal and human cases, there was extensive soil contamination persisting for some years. B. pseudomallei was considered likely to have been introduced by importation of infected animals, possibly a panda donated to France by Mao-Tse-Tung or horses from Iran. All recent isolates from other non-endemic areas appear to have been imported from known endemic areas. There has been no repeat of the outbreak described in France in the mid-1970s and known as Laffaire du Jardin des Plantes. Isolates from this latter outbreak have been examined, however, and appear phenotypically indistinguishable from clinical isolates of B. pseudomallei from elsewhere in the world, although belonging to distinct genotypes. India. During the month of October, 1994, there was a small outbreak of acute lymphadenitis in and around Pune (Maharashtra). 64 patients with acute lymphadenitis were admitted to Sassoon General Hospital, 32 of whom were children. Lymph-node aspirates from 40 patients were cultured. 12 of these (30%) samples yielded Pseudomonas pseudomallei. The clinical presentation of our patients resembled that in patients reported during the outbreak of plague-like illness in Beed. Singapore. In March 2004, a high incidence of melioidosis in Singapore, with a high rate of mortality, was identified by the Ministry of Health. This outbreak raises the possibility, although unlikely, of an intentional release of B. pseudomallei, similar to the intentional release of anthrax spores in the United States following the events of 11 September 2001. We report here a rapid approach to strain typing of the B. pseudomallei isolates obtained during the first half of 2004, in order to exclude the possibility of a point source and hence an intentional release of this pathogen. Our investigation indicated that a total of 30 different VNTR types could be distinguished in the 32 clinical isolates of B. pseudomallei obtained during this period, thus indicating that infection was unlikely to have occurred from a single source. Military cases. Melioidosis was an important cause of morbidity and mortality in foreign troops fighting in South East Asia. Dance noted that about 100 cases occurred among French forces in Indochina between 1948-1954, and by 1973, 343 cases had been reported in American troops fighting in Vietnam. Environment Human It is now clear that humans and animals are infected by exposure to B. pseudomallei present in soil and surface water in endemic locations. Three modes of acquisition, i.e., inhalation, ingestion, and inoculation, are recognized for B. pseudomallei, but the relative contributions of each are yet to be determined. As with other infectious diseases, it is likely that these factors as well as the size of the inoculum are responsible for the pattern and severity of disease. Situations likely to be associated with a high inoculum, such as near drownings, are associated with a short incubation period, even less than 24 h. The finding that periods of heavy rainfall are associated not only with higher numbers of cases but also pneumonic presentations and cases of increased severity may suggest a shift to inhalation during extreme weather events. This is supported by the recent observation that a number of patients in Singapore who presented during a period of heavy rainfall were elderly, nonambulant patients with no history of exposure to soil or surface water. It is now believed that inoculation is the major mode of acquisition. Minor wounds to the feet of rice farmers are common during the planting and harvesting seasons, when farmers spend most of the working day wading in mud and surface water; inoculation at the time of a snake bite has also been described. In the Darwin series, 25% of patients gave a history of an inoculation injury prior to presentation; in this subgroup of patients, an incubation period of 1 to 21 days has been defined. Human Human Person-to-person transmission of B. pseudomallei is very unusual. Venereal transmission was the first report of person-to-person spread of B. pseudomallei infection. Person-to-person transmission between 2 siblings may have occurred. Two cases of maternal to child transmission of melioidosis are reported from Australia's tropical north. One infant died of overwhelming sepsis. Both lactating mothers had mastitis. In 1 case, Burkholderia pseudomallei isolated from breast milk was identical on pulsed-field gel electrophoresis with that in blood and cerebrospinal fluid isolates from the infant. Mother-to-child transmission of B. pseudomallei probably occurred as a result of placental infection. The use of prednisone and the pregnancy may have increased the susceptibility to infection. Animals Human Zoonotic transmission to humans is extremely unusual, but there are many similar epidemiological and clinical features of melioidosis in animals and humans. Possible epizoonotic human infections have been implicated in at least three cases in humans in Australia. The environmental reservoirs for B. pseudomallei are surface water and soil. Burkholderia pseudomallei can survive in water at room temperature for up to 8 weeks, in muddy water for up to 7 months and in soil in the laboratory for up to 30 months. The bacterium is not particularly resistant to UV-irradiation or sunlight. Chlorine has only a bacteriostatic effect on the agent as bacteria were recovered from water containing up to 1000 p.p.m. free chlorine. Lower pH additionally reduces the effect of the disinfectant. However, it can effectively reduce the number of viable bacteria. We still know very little about the climatic, physical, chemical and biological factors which control the proliferation and survival of Burkholderia spp. in the environment. More recently, B. pseudomallei has been considered an important potential bioweapon, with increasing funding overseas for research into virulence factors and vaccine development. It is believed that biological weapons research using B. pseudomallei occurred in the former USSR, although the extent of this effort and the possibility of engineered antibiotic resistant strains remain unknown. Other countries with a military interest in B. pseudomallei included the United States and possibly Egypt. The potential risk posed by B. pseudomallei as a bioweapon is uncertain. Melioidosis carries a potentially high mortality rate, and its causative agent has intrinsic antibiotic resistance and a wide host range. However, weaponization has not been known to have been performed, the disease does not spread from person to person, and the susceptibility of immunocompetent individuals after inhalation is not clear. CDC requests that incidents involving unsafe laboratory exposure to B. pseudomallei be reported to the Meningitis and Special Pathogens Branch, National Center for Infectious Diseases, telephone 404-639-3158. Burkholderia pseudomallei would most likely be delivered as an aerosol. The lack of a vaccine and its high mortality despite treatment could make it a plausible BW agent. Animal Biosafety Level 2 practices, containment equipment, and facilities are recommended for studies utilizing experimentally infected laboratory rodents. Biosafety Level 3 practices, containment equipment, and facilities are recommended for work involving production quantities or concentrations of cultures, and for activities with a high potential for aerosol production. Human Homo sapiens Melioidosis is a disease of the rainy season in endemic areas. It mainly affects people who have direct contact with wet soils and have an underlying predisposition to infection. These are patients with diabetes mellitus, renal disease, cirrhosis, thalassaemia, alcoholism, or those who are immunosuppressed as the result of either disease or drug treatment. However, melioidosis does not seem to be associated with HIV infection. In Australia, melioidosis has also been linked with chronic lung disease and excessive consumption of kava. B pseudomallei has been recognized as a possible cause of chronic infection in patients with cystic fibrosis. Of the predisposing conditions, diabetes mellitus is the most frequent. Up to 50% of patients with melioidosis have diabetes mellitus, usually maturity onset diabetics, often with evidence of poor control of blood glucose before infection. Melioidosis may present at any age; peak incidence is in the fourth and fifth decades of life, coinciding with development of underlying predisposing illness. Infection in humans and animals is thought to occur by inoculation, ingestion or inhalation of environmental organisms. Watering of soil in the dry season, e.g. in the surroundings of water pumps or in fields leads to a higher isolation rate and presumably to a higher risk of infection. The number of registered cases of infection increases with rainfall, e.g. during the rainy season in the tropics when it is more likely that animals and humans can come into contact with muddy water and soil particles carrying bacteria from deeper layers to the surface. Animal-to-human transmission has rarely been documented but can result in fatalities as B. pseudomallei has an extremely broad host range. Disease occurs after bacterial contamination of breaks in the skin or by inhalation after contact with water or soil. A pneumonic form of the disease can also result from the inhalation of contaminated dusts and was reported in U.S. helicopter pilots during the Vietnam War. A licensed animal or human vaccine does not exist. However, there are some promising data on the possibility of developing such a vaccine in the future. In a mouse model an attenuated mutant of B. pseudomallei auxothrophic for branched amino acids due to an interruption of the ilvI gene was protective. Various other B. pseudomallei mutants failed to protect laboratory animals. A live vaccine is favoured, as human patients suffering from melioidosis show a cell mediated immune response (lymphocyte proliferation, interleukin production, increase of CD4+ and CD8+ cells), which may be essential for survival, as IgG content is not predictive for disease outcome. Cross-protection using a live tularaemia vaccine to protect against B. pseudomallei has been suggested and needs to be investigated in the future. In order to develop a subunit vaccine, the O-polysaccharide moiety of the lipopolysaccharide was covalently linked to flagellin protein. When this was used to immunize diabetic mice a clear rate of protection was achieved. In fact, in human patients, the amount of anti-LPS II antibodies is positively correlated with survival. Passive protection has been achieved with mouse monoclonal anti-EPS, anti-LPS or anti-protein antibodies when challenged with low infection doses of virulent B. pseudomallei in mice. However, when a higher dose of 1 x 10(6) colony-forming units (cfu) was applied, none of the antibodies was protective. The anti-EPS antibody was able to significantly prolong the time until death. However, no data are available as to whether total or partial immunity may result in a higher rate of subclinical chronic infection, and regarding what might happen when the 'protected' subject becomes immunocompromised. Research in this field has to be evaluated very carefully. Primary prevention involves education in endemic areas about minimizing exposure to wet-season soils and surface water, especially for diabetics. Footwear and gloves while gardening are recommended in northern Australia, but preventing occupation exposure in rice farmers may be unrealistic in Southeast Asia. Cystic fibrosis patients should consider avoiding travel to high-risk areas. Water hygiene is the predominant requirement in endemic areas where animals for human consumption are bred according to modern practice. The keeping of porkers without access to soil by rearing them on artificial, hard surfaces could not prevent infection. In some cases, the chlorination (2-6 mg/l) of water supplies interrupted the chain of infection effectively if the pH was kept at 6-7 prior to chlorination. If possible, infected animals should be removed from the contaminating source. Moreover, B. pseudomallei seems to profit from modern agricultural practices and animal mass production involving the habitual use of enormous amounts of water. Accordingly, strict control of sewage disposal is imperative in order to prevent the spread of B. pseudomallei. Infected carcasses of animals intended for human consumption have to be condemned and destroyed. The use of gloves and disinfection of contaminated knives is recommended to prevent transmission during the processing of meat. As milk from goats and dairy cows can contain B. pseudomallei pasteurization is recommended. It is noteworthy to mention, that there seem to be no reservations against treatment of pet animals such as cats in areas where melioidosis is endemic. For disinfection, the regular use of potassium hypochlorite and cresol solutions is recommended. The faeces of infected animals have to be removed several times a day. Abundant quantities of water have to be avoided or disinfected immediately. The hooves and lower legs as well as the surfaces of the stables have to be disinfected. Food and water must be given as aseptically as possible. Measurement of in vitro activity of quicklime (calcium oxide) against Burkholderia pseudomallei revealed that quicklime at concentrations of 10% or more was bactericidal for up to 35 d. The effect of quicklime as an inhibitor of B. pseudomallei in soil from a rice field was studied in a laboratory setting. The soil, collected from a rice field in north-eastern Thailand, was mixed with B. pseudomallei. In experiment 1, quicklime was mixed with the soil in different amounts. In experiment 2, quicklime was spread over the soil surface. In experiment 3, quicklime solution was poured onto the soil. It was found that the pH of the soil in experiment 1 was much higher than that in experiments 2 and 3. Only quicklime mixed with soil at a concentration of 40% or more (weight/weight) was effective in inhibiting the growth of B. pseudomallei for up to six weeks. Laboratory-acquired infections, person-to-person spread, and zoonotic infection are all very uncommon, but secondary prophylaxis with sulfamethoxazole-trimethoprim, doxycycline, or amoxicillin-clavulanate could be considered in exceptional circumstances, especially if the exposed person is diabetic of has other risk factors for melioidosis. Sixteen workers completed a 3-week regimen of trimethoprim-sulfamethoxazole, and one completed a 3-week regimen of doxycycline. Antibiotics were begun at a median of 2 days postexposure (range: 0-4 days). None of the exposed laboratory workers had symptoms consistent with melioidosis during 5 months after exposure. Two laboratory workers had titers of less than 20 for B. pseudomallei on the first serum drawn. Both workers were born in the United States, and neither demonstrated an increase in titer 6 weeks after exposure. The first (no. 17) reported sniffing a B. pseudomallei culture plate. The worker recalled previous travel to Hawaii, Europe, Mexico, and Jamaica but reported no previous illnesses consistent with melioidosis. The second worker (no. 1) reported low-risk activities. The worker reported previous travel to the Philippines and Singapore and was hospitalized in 2001 for pneumonia with pleural effusions requiring thoracenteses; no pathogen was identified. B. pseudomallei survives inside several eukaryotic cell lines and is seen within phagocytic cells in pathological specimens. After internalisation, it escapes from endocytic vacuoles into the infected cell cytoplasm and then forms membrane protrusions by inducing actin polymerisation at one pole. The actin protrusions from the infected cell membrane mediate spread of the organism from cell to cell. The role of exotoxins in the pathogenesis of melioidosis is unresolved. The high mortality of B. pseudomallei infections is related to an increased propensity to develop high bacteraemias (more than 1 cfu/mL), but the relation between bacterial counts in blood and mortality is similar to that of other gram-negative pathogens. This finding suggests that exotoxins do not contribute directly to outcome. The cell wall lipopolysaccharide (LPS), which is the immunodominant antigen, is highly conserved. High concentrations of antibodies to LPS 2 are associated with improved survival in severe melioidosis. B. pseudomallei produces a highly hydrated glycocalyx polysaccharide capsule, an important virulence determinant that helps to form a slime. This capsule facilitates formation of microcolonies in which the organism is both protected from antibiotic penetration and phenotypically altered, resulting in reduced susceptibility to antibiotics (small colony variants). Passive immunisation with antibody to this exopolysaccharide reduces the lethality of infection in mice. To date, the organisms which cause invasive disease are indistinguishable from those found in the environment. In endemic areas, seroepidemiological surveys showed that infection, mostly latent, occurred fairly commonly since childhood as 80% of children had antibodies by the age of four years. However, clinical melioidosis is more common in the elderly which in some cases are due to reactivation of primary latent infection. Since the incubation period of the reactivation can vary from weeks to many years, a vaccine or short-course secondary chemoprophylaxis may be possible interventions for the high risk group to get rid of the "time-bomb" reactivation. Incubation period from defined inoculating events was previously ascertained as 1-21 (mean 9) days. The incubation period (time between exposure and appearance of clinical symptoms) is not clearly defined, but may range from 2 days to many years. In addition, incubation periods of as long as 24 to 29 years in ex-servicemen who were in Papua New Guinea and Vietnam have been described. Prognosis is poor. Detection of the bacterium in blood culture in severe disease is associated with higher mortality. In one study 74% of people with a positive blood culture died within 24 hours. Mortality is high in severe disease (septicaemic form of melioidosis) in which the clinical course often deteriorates rapidly even with the currently available treatments, with disseminated infection associated with 40% to 90% of people dying. In people with septicaemia with only one organ involved, death rates are in the region of 20%. Treatment with the antibiotics ceftazidime and imipenem seems to reduce the number of deaths, although the numbers remain high. While 20-36% of melioidosis cases have no evident predisposing risk factor, the vast majority of fatal cases have an identified risk factor, the most important of which are diabetes, alcoholism and chronic renal disease. 46% of cases were bacteraemic and overall mortality was 19%, compared with 60% bacteraemia and 44% mortality in Thailand, and 52% bacteraemia and 46% mortality in Singapore. The mortality rate is below 10% for illness severity that lies between asymptomatic and localized melioidosis. The mortality rate rises sharply from 10% in septicemic melioidosis to 90% in melioidosis with septic shock. Melioidosis affects virtually every organ except the hair and nails, and resembles acute and chronic infections. Rare and unusual infected sites are continually being reported. Small and large abscesses have been found in the brain, prostate gland, parotid gland, intra-abdominal mesenteric root, upper-extremity joints, masticator space, and skin and soft tissues. Mycotic aneurysm of the iliac, subclavian arteries, and elsewhere is not rare. In difficult-to-treat cases, the anatomic localization of suspected abscesses in internal organs using ultrasonography or white cell scanning is an effective way of assessing the involvement of musculoskeletal, visceral and soft tissue melioidosis. The latter technique may be performed in cases who have septicemic melioidosis and are infected with susceptible micro-organisms but respond slowly, or in those who have experienced relapse soon after the cessation of therapy. Acute or subacute pneumonia was encountered in nearly half of all acute infections. Bloodstream pneumonia manifested with bilateral multi-nodular pulmonary infiltrations is most commonly associated with high mortality, followed by lobar pneumonia, lung abscess and lung mass. Empyema and pyopericardium are less common. Thoracic wall involvement, such as sternoclavicular septic arthritis, supraclavicular lymphadenopathy, is sometimes seen. The earliest descriptions of melioidosis documented the fulminant end of the clinical spectrum, with abscesses throughout both lungs and in many organs. At the other end of the spectrum are asymptomatic infections and localized skin ulcers or abscesses without systemic illness. Howe and colleagues classified melioidosis as acute, subacute, and chronic. The Infectious Disease Association of Thailand summarized 345 cases in these categories: 1. Disseminated septicemia (45% of cases, 87% mortality); 2. Nondisseminated septicemia (12% of cases, 17% mortality); 3. Localized septicemia (42% of cases, 9% mortality); 4. Transient bacteremia (0.3%). All patients with septic shock had fever of 1 weeks' duration or less. One of the patients developed renal impairment and another patient had an abnormal coagulation profile on admission. All patients had pneumonia and 2 had involvement of multiple organs. 80-90% mortality in cases treated with ceftazidime. In our study, 38.4% of cases presented with septic shock, which had an associated mortality rate of 80%. 20% of cases in the Darwin series, 16% of cases in the Kuala Lampur series, and 30% in the Sapprasithiprasong Hospital series. Pneumonia is the commonest clinical presentation of patients with melioidosis in all studies, accounting for around half the cases. Acute melioidosis pneumonia has a spectrum from fulminant septic shock (mortality 84% in the Darwin study to mild undifferentiated pneumonia, which can be acute or subacute in nature, both with little mortality. Disseminated septicemic melioidosis clinically involves more than one organ. For example, bloodstream pneumonia (multinodular bilateral pulmonary infiltration) or septic arthritis develops subsequently to pre-existing liver abscess or splenic abscess. 40-50% mortality in cases treated with ceftazidime. 45% of cases, 87% mortality Septicemic melioidosis clinically involves a single organ such as the lung, prostate gland, spleen, parotid gland, and has a positive blood culture. 10-40% mortality in cases treated with ceftazidime. 12% of cases, 17% mortality Pneumonia is the commonest clinical presentation of patients with melioidosis in all studies, accounting for around half the cases. Acute melioidosis pneumonia has a spectrum from fulminant septic shock (mortality 84% in the Darwin study to mild undifferentiated pneumonia, which can be acute or subacute in nature, both with little mortality. Liver abscess or cutaneous granuloma and negative blood culture is an example of localized melioidosis. Among patients with localized melioidosis in Thailand, head and neck involvement was the most common presentation. Dance et al reported that 38% of patients with localized melioidosis had involvement of the parotid gland. They also found an association of acute suppurative parotitis with mumps. In contrast, none of the cases in studies from Australia had parotitis. 0-10% mortality in cases treated with ceftazidime. Localized melioidosis is a more common presentation in the pediatric age group. In our study, 46.2% of the patients had localized disease, compared to approximately 65% in a study from Thailand. 42% of cases, 9% mortality Encephalomyelitis, characterized by brain stem encephalitis and flaccid paralysis, is seen in 4% of melioidosis presentations in northern Australia and is associated with considerable morbidity and mortality. Small numbers of children with a similar syndrome have been recognized in Thailand. Cultures of cerebrospinal fluid were positive in only one of seven cases, with monocytic pleocytosis the most common finding. This should be distinguished from more focal suppurative infections involving the central nervous system, which have been well described. Some of these may represent direct spread from contiguous sites, such as facial sinuses or orbital cellulitis. Primary meningitis has been observed in Thailand but more often results from ruptured cerebral abscesses . Neurological involvement has also been observed in animals 4% of cases in the Darwin series, 6% of cases in the Kuala Lampur series, and 3% of cases in the Infectious Diseases Association of Thailand series. Bone and joint infections are uncommon and may be difficult to differentiate from other causes of infection, except that the systemic features of the illness may be more prominent. Surgical drainage is often required, together with long courses of intravenous antibiotics. 4% of cases in the Darwin series, 2% of cases in the Kuala Lampur series, and 3% of cases in the Infectious Diseases Association of Thailand series. Skin and soft tissue infections are a common manifestation of melioidosis and may be the source of systemic infection or result from hematogenous spread. Presentations may be rapidly progressive, similar to necrotizing fasciitis from other organisms. Infections involving many other sites have been described, including mycotic aneurysms, mediastinal infection, and thyroid and scrotal abscesses. Corneal ulcers were described for a series of three Thai patients following corneal trauma. Extensive ulcers, subconjunctival abscesses, and hypopyon were managed with topical and intravenous ceftazidime with good outcomes. Other ocular manifestations include orbital cellulitis with contiguous spread to the sinuses. 17% of cases in the Darwin series, 24% of cases in the Kuala Lampur series, 13% of cases in the Infectious Diseases Association of Thailand series, and 13% in the Sapprasithiprasong Hospital series. 19% of cases in the Darwin series, 10% of cases in the Kuala Lampur series, 7% of cases in the Infectious Diseases Association of Thailand series, and 8% in the Sapprasithiprasong Hospital series. The high proportion of patients with prostatic infection in Australia contrasts with the higher proportions of patients with liver and spleen abscesses seen in Thailand. 4% of cases in the Darwin series, 2% of cases in the Kuala Lampur series, and 2% of cases in the Infectious Diseases Association of Thailand series. The high proportion of patients with prostatic infection in Australia contrasts with the higher proportions of patients with liver and spleen abscesses seen in Thailand. 2% of cases in the Darwin series, 4% of cases in the Kuala Lampur series, and 7% of cases in the Infectious Diseases Association of Thailand series. The high proportion of patients with prostatic infection in Australia contrasts with the higher proportions of patients with liver and spleen abscesses seen in Thailand. In Australia, the prevalence of prostatic infection (18% of male patients) mandates routine imaging, with drainage commonly required. This contrasts with other internal abscesses, which may respond to medical therapy alone 18% of cases (of males) in the Darwin series, and 0.3% of cases in the Infectious Diseases Association of Thailand series. Acute suppurative parotiditis accounts for up to 40% of pediatric cases but only small numbers of adult cases in Thailand. It seems to arise in patients with no defined risk factors and is generally associated with a good prognosis. It may be bilateral in 10% of patients and may be complicated by rupture or permanent facial nerve palsy. It has been reported only once in Australia 2% of cases in the Infectious Diseases Association of Thailand series Bacteremic melioidosis shows only a positive blood culture with mild or no fever. It may be an early clinical presentation of mycotic aneurysm in some cases. 0.3%. 0% mortality in cases treated with ceftazidime. Asymptomatic melioidosis is found in a healthy host with a positive serological test. 0% mortality in cases treated with ceftazidime. Melioidosis should be suspected in any severely ill febrile patient with an underlying predisposing condition who lives in, or has traveled from, an endemic area. In northeast Thailand, B. pseudomallei is the most common cause of septicaemic illness during the rainy season in adult diabetics. Evidence of abscess formation is often noted either in the lungs on the chest radiograph, or in the liver and spleen on ultrasound examination. Whereas liver abscess can be caused by Entamoeba histolytica or by enteric bacteria, splenic abscess is much less common, and is more likely than liver abscess to suggest melioidosis in endemic areas; in northeast Thailand 95% of splenic abscesses are caused by B pseudomallei. Up to 13% of patients with septicaemia have subcutaneous abscesses in which gram-negative rods can be detected. Haematological and biochemical findings are similar to those in patients with other causes of bacterial sepsis, although evidence of the underlying predisposing condition (hyperglycaemia or renal impairment) is often noted. The laboratory diagnosis of melioidosis is best made with a culture of the appropriate clinical material. Serology has a role in the diagnosis of this condition, particularly in patients from areas where it is not endemic who travel to an area where it is endemic and develop a suggestive clinical condition. Serum samples from patients resident in areas where it is endemic can be positive in the absence of clinical disease. This would represent previous exposure and does not necessarily imply current disease. Other diagnostic methods that have been used include latex agglutination for detection of antigen in urine and molecular detection. Before 1989, "conventional therapy" for melioidosis consisted of a combination of chloramphenicol, sulfamethoxzaole-trimethoprim, doxycycline, and sometimes kanamycin, given for 6 weeks to 6 months. Until about 15 years ago, the usual treatment for confirmed cases of acute severe melioidosis in Thailand was a combination of four drugs given intravenously - chloramphenicol (100 mg/kg per day), doxycycline (4 mg/kg per day) and trimethoprim-sulphamethoxazole (TMP-SXT, 60 mg/kg per day). These drugs are all bacteriostatic rather than bactericidal, are potentially toxic and in vitro, demonstrate mutual antagonism. Not surprisingly therefore, this four-drug 'conventional' regimen had a high failure rate, particularly in septicaemic melioidosis. As approximately 60% of patients admitted to hospital with melioidosis have positive blood cultures, the mortality with this regimen was unacceptably high (over 70%). Until 1989 the conventional therapy for melioidosis was high doses of chloramphenicol, doxycycline and SMX/TMP, often in combination with kanamycin. The mortality at this time for septicaemic melioidosis was as high as 68-95%. Death rates were high in trial arms using the older conventional regimens of chloramphenicol, doxycycline, and co-triamoxazole (trimethoprim-sulphamethoxazole): 74% in White 1989 and 47% in Sookprance 1992. In addition to emergence of resistance with this regimen, studies from the same group showed that in vitro SMX/TMP antagonised the bacteriostatic activity of doxycycline and chloramphenicol Initial intensive therapy-minimum of 10-14 days. Ceftazidime (50 mg/kg, up to 2 g) every 6 hours. Melioidosis is difficult to treat, and response to treatment is often disappointingly slow despite administration of high dose parenteral antibiotics. The antibiotic of choice is ceftazidime. Following initial intensive therapy, using ceftazidime or imipenem or meropenem, possibly in combination with sulfamethoxazole-trimethoprim, subsequent eradication therapy is considered necessary for preventing recrudescence or later relapse of melioidosis. Both duration of eradication therapy and the best antibiotics to use remain uncertain. The cost of treatment is high, especially with beta-lactam regimens. The cost of ceftazidime varies from US $70 to $100 per day for participants diagnosed with severe melioidosis, which is approximately six to seven times higher than the cost of conventional regimens. Hypersensitivity to other cephalosporins or related antibiotics, e.g.p, penicillin Serious: hypersensitivity reactions, bone marrow suppression, hemolytic anemia, pseudomembranous colitis, nephrotoxicity. The most important therapeutic study for melioidosis was an open-label randomized trial in Thailand comparing ceftazidime (120 mg/kg/day) with conventional therapy, which showed that ceftazidime was associated with a 50% lower overall mortality in severe melioidosis. Ceftazidime then became the drug of choice for initial intensive therapy for melioidosis. One strain, isolated from human infection, appeared resistant to ceftazidime with a minimum inhibitory concentration (MIC) of 64 mg/L (MICs of ceftazidime for the other strains were between 1-4 mg/L). This strain also presented a cross-resistance to ticarcillin/clavulanate, doxycycline and minocycline and was categorized intermediate for co-amoxiclav with an MIC of 16 mg/L. In a large series from Thailand nine (7%) of 127 patients had B. pseudomallei isolates that developed choramphenicol resistance while taking antibiotics (six were definitely taking chloramphenicol itself and the other three may well have been). These isolates frequently showed cross-resistance to SMX/TMP, tetracyclines and ciprofloxacin. In the same series a patient on ceftazidime and another on AMOX/CA developed resistance to these respective agents. Resistance to both ceftazidime and AMOX/CA was seen in a patient in our series who moved interstate and this has been published by Toohey et al. Also in Thailand, Chaowagul et al., describe doxycycline resistance emerging in one of the 12 relapse cases who was taking doxycycline alone in their trial comparing eradication therapy with doxycycline, SMX/TMP and chloramphenicol with doxycycline alone. There are also reports of successful use of sulfamethoxazole-trimethoprim alone and tetracycline or doxycycline alone. These "conventional antibiotics" are bacteriostatic rather than bactericidal, and in vitro studies have shown various combinations to be antagonistic. Hypersensitivity to any tetracycline, patients with esophageal obstruction, children less than 8 years. Common: nausea, vomiting diarrhea, anorexia. Serious: renal toxicity, hypersensitivity reactions, benign intracranial hypertension (pseudotumor cerebri), pericarditis, diabetes insipidus, pseudomembranous colitis, hepatitis, anaphylaxis. In a large series from Thailand nine (7%) of 127 patients had B. pseudomallei isolates that developed choramphenicol resistance while taking antibiotics (six were definitely taking chloramphenicol itself and the other three may well have been). These isolates frequently showed cross-resistance to SMX/TMP, tetracyclines and ciprofloxacin. In the same series a patient on ceftazidime and another on AMOX/CA developed resistance to these respective agents. Resistance to both ceftazidime and AMOX/CA was seen in a patient in our series who moved interstate and this has been published by Toohey et al. Also in Thailand, Chaowagul et al., describe doxycycline resistance emerging in one of the 12 relapse cases who was taking doxycycline alone in their trial comparing eradication therapy with doxycycline, SMX/TMP and chloramphenicol with doxycycline alone. Initial intensive therapy-minimum of 10-14 days. Sulfamethoxazole/trimethoprim (40/8 mg/kg, up to 1600/320 mg) every 12 hours. Eradication therapy-minimum of 3 months. Sulfamethoxazole/trimethoprim (40/8 mg/kg, up to 1600/320 mg) every 12 hours. There are also reports of successful use of sulfamethoxazole-trimethoprim alone and tetracycline or doxycycline alone. These "conventional antibiotics" are bacteriostatic rather than bactericidal, and in vitro studies have shown various combinations to be antagonistic. It has been suggested that sulfamethoxazole-trimethoprim is the critical component in the "conventional" combination therapy, and prospective studies in Australia using sulfamethoxazole-trimethoprim alone for eradication therapy support this, with relapses being almost exclusively in noncompliant patients. Following initial intensive therapy, using ceftazidime or imipenem or meropenem, possibly in combination with sulfamethoxazole-trimethoprim, subsequent eradication therapy is considered necessary for preventing recrudescence or later relapse of melioidosis. Both duration of eradication therapy and the best antibiotics to use remain uncertain. Hypersensitivity to trimethoprim or sulfonamides, thiazide diuretics, oral hypoglycemics, megaloblastic anemia due to folate deficiency, pregnancy, lactation, treatment of streptococcal pharyngitis. Common: anorexia, nausea, vomiting, glossitis, rash. Serious: Stevens-Johnson syndrome (rare), pseudomembranous colitis, agranulocytosis, aplastic anemia, megaloblstic anemia, hyperkalemia, hemolysis (patients with G6PD deficiency). The MIC50 and MIC90 of co-trimoxazole were 8 and 16 mg/L, respectively, and the majority of the strains were categorized as intermediate or resistant (breakpoints less than or equal to 2/38, greater than 8/152) to this antibiotic. This relative in vitro resistance is not correlated with clinical experience as co-trimoxazole has been traditionally used for the therapy of melioidosis. Such discrepancies between results obtained with co-trimoxazole by different susceptibility testing methods and clinical data have already been documented. The resistance profiles appear to be independent of the origin of isolates. Imipenem, ceftazidime, co-amoxiclav, piperacillin, piperacillin/tazobactam and doxycycline appear as the more effective drugs tested on this panel of isolates. These results remain consistent with the current recommendations for the treatment of melioidosis and glanders. However, the emergence of ceftazidime-resistant clinical isolates and the wide distribution of B. pseudomallei in Southeast Asia increase the risk of malicious use of those resistant strains. Piperacillin/tazobactam could be a useful alternative for treatment of both glanders and melioidosis. Hypersensitivity to penicillin or cephalosporins, IV infections. Treatment with agents to which B. pseudomallei is susceptible requires 2-4 weeks of parenteral therapy (e.g. with ceftazidime) as initial 'intensive' therapy, followed by 3-6 months of oral 'eradication' therapy (e.g. with trimethoprim-sulphamethoxazole (SMX/TMP), doxycycline or combination therapy. Hypersensitivity to any tetracycline, patients with esophageal obstruction, children less than 8 years old. SMX/TMP, doxycycline and chloramphenicol have been the most commonly used agents for eradication therapy and it is to these that resistance has emerged in relapsed and persistent cases. In a large series from Thailand nine (7%) of 127 patients had B. pseudomallei isolates that developed choramphenicol resistance while taking antibiotics (six were definitely taking chloramphenicol itself and the other three may well have been). These isolates frequently showed cross-resistance to SMX/TMP, tetracyclines and ciprofloxacin. In the same series a patient on ceftazidime and another on AMOX/CA developed resistance to these respective agents. Resistance to both ceftazidime and AMOX/CA was seen in a patient in our series who moved interstate and this has been published by Toohey et al. Also in Thailand, Chaowagul et al., describe doxycycline resistance emerging in one of the 12 relapse cases who was taking doxycycline alone in their trial comparing eradication therapy with doxycycline, SMX/TMP and chloramphenicol with doxycycline alone. Initial intensive therapy-minimum of 10-14 days. Imipenem (25 mg.kg, up to 1 g) every 6 hours. Initial intensive therapy-minimum of 10-14 days. Meropenem (25 mg/l\kg. up to 1 g) every 8 hours. The carbapenems imipenem and meropenem have the lowest minimum inhibitory concentrations against B. pseudomallei. Furthermore, in vitro time-kill studies to measure the rate of bacterial killing showed that carbapenems to perform better against B. pseudomallei than ceftazidime. High-dose imipenem has been shown in another comparative trial from Thailand to be at least as effective as ceftazidime for severe melioidosis, with no differences in mortality between the groups and with fewer treatment failures in those given imipenem. Following initial intensive therapy, using ceftazidime or imipenem or meropenem, possibly in combination with sulfamethoxazole-trimethoprim, subsequent eradication therapy is considered necessary for preventing recrudescence or later relapse of melioidosis. Both duration of eradication therapy and the best antibiotics to use remain uncertain. Imipenim, an alternative to ceftazidime, also costs about US $150 per day per person. All the isolates were susceptible to imipenem. This antibiotic was, with doxycycline and minocycline, one of the most active antibiotics tested. This has been observed previously in a study involving 211 clinical strains, and is of interest because this antibiotic is considered as a good alternative to ceftazidime in the treatment of disseminated disease. It has been recommended by the European Agency for the Evaluation of Medicinal Products (EMEA) for the treatment of suspected or confirmed melioidosis After initial favorable reports of use of amoxicillin-clavulanate, another randomized comparative trial in Thailand showed that initial therapy with high-dose intravenous amoxicillin-clavulanate was as effective as ceftazidime in preventing deaths in severe melioidosis. However, when amoxicillin/clavulanate was continued as eradication therapy, treatment failure was more common. Co-amoxiclav (amoxycillin-clavulanate) has been shown to be effective but was associated with a higher rate of treatment failure than ceftazidime. Amoxicillin-clavulanate is recommended for eradication therapy in pregnancy and is an alternative to sulfamethoxazole-trimethoprim in children. Hypersensitivity to penicillin or cephalosporins. Common: Diarrhea. Serious: Stevens-Johnson syndrome, anaphylaxis, angioedema, laryngospasm, pseudomembraneous colitis. All other strains of B. mallei and B. pseudomallei were susceptible to co-amoxiclav. In the same series a patient on ceftazidime and another on AMOX/CA developed resistance to these respective agents. Resistance to both ceftazidime and AMOX/CA was seen in a patient in our series who moved interstate and this has been published by Toohey et al. Also in Thailand, Chaowagul et al., describe doxycycline resistance emerging in one of the 12 relapse cases who was taking doxycycline alone in their trial comparing eradication therapy with doxycycline, SMX/TMP and chloramphenicol with doxycycline alone. Mus musculus. In the BALB/c and C57BL/6 inbred mouse models, BALB/c mice are susceptible, whereas C57BL/6 are relatively more resistant via intravenous and intranasal routes of infection. BALB/c mice died of septicemic disease with overwhelming bacterial loads in organs and blood, accompanied by organ inflammation and necrosis a few days after infection, reflecting a failure of the host innate immune response to contain the infection. A whole-body mouse model of pneumonic melioidosis was established for future evaluation of biodefense vaccine candidates. The aerosol 50% lethal doses of Burkholderia pseudomallei strain 1026b for BALB/c and C57BL/6 mice and the times to death, dissemination in organs, and tissue loads after exposure of the mice to low- and high-dose aerosols are reported. Mesocricetus auratus Hamsters are exquisitely sensitive to B. pseudomallei infection. The 50% lethal dose (LD[50]) of B. pseudomallei in hamster is approximately 10 bacteria. The LD(50) is independent of the route of infection as similar values are obtained with intraperitoneal (i.p.), subcutaneous and respiratory infections. In addition, hamsters do not display individual variation in susceptibility to B. pseudomallei. The infection of hamsters with B. pseudomallei typically results in acute septicemic melioidosis and death within 2-3 days. In 1984 Miller et al. described the use of hamsters in the experimental chemotherapy of melioidosis. This animal model of melioidosis has also been used to assess the relative virulence of B. pseudomallei clinical isolates and isogenic mutants. Rattus norvegicus Rats are relatively resistant to B. pseudomallei infection. The LD(50) of B. pseudomallei in infant rats can be lowered significantly by i.p. injection of the diabetogenic compound streptozotocin (STZ). The infection of infant diabetic rats with B. pseudomallei typically results in acute septicemic melioidosis and death, usually within 7 days. This animal model of melioidosis has been used in passive immunoprophylaxis studies and has been useful in assessing the relative virulence of B. pseudomallei isogenic mutants. Diabetic rats and Syrian hamsters have been shown to be exquisitely susceptible to infection, which results in acute disease and rapid death. Acanthamoeba astronyxis In common with other intracellular bacterial pathogens such as Legionella pneumophila and Listeria monocytogenes, B. pseudomallei has been shown to enter and survive within free-living amoebae belonging to the genus Acanthamoeba. The B. pseudomallei-A. astronyxis system provides a useful model with which to explore the cellular pathogenesis of melioidosis. African green monkey Cercopithecus aethiops Le bacille de Whitmore, agent de la melioidose, a ete isole de quelques animaux sauvages de la Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle de Paris. (Translation: Whitmore's bacillus, the agent of the melioidosis, was isolated from some of the wild animals in the Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle in Paris.) Sur 34 animaux ainsi examines, nous avons obtenu 19 resultats positives: 2 concernant les chevaux de Przewalski (Equus przewalskii);1 buffle de l'Inde (Bubalus bubalis) nouveau-ne; 4 ovins (Ovis canadensis, Ovis vignei, Ovis musimon); 2 antilopes (Oryx beisa), nouveau-ne et (Redunca redunca) mort-ne; 6 cervides (Sika nippon, Muntiacus muntjac); 2 singes (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 tatou (Dasypus sexcinctus). (Translation: Of the 34 animals examined, we obtained positive results from: 2 Prezwalski horses (Equus przewalskii); 1 newborn Indian buffalo (Bubalus bubalis); 4 sheep (Ovis canadensis, Ovis vignei, Ovis musimon); 2 newborn antelopes (Oryz beisa), and one stillborn (Redunca redunca); 6 deer (Sika nippon, Muntiacus muntjac); 2 monkeys (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 armadillo (Dasypus sexcinctus). Chimpanzee Pan troglodytes Melioidosis was diagnosed in a chimpanzee (Pan troglodytes). The clinical history was one of gradual general degeneration of health, multiple abscesses, and pulmonary radiographic densities. The pathologic changes in the lungs, liver, and bone were similar to those reported for man. Pseudomonas pseudomallei was identified by bacteriologic culture of liver, lung, kidney and spleen. Positive serologic test results were obtained by the hemagglutination and the complement-fixation tests. The source of infection for the chimpanzee was not definitely known. Crab-eating macaque Macaca fascicularis An outbreak of melioidosis, a bacterial infection caused by Pseudomonas pseudomallei, was identified in a batch of feral cynomolgus monkeys (Macaca fascicularis) imported to Britain from the Philippines. Thirteen confirmed or possible cases occurred among a batch of 50 animals. Subsequent investigations revealed that the infection was uncommon among imported primates from a variety of sources, although three other cases were identified in monkeys imported from Indonesia. The majority of the affected monkeys had splenic abscesses, and hepatic abscesses and infections of the soft tissues and skin were also frequently observed. Most of the infected animals had no clinical signs despite extensive abscesses, and the presence of infection was only suspected when they were shown to have serum antibodies to P. pseudomallei by an enzyme-linked immunosorbent assay. Although there was no evidence of cross infection of other animals or human handlers, this outbreak is a reminder of the dangers of working with wild-caught primates and the potential for the establishment of environmental foci of melioidosis. Common gibbon Hylobates lar The first case of melioidosis was isolated in Perak from a Serow, Capricornis sumatrensis; followed by the Johore Zoo in 1963 and Zoo Negara Malaysia in 1965 from the pig-tailed macaque, Macaca nemestrina; and in 1968 from a spider monkey, Brachytelis arachnoides and a lar gibbon, Hylobates lar in the Johore Zoo. Gorilla Gorilla gorilla The situation involved four gorillas, originally from Europe where they had been housed in a concrete environment for most of their lives before they were sent to the Singapore Zoological Gardens. They died of melioidosis within months of living in an 'open' enclosure where they were unwittingly exposed to soil and water (in the surrounding moat) containing P. pseudomallei. Isolates from the gorillas were all of the restriction endonuclease analysis (REA) II group, similar to the isolates recovered from the water of the moat, implying that the animals acquired the infection from organisms in the water. Macaques Macaca spp. A case of melioidosis in a macaque monkey is recorded. Pseudomonas pseudomallei was isolated from the lungs. Mandrill Mandrillus sphinx To date, only two serotypes, I and II, of P. pseudomallei have been described. Recently, two groups of workers reported using ribotyping which was capable of discriminating up to 22 strains of P. pseudomallei. The present study confirms that these organisms may be divided into at least 12 RE types, with most of them clustered into 5 larger groups, namely RE I to V. Isolates from other animals who died in the same zoo, namely gibbon, kangaroo, mandrill, and chimpanzee, were of the RE II group. Mitred leaf monkey Presbytis melalophos Kaufmann and others reported five cases of melioidosis in three separate outbreaks in imported non-human primates in the United States. This report describes a case of melioidosis in a banded leaf monkey (Presbytis melalophos). The animal was an adult female weighting 4-5 kg caught in the wild The source of the infection for the animal is unknown. Ps. pseudomallei has been isolated from the soil and water in Malaysia. Drinking water and that used for washing the cages and floors is chlorinated tap water. There is a possibility that the animal contacted the organism in the wild or at the trapper's premises but showed clinical effects during captivity at the primate unit. Another possibility is that the organism was brought into the unit through the vegetable or sweet potatoes that were purchased at the local market. Orangutan Pongo pygmaeus Two young orangutan (Pongo pygmaeus), a male and female, approximately 18 months old, simultaneously developed signs of mild upper respiratory disease including nasal discharge and sneezing. Microscopic examination showed the isolate to consist of short Gram-negative rods with a bipolar staining reaction. Biochemical tests showed that the organism had Pseudomonas pseudomallei characteristics. In conclusion, it seems likely that there was a latent or early Pseudomonas pseudomallei infection which was triggered off by a mild infection of the upper respiratory tract, probably of human origin. This produced an acute, fulminating, fatal bronchopneumonia. This case emphasizes the susceptibility of orangutan to human respiratory disease and the public health dangers of keeping primates in captivity without suitable precautions. Pig-tailed macaque Macaca nemestrina A case of melioidosis in a macaque (Macaca nemestrina) at the National Zoo, Kuala Lumpur, Malaysia, was diagnosed in September, 1965. Serologic evidence of infection was obtained 80 days prior to onset of clinical disease, and a source of exposure to Pseudomonas pseudomallei was found. The principal manifestation of the infection was lumbar vertebral osteomyelitis, with the formation of a paravertebral abscess that exteriorized in the right flank. The abscess regressed, and osteomyelitis healed without specific therapy. The animal recovered completely in 6 months and remains in excellent health 3 years later. The portal of entry of P. pseudomallei was thought to be through multiple lacerations sustained in fights with other macaques. Red guenon Erythrocebus patas Le bacille de Whitmore, agent de la melioidose, a ete isole de quelques animaux sauvages de la Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle de Paris. (Translation: Whitmore's bacillus, the agent of the melioidosis, was isolated from some of the wild animals in the Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle in Paris.) Sur 34 animaux ainsi examines, nous avons obtenu 19 resultats positives: 2 concernant les chevaux de Przewalski (Equus przewalskii);1 buffle de l'Inde (Bubalus bubalis) nouveau-ne; 4 ovins (Ovis canadensis, Ovis vignei, Ovis musimon); 2 antilopes (Oryx beisa), nouveau-ne et (Redunca redunca) mort-ne; 6 cervides (Sika nippon, Muntiacus muntjac); 2 singes (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 tatou (Dasypus sexcinctus). (Translation: Of the 34 animals examined, we obtained positive results from: 2 Prezwalski horses (Equus przewalskii); 1 newborn Indian buffalo (Bubalus bubalis); 4 sheep (Ovis canadensis, Ovis vignei, Ovis musimon); 2 newborn antelopes (Oryz beisa), and one stillborn (Redunca redunca); 6 deer (Sika nippon, Muntiacus muntjac); 2 monkeys (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 armadillo (Dasypus sexcinctus). Rhesus monkey Macaca mulatta An aged wild-caught male rhesus monkey (Macaca mulatta), maintained in a research facility for 10 years, developed bilateral pelvic limb paralysis without other signs of disease. Unresponsive to therapy, the monkey was killed and necropsied. Chronic inflammation with osteolysis of thoracic vertebrae 10-13 was observed. Pseudomonas pseudomallei was cultured and identified from cerebrospinal fluid obtained at the site of the thoracic lesion. In 1969, five cases of melioidosis in three separate outbreaks were diagnosed in nonhuman primates in the United States. In the first outbreak, two stump-tailed macaque monkeys (Macaca arctoides) developed signs of the disease approximately 6 months after purchase. A third animal, a chimpanzee (Pan troglodytes), probably acquired its infection from one of these monkeys. Two other unrelated cases involving a pig-tailed monkey (Macaca nemestrina) and a rhesus monkey (Macaca mulatta) were diagnosed. These monkeys had been imported 3 years and 6 months, respectively, prior to the recognized onset of their disease. These cases represent the first known occurrences of spontaneous melioidosis in nonhuman primates in the United States. Stump-tailed macaque Macaca arctoides In 1969, five cases of melioidosis in three separate outbreaks were diagnosed in nonhuman primates in the United States. In the first outbreak, two stump-tailed macaque monkeys (Macaca arctoides) developed signs of the disease approximately 6 months after purchase. A third animal, a chimpanzee (Pan troglodytes), probably acquired its infection from one of these monkeys. Two other unrelated cases involving a pig-tailed monkey (Macaca nemestrina) and a rhesus monkey (Macaca mulatta) were diagnosed. These monkeys had been imported 3 years and 6 months, respectively, prior to the recognized onset of their disease. These cases represent the first known occurrences of spontaneous melioidosis in nonhuman primates in the United States. Woolly spider monkey Brachyteles arachnoides The first case of melioidosis was isolated in Perak from a Serow, Capricornis sumatrensis; followed by the Johore Zoo in 1963 and Zoo Negara Malaysia in 1965 from the pig-tailed macaque, Macaca nemestrina; and in 1968 from a spider monkey, Brachytelis arachnoides and a lar gibbon, Hylobates lar in the Johore Zoo. Alpaca Lama pacos The body of a 7-month-old male alpaca (Lama pacos) was presented to Berrimah Veterinary Laboratories, Darwin, for necropsy examination. Around 1 month earlier the alpaca was flown to Darwin from Strathalbyn, South Australia and placed on a dairy goat farm in the rural Darwin region. Four years previously a male goat kid on the farm had confirmed melioidosis. Burkholderia pseudomallei was the only pathogen cultured from abscesses. This is the first alpaca to be brought to the Darwin region and to our knowledge the first report of melioidosis in an alpaca. Arabian camel, Dromedary Camelus dromedarius In January 1990, we isolated Pseudomonas pseudomallei from a camel at Mingela, northern Queensland, which had a severe purulent bronchopneumonia. In May 1990, 4 of 5 camels held near Cooktown were affected with a hacking cough, which was accompanied after a few days by a purulent nasal discharge and respiratory insufficiency. Three of the affected animals died and one recovered slowly. In August of the same year, 3 camels out of a herd of 8 near Rockhampton died after similar signs. In both outbreaks, the major finding at necropsy was extensive necrotic pneumonia, with scattered foci of necrosis in liver and spleen in one case. Pseudomonas pseudomallei was isolated from the affected lungs in both outbreaks. In camels, the disease tends to run a chronic course and the lung appears to be the preferred site for B. pseudomallei. Camels are usually affected with a hacking cough which is later accompanied by purulent discharge from the nose and respiratory insufficiency. Ataxia of the hind limbs, dehydration, pyrexia and listlessness have also been observed in one case. Prior to its death, the camel showed signs of wasting disease and was severely emaciated. Melioidosis was diagnosed post-mortem. Bighorn sheep Ovis canadensis Le bacille de Whitmore, agent de la melioidose, a ete isole de quelques animaux sauvages de la Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle de Paris. (Translation: Whitmore's bacillus, the agent of the melioidosis, was isolated from some of the wild animals in the Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle in Paris.) Sur 34 animaux ainsi examines, nous avons obtenu 19 resultats positives: 2 concernant les chevaux de Przewalski (Equus przewalskii);1 buffle de l'Inde (Bubalus bubalis) nouveau-ne; 4 ovins (Ovis canadensis, Ovis vignei, Ovis musimon); 2 antilopes (Oryx beisa), nouveau-ne et (Redunca redunca) mort-ne; 6 cervides (Sika nippon, Muntiacus muntjac); 2 singes (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 tatou (Dasypus sexcinctus). (Translation: Of the 34 animals examined, we obtained positive results from: 2 Prezwalski horses (Equus przewalskii); 1 newborn Indian buffalo (Bubalus bubalis); 4 sheep (Ovis canadensis, Ovis vignei, Ovis musimon); 2 newborn antelopes (Oryz beisa), and one stillborn (Redunca redunca); 6 deer (Sika nippon, Muntiacus muntjac); 2 monkeys (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 armadillo (Dasypus sexcinctus). Bohar reedbuck Redunca redunca Le bacille de Whitmore, agent de la melioidose, a ete isole de quelques animaux sauvages de la Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle de Paris. (Translation: Whitmore's bacillus, the agent of the melioidosis, was isolated from some of the wild animals in the Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle in Paris.) Sur 34 animaux ainsi examines, nous avons obtenu 19 resultats positives: 2 concernant les chevaux de Przewalski (Equus przewalskii);1 buffle de l'Inde (Bubalus bubalis) nouveau-ne; 4 ovins (Ovis canadensis, Ovis vignei, Ovis musimon); 2 antilopes (Oryx beisa), nouveau-ne et (Redunca redunca) mort-ne; 6 cervides (Sika nippon, Muntiacus muntjac); 2 singes (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 tatou (Dasypus sexcinctus). (Translation: Of the 34 animals examined, we obtained positive results from: 2 Prezwalski horses (Equus przewalskii); 1 newborn Indian buffalo (Bubalus bubalis); 4 sheep (Ovis canadensis, Ovis vignei, Ovis musimon); 2 newborn antelopes (Oryz beisa), and one stillborn (Redunca redunca); 6 deer (Sika nippon, Muntiacus muntjac); 2 monkeys (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 armadillo (Dasypus sexcinctus). Capricornis sumatrensis The first case of melioidosis was isolated in Perak from a Serow, Capricornis sumatrensis; followed by the Johore Zoo in 1963 and Zoo Negara Malaysia in 1965 from the pig-tailed macaque, Macaca nemestrina; and in 1968 from a spider monkey, Brachytelis arachnoides and a lar gibbon, Hylobates lar in the Johore Zoo. Cattle Bos taurus Melioidosis has occurred in dogs, cats and cattle but these animals are considered to be fairly resistant to disease. Disease in these species is often associated with an underlying immunosuppressive condition. Bovine melioidosis is very rare and tends to run a chronic course in adult animals. It concluded that susceptibility to B. pseudomallei in cattle is low but abscess formation may occur from infection. The clinical signs observed in one case were fever, aggressive behaviour, rapid, panting respiration, continuous profuse salivation and staggering gait. The second case developed an acute arthritis after a deep cut developed into a chronic granulating sinus. One case of acute melioidosis in a calf has been described. Some authors postulated that cattle and water buffalo may be immune to B. pseudomallei. Fallow deer Dama dama In 1988, 121 fallow deer were imported into Malaysia from New Zealand. the first death was detected as early as five days after arrival. By the eighth week, about 64% of the animals had died. In most cases there were no clinical signs except for the occasional sick animal that lagged behind the herd and two recumbent animals. Respiratory distress, limping or palpable nodules were absent. Goat Capra hircus Melioidosis affects a wide range of animal species. In Australia the most commonly affected livestock are goats, sheep and pigs. Melioidosis has been a significant cause of death in goats and sheep, which appear to be particularly susceptible to the disease. The diagnosis of naturally occurring melioidosis in goats is usually made from a combination of clinical signs, skin sensitivity, and seroagglutination methods, and is confirmed by the post-mortem examination of suspected goats. The causative organism of melioidosis (Malleomyces pseudomallei) is frequently recovered on selective culture media, or after intraperitoneal inoculation into guinea pigs (Straus reaction in male). Both acute and chronic forms are observed in sheep and goats, the chronic form being more common. Horses Equus caballus Other susceptible species reported with melioidosis in Australia include camels, horses, deer, and laboratory animals Central nervous system (CNS) disease with melioidosis has occurred in a number of animal species in Australia. It has been reported in cows, goats and a horse in northern Queensland. Mouflon Ovis aries musimon Le bacille de Whitmore, agent de la melioidose, a ete isole de quelques animaux sauvages de la Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle de Paris. (Translation: Whitmore's bacillus, the agent of the melioidosis, was isolated from some of the wild animals in the Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle in Paris.) Sur 34 animaux ainsi examines, nous avons obtenu 19 resultats positives: 2 concernant les chevaux de Przewalski (Equus przewalskii);1 buffle de l'Inde (Bubalus bubalis) nouveau-ne; 4 ovins (Ovis canadensis, Ovis vignei, Ovis musimon); 2 antilopes (Oryx beisa), nouveau-ne et (Redunca redunca) mort-ne; 6 cervides (Sika nippon, Muntiacus muntjac); 2 singes (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 tatou (Dasypus sexcinctus). (Translation: Of the 34 animals examined, we obtained positive results from: 2 Prezwalski horses (Equus przewalskii); 1 newborn Indian buffalo (Bubalus bubalis); 4 sheep (Ovis canadensis, Ovis vignei, Ovis musimon); 2 newborn antelopes (Oryz beisa), and one stillborn (Redunca redunca); 6 deer (Sika nippon, Muntiacus muntjac); 2 monkeys (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 armadillo (Dasypus sexcinctus). Muntjak Muntiacus muntjak Le bacille de Whitmore, agent de la melioidose, a ete isole de quelques animaux sauvages de la Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle de Paris. (Translation: Whitmore's bacillus, the agent of the melioidosis, was isolated from some of the wild animals in the Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle in Paris.) Sur 34 animaux ainsi examines, nous avons obtenu 19 resultats positives: 2 concernant les chevaux de Przewalski (Equus przewalskii);1 buffle de l'Inde (Bubalus bubalis) nouveau-ne; 4 ovins (Ovis canadensis, Ovis vignei, Ovis musimon); 2 antilopes (Oryx beisa), nouveau-ne et (Redunca redunca) mort-ne; 6 cervides (Sika nippon, Muntiacus muntjac); 2 singes (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 tatou (Dasypus sexcinctus). (Translation: Of the 34 animals examined, we obtained positive results from: 2 Prezwalski horses (Equus przewalskii); 1 newborn Indian buffalo (Bubalus bubalis); 4 sheep (Ovis canadensis, Ovis vignei, Ovis musimon); 2 newborn antelopes (Oryz beisa), and one stillborn (Redunca redunca); 6 deer (Sika nippon, Muntiacus muntjac); 2 monkeys (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 armadillo (Dasypus sexcinctus). Oryx beisa Le bacille de Whitmore, agent de la melioidose, a ete isole de quelques animaux sauvages de la Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle de Paris. (Translation: Whitmore's bacillus, the agent of the melioidosis, was isolated from some of the wild animals in the Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle in Paris.) Sur 34 animaux ainsi examines, nous avons obtenu 19 resultats positives: 2 concernant les chevaux de Przewalski (Equus przewalskii);1 buffle de l'Inde (Bubalus bubalis) nouveau-ne; 4 ovins (Ovis canadensis, Ovis vignei, Ovis musimon); 2 antilopes (Oryx beisa), nouveau-ne et (Redunca redunca) mort-ne; 6 cervides (Sika nippon, Muntiacus muntjac); 2 singes (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 tatou (Dasypus sexcinctus). (Translation: Of the 34 animals examined, we obtained positive results from: 2 Prezwalski horses (Equus przewalskii); 1 newborn Indian buffalo (Bubalus bubalis); 4 sheep (Ovis canadensis, Ovis vignei, Ovis musimon); 2 newborn antelopes (Oryz beisa), and one stillborn (Redunca redunca); 6 deer (Sika nippon, Muntiacus muntjac); 2 monkeys (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 armadillo (Dasypus sexcinctus). Pig Sus scrofa Melioidosis affects a wide range of animal species. In Australia the most commonly affected livestock are goats, sheep and pigs. All recent cases of melioidosis in pigs in the Northern Territory (NT) have been reported as asymptomatic abscesses, often as a cause for carcass condemnation at the abattoir. The pig is considered to have a high natural resistance to B. pseudomallei. Cases have been reported from Vietnam, Malaysia and Australia. The appearance of lesions is believed to be postponed by the route of infection, as inhalation of aerosols will produce abscess formation in the bronchial region, and ingestion will affect the mandibular lymph nodes. Rarely seen clinical signs include fever, anorexia with progressive emaciation, discharge from nose and eyes, coughing, dyspnoea, uncoordinated gait and diarrhoea. In adult animals the disease tends to run a more chronic course with few clinical signs, whereas in young pigs the disease tends to be acute. Plain's zebra, Mountain zebra, or Burchell's zebra Equus burchellii or Equus zebra Das Malaysische Zentralinstitut in Ipoh isolierte 1981 Pseudomonas pseudomallei aus einem Rind, einer Ziege, einem Kamel und zwei Zebras aus einem Safaripark und aus drei Ziegen, einem Schaf, funf Kaninchen, einem Pferd und zwei Meerschweinchen aus dem Einzugsgebiet. (Translation: The Malaysian Central Institute in Ipoh isolated Pseudomonas pseudomallei in 1981 from a cow, a goat, a camel and two zebras at a Safari park. Przewalski's horse Equus przewalskii Le bacille de Whitmore, agent de la melioidose, a ete isole de quelques animaux sauvages de la Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle de Paris. (Translation: Whitmore's bacillus, the agent of the melioidosis, was isolated from some of the wild animals in the Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle in Paris.) Sur 34 animaux ainsi examines, nous avons obtenu 19 resultats positives: 2 concernant les chevaux de Przewalski (Equus przewalskii);1 buffle de l'Inde (Bubalus bubalis) nouveau-ne; 4 ovins (Ovis canadensis, Ovis vignei, Ovis musimon); 2 antilopes (Oryx beisa), nouveau-ne et (Redunca redunca) mort-ne; 6 cervides (Sika nippon, Muntiacus muntjac); 2 singes (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 tatou (Dasypus sexcinctus). (Translation: Of the 34 animals examined, we obtained positive results from: 2 Prezwalski horses (Equus przewalskii); 1 newborn Indian buffalo (Bubalus bubalis); 4 sheep (Ovis canadensis, Ovis vignei, Ovis musimon); 2 newborn antelopes (Oryz beisa), and one stillborn (Redunca redunca); 6 deer (Sika nippon, Muntiacus muntjac); 2 monkeys (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 armadillo (Dasypus sexcinctus). Sheep Ovis aries Melioidosis affects a wide range of animal species. In Australia the most commonly affected livestock are goats, sheep and pigs. Melioidosis has been a significant cause of death in goats and sheep, which appear to be particularly susceptible to the disease. Both acute and chronic forms are observed in sheep and goats, the chronic form being more common. Naturally and experimentally infected sheep can show evidence of central nervous system (CNS) involvement, including lameness, walking in circles, nystagmus, blindness, hyperaesthesia and mild tetanic convulsions. Pneumonia with respiratory distress can be present. In rams, orchitis with testicular nodules can be seen. Sika deer Cervus nippon Le bacille de Whitmore, agent de la melioidose, a ete isole de quelques animaux sauvages de la Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle de Paris. (Translation: Whitmore's bacillus, the agent of the melioidosis, was isolated from some of the wild animals in the Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle in Paris.) Sur 34 animaux ainsi examines, nous avons obtenu 19 resultats positives: 2 concernant les chevaux de Przewalski (Equus przewalskii);1 buffle de l'Inde (Bubalus bubalis) nouveau-ne; 4 ovins (Ovis canadensis, Ovis vignei, Ovis musimon); 2 antilopes (Oryx beisa), nouveau-ne et (Redunca redunca) mort-ne; 6 cervides (Sika nippon, Muntiacus muntjac); 2 singes (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 tatou (Dasypus sexcinctus). (Translation: Of the 34 animals examined, we obtained positive results from: 2 Prezwalski horses (Equus przewalskii); 1 newborn Indian buffalo (Bubalus bubalis); 4 sheep (Ovis canadensis, Ovis vignei, Ovis musimon); 2 newborn antelopes (Oryz beisa), and one stillborn (Redunca redunca); 6 deer (Sika nippon, Muntiacus muntjac); 2 monkeys (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 armadillo (Dasypus sexcinctus). Sika deer Cervus nippon nippon This paper describes a case of melioidosis in an adult Sika deer (Cervus nippon nippon) and its calf. A 4-year-old Sika deer and its 8-month-old female calf died after showing anorexia for a week. Direct smears of the nodules and the exudate from the bronchi revealed numerous short Gram-negative rods. Organisms resembling P. pseudomallei were isolated in pure cultures on blood agar and MacConkey agar from replicate specimens. These organisms were later confirmed to be P. pseudomallei by standard cultural and biochemical tests. Urial Ovis vignei Le bacille de Whitmore, agent de la melioidose, a ete isole de quelques animaux sauvages de la Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle de Paris. (Translation: Whitmore's bacillus, the agent of the melioidosis, was isolated from some of the wild animals in the Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle in Paris.) Sur 34 animaux ainsi examines, nous avons obtenu 19 resultats positives: 2 concernant les chevaux de Przewalski (Equus przewalskii);1 buffle de l'Inde (Bubalus bubalis) nouveau-ne; 4 ovins (Ovis canadensis, Ovis vignei, Ovis musimon); 2 antilopes (Oryx beisa), nouveau-ne et (Redunca redunca) mort-ne; 6 cervides (Sika nippon, Muntiacus muntjac); 2 singes (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 tatou (Dasypus sexcinctus). (Translation: Of the 34 animals examined, we obtained positive results from: 2 Prezwalski horses (Equus przewalskii); 1 newborn Indian buffalo (Bubalus bubalis); 4 sheep (Ovis canadensis, Ovis vignei, Ovis musimon); 2 newborn antelopes (Oryz beisa), and one stillborn (Redunca redunca); 6 deer (Sika nippon, Muntiacus muntjac); 2 monkeys (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 armadillo (Dasypus sexcinctus). Water buffalo Bubalus bubalis Le bacille de Whitmore, agent de la melioidose, a ete isole de quelques animaux sauvages de la Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle de Paris. (Translation: Whitmore's bacillus, the agent of the melioidosis, was isolated from some of the wild animals in the Menagerie du Jardin des Plantes au Museum National d'Historie Naturelle in Paris.) Sur 34 animaux ainsi examines, nous avons obtenu 19 resultats positives: 2 concernant les chevaux de Przewalski (Equus przewalskii);1 buffle de l'Inde (Bubalus bubalis) nouveau-ne; 4 ovins (Ovis canadensis, Ovis vignei, Ovis musimon); 2 antilopes (Oryx beisa), nouveau-ne et (Redunca redunca) mort-ne; 6 cervides (Sika nippon, Muntiacus muntjac); 2 singes (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 tatou (Dasypus sexcinctus). (Translation: Of the 34 animals examined, we obtained positive results from: 2 Prezwalski horses (Equus przewalskii); 1 newborn Indian buffalo (Bubalus bubalis); 4 sheep (Ovis canadensis, Ovis vignei, Ovis musimon); 2 newborn antelopes (Oryz beisa), and one stillborn (Redunca redunca); 6 deer (Sika nippon, Muntiacus muntjac); 2 monkeys (Erythrocebus patas, Cercopithecus aethiops sabaeus); 1 goose (Cereopsis novae hollandiae); 1 armadillo (Dasypus sexcinctus). Cat Felis catus Melioidosis has occurred in dogs, cats and cattle but these animals are considered to