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PubMed2000

Skin infections and infestations in Aboriginal communities in northern Australia.

The most important skin infections in Aboriginal communities in central and northern Australia are scabies and streptococcal pyoderma. Scabies is endemic in many remote Aboriginal communities, with prevalences in children up to 50%. The cycles of scabies transmission underlie much of the pyoderma. Up to 70% of children have skin sores, with group A streptococcus (GAS) the major pathogen. Group A streptococcus is responsible for the continuing outbreaks of post-streptococcal glomerulonephritis and acute rheumatic fever (ARF). The cycles of scabies transmission in dogs and humans do not appear to significantly overlap. Guidelines have been developed for community control of scabies and skin sores and successful community initiated coordinated programmes have occurred. The anthropophilic dermatophyte Trichophyton rubrum is ubiquitous in many communities, again reflecting living conditions. Other skin infections related to the tropical environment include melioidosis, nocardiosis, Chromobacterium violaceum and chromoblastomycosis. Sustainable and long-term improvements in scabies, skin sores and GAS-related disease and tinea require fundamental changes that address social and economic inequities and, in particular, living conditions and overcrowding.

Adult↗
PubMed2001

Childhood infections in the tropical north of Australia.

In the tropical north of Australia there are high rates of infections in Aboriginal children living in remote communities. In addition to the burden of respiratory infections, diarrhoeal disease and skin sepsis, there are high rates of acute rheumatic fever, outbreaks of poststreptococcal glomerulonephritis and gonococcal conjunctivitis, endemic trachoma and various intestinal parasites. A number of infections generally restricted to the tropics are also present and can cause disease in both indigenous and non-indigenous children. These include melioidosis, Murray Valley encephalitis and dengue on the east coast. With global warming, these infections may become more common and more widespread within Australia and the potential for establishment of introduced infections such as Japanese encephalitis and malaria may increase.

Adolescent↗
PubMed2002

An audit of the use of granulocyte colony-stimulating factor in septic shock.

BACKGROUND: Granulocyte colony-stimulating factor (G-CSF) stimulates the production of neutrophils and modulates the function and activity of developing and mature neutrophils. In septic shock, the immune system can be considered one of the failing organ systems. G-CSF improves immune function and may be a useful adjunctive therapy in patients with septic shock. AIM: To evaluate the introduction of G-CSF as an adjunct to our standard treatment for community-acquired septic shock. METHODS: We performed a prospective data collection and analysis to determine whether the addition of G-CSF to our standard treatment for community-acquired septic shock was associated with improved hospital outcome, compared with an historical cohort of similar patients. We included all patients admitted to the Intensive Care Unit (ICU) with community-acquired septic shock between December 1998 and March 2000. Patients received 300 microg G-CSF intravenously daily for 10 days in addition to our standard treatment for community-acquired septic shock. G-CSF was discontinued early if the patient was discharged from ICU before 10 days or if the absolute neutrophil count exceeded 75 x 10(6)/mL. RESULTS: A total of 36 patients with community-acquired septic shock, an average Apache 2 score of 26.7, and a predicted mortality of 0.79, were treated with G-CSF from December 1998 to March 2000. Hospital mortality was 31% compared with an historical cohort of 11 similar patients with a hospital mortality of 73% (P = 0.018). In the subgroup of patients with melioidosis septic shock, the hospital survival improved from 5% to 100% (P < 0.0001). No significant adverse events occurred as a result of the administration of G-CSF. CONCLUSION: G-CSF is a safe adjunctive therapy in community-acquired septic shock and may be associated with improved outcome. The use of G-CSF in septic shock should undergo further investigation to define subgroups of patients who may benefit from G-CSF. The use of G-CSF in patients with septic shock due to Burkholderia pseudomallei is recommended.

Adolescent↗
PubMed2002

Synovial osteochondromatosis.

A 75-year-old man of Fijian-Indian extraction complained of a 3-year history of progressive right knee pain and stiffness which were limiting his mobility. On examination, multiple hard nodules were palpable in the popliteal fossa and along the path of the quadriceps tendon. The joint line was not tender, knee flexion was limited to 60 degrees and there was a fixed flexion deformity of 5 degrees. The knee ligaments were intact. Examination of other joints did not reveal nodules. His past medical history included: (i) polyarticular gout, (ii) osteoarthritis of the left knee requiring total knee joint replacement 7 years previously, (iii) ischaemic cardiomyopathy, (iv) chronic atrial fibrillation, (v) chronic renal impairment, (vi) recent bacteraemic melioidosis without a primary focus, (vii) chronic bilateral rotator cuff tears, (viii) low-grade multiple myeloma and (ix) idiopathic pulmonary fibrosis.

Aged↗
PubMed2000

Exotic pulmonary infections.

Pulmonary infections are the commonest type of illnesses seen in everyday practice. Although most infections are caused by a few familiar pathogens, an increase in global travel has led to the occurrence of rare and exotic diseases that often do not manifest until after the traveller returns home. Previously innocuous organisms may also be the cause of exotic infections in patients undergoing transplantation, or very aggressive immunosupression. Such treatment regimes may reactivate quiescent organisms acquired years previously, for example melioidosis and strongyloides stercoralis. In most developed countries there is also an increasing incidence of zoonotic infections, with a number of these presenting with mainly pulmonary symptoms. A carefully taken history of recent travel, exposure to wild or domestic animals or the presence of immunosuppression, is extremely helpful in identifying problematic infections that fall into the realm of the exotic. This review discusses some of the respiratory infections in each of these groups with an emphasis on imported infections.

Animals↗
PubMed2000

Disseminated infection due to rapidly growing mycobacteria in immunocompetent hosts presenting with chronic lymphadenopathy: a previously unrecognized clinical entity.

Disseminated infection due to rapidly growing mycobacteria is uncommon and occurs mostly in immunocompromised patients. We report 16 cases of such infection with an unusual presentation seen at Srinagarind Hospital, a university hospital in northeastern Thailand. The clinical features were different from those in previous reports. All of the patients presented with chronic bilateral cervical lymphadenopathy. Twelve had mycobacterial involvement of other organs (sinuses, 6 patients; lungs, 4; liver, 4; spleen, 3; skin, 3; bone and joint, 2; and tonsils, 2). An interesting occurrence in 11 patients was 14 episodes of reactive skin manifestations (Sweet's syndrome, 9; generalized pustulosis and erythema nodosum, 2 each; and pustular psoriasis, 1). No identifiable predisposing factors, including human immunodeficiency disease, were found in these patients. However, 8 patients had 11 episodes of prior infection or coinfection with other opportunistic pathogens (salmonellosis, 4; penicilliosis, 3; pulmonary tuberculosis, 2; and melioidosis and cryptococcosis, 1 each). These findings suggest that cell-mediated immunity is defective in these patients.

Adult↗
PubMed2002

Cloning of the class D beta-lactamase gene from Burkholderia pseudomallei and studies on its expression in ceftazidime-susceptible and -resistant strains.

Ceftazidime is the antibiotic of choice for the treatment of melioidosis. Ceftazidime-resistant Burkholderia pseudomallei have been identified and beta-lactamase production implicated in resistance. In this study, 25 strains of B. pseudomallei (15 clinical and 10 environmental strains) were examined for their ability to yield mutants that overexpress beta-lactamase. Ceftazidime-resistant mutants were selected readily at high frequency and displayed four- to eight-fold increases in the MICs of ceftazidime. beta-Lactamase activities in both parent and mutant B. pseudomallei strains were examined by a spectrophotometric method. Twelve mutants (48%) showed approximately two- to 31-fold higher ceftazidimase activity compared with their parent strains and 10 (40%) demonstrated more than two-fold increases in imipenemase activity. A class D beta-lactamase gene from B. pseudomallei was cloned and sequenced. The encoded enzyme is an oxacillinase and is homologous to oxacillinases from Ralstonia pickettii and members of the genus Aeromonas. Reverse transcriptase PCR showed that transcription of the class D beta-lactamase gene is increased in ceftazidime-resistant mutants.

Amino Acid Sequence↗
PubMedDate not supplied

Infections in E-beta thalassemia.

Infection is a major complication and the leading cause of death in thalassemia, especially E-beta thalassemia. The spectrum of infections in E-beta thalassemia include mild and severe infections, therapy-related infections such as Yersinia enterocolitica infection associated with desferrioxamine (DFO) therapy, and transfusion-transmitted disease, as well as unique infections such as with pythiosis. Prospective studies in Thailand indicate that patients with E-beta thalassemia had more frequent episodes of both mild and severe infections. The former included upper respiratory tract infection, acute gastroenteritis, cutaneous abscess, and gingivitis. Severe infections occurred more commonly in patients with splenectomy and included septicemia, pneumonia, biliary tract infection, salmonellosis, and urinary tract infection. Responsible organisms were Escherichia coli (26%), Klebsiella pneumoniae (23%), Salmonella (15%), and Streptococcus pneumoniae (13%). Other organisms included Pseudomonas, Staphylococci, Burkholderia pseudomallei (melioidosis), and Aeromonas. Patients undergoing DFO therapy are at risk for Y. enterocolitica infection which may be localized to mesenteric nodes and tonsils or occur as a generalized form such as septicemia. Recently, we have seen a unique infection so-called vascular pythiosis. Patients usually presented with clinical features of vascular occlusion of lower limbs from ascending arteritis and thrombosis. The causative organism, Pythium insidiosum, is fungus-like, in the kingdom Stramenopila, and in the class Oomycetes. The mortality rate is high and the only effective treatment has been early amputation or possibly immunotherapy. The predisposing factors of infections in thalassemia include splenectomy, iron overload, anemia, and granulocyte dysfunctions. General management of infections in thalassemia consist of prevention, i.e., immunization with pneumococcal and hepatitis vaccines, oral penicillins especially in patients with splenectomy, removal of predisposing factors such as gallstones, iron overload, and appropriate antibiotics.

Bacterial Infections↗
PubMed2001

Septic arthritis caused by Burkholderia pseudomallei: case report and review of the literature.

We describe a case of septic arthritis and bacteremia caused by Burkholderia pseudomallei, a bacterium that is endemic in East Asia and northern Australia. We believe that dissemination occurred in our patient after surgical excision of a pulmonary nodule. Bacteremic melioidosis can present with musculoskeletal involvement in 2-10% of patients, but septic arthritis is uncommon. A review of the literature shows a total of 66 patients reported with septic arthritis caused by this organism. Patients with septic arthritis caused by Burkholderia pseudomallei were likely to have diabetes mellitus, and the knee is the joint most frequently affected by this organism. Recommended initial treatment consists of ceftazidime, alone or in combination with trimethoprim/sulfamethoxazole, high dose imipenem/cilastatin, or high dose cefoperazone/sulbactam. This is followed by a 12-20 week course of oral therapy (based on susceptibilities) to eradicate the organism. Most patients with subacute or latent disease do well after full antibiotic treatment, but relapses are common if full treatment is not given. Awareness of this disease is important even in areas outside of Asia given the increasing frequency of international travel and the growing likelihood of imported cases, along with an aging population of Vietnam veterans and immigrants.

Journal Article↗
PubMed1976

Malaria of the orang-utan (Pongo pygmaeus) in Borneo.

The primary objective of this project was to study the life cycle and ecology of Plasmodium pitheci, a malaria parasite of the orang-utan. The field work was based on the orang-utan rehabilitation centre in the Sepilok Forest Reserve of eastern Sabah. Two visits were made to Sepilok, the first in February and March, 1972, and the second (by W.P.) in January 1974. On the first visit two species of "surrogate host" were taken to Sabah, i.e. chimpanzees and Aotus monkeys for experimental work. The arboreal habitat of the orang-utan in the dipterocarp forests of eastern Sabah is described. In the Sepilok Forest Reserve dwell gibbons and leaf-monkeys, in addition to a small population of semi-domesticated and wild, free-ranging orang-utans of various ages. Although numerous species of anopheline mosquitoes have been collected in eastern Sabah, longitudinal studies are not available. Anopheles balabacensis was caught both attracted to orang-utans and to man at Sepilok. This species which is the main vector of human malaria in the north of Borneo, is suspected also of transmitting orang-utan malaria in this part of Sabah. Repeated blood examinations have been made on a number of orang-utans in the centre since 1966 and a high prevalence of infection was recorded with Plasmodium pitheci. In 1966 10 out of 19 animals had demonstrable parasitaemia. Detailed case histories are presented to show the course of parasitaemia in several orang-utans. Infections of P. pitheci were found to run a very chronic course. During the 1972 expedition a second, previously undescribed malaria parasite of the orang-utan was discovered, and was named P. silvaticum. The new parasite was successfully transmitted both by blood inoculation and, later, by sporozoite inoculation, into splenectomized chimpanzees. Although both species of malaria parasite may cause transitory signs of illness, orang-utans in general appear to be little discomforted by the infection. The animals do however suffer from other infectious diseases such as amoebic and balantidial dysentery, and melioidosis is a serious natural hazard which may have accounted for several deaths of wild orang-utans. An unidentified, intraerythrocytic structure that appeared in the blood of one chimpanzee, which had been inoculated with blood from an orang-utan, may have contributed to its death. Detailed descriptions and illustrations of P. pitheci and P. silvaticum are given. All stages of the life cycle of P. silvaticum are known (the tissue stages having been described in the liver of a "surrogate host", the chimpanzee) but only the blood and sporogonic stages of P. pitheci have been seen. This species was not infective to a chimpanzee, although there is an earlier report of a transient infection in this host by other workers. In the blood both parasites showed a tertian periodicity. From the appearance of the tissue schizonts on the seventh day it was estimated that the complete pre-erythrocytic cycle of P. silvaticum in the chimpanzee would occupy 8 days. P...

Animals↗
PubMed2000

Cloning and analysis of genomic differences unique to Burkholderia pseudomallei by comparison with B. thailandensis.

Melioidosis is an infectious disease caused by Burkholderia pseudomallei. Genomic subtractive hybridisation was performed with the closely related avirulent species B. thailandensis to identify virulence genes of B. pseudomallei. The subtractive hybridisation products were highly specific for B. pseudomallei. Sequence analysis revealed a number of putative virulence factors, as well as apparently novel sequences of unknown function. The subtracted library contained DNA regions of relatively low G + C mol% content, which were distributed throughout the B. pseudomallei genome. The distribution of subtracted sequences amongst a collection of 22 B. pseudomallei isolates was found to be variable, with the exception of three strains which almost universally lacked the subtracted sequences. These three strains also differed in that they were highly haemolytic, indicating a possible separate virotype.

Burkholderia↗
PubMed2002

Distribution of type III secretion gene clusters in Burkholderia pseudomallei, B. thailandensis and B. mallei.

Burkholderia pseudomallei, the causative agent of melioidosis, carries a cluster of genes closely related in organisation to the type III secretion (TTS) system gene clusters of the plant pathogens Ralstonia solanacearum and Xanthomonas spp. The TTS gene cluster (TTS1) is present only in B. pseudomallei and not in avirulent B. thailandensis. Adjacent to the gene cluster encoding putative secreton structural proteins lie a number of open reading frames (ORFs) encoding putative proteins with little or no homology to known proteins, with the exception of one predicted protein with homology to Pseudomonas syringae HrpK. In both R. solanacearum and Xanthomonas spp., genes in this location encode secreted effector proteins. RT-PCR analysis indicated that TTS genes, including two of these ORFs, are expressed in broth at 37 degrees C. Analysis of genome sequence data identified a second cluster of TTS genes (TTS2) present in both B. pseudomallei and B. mallei (99% identity). However, B. mallei appears to lack the TTS1 gene cluster. PCR assays indicated that TTS2 was also present in B. thailandensis. TTS1 and TTS2 are similar in gene organisation, but nucleotide sequences are sufficiently divergent to suggest that the two TTS systems may have different roles.

Amino Acid Sequence↗
PubMed1990

Survival of Pseudomonas pseudomallei in human phagocytes.

Pseudomonas pseudomallei causes the disease melioidosis, with protean manifestations, protracted clinical course and unpredictable response to antimicrobial treatment. Intracellular location of the organism is suspected to be the cause of these properties. This study was undertaken to examine the intracellular growth of this bacterium. Intracellular growth and survival was assessed at different time intervals, by Gram's stain and electronmicroscopic examination. During the first 5 h, the numbers of P. pseudomallei within phagocytes did not change significantly. By 18-21 h, gram-stained preparations revealed that P. pseudomallei cells completely filled the phagocytes and electronmicroscopy showed evidence of binary fission. During that time the number of cfu of P. pseudomallei growing simultaneously in vitro increased by log10 2-3. The phagocytes remained viable throughout the observation period and retained their capacity to produce an oxidative burst for the first hour of incubation. The ability of P. pseudomallei to survive and multiply in phagocytes shows that it is a facultative intracellular bacterium. This finding is relevant to the selection of antimicrobial regimens, and the management of the disease.

Colony Count, Microbial↗
PubMed2006

Quorum sensing regulates dpsA and the oxidative stress response in Burkholderia pseudomallei.

Burkholderia pseudomallei is the causative agent of melioidosis, a fatal human tropical disease. The non-specific DNA-binding protein DpsA plays a key role in protecting B. pseudomallei from oxidative stress mediated, for example, by organic hydroperoxides. The regulation of dpsA expression is poorly understood but one possibility is that it is regulated in a cell population density-dependent manner via N-acylhomoserine lactone (AHL)-dependent quorum sensing (QS) since a lux-box motif has been located within the dpsA promoter region. Using liquid chromatography and tandem mass spectrometry, it was first established that B. pseudomallei strain PP844 synthesizes AHLs. These were identified as N-octanoylhomoserine lactone (C8-HSL), N-(3-oxooctanoyl)homoserine lactone (3-oxo-C8-HSL), N-(3-hydroxyoctanoyl)-homoserine lactone (3-hydroxy-C8-HSL), N-decanoylhomoserine lactone (C10-HSL), N-(3-hydroxydecanoyl) homoserine lactone (3-hydroxy-C10-HSL) and N-(3-hydroxydodecanoyl)homoserine lactone (3-hydroxy-C12-HSL). Mutation of the genes encoding the LuxI homologue BpsI or the LuxR homologue BpsR resulted in the loss of C8-HSL and 3-oxo-C8-HSL synthesis, demonstrating that BpsI was responsible for directing the synthesis of these AHLs only and that bpsI expression and hence C8-HSL and 3-oxo-C8-HSL production depends on BpsR. In bpsI, bpsR and bpsIR mutants, dpsA expression was substantially down-regulated. Furthermore, dpsA expression in Escherichia coli required both BpsR and C8-HSL. bpsIR-deficient mutants exhibited hypersensitivity to the organic hydroperoxide tert-butyl hydroperoxide by displaying a reduction in cell viability which was restored by provision of exogenous C8-HSL (bpsI mutant only), by complementation with the bpsIR genes or by overexpression of dpsA. These data indicate that in B. pseudomallei, QS regulates the response to oxidative stress at least in part via the BpsR/C8-HSL-dependent regulation of DpsA.

4-Butyrolactone↗
PubMed2006

Crystallization and preliminary X-ray diffraction analysis of BipD, a virulence factor from Burkholderia pseudomallei.

Burkholderia pseudomallei, the causative agent of melioidosis, possesses a protein-secretion apparatus that is similar to those found in Salmonella and Shigella. A major function of these secretion systems is to secrete virulence-associated proteins into target cells of the host organism. The BipD gene of B. pseudomallei encodes a secreted virulence factor that is similar in sequence and most likely functionally analogous to IpaD from Shigella and SipD from Salmonella. Thus, the BipD protein is likely to be a component of a type III protein-secretion system (TTSS) in B. pseudomallei. Proteins in the same class as BipD, such as IpaD and SipD, are thought to act as extracellular chaperones to help the hydrophobic translocator proteins enter the target cell membrane, where they form a pore and might even link the translocon pore with the secretion needle. There is evidence that the translocator proteins also bind an integrin which stimulates actin-mediated insertion of the bacterium into the host-cell membrane. Native BipD has been crystallized in a monoclinic crystal form that diffracts X-rays to 2.5 angstroms resolution. BipD protein which incorporates selenomethionine (SeMet-BipD) has also been expressed and forms crystals which diffract to a higher resolution of 2.1 angstroms.

Bacterial Proteins↗
PubMed1999

Differences in genomic macrorestriction patterns of arabinose-positive (Burkholderia thailandensis) and arabinose-negative Burkholderia pseudomallei.

We reported previously two biochemically and antigenically distinct biotypes of Burkholderia pseudomallei. These two distinct biotypes could be distinguished by their ability to assimilate L-arabinose. Some B. pseudomallei isolated from soil samples could utilize this substrate (Ara+), whereas the other soil isolates and all clinical isolates could not (Ara-). Only the Ara isolates were virulent in animals and reacted with monoclonal antibody directed at the surface envelope, most likely the exopolysaccharide component. In the present study, pulsed-field gel electrophoresis was employed for karyotyping of these previously identified B. pseudomallei strains. We demonstrate here that the DNA macrorestriction pattern allows the differentiation between B. pseudomallei, which can assimilate L-arabinose, and the proposed B. thailandensis, which cannot do so. Bacterial strains from 80 melioidosis patients and 33 soil samples were examined by genomic DNA digestion with NcoI. Two major reproducible restriction patterns were observed. All clinical (Ara-) isolates and 9 Ara- soil isolates exhibited macrorestriction pattern I (MPI), while 24 soil isolates (Ara+) from central and northeastern Thailand displayed macrorestriction pattern II (MPII). The study here demonstrated pulsed-field gel electrophoresis to be a useful tool in epidemiological investigation possibly distinguishing virulent B. pseudomallei from avirulent B. thailandensis or even identifying closely related species of Burkholderia.

Arabinose↗
PubMed2002

Antigenic relatedness between Burkholderia pseudomallei and Burkholderia mallei.

Burkholderia pseudomallei and Burkholderia mallei are causative agents of distinct diseases, namely, melioidosis and glanders, respectively. The two species are very closely related, based on DNA-DNA homology, base sequence of the 16S rRNA, and phenotypic characteristics. Based on the use of polyclonal antisera, B. pseudomallei and B. mallei are also found to be antigenically closely related to one another. We previously reported the production of monoclonal antibodies (MAbs) against B. pseudomallei antigens; one group was specific for the 200-kDa exopolysaccharide present on the surface of all B. pseudomallei isolates, and the other was specific for the lipopolysaccharide (LPS) structure present on more than 95% of the B. pseudomallei tested. In the present study, we showed that the MAbs against 200-kDa antigen of B. pseudomallei cross-reacted with a component present also in some B. mallei isolates (3/6), but the positive immunoblot reaction was noted below the 200-kDa position. On the other hand, none of the six B. mallei isolates reacted with the MAb specific for B. pseudomallei LPS. It was of interest to observe that only the 3 exopolysaccharide-positive B. mallei isolates reacted with a commercial MAb against B. mallei LPS. The data presented suggest that B. mallei can be classified antigenically into two types based on their reactivities with different MAbs, i.e., the presence or absence of exopolysaccharide and the types of lipopolysaccharide. The heterogeneity of the LPS from these two closely related organisms is most likely related to the differences in its O-polysaccharide side chain.

Antigens, Bacterial↗
PubMed1997

Community acquired pneumonia in north eastern Australia--a hospital based study of aboriginal and non-aboriginal patients.

BACKGROUND: Although the most important organism causing community acquired pneumonia continues to be Streptococcus pneumoniae, the frequency of other pathogens varies considerably across the world. AIMS: To look for the causes of community acquired pneumonia (CAP) in north east Australia. To examine the differences between Aboriginal and non-Aboriginal subjects with emphasis on prevalence, risk factors, causative organisms and prognosis. METHODS: The records of 200 consecutive patients admitted to Cairns Hospital during 1992 with a diagnosis of pneumonia were studied. RESULTS: Aboriginal patients made up half the numbers admitted, but only 13% of the population. More Aboriginal adults died than non-Aboriginal adults, but no child died. Heavy alcohol use, chronic lung disease and diabetes mellitus were the commonest risk factors for Aborigines (alcohol, chronic lung disease and cancer for non-Aboriginal subjects). S. pneumoniae, followed by Haemophilus influenzae were the most common pathogens found. Both were sensitive to amoxycillin. The yield of definite pathogens was low. Staphylococcal and melioidosis pneumonia were confined to Aboriginal patients. Chlamydia, legionella and Mycoplasma pneumoniae were not identified.

Adult↗