Comparison of the CD11b activation epitope on peripheral and transmigrated neutrophils was analysed by Wilcoxon matched pairs test. Correlations between IL-8, both endogenous and recombinant, and the expression of CD11b were analysed by Spearman’s rank order analysis. Significant correlations with a regression coefficient (R) ≥0.7

were further analysed. A P < 0.05 was considered significant. The median number of transmigrated cells per skin chamber was 2.14 (1.59–3.96) 106 cells with 82.1 (77.6–84.8) % granulocytes, 13.2 (10.3–16.4) % monocytes and 2.82 (2.37–4.37) % lymphocytes. In the peripheral circulation, the number of leucocytes was 4.85 (3.6–6.1)*109 leucocytes/l with 54.1 (50.5–58.9) % granulocytes, 8.51 (7.61–10.5) % monocytes and 33.3 (30.8–37.9) % lymphocytes. From the original skin blister, analysed for CD11b activation after 14 h of incubation, Talazoparib cost the median number of selleck chemicals extravasated leucocytes was 0.11 (0.04–0.14) million cells per skin blister. The expression of CD11b activation epitope on extravasated neutrophils from the original 14-h blister was 73.2 (18.9–83.4) % and corresponding expression on circulating neutrophils was 1.96 (1.29–2.14) %, P = 0.04. The concentration of IL-8 in serum was 8.5 (1.9–11) pg/ml and in the 14-h blister fluid 338 (194–10,627) pg/ml, P = 0.04. The concentration of soluble mediators in serum and

in the skin chamber fluid was assessed by Milliplex multi-analysis and ELISA and

is presented in Fig. 1. Significantly higher concentrations of soluble markers were detected in the skin chamber fluid compared to that in serum for all markers Mannose-binding protein-associated serine protease except eotaxin (P < 0.01 for IL-4 and IL-10 and P < 0.001 for the remaining markers). TCC was analysed in chamber fluid, and median concentration was 28 (17–40) AU/ml. Figure 2 demonstrates the correlation between the number of in vivo extravasated neutrophils and the concentration of IL-8 in the chamber fluid at P < 0.05 and R = 0.79. In addition, the number of in vivo extravasated neutrophils also correlated with IL-1β, R = 0.83; IL-6, R = 0.73; IL-7 R = 0.71; and TNF-α, R = 0.71, all at P < 0.05. When the total number of extravasated leucocytes were analysed, the corresponding numbers were IL-8, R = 0.83; IL-1β, R = 0.81; IL-6, R = 0.72; IL-7 R = 0.71 and TNF-α, R = 0.70, also at P < 0.05. Following in vitro transmigration, the mean percentage of neutrophils that migrated towards chamber fluid was 34.2 ± 5.4% and towards cell culturing medium was 1.16 ± 0.55%. The percentage of transmigrated neutrophils correlated with the concentration of IL-8 (R = 0.79), IL-1β (R = 0.77) and TNFα (R = 0.79) at P < 0.05. The expression of CD11b activation epitope was measured following in vitro incubation with serum and skin chamber fluid. Figure 3 displays the expression of CD11b activation epitope following incubation with 50% serum, 50% skin camber fluid or IL-8 at 100 ng/ml.

Such materials are peer reviewed and may be re-organized Hormones antagonist for online delivery, but are not copy-edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors. Figure 1. Gating strategy, abundance of TAM subsets and expression of Gr-1 and Ly6C in MMTVneu tumors. Figure 2. Expression of M1, M2 and functional macrophage markers in CD11bloF4/80hi and CD11bhiF4/80lo TAMs. Figure 3. Localization of TAMs in tumors.

Figure 4. Flow cytometry gating strategy for detection of CD64 and MERTK in TAM populations. Figure 5. Long-term in vivo BrdU labeling of blood monocytes and TAMs. Figure 6. Efficacy of monocyte depletion with Clodronate-loaded liposomes. Figure 7. Population definitions applied in the bone-marrow transfer experiment. Figure 8. Time-course of blood leukocyte chimerism after bone marrow transfer. Figure 9. Level of chimerism within lung macrophages. Figure 10. Presence

LY294002 cost of eFluor670+ grafted macrophages in recipient tumors. Figure 11. Differentiation of adoptively transferred monocytes in circulation of recipient animals. Figure 12. Anti-BrdU and 7AAD staining of MMTVneu tumors, BrdU incorporation in bone marrow and blood monocytes. Figure 13. Blockade of cell cycle progression in TAMs by doxorubicin. Figure 14. Influence of CSF-1R blockade on blood monocyte populations. Figure 15. In silico promoter analysis of murine Csf1 gene. Table 1. Characteristics of Innsbruck and TCGA breast cancer patient Tolmetin cohorts. Table 2. Antibodies applied in flow cytometry and immunofluorescence. Table 3. Primers used in quantitative Real-Time PCR (qPCR). Table 4. Primers used for PCR after Chromatin Immunoprecipitation (ChIP). “
“Cross-presentation is an important mechanism by which DCs present exogenous antigens on MHC-I molecules, and activate CD8+ T cells,

cells that are crucial for the elimination of tumors. We investigated the feasibility of exploiting the capacity of the mannose receptor (MR) to improve both cross-presentation of tumor antigens and Th polarization, processes that are pivotal for the anti-tumor potency of cytotoxic T cells. To this end, we selected two glycan ligands of the MR, 3-sulfo-LewisA and tri-GlcNAc (N-acetylglucosamine), to conjugate to the model antigen OVA and assessed in vitro the effect on antigen presentation and Th differentiation. Our results demonstrate that conjugation of either 3-sulfo-LewisA or tri-GlcNAc specifically directs antigen to the MR. Both neo-glycoconjugates showed, even at low doses, improved uptake as compared with native OVA, resulting in enhanced cross-presentation. Using MR−/− and MyD88-TRIFF−/− bone marrow-derived DCs (BMDCs), we show that the cross-presentation of the neo-glycoconjugates is dependent on MR and independent of TLR-mediated signaling.

Nonetheless, those changes in chromatin structure do not fully explain the changes of mRNA steady-state levels across the intra-erythrocytic cycle, with the exception of ring stage- or exo-erythrocytic-specific genes (13,14). Such observations are consistent JNK inhibitor in vivo with recent data, demonstrating that mRNA steady-state

levels and transcription rate do not correlate for about half of the parasite’s genes (86). In that case, genes could be massively transcribed at the trophozoite stage followed by major regulations at the post-transcriptional level. This hypothesis finds support in the fact that the parasite’s preinitiation complex interacts with both stage-specific ‘active’ and ‘inactive’ promoters (87) and that mRNA decay rates are significantly lengthened during the intra-erythrocytic cycle suggesting major post-transcriptional regulations (65). To further MK-1775 clinical trial complement these data, Bartfai et al. used

a ChIP-seq approach to show that, unlike in other eukaryotes, the histone H2A variant H2A.z is a constant and ubiquitous feature of all intergenic regions throughout the parasite erythrocytic cycle (7). As H2A.z is usually involved in chromatin destabilization and active transcription in eukaryotes (88–90), these results are consistent with a transcriptionally permissive state of P. falciparum’s chromatin during the asexual cycle. In addition, previous

mass spectrometry studies showed that, unlike the abundant and more variable canonical histones, H2A.z is present at low and constant level throughout the parasite’s cycle (33,38). This observation, combined with the high sensitivity of H2A.z to MNase digestion Liothyronine Sodium (88,89), is consistent with the relative nucleosome depletion that was observed by MAINE-seq and ChIP-on-chip in noncoding regions of the genome (6,52). Given the low levels of H2A.z and its extreme sensitivity to MNase digestion, H2A.z-containing nucleosomes can mostly be detected by targeted and specific immunoprecipitation-based sample enrichments. Quantitative measurements in such experiments, however, imply a careful normalization of histone variant levels vs. canonical histones. All together, these data confirm an unusual parasite chromatin structure and speculate an active transcriptional state during most of the erythrocytic cycle with a few exceptions such as clonally variant genes as well as genes known to be essential to early erythrocytic and sexual stage differentiation. It is therefore possible that part of transcriptional regulation in P. falciparum could occur during elongation rather than initiation. This hypothesis is supported by the recent observation that H2A.z seems to facilitate the passage of the RNA polymerase II (90).

These results strongly

suggested integration of the retroviral transgenes Fulvestrant mw into schistosome chromosomes (27). A follow-up investigation by Southern hybridization analysis (29) showed the presence of proviral MLV retrovirus in the transduced schistosomes. Fragments of the MMLV transgene and flanking schistosome sequences recovered using an anchored PCR-based approach demonstrated without doubt that somatic transgenesis of schistosome chromosomes had taken place and, moreover, widespread retrovirus integration into schistosome chromosomes was observed. Although these reports could conclusively show that viral vectors have the capacity to mediate chromosomal integration in schistosomes none of the experiments performed to date could demonstrate heredity of the transgenes. Recently, it has been

shown that parasite eggs are also amenable to transfection using retroviruses. The first report targeting the schistosome egg was published by Kines et al. (30). Schistosome eggs were exposed to VSVG-pseudotyped MMLV virions and proviral transgenes were detected by PCR in genomic DNA from miracidia hatched from virion-exposed eggs, indicating the presence of transgenes in larval schistosomes that had been either soaked or electroporated. In addition, quantitative PCR (qPCR) analysis showed that https://www.selleckchem.com/products/DMXAA(ASA404).html electroporation of virions resulted in 2–3 times as many copies of provirus in these schistosomes compared to soaking alone. Transfection of schistosome eggs might be a way forward to finally achieve germline transformation and we are currently investigating the use of lentiviral constructs carrying the mCherry reporter gene to achieve this elusive aim (J. Hagen and B. H. Kalinna, unpublished data). In our laboratory we have also

used this viral system to combine efficient transduction with integrative delivery of shRNA which resulted in complete ablation of cathepsin B1 expression in transduced worms (31). This is described in more detail Resminostat later. Vector-based RNAi may circumvent some of the problems known for conventional RNAi like difficulties of delivery of dsRNA, incomplete knock-down with an associated partial phenotype and transience of the phenotype. Recently, viral transduction was also attempted in S. japonicum schistosomula (32). The VSVG-pseudotyped pantropic retroviral vector pBABE-puro was modified to incorporate the human telomerase reverse transcriptase gene (hTERT) as a reporter, under the control of the retroviral long terminal repeat. The authors used RT-PCR, immunohistochemistry and immunoblot analysis to show expression of hTERT in the transduced worms. Like S. mansoni, S. japonicum could be effectively transduced by VSVG-pseudotyped retrovirus confirming the utility of this approach to transduce schistosomes. We and colleagues have also used the transposon piggyBac to accomplish transformation of S. mansoni (28).

The labelled band was detected using an enhanced chemiluminescence detection kit and developed with Hyperfilm-enhanced chemiluminescence (Amersham Pharmacia Biotech, Piscataway, NJ). Data were expressed as mean ± SEM. Statistical comparisons were performed using one-way analysis of variance followed by the Fisher’s CH5424802 in vivo test. Significant differences between groups were determined using the unpaired Student’s t-test. Values of P < 0·05 were considered to be statistically significant. We have developed

a mouse model of airway remodelling through repetitive OVA challenge. Mice were subjected to OVA challenge three times a week for 8 weeks and developed significant eosinophilic inflammation and airway remodelling similar

to that observed in human chronic EMD 1214063 asthma. In this study, we used the ratios WAt/Pbm and WAm/Pbm to evaluate airway remodelling. Image analysis revealed that, for WAt/Pbm: the 8-week OVA-challenged mice (OVA group) presented thicker airway walls (17·9 ± 1·2 versus 10·8 ± 1·2 μm2/μm, Fig. 1a,b, Table 1, P < 0·01) than the Control group after correction for airway basement perimeter. Triptolide and dexamethasone were equally effective in reducing airway wall thickening (12·6 ± 1·2 versus 13·0 ± 1·3 μm2/μm, Fig. 1c,d, Table 1, P > 0·05). There was no significant difference between the TRP and DEX groups. For WAm/Pbm, the OVA group

had an increased smooth muscle layer compared with the Control group (6·34 ± 0·66) versus 3·35 ± 0·34 μm2/μm, Fig. 1a,b, Table 1, P < 0·01). Triptolide and dexamethasone were equally effective in reducing myocyte hyperplasia (4·8 ± 0·5 versus 4·9 ± 0·4 μm2/μm, Fig. 1c,d, Table 1, P > 0·05). There was no significant difference between the TRP and DEX groups. Mucus hypersecretion, which is one of the pathological features in asthma and contributes significantly to airflow limitation, is accompanied by mucous gland hypertrophy and goblet cell hyperplasia. Therefore, the mucous index in lung sections was quantified find more using PAS staining. Goblet cell hyperplasia was observed in the OVA group but not in the Control group (41·70 ± 1·67 versus 1·97 ± 0·16% of airway cells, Fig. 1e,f, Table 1, P < 0·01). Compared with the OVA group, a significant decrease was noticed in airway secretion in the TRP group – the mucous index was 24·08 ± 1·29% (Fig. 1f,g, Table 1, P < 0·01, TRP versus OVA), which indicated that triptolide markedly reduced goblet cell hyperplasia in airways. Dexamethasone also reduced airway mucous index compared with the OVA group (23·72 ± 1·09 versus 41·70 ± 1·67%, Fig. 1f,h, Table 1, P < 0·01). There was no significant difference in mucous index between the TRP and DEX groups (24·08 ± 1·29 versus 23·72 ± 1·09%, Fig. 1g,h, Table 1, P > 0·05).

Efficient responses to the fungus require a complex network of immunological mechanisms. Together with alveolar macrophages and neutrophils, which constitute a primary line of innate cellular defence against A. fumigatus,1,2 the crucial role of the adaptive immunity has been extensively demonstrated.3 Indeed, besides the well-characterized protective role of T helper type 1 (Th1) lymphocytes,4–7 the newly described regulatory T cells and interleukin-17 (IL-17) -producing cells (Th17) represent important mediators of the inflammatory and anti-inflammatory

Fulvestrant cost host responses against A. fumigatus.8 However, dendritic cells (DCs) also play a fundamental function in initiating and modulating the specific immune responses upon recognition of A. fumigatus.5,9,10 After internalization of A. fumigatus conidia, DCs mature and acquire the capacity to polarize

naive T cells and, in turn, to promote a protective response.9 In keeping with these findings, in vivo results on the migration of lung DCs into lymphoid organs, where they drive an appropriate T-cell response to fungal antigens,11 have brought DCs centre stage as promising targets for intervention in immunotherapy and fungal vaccine development.12 In addition, it is important drug discovery to consider several studies that have recently pointed to DCs and type I interferons (IFNs) as special players in the immune response tailored to combat tumours and infections.13–15 Indeed, although the anti-microbial properties of these cytokines have not been fully characterized yet, type I IFNs represent important immunomodulators of the innate, as well as the adaptive, arm of the immune system. Type I IFN can promote

the differentiation of human blood monocytes into DCs and contribute to their maturation.16,17 This leads to the generation of DCs able to stimulate a primary human antibody response, a Th1 proliferation,18 and a cross-priming of CD8 T cells against viral antigens.19 In addition, one crucial outcome of type I IFN-induced effects is the ability to directly stimulate IFN-γ production in natural killer and T cells,20–22 which in turn promotes the development of a cell-mediated immune response. Based on these immunoregulatory properties, in this work the expression and the through capacity of type I IFN, namely IFN-β, to modulate the T-cell polarizing capacity of A. fumigatus-infected DCs was investigated in an attempt to evaluate the effects induced by this cytokine on anti-fungal immunity. Although the phagocytosis of the fungus was not affected by IFN-β treatment, the maturation induced by A. fumigatus infection was enhanced in IFN-β-primed DCs, as evaluated by analysing the immunophenotype and the release of pro-inflammatory and regulatory cytokines. Accordingly, IFN-β endowed DCs with potent Th1 polarizing capacity because an enhanced IFN-γ production in T cells co-cultured with A. fumigatus-infected DCs was observed in the presence of IFN-β.

Helminth infections in endemic areas can be either mild (low transmission) or severe (high transmission) depending on the area in question (25,26). In an attempt to study the protective immune responses against migrating larvae, we used an infection model that more closely resembles mild infections. This

study evaluated S. venezuelensis challenge infection in mice previously infected with different larvae loads. For the experiments described herein, 8- to 10-week-old Swiss male mice were used. Mice were provided from an established colony at the University’s mouse facility and were maintained at the Department of Parasitology (ICB, UFMG, Brazil), fed with standard chow (Primor, Moinho Primor, São Paulo, Brazil) and given tap water ad libitum. Animal care and experimental procedures were performed under the approval of the local animal ethics committee. Animals MEK inhibitor check details were divided into six experimental groups depending on the parasite exposure of the primary infection, as detailed in Figure 1. Strongyloides venezuelensis was initially isolated from Rattus novergicus (27) and has been maintained in the Department of Parasitology (ICB, UFMG, Belo Horizonte, Brazil), by serial passage in Wistar rats. Infective filiform larvae (L3) were isolated from 72 h granular charcoal culture of infected

rat faeces using the Baermann method. After extensive wash in phosphate-buffered saline (PBS, pH 7·4), the larvae were

counted and concentration was adjusted to 1, 10, 100, 500 L3 per 100 μL of PBS for the infections. For the experiments, mice from primary infected group (L0) were inoculated only with 100 μL of PBS, while from the animals from the groups, very low-dose (L1), low-dose (L10), normal-dose (L100) and high-dose (L500), were individually inoculated with 100 μL of PBS containing 1, 10, 100 or 500 S. venezuelensis L3 respectively (Figure 1). Fourteen days after the primary inoculation, each animal was individually infected with 500 L3 and parasitological and immunological analyses were performed after 2 and 7 days of the challenge infection, as detailed below. Five male mice were kept noninfected and under the same experimental conditions (no dose) as baseline controls. The inoculations were carried out by subcutaneous injection at the abdominal region of each mouse, as previously described by Negrão-Corrêa (15). The success of the primary infection was confirmed by egg counts at 7 days post-infection. At 2 and 7 days after last infection, five animals of each experimental group were anaesthetized via intraperitoneal (i.p.) injection of a mixture of ketamine (Dopalen®/Vetbrands; 600 mg/kg) and xylazine (Calmiun®/Agener União; 40 mg/kg) and bled via brachial plexus vein.

Several studies, including gene-fate mapping studies [54, 55], have now provided convincing evidence that most Th cells have a great degree of flexibility in their differentiation options. In the human system, it has been shown that Treg cells could acquire the HSP inhibitor capacity to produce IL-17, while maintaining the capacity to suppress T-cell effector functions [56, 57], while Th17 cells from the synovial fluid of oligoarticular-onset juvenile idiopathic arthritic patients shift in vitro from a Th17 to a Th17/Th1 or Th1 phenotype [58]. The time-dependent regulation of IL-17 and IL-10 production in Th17 cells that was discussed

above [37] may be considered as yet another example of Th-cell flexibility that underlines the robust and adaptive behavior of effector T cells in the immune response. The extent to which the immune system uses this flexibility and the consequences for

protection or immunopathology remain poorly understood and represent a challenge and an opportunity for future studies. The work in the authors’ laboratories is supported by grants from the Swiss National Science Foundation (N. 131092 to F.S. STI571 and 126027 to A.L.) and the European Research Council. The Institute for Research in Biomedicine is supported by the Helmut Horten Foundation The authors declare no financial or commercial conflict of interest. “
“Multiple sclerosis (MS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) represent chronic, autoimmune demyelinating disorders of the central and peripheral Carbohydrate nervous system. Although both disorders share some fundamental pathogenic elements, treatments do not provide uniform effects across both disorders. We aim at providing an overview of current and future disease-modifying strategies in these disorders to demonstrate communalities and distinctions. Intravenous immunoglobulins (IVIG) have demonstrated short- and long-term beneficial effects in CIDP but are not effective in MS. Dimethyl fumarate (BG-12), teriflunomide and laquinimod are orally administered immunomodulatory

drugs that are already approved or likely to be approved in the near future for the basic therapy of patients with relapsing–remitting MS (RRMS) due to positive results in Phase III clinical trials. However, clinical trials with these drugs in CIDP have not (yet) been initiated. Natalizumab and fingolimod are approved for the treatment of RRMS, and trials to evaluate their safety and efficacy in CIDP are now planned. Alemtuzumab, ocrelizumab and daclizumab respresent monoclonal antibodies in advanced stages of clinical development for their use in RRMS patients. Attempts to study the safety and efficacy of alemtuzumab and B cell-depleting anti-CD20 antibodies, i.e. rituximab, ocrelizumab or ofatumumab, in CIDP patients are currently under way. We provide an overview of the mechanism of action and clinical data available on disease-modifying immunotherapy options for MS and CIDP.

Specimens were collected by swabbing the denture and underlying mucosa. Isolates were previously identified by conventional mycological and genotypic methods. The phospholipase and proteinase activities were evaluated by agar plate methods. A total of 152 isolates were recovered from denture and underlying mucosa, including 101 Candida albicans, 18 Candida tropicalis, 14 Candida glabrata, 11 Candida guilliermondii, four Candida parapsilosis, two Saccharomyces cerevisiae and one isolate each of Candida dubliniensis and Candida krusei. Most C. albicans (97%) showed phospholipase activity; furthermore, the unique C. dubliniensis isolate showed a moderate phospholipase activity. The isolation of C. albicans (chi-square

test, P = 0.0016) and phospholipase production by Candida check details spp. (chi-square test, P = 0.0213) was found to be significantly associated with denture stomatitis. Proteinase production was observed in <30% of

isolates, and it was not related to the presence of denture stomatitis (P = 0.7675). Candida albicans isolates may produce both virulence factors, although the proteinase production was only observed in <30% of the isolates. Phospholipase production was exclusive of C. albicans and C. dubliniensis. "
“Systematic studies about pet guinea pigs with Seliciclib cost dermatophytosis are rare. The aim of this study was to evaluate clinical signs, therapy and zoonotic risk of pet guinea pigs with dermatophytosis. Questionnaires from both owners (n = 74) of pet guinea pigs with dermatophytosis and their veterinarians (n = 101) were analysed regarding clinical signs, therapy and data pertinent to zoonotic potential. Trichophyton (T.) mentagrophytes was found in 97% of cases. In the weeks preceding the onset of the clinical signs, a new guinea pig joined the household in 43% of cases. One third of the affected guinea pigs had lived in the household for less than 3 months. Cyclin-dependent kinase 3 Predominant clinical signs were alopecia (83%), scaling (73%) and crusting (70%). The most commonly affected body site was the head (75%). In approximately one quarter

of the cases humans showed clinical signs of dermatophytosis, in half the households, only children were affected. Skin lesions were seen most often on the face, the neck and the arms. Pet guinea pigs carrying dermatophytes must be considered a serious zoonotic risk for their owners, especially for children. A major risk factor for dermatophytosis seems to be a recent acquisition of a new guinea pig. “
“Adherence of Candida has been implicated as the initial process in the pathogenesis of oral candidosis. Candidal germ tubes and its relative cell-surface hydrophobicity (CSH) are contributory attributes. Candida dubliniensis is currently documented as an opportunistic pathogen allied with recurrent oral candidosis. Oral candidosis can be treated with polyene and azole antifungals such as amphotericin B, ketoconazole and fluconazole.

[17, 18] In endemic areas, immunosuppressive therapy with high-dose prednisolone and/or other immunosuppressants such as cyclosporine and methotrexate has been shown to be associated with increased risk for melioidosis in 6–12% of cases.[12, 19] Melioidosis has been twice reported previously in renal transplant recipients presenting with septic

arthritis and urinary tract infection respectively, with presence of diabetes mellitus as an additional risk in the former.[20, 21] At least five cases of melioidosis have been documented in renal transplant recipients in Australia (Chris Heath and Zulfikar Jabbar, unpubl. data, 2012). Although therapeutic immunosuppression has been shown to be a risk factor, there is evidence suggesting that HIV-AIDS is not a risk factor for increasing either the susceptibility to, or the severity of melioidosis.[22, 23] The incubation period and

clinical Selleckchem Fulvestrant course of melioidosis following infection may be determined by a combination of host and environmental risk factors, mode of infection, infecting dose of bacteria and yet to be determined differences in strain virulence. Incubation period following documented exposure events was shown Compound Library molecular weight to be 1–21 days (mean 9 days) in an Australian series from Darwin.[24] Nevertheless the ability of B. pseudomallei to remain dormant after asymptomatic infection has been considered responsible for the very uncommon but remarkable cases documented to occur in individuals many years after they have left an endemic area. The longest described

such ‘latency’ is 62 years in a man taken as a prisoner of war during World War II.[25] In those exposed to B. pseudomallei, asymptomatic infection without any subsequent disease is actually thought to be far more common than melioidosis itself. In all series, the most common presentation of melioidosis is community-acquired pneumonia, occurring in over half of all cases.[12, 14, 26] In the Darwin Prospective Study involving 540 cases of documented melioidosis over a 20-year period, the most common primary presentation was pneumonia in 51%, followed through by genitourinary infection in 14%, skin infection in 13%, isolated bacteremia in 11%, septic arthritis or osteomyelitis in 4% and neurologic involvement in 3%. Deep visceral abscesses and secondary foci in lungs or joints were common.[12] Overall 11% of cases had been sick for at least 2 months at the time of presentation. These chronic melioidosis cases were mostly low grade pneumonia often mimicking tuberculosis or non-healing skin infections. The clinical pattern in northern Australia is generally similar to that in Thailand but with some notable differences. Parotid abscess occurs in up to 40% of paediatric melioidosis cases in Thailand but is extremely rare in Australia.