Human T-cell leukaemia virus type 1 and Adult T-cell leukaemia/lymphoma in Queensland, Australia: a retrospective cross-sectional study.

OBJECTIVES: Human T-cell leukaemia virus type 1 (HTLV-1), an STI, is reported to be highly prevalent in Indigenous communities in Central Australia. HTLV-1 is an incurable, chronic infection which can cause Adult T-cell leukaemia/lymphoma (ATL). ATL is associated with high morbidity and mortality, with limited treatment options. We studied the prevalence of HTLV-1 and ATL in the state of Queensland, Australia. METHODS: Serum samples stored at healthcare services in Brisbane, Townsville and Cairns and at haemodialysis units in Brisbane (2018-2019) were screened for HTLV-1/2 antibodies using the Abbott ARCHITECT chemiluminescent microparticle immunoassay (CMIA) for antibodies against gp46-I, gp46-II and GD21 (Abbott CMIA, ARCHITECT). Reactive samples were confirmed through Western blot. Pooled Australian National Cancer Registry surveillance data reporting on cases coded for ATL (2004-2015) were analysed. RESULTS: Two out of 2000 hospital and health services samples were confirmed HTLV-1-positive (0.1%, 95% CI 0.02% to 0.4%), both in older women, one Indigenous and one non-Indigenous. All 540 haemodialysis samples tested negative for HTLV. All samples were HTLV-2-negative. Ten out of 42 (24.8%) reported cases of ATL in Australia were from Queensland (crude incidence rate 0.025/100 000; 95% CI 0.011 to 0.045); most cases were seen in adult men of non-Indigenous origin. Nineteen deaths due to ATL were recorded in Australia. CONCLUSION: We confirm that HTLV-1 and ATL were detected in Queensland in Indigenous and non-Indigenous people. These results highlight the need for HTLV-1 prevalence studies in populations at risk of STIs to allow the implementation of focused public health sexual and mother-to-child transmission prevention strategies.

The effect of climate on melioidosis incidence in Townsville, Australia: a dry tropical region.

BACKGROUND: Townsville is in the dry tropics in Northern Australia and an endemic region for melioidosis. Melioidosis is an infectious disease caused by Burkholderia pseudomallei, a soil dwelling organism. The incidence of melioidosis is associated with high levels of rainfall and has been linked to multiple weather variables in other melioidosis endemic regions such as in Darwin. In contrast to Townsville, Darwin is in the wet-dry tropics in Northern Australia and receives 40% more rainfall. We assessed the relationship between melioidosis incidence and weather conditions in Townsville and compared the patterns to the findings in Darwin and other melioidosis endemic regions. METHOD: Performing a time series analysis from 1996 to 2020, we applied a negative binomial regression model to evaluate the link between the incidence of melioidosis in Townsville and various weather variables. Akaike's information criterion was used to assess the most parsimonious model with best predictive performance. Fourier terms and lagged deviance residuals were included to control long term seasonal trends and temporal autocorrelation. RESULTS: Humidity is the strongest predictor for melioidosis incidence in Townsville. Furthermore, the incidence of melioidosis showed a three-times rise in the Townsville region when >200 mm of rain fell within the fortnight. Prolonged rainfall had more impact than a heavy downpour on the overall melioidosis incident rate. There was no statistically significant increase in incidence with cloud cover in the multivariable model. CONCLUSION: Consistent with other reports, melioidosis incidence can be attributed to humidity and rainfall in Townsville. In contrast to Darwin, there was no strong link between melioidosis cases and cloud cover and nor single large rainfall events.

The bacterial gut microbiome of probiotic-treated very-preterm infants: changes from admission to discharge.

BACKGROUND: Preterm birth is associated with the development of acute and chronic disease, potentially, through the disruption of normal gut microbiome development. Probiotics may correct for microbial imbalances and mitigate disease risk. Here, we used amplicon sequencing to characterise the gut microbiome of probiotic-treated premature infants. We aimed to identify and understand variation in bacterial gut flora from admission to discharge and in association with clinical variables. METHODS: Infants born <32 weeks gestation and <1500 g, and who received probiotic treatment, were recruited in North Queensland Australia. Meconium and faecal samples were collected at admission and discharge. All samples underwent 16S rRNA short amplicon sequencing, and subsequently, a combination of univariate and multivariate analyses. RESULTS: 71 admission and 63 discharge samples were collected. Univariate analyses showed significant changes in the gut flora from admission to discharge. Mixed-effects modelling showed significantly lower alpha diversity in infants diagnosed with either sepsis or retinopathy of prematurity (ROP) and those fed formula. In addition, chorioamnionitis, preeclampsia, sepsis, necrotising enterocolitis and ROP were also all associated with the differential abundance of several taxa. CONCLUSIONS: The lower microbial diversity seen in infants with diagnosed disorders or formula-fed, as well as differing abundances of several taxa across multiple variables, highlights the role of the microbiome in the development of health and disease. This study supports the need for promoting healthy microbiome development in preterm neonates. IMPACT: Low diversity and differing taxonomic abundances in preterm gut microbiota demonstrated in formula-fed infants and those identified with postnatal conditions, as well as differences in taxonomy associated with preeclampsia and chorioamnionitis, reinforcing the association of the microbiome composition changes due to maternal and infant disease. The largest study exploring an association between the preterm infant microbiome and ROP. A novel association between the preterm infant gut microbiome and preeclampsia in a unique cohort of very-premature probiotic-supplemented infants.

Exploring the long-term colonisation and persistence of probiotic-prophylaxis species on the gut microbiome of preterm infants: a pilot study.

Preterm infants suffer from a higher incidence of acute diseases such as necrotising enterocolitis and sepsis. This risk can be mitigated through probiotic prophylaxis during admission. This reduction in risk is likely the result of acute modulation of the gut microbiome induced by probiotic species, which has been observed to occur up until discharge. We aimed to determine if this modulation, and the associated probiotic species, persisted beyond discharge. We conducted both a cross-sectional analysis (n = 18), at ~ 18 months of age, and a longitudinal analysis (n = 6), from admission to 18 months of the gut microbiome of preterm infants using both shotgun metagenomics and 16S rRNA profiling respectively. The 16S amplicon sequencing revealed that the microbial composition of the probiotic-supplemented infants changed dramatically over time, stabilising at discharge. However, species from the probiotic Infloran®, as well as positive modulatory effects previously associated with supplementation, do not appear to persist beyond discharge and once prophylaxis has stopped.    Conclusions: Although differences exist between supplemented and non-supplemented groups, the implications of these differences remain unclear. Additionally, despite a lack of long-term colonisation, the presence of probiotics during early neonatal life may still have modulatory effects on the microbiome assembly and immune system training. What is Known: • Evidence suggests modulation of the microbiome occurs during probiotic prophylaxis, which may support key taxa that exert positive immunological benefits. • Some evidence suggests that this modulation can persist post-prophylaxis. What is New: • We present support for long-term modulation in association with probiotic prophylaxis in a cohort of infants from North Queensland Australia. • We also observed limited persistence of the probiotic species post-discharge.

Group B streptococcal bacteraemia: changing trends in a tropical region of Australia.

BACKGROUND: Group B streptococcus (GBS) is a recognised perinatal and neonatal pathogen. There are reports of increasing GBS sepsis globally outside this demographic. North Queensland is part of tropical Australia, with a relatively high proportion of Indigenous Australians. AIMS: To analyse the epidemiology of GBS bacteraemia and explore associated risk factors. METHODS: This was a 10-year retrospective review of GBS bacteraemia in a tertiary facility in North Queensland, between 2010 and February 2020. Data variables collected included: demographics, risk factors, clinical source and outcomes. Multivariable logistic regression was performed to examine the association of indigenous status and other relevant clinical factors with mortality from GBS bacteraemia at 3 months. RESULTS: Of the 164 total cases, 123 were not pregnancy related. The annual rate of GBS bacteraemia for the indigenous population was 12.48 per 100 000 and 4.84 per 100 000 for the non-indigenous population. Indigenous patients were more likely to have diabetes and chronic kidney disease compared with the non-indigenous patients. Males (adjusted odds ratio (AOR) = 4.34; 95% CI 1.14-16.56; P = 0.031) and immunosuppressed patients (AOR = 11.49; 95% CI 2.73-48.42; P < 0.001) were more likely to experience mortality at 3 months from GBS bacteraemia even after adjusting for other risk factors respectively. CONCLUSION: GBS bacteraemia is deviating from being primarily a neonatal disease. While the indigenous population of North Queensland are disproportionately affected, the demographics affected differ. GBS appears to target the older non-indigenous patients with greater comorbidities. In the non-indigenous population, invasive GBS disease is an emerging issue. Three-month mortality appears to be increased in males and the immunosuppressed.

Cytomegalovirus infection in a single-centre Australian neonatal cohort.

AIM: Congenital cytomegalovirus (cCMV) is the most common infectious cause of congenital malformation, non-genetic sensorineural hearing loss and neurodevelopmental sequelae in childhood. The primary aim of this retrospective cohort study was to identify the birth and neurodevelopmental outcomes of neonates diagnosed with symptomatic and asymptomatic cCMV in a large regional tertiary referral hospital. METHODS: This was a retrospective cohort study of laboratory-based cCMV diagnoses in neonates born at a single study centre between January 2005 and January 2020. Audit of medical records was undertaken to evaluate maternal characteristics, symptom patterns, radiological and neurodevelopmental outcomes of neonates meeting the laboratory diagnostic criteria during the first 24 months. RESULTS: There were 45 neonates with proven CMV infection and 27 mothers with proven infection with an associated pregnancy outcome. Nineteen neonates were born at term (>37 weeks). Of these, 32 (71.1%) neonates had a significant intercurrent comorbidity and 22 (48.9%) neonates were reported to have a degree of delay in one or more developmental domains. A large proportion (77.3%) of the symptomatic untreated neonates had an unknown history of maternal infection compared to the asymptomatic (10.0%) and symptomatic treated (53.8%) neonates (P = 0.001). CONCLUSION: Up to half of the neonates with cCMV were at risk of developing a degree of developmental delay at our centre. Whether these outcomes are related primarily to CMV infection or are confounded by the co-existence of prematurity is unclear and needs further evaluation in prospective studies.

Q Fever awareness and risk profiles among agricultural show attendees.

OBJECTIVE: To assess awareness and risk of Q fever among agricultural show attendees. SETTING: University of New England's Farm of the Future Pavilion, 2019, Sydney Royal Agricultural Show. PARTICIPANTS: Participants were ≥18 years, fluent in English, Australian residents, and gave their informed consent. MAIN OUTCOME MEASURES: Participants reported whether they had ever heard of Q fever and then completed the 'Q Tool' (www.qfevertool.com), which was used to assess participants' demographics and risk profiles. Cross-tabulations and logistic regression analyses were used to examine the relationship between these factors. RESULTS: A total of 344 participants were recruited who, in general, lived in major NSW cities and were aged 40-59 years. 62% were aware of Q fever. Living in regional/remote areas and regular contact with livestock, farms, abattoirs and/or feedlots increased the likelihood of Q fever awareness. Direct or indirect contact with feral animals was not associated with Q fever awareness after controlling for the latter risk factors. 40% of participants had a high, 21% a medium, and 30% a low risk of exposure. Slightly less than 10% reported a likely existing immunity or vaccination against Q fever. Among those who were not immune, living in a regional or remote area and Q fever awareness were independently associated with increased likelihood of exposure. CONCLUSIONS: Awareness of Q fever was relatively high. Although 61% of participants had a moderate to high risk of exposure to Q fever, they had not been vaccinated. This highlights the need to explore barriers to vaccination including accessibility of providers and associated cost.

Burkholderia pseudomallei Clinical Isolates Are Highly Susceptible In Vitro to Cefiderocol, a Siderophore Cephalosporin.

Cefiderocol is a cephalosporin designed to treat multidrug-resistant Gram-negative infections. By forming a chelated complex with ferric iron, cefiderocol is transported into the periplasmic space via bacterial iron transport systems and primarily binds to penicillin-binding protein 3 (PBP3) to inhibit peptidoglycan synthesis. This mode of action results in cefiderocol having greater in vitro activity against many Gram-negative bacilli than currently used carbapenems, ß-lactam/ß-lactamase inhibitor combinations, and cephalosporins. Thus, we investigated the in vitro activity of cefiderocol against a total of 246 clinical isolates of Burkholderia pseudomallei from Queensland, Australia. The collection was composed primarily of bloodstream (56.1%), skin and soft tissue (16.3%), and respiratory (15.9%) isolates. MICs of cefiderocol ranged from ≤0.03 to 16 mg/liter, whereas the MIC90 was 0.125 mg/liter. Based upon CLSI clinical breakpoints for cefiderocol against Pseudomonas aeruginosa, Acinetobacter baumannii, and Stenotrophomonas maltophilia, three isolates (1.2%) would be classified as nonsusceptible (MIC > 4 mg/liter). Using EUCAST non-species-specific (pharmacokinetic/pharmacodynamic [PK/PD]) clinical breakpoints or those set for Pseudomonas aeruginosa, four isolates (1.6%) would be resistant (MIC > 2 mg/liter). Further testing for coresistance to meropenem, ceftazidime, trimethoprim-sulfamethoxazole, amoxicillin-clavulanate, and doxycycline was performed on the four isolates with elevated cefiderocol MICs (>2 mg/liter); all isolates exhibited resistance to amoxicillin-clavulanic acid, while three isolates also displayed resistance to at least one other antimicrobial. Cefiderocol was found to be highly active in vitro against B. pseudomallei primary clinical isolates. This compound shows great potential for the treatment of melioidosis in countries of endemicity and should be explored further.

The Laboratory Diagnosis of Syphilis.

Syphilis is a multisystem infection caused by the spirochete Treponema pallidum. Currently, cases of possible syphilis are commonly investigated using the treponemal serological tests T. pallidum IgG chemiluminescence immunoassay (CLIA) and the T. pallidum particle agglutination (TPPA). The nontreponemal rapid plasma reagin (RPR) flocculation test is used to assess disease activity. There has been a resurgence of syphilis diagnoses in Australia. Large foci of infection have been identified in isolated communities. The remoteness of these locations, in conjunction with the particular sociocultural characteristics of the population, pose unique challenges to the traditional diagnostic and treatment paradigms for syphilis. As a consequence of this increased incidence of syphilis, there has been interest in the utility of point-of-care tests (POCTs), nucleic acid amplification tests (NAATs), the role of IgM testing in suspected congenital syphilis, and the laboratory investigation of possible neurosyphilis. This review looks at the current status of traditional serological assays and provides an update on more recent methods. It assesses the published literature in this area and makes recommendations for the rational use of pathology testing to aid in the diagnosis of the many facets of syphilis.

Laboratory Safety: Handling Burkholderia pseudomallei Isolates without a Biosafety Cabinet.

Burkholderia pseudomallei is a tier 1 select agent that is associated with laboratory-acquired melioidosis, with international guidelines recommending isolate handling within a class II biosafety cabinet (BSC) in a biosafety level 3 (BSL3) facility. In low-resource settings, this may not be practical; therefore, we aimed to assess the risk of laboratory-acquired melioidosis during routine work. Prior exposure to the organism was determined with a questionnaire and concomitant serology. Of 30 laboratory scientists handling B. pseudomallei on 1,267 occasions outside a biosafety cabinet, no infections were documented and all participants remained seronegative. Additionally, we performed controlled environmental air sampling during 78 laboratory handling events, including plate opening, oxidase testing, and McFarland suspension creation. None of the experiments demonstrated aerosolization of the organism. This study suggests the risk of laboratory-acquired melioidosis is low. However, individual laboratories will need to undertake a risk assessment, including melioidosis endemicity, availability of resources for containment, the nature of routine handling to be undertaken, and the presence of predisposing risk factors for infection in the staff concerned. Additionally, laboratories should take region-specific guidelines into consideration. Further research is required to better inform on the overall risk of infection in the microbiology laboratory.

A multi-country study using MALDI-TOF mass spectrometry for rapid identification of Burkholderia pseudomallei.

BACKGROUND: Burkholderia pseudomallei is the bacterial causative agent of melioidosis, a difficult disease to diagnose clinically with high mortality if not appropriately treated. Definitive diagnosis requires isolation and identification of the organism. With the increased adoption of MALDI-TOF MS for the identification of bacteria, we established a method for rapid identification of B. pseudomallei using the Vitek MS, a system that does not currently have B. pseudomallei in its in-vitro diagnostic database. RESULTS: A routine direct spotting method was employed to create spectra and SuperSpectra. An initial B. pseudomallei SuperSpectrum was created at Shoklo Malaria Research Unit (SMRU) from 17 reference isolates (46 spectra). When tested, this initial SMRU SuperSpectrum was able to identify 98.2 % (54/55) of Asian isolates, but just 46.7 % (35/75) of Australian isolates. Using spectra (430) from different reference and clinical isolates, two additional SMRU SuperSpectra were created. Using the combination of all SMRU SuperSpectra with seven existing SuperSpectra from Townsville, Australia 119 (100 %) Asian isolates and 31 (100 %) Australian isolates were correctly identified. In addition, no misidentifications were obtained when using these 11 SuperSpectra when tested with 34 isolates of other bacteria including the closely related species Burkholderia thailandensis and Burkholderia cepacia. CONCLUSIONS: This study has established a method for identification of B. pseudomallei using Vitek MS, and highlights the impact of geographical differences between strains for identification using this technique.

Group G Streptococcus Induces an Autoimmune Carditis Mediated by Interleukin 17A and Interferon γ in the Lewis Rat Model of Rheumatic Heart Disease.

Acute rheumatic fever and rheumatic heart disease (ARF/RHD) have long been described as autoimmune sequelae of Streptococcus pyogenes or group A streptococcal (GAS) infection. Both antibody and T-cell responses against immunodominant GAS virulence factors, including M protein, cross-react with host tissue proteins, triggering an inflammatory response leading to permanent heart damage. However, in some ARF/RHD-endemic regions, throat carriage of GAS is low. Because Streptococcus dysgalactiae subspecies equisimilis organisms, also known as ß-hemolytic group C streptococci and group G streptococci (GGS), also express M protein, we postulated that streptococci other than GAS may have the potential to initiate or exacerbate ARF/RHD. Using a model initially developed to investigate the uniquely human disease of ARF/RHD, we have discovered that GGS causes interleukin 17A/interferon γ-induced myocarditis and valvulitis, hallmarks of ARF/RHD. Remarkably the histological, immunological, and functional changes in the hearts of rats exposed to GGS are identical to those exposed to GAS. Furthermore, antibody cross-reactivity to cardiac myosin was comparable in both GGS- and GAS-exposed animals, providing additional evidence that GGS can induce and/or exacerbate ARF/RHD.

Retrospective Review of Treponema pallidum PCR and Serology Results: Are Both Tests Necessary?

There has been a resurgence of syphilis diagnoses in Australia. We investigated whether our Treponema pallidum PCR test provides any additional diagnostic information over syphilis serology (chemiluminescence immunoassay [CMIA], Treponema pallidum particle agglutination [TPPA] assay, and the rapid plasma reagin [RPR] flocculation test). A retrospective audit of all T. pallidum PCR requests that came through our laboratory from January 2010 to June 2017 was conducted; data collected included age, gender, site of swab, and results from T. pallidum PCR, syphilis serology, and herpes simplex virus 1 (HSV-1) and HSV-2 PCRs. A total of 441 T. pallidum PCR tests were performed; on average, 3 T. pallidum PCRs per month were requested in 2011, and this rate increased to 17.2 requests per month in 2017. A total of 323 patients had both T. pallidum PCR and syphilis serology performed, with 67% of swabs taken from the genitals. T. pallidum PCR gave positive results for 61/323 (19%) patients; of these 61 patients, 59 (97%) also had positive syphilis serology results (T. pallidum PCR sensitivity, 68%; specificity, 99%; positive predictive value, 97%; negative predictive value, 89%). Syphilis serology was positive for 91/323 patients (28%); of these 91 patients, 61 (66%) were also T. pallidum PCR positive (syphilis serology sensitivity, 97%; specificity, 88%; positive predictive value, 60%; negative predictive value, 99%). The Cohen's kappa value was 0.74, indicating substantial agreement between the two tests. Our results show that most patients with positive T. pallidum PCR results also had positive syphilis serology. Therefore, T. pallidum PCR adds little clinical value over serology for the diagnosis of syphilis in certain clinical settings.

Paediatric thoracic empyema in the tropical North Queensland region of Australia: Epidemiological trends over a decade.

AIM: The Townsville Hospital and Health Service is the regional referral centre for children in the north of Queensland. Aboriginal and Torres Strait Islander (ATSI) people make up 7-10% of the population. Increasing numbers of children with paediatric thoracic empyema (pTE) are being referred to Townsville Hospital and Health Service for management. This study aims to describe the incidence rates, epidemiology, microbiology and trends of this disease in North Queensland over a 10-year period. METHODS: A retrospective chart review of all children (1 month to 16 years), admitted in the years 2007-2016, with community-acquired pTE was conducted. International Classification of Diseases codes were used to identify the patients. Epidemiological and microbiological data were extracted from records. RESULTS: Of the 123 cases identified, incidence rates per 100 000 were 8.5 (95% confidence interval (CI) 8.4-8.6) in all children and much higher at 19.8 (95% CI: 19.5-21.9) in ATSI children. The under 5 years age group had the highest rate (24.5; 95% CI: 24.4-24.6). There was a progressive rise in incidence during the 10-year period, with the highest incidence of 15.2 (95% CI: 15.1-15.2) occurring in 2016. A pathogen was isolated in 76% of cases. Non-multi-resistant methicillin-resistant Staphylococcus aureus was the most common pathogen isolated in 22 of 64 ATSI children (34%), while Streptococcus pneumoniae was the most common pathogen isolated in 27 of 59 non-ATSI children (46%). CONCLUSIONS: A high and increasing incidence of pTE in North Queensland is being observed. ATSI children have higher incidence rates and are more likely to have non-multi-resistant methicillin-resistant Staphylococcus aureus as a causative agent.

Elevated atmospheric [CO2 ] can dramatically increase wheat yields in semi-arid environments and buffer against heat waves.

Wheat production will be impacted by increasing concentration of atmospheric CO2 [CO2 ], which is expected to rise from about 400 µmol mol(-1) in 2015 to 550 µmol mol(-1) by 2050. Changes to plant physiology and crop responses from elevated [CO2 ] (e[CO2 ]) are well documented for some environments, but field-level responses in dryland Mediterranean environments with terminal drought and heat waves are scarce. The Australian Grains Free Air CO2 Enrichment facility was established to compare wheat (Triticum aestivum) growth and yield under ambient (~370 µmol(-1) in 2007) and e[CO2 ] (550 µmol(-1) ) in semi-arid environments. Experiments were undertaken at two dryland sites (Horsham and Walpeup) across three years with two cultivars, two sowing times and two irrigation treatments. Mean yield stimulation due to e[CO2 ] was 24% at Horsham and 53% at Walpeup, with some treatment responses greater than 70%, depending on environment. Under supplemental irrigation, e[CO2 ] stimulated yields at Horsham by 37% compared to 13% under rainfed conditions, showing that water limited growth and yield response to e[CO2 ]. Heat wave effects were ameliorated under e[CO2 ] as shown by reductions of 31% and 54% in screenings and 10% and 12% larger kernels (Horsham and Walpeup). Greatest yield stimulations occurred in the e[CO2 ] late sowing and heat stressed treatments, when supplied with more water. There were no clear differences in cultivar response due to e[CO2 ]. Multiple regression showed that yield response to e[CO2 ] depended on temperatures and water availability before and after anthesis. Thus, timing of temperature and water and the crop's ability to translocate carbohydrates to the grain postanthesis were all important in determining the e[CO2 ] response. The large responses to e[CO2 ] under dryland conditions have not been previously reported and underscore the need for field level research to provide mechanistic understanding for adapting crops to a changing climate.

Primary amoebic meningoencephalitis in North Queensland: the paediatric experience.

Primary amoebic meningoencephalitis (PAM) is a fulminant, diffuse haemorrhagic meningoencephalitis caused by Naegleria fowleri, with an almost invariably fatal outcome. In Australia and the developed world, PAM remains a rare disease, although it is very likely that large numbers of cases go undetected in developing countries. N. fowleri is a thermophilic, free-living amoeba with a worldwide distribution. It is acquired when contaminated fresh water is flushed into the nose and penetrates the central nervous system via the cribriform plate. Clinical features are similar to those of bacterial meningitis, but it does not respond to standard therapy and rapid progression to death occurs in most cases. Some survivors have been reported; these patients received early treatment with amphotericin B in combination with a variety of other medications. Our review describes the local and worldwide experience of this disease and its clinical features, and discusses the associated diagnostic challenges. We hope that by detailing the local response to a recent case, and the outcomes of our public health campaign, we can improve the knowledge of this rare disease for doctors working in rural and remote Australia.

Pathogens penetrating the central nervous system: infection pathways and the cellular and molecular mechanisms of invasion.

The brain is well protected against microbial invasion by cellular barriers, such as the blood-brain barrier (BBB) and the blood-cerebrospinal fluid barrier (BCSFB). In addition, cells within the central nervous system (CNS) are capable of producing an immune response against invading pathogens. Nonetheless, a range of pathogenic microbes make their way to the CNS, and the resulting infections can cause significant morbidity and mortality. Bacteria, amoebae, fungi, and viruses are capable of CNS invasion, with the latter using axonal transport as a common route of infection. In this review, we compare the mechanisms by which bacterial pathogens reach the CNS and infect the brain. In particular, we focus on recent data regarding mechanisms of bacterial translocation from the nasal mucosa to the brain, which represents a little explored pathway of bacterial invasion but has been proposed as being particularly important in explaining how infection with Burkholderia pseudomallei can result in melioidosis encephalomyelitis.

Melioidosis diagnostic workshop, 2013.

Melioidosis is a severe disease that can be difficult to diagnose because of its diverse clinical manifestations and a lack of adequate diagnostic capabilities for suspected cases. There is broad interest in improving detection and diagnosis of this disease not only in melioidosis-endemic regions but also outside these regions because melioidosis may be underreported and poses a potential bioterrorism challenge for public health authorities. Therefore, a workshop of academic, government, and private sector personnel from around the world was convened to discuss the current state of melioidosis diagnostics, diagnostic needs, and future directions.