Gametocyte carriage in Plasmodium falciparum-infected travellers.

BACKGROUND: Gametocytes are the sexual stage of Plasmodium parasites. The determinants of gametocyte carriage have been studied extensively in endemic areas, but have rarely been explored in travellers with malaria. The incidence of gametocytaemia, and factors associated with gametocyte emergence in adult travellers with Plasmodium falciparum malaria was investigated at the Hospital for Tropical Diseases in London. METHODS: Clinical, parasitological and demographic data for all patients presenting with P. falciparum malaria between January 2001 and December 2011 were extracted from a prospective database. These data were supplemented by manual searches of laboratory records and patient case notes. RESULTS: Seven hundred and seventy three adult patients with laboratory-confirmed P. falciparum malaria were identified. Four hundred and sixty five (60%) were born in a country where malaria is endemic. Patients presented to hospital a median of four days into their illness. The median maximum parasite count was 0.4%. One hundred and ninety six patients (25%) had gametocytes; 94 (12%) on admission, and 102 (13%) developing during treatment. Gametocytaemia on admission was associated with anaemia and a lower maximum parasitaemia. Patients with gametocytes at presentation were less likely to have thrombocytopenia or severe malaria. Patients who developed gametocytes during treatment were more likely to have had parasitaemia of long duration, a high maximum parasitaemia and to have had severe malaria. There was no apparent association between the appearance of gametocytes and treatment regimen. CONCLUSIONS: The development of gametocytaemia in travellers with P. falciparum is associated with factors similar to those reported among populations in endemic areas. These data suggest that acquired immunity to malaria is not the only determinant of patterns of gametocyte carriage among patients with the disease

The presence of PHOSPHO1 in matrix vesicles and its developmental expression prior to skeletal mineralization

PHOSPHO1 is a phosphoethanolamine/phosphocholine phosphatase that has previously been implicated in generating inorganic phosphate (Pi) for matrix mineralization. In this study, we have investigated PHOSPHO1 mRNA expression during embryonic development in the chick. Whole-mount in situ hybridization indicated that PHOSPHO1 expression occurred prior to E6.5 and was initially restricted to the bone collar within the mid-shaft of the diaphysis of long bones but by E11.5 expression was observed over the entire length of the diaphysis. Alcian blue/alizarin red staining revealed that PHOSPHO1 expression seen in the primary regions of ossification preceded the deposition of mineral, suggesting that it is involved in the initial events of mineral formation. We isolated MVs from growth plate chondrocytes and confirmed the presence of high levels of PHOSPHO1 by immunoblotting. Expression of PHOSPHO1, like TNAP activity, was found to be up-regulated in MVs isolated from chondrocytes induced to differentiate by the addition of ascorbic acid. This suggests that both enzymes may be regulated by similar mechanisms. These studies provide for the first time direct evidence that PHOSPHO1 is present in MVs, and its developmental expression pattern is consistent with a role in the early stages of matrix mineralization

Community seroprevalence survey for yaws and trachoma in the Western Division of Fiji.

BACKGROUND: Both yaws and trachoma are endemic in several countries in the Pacific. In co-endemic countries there may be potential synergies between both control programmes. METHODS: We undertook a cluster randomised trachoma and yaws seroprevalence survey of children in the Western Division of Fiji. Children were examined for skin lesions consistent with active yaws. A dried blood spot was collected which was tested using the Treponema pallidum particle agglutination (TPPA) test and an ELISA to detect antibodies against Pgp3. RESULTS: A total of 607 children from 305 households across 23 villages were recruited into the survey. On skin examination, no child had clinical evidence of yaws, and the TPPA assay was negative in all children (0%, 95% CI 0.0-0.6). The seroprevalence of Pgp3 antibodies was 20.9% (95% CI 17.8-24.6%). DISCUSSION: In this study there was neither clinical nor serological evidence that transmission of yaws was ongoing. The Pgp3 seroprevalence pattern was consistent with either low level transmission of ocular Chlamydia trachomatis or exposure to C. trachomatis in the birth canal which is consistent with a survey conducted in the same region in 2013. These data suggest neither yaws nor ocular chlamydia infection are a significant public health problem in the Western Division of Fiji

Northeastern Atlantic cold-water coral reefs and climate

U-series age patterns obtained on reef framework-forming cold-water corals collected over a nearly 6,000 km long continental margin sector, extending from off Mauritania to the south-western Barents Sea reveal strong climate influences on the geographical distribution and sustained development of these ecosystems. During glacial times densely populated cold-water coral reefs flourished in the temperate east Atlantic, where at present only scarce live coral occurrences exist. In contrast, climate warming induces a rapid northward colonization of cold-water coral reefs with the biogeographic limit advancing from ~45°N to ~70°N. Thus, we invoke here that north-south oscillations of the polar front during the past glacial-interglacial cycles and the consequent displacement of cold nutrient-rich intermediate waters and productivity drives the decline and expansion of cold-water coral ecosystems and its biogeographic limits in the northeast Atlantic

Low Prevalence of Ocular Chlamydia trachomatis Infection and Active Trachoma in the Western Division of Fiji.

BACKGROUND: Trachoma is the leading infectious cause of blindness and is caused by ocular infection with the bacterium Chlamydia trachomatis (Ct). While the majority of the global disease burden is found in sub-Saharan Africa, the Western Pacific Region has been identified as trachoma endemic. Population surveys carried out throughout Fiji have shown an abundance of both clinically active trachoma and trachomatous trichiasis in all divisions. This finding is at odds with the clinical experience of local healthcare workers who do not consider trachoma to be highly prevalent. We aimed to determine whether conjunctival infection with Ct could be detected in one administrative division of Fiji. METHODS: A population-based survey of 2306 individuals was conducted using the Global Trachoma Mapping Project methodology. Population prevalence of active trachoma in children and trichiasis in adults was estimated using the World Health Organization simplified grading system. Conjunctival swabs were collected from 1009 children aged 1-9 years. DNA from swabs was tested for the presence of the Ct plasmid and human endogenous control. RESULTS: The prevalence of active trachoma in 1-9 year olds was 3.4%. The age-adjusted prevalence was 2.8% (95% CI: 1.4-4.3%). The unadjusted prevalence of ocular Ct infection in 1-9 year-olds was 1.9% (19/1009), and the age-adjusted infection prevalence was 2.3% (95% CI: 0.4-2.5%). The median DNA load was 41 Ct plasmid copies per swab (min 20, first quartile 32, mean 6665, third quartile 161, max 86354). There was no association between current infection and follicular trachoma. No cases of trachomatous trichiasis were identified. DISCUSSION: The Western Division of Fiji has a low prevalence of clinical trachoma. Ocular Ct infections were observed, but they were predominantly low load infections and were not correlated with clinical signs. Our study data suggest that trachoma does not meet the WHO definition of a public health problem in this Division of Fiji, but the inconsistency with previous studies warrants further investigation

Saturable elimination of piperacillin in critically ill patients:implications for continuous infusion

The study aimed to evaluate saturation of piperacillin elimination in critically ill adult patients. Seventeen critically ill adult patients received continuous and intermittent infusion of piperacillin/tazobactam. Piperacillin plasma concentrations (n = 217) were analysed using population pharmacokinetic (PopPK) modelling. Post-hoc simulations were performed to evaluate the type I error rate associated with the study. Unseen data were used to validate the final model. The mean error (ME) and root mean square error (RMSE) were calculated as a measure of bias and imprecision, respectively. A PopPK model with parallel linear and non-linear elimination best fitted the data. The median and 95% confidence interval (CI) for the model parameters drug clearance (CL), volume of central compartment (V), volume of peripheral compartment (V-p) and intercompartmental clearance (Q) were 9 (7.69-11) L/h, 6.18 (4.93-11.2) L, 11.17 (7.26-12) L and 15.61 (12.66-23.8) L/h, respectively. The Michaelis-Menten constant (K-m) and the maximum elimination rate for Michaelis-Menten elimination (V-max) were estimated without population variability in the model to avoid overfitting and inflation of the type I error rate. The population estimates for K-m and V-max were 37.09 mg/L and 353.57 mg/h, respectively. The bias (ME) was -20.8 (95% CI -26.2 to -15.4) mg/L, whilst imprecision (RMSE) was 49.2 (95% CI 41.2-56) mg/L. In conclusion, piperacillin elimination is (partially) saturable. Moreover, the population estimate for K-m lies within the therapeutic window and therefore saturation of elimination should be accounted for when defining optimum dosing regimens for piperacillin in critically ill patients. (C) 2019 Elsevier B.V. and International Society of Chemotherapy. All rights reserved

Human neutrophil clearance of bacterial pathogens triggers anti-microbial gamma delta T cell responses in early infection

Human blood Vc9/Vd2 T cells, monocytes and neutrophils share a responsiveness toward inflammatory chemokines and are rapidly recruited to sites of infection. Studying their interaction in vitro and relating these findings to in vivo observations in patients may therefore provide crucial insight into inflammatory events. Our present data demonstrate that Vc9/Vd2 T cells provide potent survival signals resulting in neutrophil activation and the release of the neutrophil chemoattractant CXCL8 (IL-8). In turn, Vc9/Vd2 T cells readily respond to neutrophils harboring phagocytosed bacteria, as evidenced by expression of CD69, interferon (IFN)-c and tumor necrosis factor (TNF)-a. This response is dependent on the ability of these bacteria to produce the microbial metabolite (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMB-PP), requires cell-cell contact of Vc9/Vd2 T cells with accessory monocytes through lymphocyte function-associated antigen-1 (LFA-1), and results in a TNF-a dependent proliferation of Vc9/Vd2 T cells. The antibiotic fosmidomycin, which targets the HMB-PP biosynthesis pathway, not only has a direct antibacterial effect on most HMB-PP producing bacteria but also possesses rapid anti-inflammatory properties by inhibiting cd T cell responses in vitro. Patients with acute peritoneal-dialysis (PD)-associated bacterial peritonitis – characterized by an excessive influx of neutrophils and monocytes into the peritoneal cavity – show a selective activation of local Vc9/Vd2 T cells by HMB-PP producing but not by HMB-PP deficient bacterial pathogens. The cd T celldriven perpetuation of inflammatory responses during acute peritonitis is associated with elevated peritoneal levels of cd T cells and TNF-a and detrimental clinical outcomes in infections caused by HMB-PP positive microorganisms. Taken together, our findings indicate a direct link between invading pathogens, neutrophils, monocytes and microbe-responsive cd T cells in early infection and suggest novel diagnostic and therapeutic approaches.Martin S. Davey, Chan-Yu Lin, Gareth W. Roberts, Sinéad Heuston, Amanda C. Brown, James A. Chess, Mark A. Toleman, Cormac G.M. Gahan, Colin Hill, Tanya Parish, John D. Williams, Simon J. Davies, David W. Johnson, Nicholas Topley, Bernhard Moser and Matthias Eber