Increased HIV Incidence in Men Who Have Sex with Men Despite High Levels of ART-Induced Viral Suppression: Analysis of an Extensively Documented Epidemic

Background: There is interest in expanding ART to prevent HIV transmission, but in the group with the highest levels of ART use, men-who-have-sex-with-men (MSM), numbers of new infections diagnosed each year have not decreased as ART coverage has increased for reasons which remain unclear. Methods: We analysed data on the HIV-epidemic in MSM in the UK from a range of sources using an individual-based simulation model. Model runs using parameter sets found to result in good model fit were used to infer changes in HIV-incidence and risk behaviour. Results: HIV-incidence has increased (estimated mean incidence 0.30/100 person-years 1990–1997, 0.45/100 py 1998–2010), associated with a modest (26%) rise in condomless sex. We also explored counter-factual scenarios: had ART not been introduced, but the rise in condomless sex had still occurred, then incidence 2006–2010 was 68% higher; a policy of ART initiation in all diagnosed with HIV from 2001 resulted in 32% lower incidence; had levels of HIV testing been higher (68% tested/year instead of 25%) incidence was 25% lower; a combination of higher testing and ART at diagnosis resulted in 62% lower incidence; cessation of all condom use in 2000 resulted in a 424% increase in incidence. In 2010, we estimate that undiagnosed men, the majority in primary infection, accounted for 82% of new infections. Conclusion: A rise in HIV-incidence has occurred in MSM in the UK despite an only modest increase in levels of condomless sex and high coverage of ART. ART has almost certainly exerted a limiting effect on incidence. Much higher rates of HIV testing combined with initiation of ART at diagnosis would be likely to lead to substantial reductions in HIV incidence. Increased condom use should be promoted to avoid the erosion of the benefits of ART and to prevent other serious sexually transmitted infections

The origins of the trypanosome genome strains Trypanosoma brucei brucei TREU 927, T. b. gambiense DAL 972, T. vivax Y486 and T. congolense IL3000

The genomes of several tsetse-transmitted African trypanosomes (Trypanosoma brucei brucei, T. b. gambiense, T. vivax, T. congolense) have been sequenced and are available to search online. The trypanosome strains chosen for the genome sequencing projects were selected because they had been well characterised in the laboratory, but all were isolated several decades ago. The purpose of this short review is to provide some background information on the origins and biological characterisation of these strains as a source of reference for future users of the genome data. With high throughput sequencing of many more trypanosome genomes in prospect, it is important to understand the phylogenetic relationships of the genome strains

Managing Tsetse Transmitted Trypanosomosis by Insecticide Treated Nets - an Affordable and Sustainable Method for Resource Poor Pig Farmers in Ghana

An outbreak of tsetse-transmitted trypanosomiasis resulted in more than 50% losses of domestic pigs in the Eastern Region of Ghana (source: Veterinary Services, Accra; April 2007). In a control trial from May 4th–October 10th 2007, the efficacy of insecticide-treated mosquito fences to control tsetse was assessed. Two villages were selected – one serving as control with 14 pigsties and one experimental village where 24 pigsties were protected with insecticide treated mosquito fences. The 100 cm high, 150denier polyester fences with 100 mg/m2 deltamethrin and a UV protector were attached to surrounding timber poles and planks. Bi-monthly monitoring of tsetse densities with 10 geo-referenced bi-conical traps per village showed a reduction of more than 90% in the protected village within two months. Further reductions exceeding 95% were recorded during subsequent months. The tsetse population in the control village was not affected, only displaying seasonal variations. Fifty pigs from each village were ear-tagged and given a single curative treatment with diminazene aceturate (3.5 mg/kg bw) after their blood samples had been taken. The initial trypanosome prevalence amounted to 76% and 72% of protected and control animals, respectively, and decreased to 16% in protected as opposed to 84% in control pigs three months after intervention. After six months 8% of the protected pigs were infected contrasting with 60% in the control group

The FERM and PDZ Domain-Containing Protein Tyrosine Phosphatases, PTPN4 and PTPN3, Are Both Dispensable for T Cell Receptor Signal Transduction

PTPN3 and PTPN4 are two closely-related non-receptor protein tyrosine phosphatases (PTP) that, in addition to a PTP domain, contain FERM (Band 4.1, Ezrin, Radixin, and Moesin) and PDZ (PSD-95, Dlg, ZO-1) domains. Both PTP have been implicated as negative-regulators of early signal transduction through the T cell antigen receptor (TCR), acting to dephosphorylate the TCRζ chain, a component of the TCR complex. Previously, we reported upon the production and characterization of PTPN3-deficient mice which show normal TCR signal transduction and T cell function. To address if the lack of a T cell phenotype in PTPN3-deficient mice can be explained by functional redundancy of PTPN3 with PTPN4, we generated PTPN4-deficient and PTPN4/PTPN3 double-deficient mice. As in PTPN3 mutants, T cell development and homeostasis and TCR-induced cytokine synthesis and proliferation were found to be normal in PTPN4-deficient and PTPN4/PTPN3 double-deficient mice. PTPN13 is another FERM and PDZ domain-containing non-receptor PTP that is distantly-related to PTPN3 and PTPN4 and which has been shown to function as a negative-regulator of T helper-1 (Th1) and Th2 differentiation. Therefore, to determine if PTPN13 might compensate for the loss of PTPN3 and PTPN4 in T cells, we generated mice that lack functional forms of all three PTP. T cells from triple-mutant mice developed normally and showed normal cytokine secretion and proliferative responses to TCR stimulation. Furthermore, T cell differentiation along the Th1, Th2 and Th17 lineages was largely unaffected in triple-mutants. We conclude that PTPN3 and PTPN4 are dispensable for TCR signal transduction

Early bilirubinemia after allogeneic stem cell transplantation - an endothelial complication

Hyperbilirubinemia occurs frequently after allogeneic stem cell transplantation. Causes include primary liver damage and endothelial complications as major contributors. Here, we have investigated the impact of early bilirubinemia (EB) on posttransplant outcomes. Maximum total bilirubin levels (days 0-28) were categorized using maximally selected log rank statistics to identify a cut off for the endpoint non-relapse mortality (NRM) in a training cohort of 873 patients. EB above this cut off was correlated with NRM and overall survival (OS) and with pre- and posttransplant Angiopoietin-2, interleukin (IL)18, CXCL8 and suppressor of tumorigenicity-2 (ST2) serum levels, and the endothelial activation and stress index (EASIX). Clinical correlations were validated in a sample of 388 patients transplanted in an independent institution. The EB cut off was determined at 3.6 mg/dL (61.6 mu M). EB predicted OS (HR 1.60, 95% CI 1.21-2.12, p < 0.001), and NRM (CSHR 2.14; 1.28-3.56, p = 0.004), also independent of typical endothelial complications such as veno-occlusive disease, refractory acute graft-versus-host disease, or transplant-associated microangiopathy. However, EB correlated with high Angiopoietin-2, EASIX-pre and EASIX-day 0, as well as increased levels of posttransplant CXCL8, IL18, and ST2. In summary, EB indicates a poor prognosis. The association of EB with endothelial biomarkers suggests an endothelial pathomechanism also for this posttransplant complication

Effects of two oil dispersants on phototaxis and swimming behaviour of barnacle larvae

The effects of two oil dispersants (Vecom B-1425 GL and Norchem OSD-570) mixed with diesel oil on the survival and behaviour of the stage II nauplii of the barnacle Balanus amphitrite were investigated. The 24 and 48-hour LC50 values for Vecom B-1425 GL:diesel mixture were 514 and 48 mg 1-1 respectively, while respective values for Norchem OSD-570:diesel mixture were 505 and 71 mg 1-1. Under sublethal concentrations, increased levels of the dispersant:diesel mixtures caused a reduction in phototactic responses. Balanus amphitrite nauplii failed to exhibit phototactic responses when exposed to Vecom B-1425 GL:diesel mixtures of 400 mg 1-1 and higher for 24 hours. A longer exposure time of 48 hours further reduced the Lowest Observable Effect Concentrations (LOECs) to 60 mg 1-1. The LOECs for Norchem OSD-570:diesel mixtures under exposure periods of 24 and 48 hours were 400 and 80 mg 1-1 respectively. The curvilinear velocities (VCL) and straight-line velocities (VSL) of the stage II nauplii ranged from 0.7-1.1 and 0.2-0.4 mm s-1 respectively. Increased concentrations of dispersant:diesel mixtures caused a significant change in the curvilinear and straight-line velocities. Both oil dispersants, dispersant:diesel mixtures of 20 to 40 mg 1-1 caused significant increases in VCL, but no significant change in VSL. Dispersant:diesel mixtures of 100 mg 1-1 and higher resulted in a reduction in VSL for both dispersants. ©1997 Kluwer Academic Publishers.link_to_subscribed_fulltex