Seroepidemiology of <i>Trichomonas vaginalis</i> in rural women in Zimbabwe and patterns of association with HIV infection

Serological assays using dried blood spots from 5221 women in rural areas of eastern Zimbabwe were used to assess the epidemiology of Trichomonas vaginalis infection, and its association with HIV. Antibodies to T. vaginalis and to HIV were detected by enzyme immunoassays. Behavioural and demographic data were collected by confidential questionnaires. In total, 516 (9.9%) women were seropositive for T. vaginalis and seroprevalence increased with age among younger women. Divorced, widowed and single women were more likely to be seropositive. After controlling for age, seropositivity was significantly associated with being sexually active, having multiple sex partners, having a partner who had multiple sex partners, and having a new sex partner in the past year. Seropositivity was associated with a recent history of genital discharge. Overall, 208 (40.3%) T. vaginalis-positive samples were also positive for HIV, compared with 1106 (23.5%) T. vaginalis-negative samples (age and sex adjusted OR 2.11, 95% CI 1.74–2.55, P&lt;0.001). There was increased risk for being HIV-positive amongst T. vaginalis-seropositive women regardless of residence, employment or education. In a logistic regression controlling for common risk factors, the association remained significant. T. vaginalis-seropositive young women with a history of genital discharge were much more likely to be HIV-positive than women who were T. vaginalis-seronegative and had no history of discharge (OR 6.08, 95% CI 2.95–12.53). Although a causal relationship cannot be assumed, detection and treatment of trichomoniasis may be important in strategies to reduce HIV transmission through sexually transmitted infection control

dedicated to professor piero cappuccinelli the man for cooperation with developing countries

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Curing is caring? Liability reforms, defensive medicine and malpractice litigation in a post-pandemic world

We analyze different scenarios of defensive medicine in a unique game theoretic framework, representing a healing relationship between a physician and a patient. The physician should choose between providing the optimal treatment or an inferior one, which can amount to practicing defensive medicine. The patient should choose whether to litigate or not, if an adverse event occurs. When both agents have no dominant strategy, we obtain four scenarios representing the positive and negative forms of defensive medicine, with or without physician's moral hazard. We find that certain legal parameters can have opposite effects on the probabilities that physicians practice defensive medicine and that patients litigate, depending respectively on the form of defensive medicine and on the presence of moral hazard. This result can explain the ambiguous results, reported in empirical literature, of legal reforms aimed at discouraging defensive medicine and medical malpractice litigation

A New automatic system of cell colony counting

The counting process of cell colonies is always a long and laborious process that is dependent on the judgment and ability of the operator. The judgment of the operator in counting can vary in relation to fatigue. Moreover, since this activity is time consuming it can limit the usable number of dishes for each experiment. For these purposes, it is necessary that an automatic system of cell colony counting is used. This article introduces a new automatic system of counting based on the elaboration of the digital images of cellular colonies grown on petri dishes. This system is mainly based on the algorithms of region-growing for the recognition of the regions of interest (ROI) in the image and a Sanger neural net for the characterization of such regions. The better final classification is supplied from a Feed-Forward Neural Net (FF-NN) and confronted with the K-Nearest Neighbour (K-NN) and a Linear Discriminative Function (LDF). The preliminary results are shown

Trichomonas vaginalis vast BspA-like gene family: evidence for functional diversity from structural organisation and transcriptomics

<p>Abstract</p> <p>Background</p> <p><it>Trichomonas vaginalis </it>is the most common non-viral human sexually transmitted pathogen and importantly, contributes to facilitating the spread of HIV. Yet very little is known about its surface and secreted proteins mediating interactions with, and permitting the invasion and colonisation of, the host mucosa. Initial annotations of <it>T. vaginalis </it>genome identified a plethora of candidate extracellular proteins.</p> <p>Results</p> <p>Data mining of the <it>T. vaginalis </it>genome identified 911 BspA-like entries (TvBspA) sharing TpLRR-like leucine-rich repeats, which represent the largest gene family encoding potential extracellular proteins for the pathogen. A broad range of microorganisms encoding BspA-like proteins was identified and these are mainly known to live on mucosal surfaces, among these <it>T. vaginalis </it>is endowed with the largest gene family. Over 190 TvBspA proteins with inferred transmembrane domains were characterised by a considerable structural diversity between their TpLRR and other types of repetitive sequences and two subfamilies possessed distinct classic sorting signal motifs for endocytosis. One TvBspA subfamily also shared a glycine-rich protein domain with proteins from <it>Clostridium difficile </it>pathogenic strains and <it>C. difficile </it>phages. Consistent with the hypothesis that TvBspA protein structural diversity implies diverse roles, we demonstrated for several TvBspA genes differential expression at the transcript level in different growth conditions. Identified variants of repetitive segments between several TvBspA paralogues and orthologues from two clinical isolates were also consistent with TpLRR and other repetitive sequences to be functionally important. For one TvBspA protein cell surface expression and antibody responses by both female and male <it>T. vaginalis </it>infected patients were also demonstrated.</p> <p>Conclusions</p> <p>The biased mucosal habitat for microbial species encoding BspA-like proteins, the characterisation of a vast structural diversity for the TvBspA proteins, differential expression of a subset of TvBspA genes and the cellular localisation and immunological data for one TvBspA; all point to the importance of the TvBspA proteins to various aspects of <it>T. vaginalis </it>pathobiology at the host-pathogen interface.</p

Acanthamoeba castellanii (genotype T4) stimulates the production of interleukin-10 as well as pro-inflammatory cytokines in THP-1 cells, human peripheral blood mononuclear cells and human monocyte-derived macrophages

Free-living amoebae of the genus Acanthamoeba can cause severe and chronic infections in humans, mainly localized in immune privileged sites, as the brain and the eye. Monocytes/macrophages are thought to be involved in Acanthamoeba infections, but little is known about how these facultative parasites influence their functions. The aim of this work was to investigate the effects of Acanthamoeba on human monocytes/macrophages, during the early phase of infection. Herein, THP-1 cells, primary human monocytes isolated from peripheral blood and human monocyte-derived macrophages were either co-incubated with trophozoites of a clinical isolate of Acanthamoeba (genotype T4) or stimulated with amoeba-derived cell free conditioned medium. Production of pro-inflammatory cytokines (TNF-α, IL-6, IL-12), anti-inflammatory cytokine (IL-10) and chemokine (IL-8) was evaluated at specific hours post-stimulation (ranging from 1.30 h to 23 h). We showed that both Acanthamoeba trophozoites and soluble amoebic products induce an early anti-inflammatory monocyte-macrophage phenotype, characterized by a significant production of IL-10; furthermore, challenge with either trophozoites or their soluble metabolites stimulate both pro-inflammatory cytokines and chemokine production, suggesting that this protozoan infection may result from the early induction of coexisting, opposed immune responses. Results reported in this paper confirm that the production of pro-inflammatory cytokines and chemokines by monocytes and macrophages can play a role in the development of the inflammatory response during Acanthamoeba infections. Furthermore, we demonstrate for the first time that Acanthamoeba stimulates IL-10 production in human innate immune cells, which might both promote the immune evasion of Acanthamoeba and limit the induced inflammatory response

Identification of <i>Trichomonas vaginalis</i> alpha-actinin as the most common immunogen recognized by sera of women exposed to the parasite

A study on presence of antibodies to Trichomonis vaginalis in serum was done on a group of 500 pregnant, asymptomatic Angolan women. A serologic screening, done by ELISA, revealed that 41% of the women had IgG and IgM against the parasite. Analysis of sera by immunoblotting revealed that 94.4% of sera with anti-T. vaginalis IgG class antibodies were reactive against a common immunogenic protein of 115 kDa. The common immunogen was identified as the protozoan α-actinin. All sera recognizing the 115-kDa antigen were reactive against both native and recombinant T. vaginalis α-actinin and nonreactive against human α-actinin. The findings presented in this work offer a new tool for epidemiologic studies and open new perspectives for vaccination

<i>Trichomonas vaginalis</i> vast BspA-like gene family: evidence for functional diversity from structural organisation and transcriptomics

Background. Trichomonas vaginalis is the most common non-viral human sexually transmitted pathogen and importantly, contributes to facilitating the spread of HIV. Yet very little is known about its surface and secreted proteins mediating interactions with, and permitting the invasion and colonisation of, the host mucosa. Initial annotations of T. vaginalis genome identified a plethora of candidate extracellular proteins. Results. Data mining of the T. vaginalis genome identified 911 BspA-like entries (TvBspA) sharing TpLRR-like leucine-rich repeats, which represent the largest gene family encoding potential extracellular proteins for the pathogen. A broad range of microorganisms encoding BspA-like proteins was identified and these are mainly known to live on mucosal surfaces, among these T. vaginalis is endowed with the largest gene family. Over 190 TvBspA proteins with inferred transmembrane domains were characterised by a considerable structural diversity between their TpLRR and other types of repetitive sequences and two subfamilies possessed distinct classic sorting signal motifs for endocytosis. One TvBspA subfamily also shared a glycine-rich protein domain with proteins from Clostridium difficile pathogenic strains and C. difficile phages. Consistent with the hypothesis that TvBspA protein structural diversity implies diverse roles, we demonstrated for several TvBspA genes differential expression at the transcript level in different growth conditions. Identified variants of repetitive segments between several TvBspA paralogues and orthologues from two clinical isolates were also consistent with TpLRR and other repetitive sequences to be functionally important. For one TvBspA protein cell surface expression and antibody responses by both female and male T. vaginalis infected patients were also demonstrated. Conclusions. The biased mucosal habitat for microbial species encoding BspA-like proteins, the characterisation of a vast structural diversity for the TvBspA proteins, differential expression of a subset of TvBspA genes and the cellular localisation and immunological data for one TvBspA; all point to the importance of the TvBspA proteins to various aspects of T. vaginalis pathobiology at the host-pathogen interface

Gut microbiota and polycystic ovary syndrome, focus on genetic associations: a bidirectional Mendelian randomization study

BackgroundThe contribution of gut microbiota to the pathogenesis of polycystic ovary syndrome (PCOS) is controversial. The causal relationship to this question is worth an in-depth comprehensive of known single nucleotide polymorphisms associated with gut microbiota.MethodsWe conducted bidirectional Mendelian randomization (MR) utilizing instrumental variables associated with gut microbiota (N = 18,340) from MiBioGen GWAS to assess their impact on PCOS risk in the FinnGen GWAS (27,943 PCOS cases and 162,936 controls). Two-sample MR using inverse variance weighting (IVW) was undertaken, followed by the weighted median, weighted mode, and MR-Egger regression. In a subsample, we replicated our findings using the meta-analysis PCOS consortium (10,074 cases and 103,164 controls) from European ancestry.ResultsIVWMR results suggested that six gut microbiota were causally associated with PCOS features. After adjusting BMI, SHBG, fasting insulin, testosterone, and alcohol intake frequency, the effect sizes were significantly reduced. Reverse MR analysis revealed that the effects of PCOS features on 13 gut microbiota no longer remained significant after sensitivity analysis and Bonferroni corrections. MR replication analysis was consistent and the results suggest that gut microbiota was likely not an independent cause of PCOS.ConclusionOur findings did not support the causal relationships between the gut microbiota and PCOS features at the genetic level. More comprehensive genome-wide association studies of the gut microbiota and PCOS are warranted to confirm their genetic relationship.DeclarationThis study contains 3533 words, 0 tables, and six figures in the text as well as night supplementary files and 0 supplementary figures in the Supplementary material

Viruses of protozoan parasites and viral therapy: Is the time now right?

Infections caused by protozoan parasites burden the world with huge costs in terms of human and animal health. Most parasitic diseases caused by protozoans are neglected, particularly those associated with poverty and tropical countries, but the paucity of drug treatments and vaccines combined with increasing problems of drug resistance are becoming major concerns for their control and eradication. In this climate, the discovery/repurposing of new drugs and increasing effort in vaccine development should be supplemented with an exploration of new alternative/synergic treatment strategies. Viruses, either native or engineered, have been employed successfully as highly effective and selective therapeutic approaches to treat cancer (oncolytic viruses) and antibiotic-resistant bacterial diseases (phage therapy). Increasing evidence is accumulating that many protozoan, but also helminth, parasites harbour a range of different classes of viruses that are mostly absent from humans. Although some of these viruses appear to have no effect on their parasite hosts, others either have a clear direct negative impact on the parasite or may, in fact, contribute to the virulence of parasites for humans. This review will focus mainly on the viruses identified in protozoan parasites that are of medical importance. Inspired and informed by the experience gained from the application of oncolytic virus- and phage-therapy, rationally-driven strategies to employ these viruses successfully against parasitic diseases will be presented and discussed in the light of the current knowledge of the virus biology and the complex interplay between the viruses, the parasite hosts and the human host. We also highlight knowledge gaps that should be addressed to advance the potential of virotherapy against parasitic diseases