Evolution of retrovirus-infected premalignant T-cell clones prior to adult T-cell leukemia/lymphoma diagnosis.

Adult T-cell leukemia/lymphoma (ATL) is an aggressive hematological malignancy caused by human T-cell leukemia virus type-1 (HTLV-1). ATL is preceded by decades of chronic HTLV-1 infection, and the tumors carry both somatic mutations and proviral DNA integrated into the tumor genome. In order to gain insight into the oncogenic process, we used targeted sequencing to track the evolution of the malignant clone in 6 individuals, 2 to 10 years before the diagnosis of ATL. Clones of premalignant HTLV-1-infected cells bearing known driver mutations were detected in the blood up to 10 years before individuals developed acute and lymphoma subtype ATL. Six months before diagnosis, the total number and variant allele fraction of mutations increased in the blood. Peripheral blood mononuclear cells from premalignant cases (1 year prediagnosis) had significantly higher mutational burden in genes frequently mutated in ATL than did high-risk, age-matched HTLV-1 carriers who remained ATL-free after a median of 10 years of follow-up. These data show that HTLV-1-infected T-cell clones carrying key oncogenic driver mutations can be detected in cases of ATL years before the onset of symptoms. Early detection of such mutations may enable earlier and more effective intervention to prevent the development of ATL.

Evaluation of curcuma and ginger mixture ability to prevent ROS production induced by bisphenol S: an in vitro study.

The use of bisphenol S (BPS) as a substitute of Bisphenol A is increasing in several products and it can be found in different environmental and biological matrices. Its toxicity has been studied at different levels and one of BPS toxic mechanisms at high concentrations seems to be the induction of oxidative stress through the generation of reactive oxygen species (ROS). This study evaluates the ability of a curcuma and ginger (CG) mixture to exert an antioxidant effect on rat hepatocytes treated with BPS. The effects of the mixture were compared to those of a well-known antioxidant (Trolox). Three different BPS concentrations were used in order to verify ROS production. 70 µg/mL and 150 µg/mL of BPS generated a significant ROS increase (p < 0.01) as compared to control, while CG mixture was able to decrease this ROS production in hepatic cells, as compared to cells treated with 70 µg/ml of BPS (p < 0.01) restoring control levels. BPS 70 µg/mL was tested for total antioxidant capacity (TEAC), superoxide dismutase (SOD) and total thiols. TEAC and SOD significant decreased (p < 0.05 and p < 0.01, respectively) as compared to controls and CG mixture was able to restore control values. Given the widespread BPS use, results obtained in this study can be of high impact for the community, demonstrating the ability of a mixture of natural products to prevent BPS-induced oxidative stress.

Switching and loss of cellular cytokine producing capacity characterize in vivo viral infection and malignant transformation in human T- lymphotropic virus type 1 infection.

Adult T-cell leukaemia/lymphoma (ATL) arises from chronic non-malignant human T lymphotropic virus type-1 (HTLV-1) infection which is characterized by high plasma pro-inflammatory cytokines whereas ATL is characterized by high plasma anti-inflammatory (IL-10) concentrations. The poor prognosis of ATL is partly ascribed to disease-associated immune suppression. ATL cells have a CD4+CCR4+CD26-CD7- immunophenotype but infected cells with this immunophenotype ('ATL-like' cells) are also present in non-malignant HTLV-1 infection. We hypothesized that 'ATL-like' and ATL cells have distinct cytokine producing capacity and a switch in the cytokines produced occurs during leukemogenesis. Seventeen asymptomatic carriers (ACs), 28 patients with HTLV-1-associated myelopathy (HAM) and 28 with ATL were studied. Plasma IL-10 concentration and the absolute frequency of IL-10-producing CD4+ T cells were significantly higher in patients with ATL compared to AC. IL-10-producing ATL cells were significantly more frequent than 'ATL-like' cells. The cytokine-producing cells were only a small fraction of ATL cells. Clonality analysis revealed that even in patients with ATL the ATL cells were composed not only of a single dominant clone (putative ATL cells) but also tens of non-dominant infected clones ('ATL-like' cells). The frequency of cytokine-producing cells showed a strong inverse correlation with the relative abundance of the largest clone in ATL cells suggesting that the putative ATL cells were cytokine non-producing and that the 'ATL-like' cells were the primary cytokine producers. These findings were confirmed by RNAseq with cytokine mRNA expression in ATL cells in patients with ATL (confirmed to be composed of both putative ATL and 'ATL-like' cells by TCR analysis) significantly lower compared to 'ATL-like' cells in patients with non-malignant HTLV-1 infection (confirmed to be composed of hundreds of non-dominant clones by TCR analysis). A significant inverse correlation between the relative abundance of the largest clone and cytokine mRNA expression was also confirmed. Finally, 'ATL-like' cells produced less pro- and more anti-inflammatory cytokines than non 'ATL-like' CD4+ cells (which are predominantly HTLV uninfected). In summary, HTLV-1 infection of CD4+ T cells is associated with a change in cytokine producing capacity and dominant malignant clonal growth is associated with loss of cytokine producing capacity. Non-dominant clones with 'ATL-like' cells contribute to plasma cytokine profile in patients with non-malignant HTLV-1 infection and are also present in patient with ATL.

Investigation of the effects of Lycium barbarum polysaccharides against cadmium induced damage in testis.

This study describes the effects of Lycium barbarum polysaccharides (LBP) on testicular damage induced by cadmium (Cd). Adult male rats were i.p. injected with CdCl2 (4mg/Kg, once) with or without LBP pretreatment (300mg/Kg orally, once a day, for 30days). Testis weight, morphological/histological structure and oxidative stress parameters were evaluated. Several adverse effects were observed after CdCl2 injection, with a significant decrease in body/testis weight ratio (P<0.05), gross morphological changes with hyperemia of the parenchyma, increased volume and alteration in the structure of the seminiferous tubules. Furthermore, Cd intoxication caused a significant decrease of glutathione (GSH) and Trolox equivalent antioxidant capacity (TEAC) in testis (P<0.05) together with a significant increase (P<0.01) of 3-nitro-l-tyrosine (3NT) while malondialdehyde (MDA) did not change. LBP pretreatment caused slight signs of improvement in the morphology of the seminiferous tubules. Our results confirm that Cd induces testicular damage and suggest the oxidative stress involvement. LBP could ameliorate Cd testicular damage but further investigations are needed.

Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients.

BACKGROUND: Human T-lymphotropic virus type 1 (HTLV-1) infects an estimated 10 million persons globally with transmission resulting in lifelong infection. Disease, linked to high proviral load, occurs in a minority. In established infection HTLV-1 replicates through infectious spread and clonal expansion of infected lymphocytes. Little is known about acute HTLV-1 infection. The kinetics of early HTLV-1 infection, following transplantation-acquired infection in three recipients from one HTLV-1 infected donor, is reported. The recipients were treated with two HTLV-1 enzyme inhibitors 3 weeks post exposure following the detection of HTLV-1 provirus at low level in each recipient. HTLV-1 infection was serially monitored by serology, quantification of proviral load and HTLV-1 2LTR DNA circles and by HTLV-1 unique integration site analysis. RESULTS: HTLV-1 antibodies were first detected 16-39 days post-transplantation. HTLV-1 provirus was detected by PCR on day 16-23 and increased by 2-3 log by day 38-45 with a peak proviral doubling time of 1.4 days, after which steady state was reached. The rapid proviral load expansion was associated with high frequency of HTLV-1 2LTR DNA circles. The number of HTLV-1 unique integration sites was high compared with established HTLV-1 infection. Clonal expansion of infected cells was detected as early as day 37 with high initial oligoclonality index, consistent with early mitotic proliferation. CONCLUSIONS: In recipients infected through organ transplantation HTLV-1 disseminated rapidly despite early anti-HTLV-1 treatment. Proviral load set point was reached within 6 weeks. Seroconversion was not delayed. Unique integration site analysis and HTLV-1 2LTR DNA circles indicated early clonal expansion and high rate of infectious spread.

HTLV-1 viral RNA is detected rarely in plasma of HTLV-1 infected subjects.

Plasma of patients infected with HTLV-1 is considered non-infectious but detection of HTLV-1 genomic RNA in plasma has been recently reported. The aim of this project was to detect and quantify HTLV-1 RNA in plasma and assess its potential value in diagnosis and prognosis. RNA from 1 ml of plasma from 65 subjects infected with HTLV-1 (27 asymptomatic carriers [AC]), 17 patients with HTLV-1-associated myelopathy (HAM/TSP), 14 with adult T-cell leukemia/lymphoma (ATLL), two co-infected with HIV, and five with other HTLV-1-associated disease, was extracted and reverse transcribed. HTLV-1 specific nested PCR was performed using primers to amplify the conserved Tax region. All samples were run in quadruplicate, nested PCR products were detected by gel electrophoresis. HTLV-1 RNA was detected in plasma from 18 (28%) patients, always at a very low copy number (3-13 copies viral cDNA per milliliter of plasma). Mean values of HTLV-1 proviral load did not differ between patients in whom HTLV-1 RNA was detected and patients in whom it was not possible to detect HTLV-1 RNA in plasma. HTLV-1 genomic RNA can be detected in the plasma of a minority of patients but not at a level or frequency to be useful clinically or diagnostically. Lack of transmission of HTLV-1 by plasma is due to the rare presence of HTLV-1 virions, regardless of any other factor.

Investigation on gabapentin residues in eggs from free-range hens exposed to saline slags from pharmaceutical industry.

A simple, sensitive and rapid liquid chromatography-tandem mass spectrometry method (LC-MS/MS) was developed and validated to monitor the presence of gabapentin as environmental contaminant in albumen and yolk of eggs from grazing flocks exposed to open air stored saline wastes from pharmaceutical industry. The method involved a simple liquid extraction followed by a gradient elution with formic acid 0.2 % and acetonitrile in reverse phase. ESI ionization was performed in positive ion mode. The tandem mass spectrometer was operated in multiple reaction monitoring mode. The calibration curves were linear in the concentration range from 5 to 400 ng/g for the two matrices with correlation coefficients that exceeded 0.990. The limits of quantitation were 12.0 and 14.8 ng/g in albumen and yolk, respectively. Results are discussed in light of the pharmacokinetics of gabapentin in experimentally exposed hens, accounting for the top soil intake in such free grazing animals.

Contaminants of Emerging Concern: Antibiotics Research in Mussels from the Coasts of the Tyrrhenian Sea (Sardinia, Italy).

Contaminants of emerging concern (CECs) are compounds found in several environmental compartments whose ubiquitous presence can cause toxicity for the entire ecosystem. Several personal care products, including antibiotics, have entered this group of compounds, constituting a major global threat. It is essential to develop simple and reliable methods by which to quantify these contaminants in several matrices. In this work, mussels were chosen as sentinel organisms to assess environmental pollution and the safety of bivalve mollusk consumption according to the "One Health perspective". A liquid chromatographic tandem mass spectrometry method (LC-MS/MS) was developed for the quantification of two macrolides, erythromycin (ERY) and azithromycin (AZI), in mussels. This new method was validated according to international guidelines, showing high selectivity, good recoveries (>60% for both of them), sensitivity, and precision. The method was successfully applied for ERY and AZI research in mussels farmed along the Sardinian coasts (Italy), demonstrating itself to be useful for routine analysis by competent authorities. The tested macrolides were not determined in the analyzed sites at concentrations above the limits of detection (LODs). These results demonstrate the food safety of mussels (as concerns the studied antibiotics) and a negligible amount of pollution derived from these drugs in the studied area.

Ovine papillomavirus type 3 virus-like particle-based tools for diagnosis and detection of infection.

The design of prophylactic and diagnostic tools specific to animal papillomaviruses is hampered by the difficulties of viral in vitro manipulation and by the scarce availability of dedicated biotechnological tools. This paper reports the production of Ovine Papillomavirus 3 (OaPV3)-based virus-like particles (OaPV3-VLPs) in the baculovirus system and their use to investigate host humoral immune response through the establishment of an indirect ELISA test., Polyclonal sera and monoclonal antibodies were generated against OaPV3-VLPs, and their isotype and reactivity were determined. Additionally, antibodies allowed OaPV3 detection in ovine squamous cell carcinoma (SCC) samples by immunohistochemistry. Results encourage the standardization of OaPV3-specific prophylactic and serological diagnostic tools, and open new perspectives for the study of host-viral interaction and SCC development.

Development of immunodiagnostic tools for in situ investigation of Ovis aries papillomavirus 3 (OaPV3).

Cutaneous squamous cell carcinoma (cSCC) is a malignant lesion characterized by proliferation and transformation of keratinocytes in the epidermis and infiltrating derma. cSCC is reported in domestic and wild animal species, worldwide. The occurrence and development of cSCC rely on synergic multifactorial conditions, most importantly sunlight exposure and Papillomavirus (PV) infection. In sheep, the development of such lesions represents a threat both to animal welfare and milk production. Ovis aries papillomavirus 3 (OaPV3) is the main cSCC viral determinant and oncogenic properties of viral E6 and E7 proteins were preliminarily investigated. However, E6 and E7 role and mechanisms resulting in cSCC have not been fully clarified, mainly due to the lack specific immunological tools, such as antibodies for in situ detection of ovine papillomavirus. This paper reports the development of specific serological tools for the investigation of OaPV3 pathogenicity, and their preliminary use to screen 4 ovine cSSC formalin-fixed paraffin embedded tissues. Relevance of immunological tools to investigation of viral biological properties and diagnosis are also discussed.

In vivo expression of human T-lymphotropic virus type 1 basic leucine-zipper protein generates specific CD8+ and CD4+ T-lymphocyte responses that correlate with clinical outcome.

BACKGROUND: The roles of the human T-lymphotropic virus type 1 (HTLV-1) basic leucine zipper (HBZ) gene are not clearly understood. We examined CD8+ and CD4+ T cell responses to HBZ and compared these with Tax responses. METHOD: Interferon (IFN)-γ and interleukin (IL)-2-secreting T cells were detected by enzyme-linked immunosorbent spot (ELISpot) assays of freshly isolated peripheral blood mononuclear cells (PBMCs) stimulated with synthetic HBZ or Tax peptides. Ten patients with HTLV-1-associated myelopathy (HAM) and 20 asymptomatic HTLV-1 carriers (ACs), (10 high, 10 low viral load). RESULTS: Of 30 study participants, 17 had detectable HBZ-specific CD4+ T cells and 12 had HBZ-specific CD8+ T cell responses. Detection of Tax-specific CD4+ T cells (IL-2- or IFN-γ-secreting) did not differ by disease status, but Tax-specific CD8+ T cell responses were more commonly detected in patients with HAM. HBZ-specific CD4+ or CD8+ T cells were less likely to be detected than Tax-specific T cells. IL-2-secreting Tax-specific CD8+ T cells, and IFN-γ-secreting Tax-specific CD4+ T cells were associated with HAM. Low viral load, asymptomatic HTLV-1 carriage was associated with IL-2-secreting CD8+ T cells specific for HBZ. CONCLUSION: HBZ protein is expressed in vivo in patients with HAM and in ACs. Our results are consistent with the idea that the T cell response to HBZ plays an important part in restricting HTLV-1 viral load.

Single-Nucleotide Polymorphisms in the Beta-Tubulin Gene and Its Relationship with Treatment Response to Albendazole in Human Soil-Transmitted Helminths in Southern Mozambique.

Soil-transmitted helminth (STH) cornerstone control strategy is mass drug administration (MDA) with benzimidazoles. However, MDA might contribute to selection pressure for anthelmintic resistance, as occurred in livestock. The aim of this study is to evaluate the treatment response to albendazole and the relationship with the presence of putative benzimidazole resistance single-nucleotide polymorphisms (SNPs) in the ß-tubulin gene of STH in Southern Mozambique. After screening 819 participants, we conducted a cohort study with 184 participants infected with STH in Manhiça district, Southern Mozambique. A pretreatment and a posttreatment stool samples were collected and the STH infection was identified by duplicate Kato-Katz and quantitative polymerase chain reaction (qPCR). Cure rate and egg reduction rates were calculated. Putative benzimidazole resistance SNPs (F167Y, F200T, and E198A) in Trichuris trichiura and Necator americanus were assessed by pyrosequencing. Cure rates by duplicate Kato-Katz and by qPCR were 95.8% and 93.6% for Ascaris lumbricoides, 28% and 7.8% for T. trichiura, and 88.9% and 56.7% for N. americanus. Egg reduction rate by duplicate Kato-Katz was 85.4% for A. lumbricoides, 34.9% for T. trichiura, and 40.5% for N. americanus. Putative benzimidazole resistance SNPs in the ß-tubulin gene were detected in T. trichiura (23%) and N. americanus (21%) infected participants at pretreatment. No statistical difference was observed between pretreatment and posttreatment frequencies for none of the SNPs. Although treatment response to albendazole was low, particularly in T. trichiura, the putative benzimidazole resistance SNPs were not higher after treatment in the population studied. New insights are needed for a better understanding and monitoring of human anthelmintic resistance.

Evaluation of antibody serology to determine current helminth and Plasmodium falciparum infections in a co-endemic area in Southern Mozambique.

BACKGROUND: Soil-transmitted helminths (STH), Schistosoma spp. and Plasmodium falciparum are parasites of major public health importance and co-endemic in many sub-Saharan African countries. Management of these infections requires detection and treatment of infected people and evaluation of large-scale measures implemented. Diagnostic tools are available but their low sensitivity, especially for low intensity helminth infections, leaves room for improvement. Antibody serology could be a useful approach thanks to its potential to detect both current infection and past exposure. METHODOLOGY: We evaluated total IgE responses and specific-IgG levels to 9 antigens from STH, 2 from Schistosoma spp., and 16 from P. falciparum, as potential markers of current infection in a population of children and adults from Southern Mozambique (N = 715). Antibody responses were measured by quantitative suspension array Luminex technology and their performance was evaluated by ROC curve analysis using microscopic and molecular detection of infections as reference. PRINCIPAL FINDINGS: IgG against the combination of EXP1, AMA1 and MSP2 (P. falciparum) in children and NIE (Strongyloides stercoralis) in adults and children had the highest accuracies (AUC = 0.942 and AUC = 0.872, respectively) as markers of current infection. IgG against the combination of MEA and Sm25 (Schistosoma spp.) were also reliable markers of current infection (AUC = 0.779). In addition, IgG seropositivity against 20 out of the 27 antigens in the panel differentiated the seropositive endemic population from the non-endemic population, suggesting a possible role as markers of exposure although sensitivity could not be assessed. CONCLUSIONS: We provided evidence for the utility of antibody serology to detect current infection with parasites causing tropical diseases in endemic populations. In addition, most of the markers have potential good specificity as markers of exposure. We also showed the feasibility of measuring antibody serology with a platform that allows the integration of control and elimination programs for different pathogens.

An Overview of Antibiotics as Emerging Contaminants: Occurrence in Bivalves as Biomonitoring Organisms.

Antibiotics are used for therapeutic and prophylactic purposes in both human and veterinary medicine and as growth promoting agents in farms and aquaculture. They can accumulate in environmental matrices and in the food chain, causing adverse effects in humans and animals including the development of antibiotic resistance. This review aims to update and discuss the available data on antibiotic residues, using bivalves as biomonitoring organisms. The current research indicates that antibiotics' presence in bivalves has been investigated along European, American and Asian coasts, with the majority of studies reported for the last. Several classes of antibiotics have been detected, with a higher frequency of detection reported for macrolides, sulfonamides and quinolones. The highest concentration was instead reported for tetracyclines in bivalves collected in the North Adriatic Sea. Only oxytetracycline levels detected in this latter site exceeded the maximum residual limit established by the competent authorities. Moreover, the risk that can be derived from bivalve consumption, calculated considering the highest concentrations of antibiotics residues reported in the analyzed studies, is actually negligible. Nevertheless, further supervisions are needed in order to preserve the environment from antibiotic pollution, prevent the development of antimicrobial resistance and reduce the health risk derived from seafood consumption.

Bisphenols' occurrence in bivalves as sentinel of environmental contamination.

Bisphenols are massively used in several manufacture processes such that bisphenol A (BPA) is ubiquitous in environment worldwide. After the implementation of regulations about BPA use, manufacturers have moved their production toward alternative substances structurally similar to it. Unfortunately, BPA analogues, given their structural similarity, exert also similar adverse effects. This review aims to investigate the occurrence of bisphenols (BPs) in bivalve molluscs. In this way, valuable information on the amount of BPs released into the environment in different areas are given. The current research indicates that BPA presence in bivalve molluscs has been investigated in Asia (Indian Ocean and Pacific Ocean), Europe (Mediterranean Sea, Baltic Sea and Atlantic Ocean) and America (Lake Mead, Nevada) with the highest amount of studies reported in bivalves harvested in Asian Coasts. BPA analogues are frequently detected in several matrices and their levels will continuously increase in the environment. Nevertheless, there is a current lack of studies analysing BPs other than BPA in bivalves. Further investigations should be conducted in this direction, in order to assess environmental distribution and the hazard for animals and human health given that seafood consumption could be an important pathway of bisphenols intake.

Improving stool sample processing and pyrosequencing for quantifying benzimidazole resistance alleles in Trichuris trichiura and Necator americanus pooled eggs.

BACKGROUND: There is an urgent need for an extensive evaluation of benzimidazole efficacy in humans. In veterinary science, benzimidazole resistance has been mainly associated with three single-nucleotide polymorphisms (SNPs) in the isotype-1 ß-tubulin gene. In this study, we optimized the stool sample processing methodology and resistance allele frequency assessment in Trichuris trichiura and Necator americanus anthelmintic-related SNPs by pyrosequencing, and standardized it for large-scale benzimidazole efficacy screening use. METHODS: Three different protocols for stool sample processing were compared in 19 T. trichiura-positive samples: fresh stool, egg concentration using metallic sieves with decreasing pore size, and egg concentration followed by flotation with saturated salt solution. Yield of each protocol was assessed by estimating the load of parasite DNA by real-time PCR. Then, we sequenced a DNA fragment of the ß-tubulin gene containing the putative benzimidazole resistance SNPs in T. trichiura and N. americanus. Afterwards, resistant and susceptible-type plasmids were produced and mixed at different proportions, simulating different resistance levels. These mixtures were used to compare previously described pyrosequencing assays with processes newly designed by our own group. Once the stool sample processing and the pyrosequencing methodology was defined, the utility of the protocols was assessed by measuring the frequencies of putative resistance SNPs in 15 T. trichiura- and 15 N. americanus-positive stool samples. RESULTS: The highest DNA load was provided by egg concentration using metallic sieves with decreasing pore size. Sequencing information of the ß-tubulin gene in Mozambican specimens was highly similar to the sequences previously reported, for T. trichiura and N. americanus, despite the origin of the sample. When we compared pyrosequencing assays using plasmids constructs, primers designed in this study provided the most accurate SNP frequencies. When pooled egg samples were analysed, none of resistant SNPs were observed in T. trichiura, whereas 17% of the resistant SNPs at codon 198 were found in one N. americanus sample. CONCLUSIONS: We optimized the sample processing methodology and standardized pyrosequencing in soil-transmitted helminth (STH) pooled eggs. These protocols could be used in STH large-scale screenings or anthelmintic efficacy trials.

Towards soil-transmitted helminths transmission interruption: The impact of diagnostic tools on infection prediction in a low intensity setting in Southern Mozambique.

World Health Organization goals against soil-transmitted helminthiases (STH) are pointing towards seeking their elimination as a public health problem: reducing to less than 2% the proportion of moderate and heavy infections. Some regions are reaching WHO goals, but transmission could rebound if strategies are discontinued without an epidemiological evaluation. For that, sensitive diagnostic methods to detect low intensity infections and localization of ongoing transmission are crucial. In this work, we estimated and compared the STH infection as obtained by different diagnostic methods in a low intensity setting. We conducted a cross-sectional study enrolling 792 participants from a district in Mozambique. Two stool samples from two consecutive days were collected from each participant. Samples were analysed by Telemann, Kato-Katz and qPCR for STH detection. We evaluated diagnostic sensitivity using a composite reference standard. By geostatistical methods, we estimated neighbourhood prevalence of at least one STH infection for each diagnostic method. We used environmental, demographical and socioeconomical indicators to account for any existing spatial heterogeneity in infection. qPCR was the most sensitive technique compared to composite reference standard: 92% (CI: 83%- 97%) for A. lumbricoides, 95% (CI: 88%- 98%) for T. trichiura and 95% (CI: 91%- 97%) for hookworm. qPCR also estimated the highest neighbourhood prevalences for at least one STH infection in a low intensity setting. While 10% of the neighbourhoods showed a prevalence above 20% when estimating with single Kato-Katz from one stool and Telemann from one stool, 86% of the neighbourhoods had a prevalence above 20% when estimating with qPCR. In low intensity settings, STH estimated prevalence of infection may be underestimated if based on Kato-Katz. qPCR diagnosis outperformed the microscopy methods. Thus, implementation of qPCR based predictive maps at STH control and elimination programmes would disclose hidden transmission and facilitate targeted interventions for transmission interruption.

Plasmodium falciparum and Helminth Coinfections Increase IgE and Parasite-Specific IgG Responses.

Coinfection with Plasmodium falciparum and helminths may impact the immune response to these parasites because they induce different immune profiles. We studied the effects of coinfections on the antibody profile in a cohort of 715 Mozambican children and adults using the Luminex technology with a panel of 16 antigens from P. falciparum and 11 antigens from helminths (Ascaris lumbricoides, hookworm, Trichuris trichiura, Strongyloides stercoralis, and Schistosoma spp.) and measured antigen-specific IgG and total IgE responses. We compared the antibody profile between groups defined by P. falciparum and helminth previous exposure (based on serology) and/or current infection (determined by microscopy and/or qPCR). In multivariable regression models adjusted by demographic, socioeconomic, water, and sanitation variables, individuals exposed/infected with P. falciparum and helminths had significantly higher total IgE and antigen-specific IgG levels, magnitude (sum of all levels) and breadth of response to both types of parasites compared to individuals exposed/infected with only one type of parasite (P ≤ 0.05). There was a positive association between exposure/infection with P. falciparum and exposure/infection with helminths or the number of helminth species, and vice versa (P ≤ 0.001). In addition, children coexposed/coinfected tended (P = 0.062) to have higher P. falciparum parasitemia than those single exposed/infected. Our results suggest that an increase in the antibody responses in coexposed/coinfected individuals may reflect higher exposure and be due to a more permissive immune environment to infection in the host. IMPORTANCE Coinfection with Plasmodium falciparum and helminths may impact the immune response to these parasites because they induce different immune profiles. We compared the antibody profile between groups of Mozambican individuals defined by P. falciparum and helminth previous exposure and/or current infection. Our results show a significant increase in antibody responses in individuals coexposed/coinfected with P. falciparum and helminths in comparison with individuals exposed/infected with only one of these parasites, and suggest that this increase is due to a more permissive immune environment to infection in the host. Importantly, this study takes previous exposure into account, which is particularly relevant in endemic areas where continuous infections imprint and shape the immune system. Deciphering the implications of coinfections deserves attention because accounting for the real interactions that occur in nature could improve the design of integrated disease control strategies.

Brain renin-angiotensin system modifies the blood pressure response to intracerebroventricular cadmium in rats.

In order to elucidate the involvement of the brain renin-angiotensin system (RAS) in cadmium intracerebroventricular (ICV) hypertension, we evaluated the effects of a pretreatment with different drugs: clonidine, an alpha(2) adrenergic agonist, enalapril and captopril, both ACE inhibitors, and saralasin, a competitive nonselective AT(1) and AT(2) receptor antagonist. We used a rat strain with low levels of kallikrein (LKR) that was more sensitive to ICV cadmium hypertension, compared with normal kallikrein rats (NKRs), the control strain. The interplay between the kallikrein-kinin system and the RAS in the LKR strain caused various hemodynamic alterations, which we believe were the result of elevated RAS activity in these animals. Moreover, we suggest that the defective kallikrein-kinin system in LKR may also cause an alteration in the activation of brain RAS in these animals. The LKR displayed elevated concentrations of plasma AII, hypertrophy of the myocardium, and initial alterations in the renal glomerulotubular system. With the exception of clonidine, all of the other drugs showed greater antihypertensive effects of differing statistical significance in LKR, compared with NKR. Both ACE inhibitors were able to significantly reduce pressor response to cadmium ICV in LKR throughout the experiment, whereas in NKR, they were only able to reduce the hypertensive peak of cadmium. A significant protective effect was also observed in LKR pretreated with saralasin, while no effect was observed in NKR. These findings confirm the presence of brain RAS activation in LKR and its contribution to the central control of pressor response to cadmium ICV.