Antimicrobial activity of polyhexamethylene biguanide nanoparticles against mastitis-causing Staphylococcus aureus

Postmilking teat disinfection is one of the main measures used to prevent mastitis caused by contagious pathogens, such as Staphylococcus aureus. The present study evaluated the antimicrobial activity of polyhexamethylene biguanide (PHMB) and PHMB nanoparticles (NP) against mastitis-causing Staph. aureus using a microdilution assay methodology. A total of 20 mastitis-causing Staph. aureus isolates were used to determine the minimum inhibitory concentrations (MIC) of PHMB and PHMB NP compared with 3 disinfectants commonly used for teat disinfection (chlorhexidine digluconate, povidone-iodine, and sodium dichloroisocyanurate). The MIC90 was defined at the concentrations required to inhibit the growth of 90% of Staph. aureus. Our results indicated that PHMB NP presented the lowest MIC value (<0.03 µg/mL) to inhibit 90% of Staph. aureus, followed by chlorhexidine digluconate (≥0.25 µg/mL) and PHMB (≥0.5 µg/mL). On the other hand, sodium dichloroisocyanurate (≥500 µg/mL) and povidone-iodine (≥8,000 µg/mL) presented the highest concentrations to inhibit the growth of most Staph. aureus. Our preliminary results suggested that both PHMB and PHMB NP have antimicrobial activity against mastitis-causing Staph. aureus, which indicates the potential for both to be used as a teat-dip disinfectant to prevent bovine mastitis

Modulation of CD4 T cell function via CD6-targeting

In recent years molecules involved on the immune synapse became successful targets for therapeutic immune modulation. CD6 has been extensively studied, yet, results regarding CD6 biology have been controversial, in spite of the ubiquitous presence of this molecule on virtually all CD4 T cells. We investigated the outcome of murine and human antibodies targeting CD6 domain 1. We found that CD6-targeting had a major impact on the functional specialization of CD4 cells, both human and murine. Differentiation of CD4 T cells towards a Foxp3+ Treg fate was prevented with increasing doses of anti-CD6, while Th1 polarization was favoured. No impact was observed on Th2 or Th17 specialization. These in vitro results provided an explanation for the dose-dependent outcome of in vivo anti-CD6 administration where the anti-inflammatory action is lost at the highest doses. Our data show that therapeutic targeting of the immune synapse may lead to paradoxical dose-dependent effects due to modification of T cell fate.Funded by UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT) / Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) throught Fundos do Orçamento do Estado, pela Fundação para a Ciência e a Tecnologia (FCT) ( PTDC/DTP-FTO/3080/2014 ); and by the project SRecognite Infect - ERA/0003/2015 using national funds through FCT . Funders did not have a role in study design, data collection, analysis, and interpretation, or in the writing of the manuscript

G6PD deficiency alleles in a malaria-endemic region in the Western Brazilian Amazon.

BACKGROUND: Plasmodium vivax parasites are the predominant cause of malaria infections in the Brazilian Amazon. Infected individuals are treated with primaquine, which can induce haemolytic anaemia in glucose-6-phosphate dehydrogenase (G6PD)-deficient individuals and may lead to severe and fatal complications. This X-linked disorder is distributed globally and is caused by allelic variants with a geographical distribution that closely reflects populations exposed historically to endemic malaria. In Brazil, few studies have reported the frequency of G6PD deficiency (G6PDd) present in malaria-endemic areas. This is particularly important, as G6PDd screening is not currently performed before primaquine treatment. The aim of this study was to determine the prevalence of G6PDd in the region of Alto do Juruá, in the Western Brazilian Amazon, an area characterized by a high prevalence of P. vivax infection. METHODS: Five-hundred and sixteen male volunteers were screened for G6PDd using the fluorescence spot test (Beutler test) and CareStart™ G6PD Biosensor system. Demographic and clinical-epidemiological data were acquired through an individual interview. To assess the genetic basis of G6PDd, 24 SNPs were genotyped using the Kompetitive Allele Specific PCR assay. RESULTS: Twenty-three (4.5%) individuals were G6PDd. No association was found between G6PDd and the number of malaria cases. An increased risk of reported haemolysis symptoms and blood transfusions was evident among the G6PDd individuals. Twenty-two individuals had the G6PDd A(-) variant and one the G6PD A(+) variant. The Mediterranean variant was not present. Apart from one polymorphism, almost all SNPs were monomorphic or with low frequencies (0-0.04%). No differences were detected among ethnic groups. CONCLUSIONS: The data indicates that ~1/23 males from the Alto do Juruá could be G6PD deficient and at risk of haemolytic anaemia if treated with primaquine. G6PD A(-) is the most frequent deficiency allele in this population. These results concur with reported G6PDd in other regions in Brazil. Routine G6PDd screening to personalize primaquine administration should be considered, particularly as complete treatment of patients with vivax malaria using chloroquine and primaquine, is crucial for malaria elimination

Distinct placental malaria pathology caused by different Plasmodium berghei lines that fail to induce cerebral malaria in the C57BL/6 mouse

Abstract\ud \ud Background\ud Placental malaria (PM) is one major feature of malaria during pregnancy. A murine model of experimental PM using BALB/c mice infected with Plasmodium berghei ANKA was recently established, but there is need for additional PM models with different parasite/host combinations that allow to interrogate the involvement of specific host genetic factors in the placental inflammatory response to Plasmodium infection.\ud \ud \ud Methods\ud A mid-term infection protocol was used to test PM induction by three P. berghei parasite lines, derived from the K173, NK65 and ANKA strains of P. berghei that fail to induce experimental cerebral malaria (ECM) in the susceptible C57BL/6 mice. Parasitaemia course, pregnancy outcome and placenta pathology induced by the three parasite lines were compared.\ud \ud \ud Results\ud The three P. berghei lines were able to evoke severe PM pathology and poor pregnancy outcome features. The results indicate that parasite components required to induce PM are distinct from ECM. Nevertheless, infection with parasites of the ANKAΔpm4 line, which lack expression of plasmepsin 4, displayed milder disease phenotypes associated with a strong innate immune response as compared to infections with NK65 and K173 parasites.\ud \ud \ud Conclusions\ud Infection of pregnant C57BL/6 females with K173, NK65 and ANKAΔpm4 P. berghei parasites provide experimental systems to identify host molecular components involved in PM pathogenesis mechanisms

Towards a characterization of behavior-disease models

The last decade saw the advent of increasingly realistic epidemic models that leverage on the availability of highly detailed census and human mobility data. Data-driven models aim at a granularity down to the level of households or single individuals. However, relatively little systematic work has been done to provide coupled behavior-disease models able to close the feedback loop between behavioral changes triggered in the population by an individual's perception of the disease spread and the actual disease spread itself. While models lacking this coupling can be extremely successful in mild epidemics, they obviously will be of limited use in situations where social disruption or behavioral alterations are induced in the population by knowledge of the disease. Here we propose a characterization of a set of prototypical mechanisms for self-initiated social distancing induced by local and non-local prevalence-based information available to individuals in the population. We characterize the effects of these mechanisms in the framework of a compartmental scheme that enlarges the basic SIR model by considering separate behavioral classes within the population. The transition of individuals in/out of behavioral classes is coupled with the spreading of the disease and provides a rich phase space with multiple epidemic peaks and tipping points. The class of models presented here can be used in the case of data-driven computational approaches to analyze scenarios of social adaptation and behavioral change.Comment: 24 pages, 15 figure