Advances in Non-Chemical Tools to Control Poultry Hematophagous Mites.

The blood-sucking mites Dermanyssus gallinae ("red mite"), Ornithonyssus sylviarum ("northern fowl mite"), and Ornithonyssus bursa ("tropical fowl mite") stand out for causing infestations in commercial poultry farms worldwide, resulting in significant economic damage for producers. In addition to changes in production systems that include new concerns for animal welfare, global climate change in recent years has become a major challenge in the spread of ectoparasites around the world. This review includes information regarding the main form of controlling poultry mites through the use of commercially available chemicals. In addition, non-chemical measures against blood-sucking mites were discussed such as extracts and oils from plants and seeds, entomopathogenic fungi, semiochemicals, powder such as diatomaceous earth and silica-based products, and vaccine candidates. The control of poultry mites using chemical methods that are currently used to control or eliminate them are proving to be less effective as mites develop resistance. In contrast, the products based on plant oils and extracts, powders of plant origin, fungi, and new antigens aimed at developing transmission-blocking vaccines against poultry mites provide some encouraging options for the rational control of these ectoparasites.

A Review of Major Patents on Potential Malaria Vaccine Targets.

Malaria is a parasitic infection that is a great public health concern and is responsible for high mortality rates worldwide. Different strategies have been employed to improve disease control, demonstrating the ineffectiveness of controlling vectors, and parasite resistance to antimalarial drugs requires the development of an effective preventive vaccine. There are countless challenges to the development of such a vaccine directly related to the parasite's complex life cycle. After more than four decades of basic research and clinical trials, the World Health Organization (WHO) has recommended the pre-erythrocytic Plasmodium falciparum (RTS, S) malaria vaccine for widespread use among children living in malaria-endemic areas. However, there is a consensus that major improvements are needed to develop a vaccine with a greater epidemiological impact in endemic areas. This review discusses novel strategies for malaria vaccine design taking the target stages within the parasite cycle into account. The design of the multi-component vaccine shows considerable potential, especially as it involves transmission-blocking vaccines (TBVs) that eliminate the parasite's replication towards sporozoite stage parasites during a blood meal of female anopheline mosquitoes. Significant improvements have been made but additional efforts to achieve an efficient vaccine are required to improve control measures. Different strategies have been employed, thus demonstrating the ineffectiveness in controlling vectors, and parasite resistance to antimalarial drugs requires the development of a preventive vaccine. Despite having a vaccine in an advanced stage of development, such as the RTS, S malaria vaccine, the search for an effective vaccine against malaria is far from over. This review discusses novel strategies for malaria vaccine design taking into account the target stages within the parasite's life cycle.

Rhipicephalus microplus: An overview of vaccine antigens against the cattle tick.

Rhipicephalus microplus, popularly known as the cattle tick, is the most important tick of livestock as it is responsible for significant economic losses. The use of chemical acaricides is still the most widely used control method despite its known disadvantages. Vaccination would be a safe alternative for the control of R. microplus and holds advantages over the use of chemical acaricides as it is environmental-friendly and leaves no residues in meat or milk. Two vaccines based on the Bm86 protein were commercialized, TickGARD® and Gavac®, with varying reported efficacies in different countries. The use of other vaccines, such as Tick Vac®, Go-Tick®, and Bovimune Ixovac® have been restricted to some countries. Several other proteins have been analyzed as possible antigens for more effective vaccines against R. microplus, including peptidases, serine proteinase inhibitors, glutathione S-transferases, metalloproteases, and ribosomal proteins, with efficacies ranging from 14% to 96%. Nonetheless, more research is needed to develop safe and efficient tick vaccines, such as the evaluation of the efficacy of antigens against other tick species to verify cross-reactivity and inclusion of additional antigens to promote the blocking of the infection and spreading of tick-borne diseases. This review summarizes the discoveries of candidate antigens for R. microplus tick vaccines as well as the methods used to test their efficacy.

Vaccine approaches applied to controlling dog ticks.

Ticks are considered the most important vectors in veterinary medicine with a profound impact on animal health worldwide, as well as being key vectors of diseases affecting household pets. The leading strategy applied to dog tick control is the continued use of acaricides. However, this approach is not sustainable due to surging tick resistance, growing public concern over pesticide residues in food and in the environment, and the rising costs associated with their development. In contrast, tick vaccines are a cost-effective and environmentally friendly alternative against tick-borne diseases by controlling vector infestations and reducing pathogen transmission. These premises have encouraged researchers to develop an effective vaccine against ticks, with several proteins having been characterized and used in native, synthetic, and recombinant forms as antigens in immunizations. The growing interaction between domestic pets and people underscores the importance of developing new tick control measures that require effective screening platforms applied to vaccine development. However, as reviewed in this paper, very little progress has been made in controlling ectoparasite infestations in pets using the vaccine approach. The control of tick infestations and pathogen transmission could be obtained through immunization programs aimed at reducing the tick population and interfering in the pathogenic transmission that affects human and animal health on a global scale.

Canine visceral leishmaniasis biomarkers and their employment in vaccines.

The natural history of canine visceral leishmaniasis (CVL) has been well described, particularly with respect to the parasite load in different tissues and immunopathological changes according to the progression of clinical forms. The biomarkers evaluated in these studies provide support for the improvement of the tools used in developing vaccines against CVL. Thus, we describe the major studies using the dog model that supplies the rationale for including different biomarkers (tissue parasitism, histopathology, hematological changes, leucocytes immunophenotyping, cytokines patterns, and in vitroco-culture systems using purified T-cells subsets and macrophages infected with L. infantum) for immunogenicity and protection evaluations in phases I and II applied to pre-clinical and clinical vaccine trials against CVL. The search for biomarkers related to resistance or susceptibility has revealed a mixed cytokine profile with a prominent proinflammatory immune response as relevant for Leishmania replication at low levels as observed in asymptomatic dogs (highlighted by high levels of IFN-γ and TNF-α and decreased levels in IL-4, TGF-ß and IL-10). Furthermore, increased levels in CD4+ and CD8+ T-cell subsets, presenting intracytoplasmic proinflammatory cytokine balance, have been associated with a resistance profile against CVL. In contrast, a polyclonal B-cell expansion towards plasma cell differentiation contributes to high antibody production, which is the hallmark of symptomatic dogs associated with high susceptibility in CVL. Finally, the different studies used to analyze biomarkers have been incorporated into vaccine immunogenicity and protection evaluations. Those biomarkers identified as resistance or susceptibility markers in CVL have been used to evaluate the vaccine performance against L. infantum in a kennel trial conducted before the field trial in an area known to be endemic for visceral leishmaniasis. This rationale has been a guiding force in the testing and selection of the best vaccine candidates against CVL and provides a way for the veterinary industry to register commercial immunobiological products.

Regulatory monocytes in helminth infections: insights from the modulation during human hookworm infection.

BACKGROUND: While the macrophage polarization is well characterized in helminth infections, the natural heterogeneity of monocytes with multiple cell phenotypes might influence the outcome of neglected diseases, such hookworm infection. Here, we report the profile of monocytes in human hookworm infections as a model to study the regulatory subpopulation of monocytes in helminth infections. METHODS: Blood samples were collected from 19 Necator americanus-infected individuals and 13 healthy individuals. Peripheral blood mononuclear cells (PBMCs) were isolated, and immunophenotyping was conducted by flow cytometry. The expressions of genes encoding human nitric oxide synthase (iNOS), interleukin 4 (IL-4), arginase-1 (Arg-1) and glyceraldehyde 3-phosphate dehydrogenase were quantified by qPCR. Plasma levels of IL-4 were determined by sandwich ELISA. Unpaired t-tests or Mann-Whitney tests were used depending on the data distribution. RESULTS: Hookworm infected individuals (HWI) showed a significant increase in the number of monocytes/mm3 (555.2 ± 191.0) compared to that of the non-infected (NI) individuals (120.4 ± 44.7) (p < 0.0001). While the frequencies of CD14+IL-10+ and CD14+IL-12+ cells were significantly reduced in the HWI compared to NI group (p = 0.0289 and p < 0.0001, respectively), the ratio between IL-10/IL-12 producing monocytes was significantly elevated in HWI (p = 0.0004), indicating the potential regulatory activity of these cells. Measurement of IL-4 levels and gene expression of IL-4 and Arg-1 (highly expressed in alternatively activated macrophages) revealed no significant differences between the NI and HWI groups. Interestingly, individuals from the HWI group had higher expression of the iNOS gene (associated with a regulatory profile) (20.27 ± 2.97) compared to the NI group (11.28 ± 1.18, p = 0.0409). Finally, individuals from the HWI group had a significantly higher frequency of CD206+CD23+IL-10+ (7.57 ± 1.96) cells compared to individuals from the NI group (0.35 ± 0.09) (p < 0.001), suggesting that activated monocytes are a potential source of regulatory cytokines during hookworm infection. CONCLUSIONS: Natural hookworm infection induces a high frequency of circulating monocytes that present a regulatory profile and promote the downmodulation of the proinflammatory response, which may contribute to prolonged survival of the parasite in the host.

Baccharis trimera inhibits reactive oxygen species production through PKC and down-regulation p47 phox phosphorylation of NADPH oxidase in SK Hep-1 cells.

Baccharis trimera, popularly known as "carqueja", is a native South-American plant possessing a high concentration of polyphenolic compounds and therefore high antioxidant potential. Despite the antioxidant potential described for B. trimera, there are no reports concerning the signaling pathways involved in this process. So, the aim of the present study was to assess the influence of B. trimera on the modulation of PKC signaling pathway and to characterize the effect of the nicotinamide adenine dinucleotide phosphate oxidase enzyme (NOX) on the generation of reactive oxygen species in SK Hep-1 cells. SK-Hep 1 cells were treated with B. trimera, quercetin, or rutin and then stimulated or not with PMA/ionomycin and labeled with carboxy H2DCFDA for detection of reactive oxygen species by flow cytometer. The PKC expression by Western blot and enzyme activity was performed to evaluate the influence of B. trimera and quercetin on PKC signaling pathway. p47 phox and p47 phox phosphorylated expression was performed by Western blot to evaluate the influence of B. trimera on p47 phox phosphorylation. The results showed that cells stimulated with PMA/ionomycin (activators of PKC) showed significantly increased reactive oxygen species production, and this production returned to baseline levels after treatment with DPI (NOX inhibitor). Both B. trimera and quercetin modulated reactive oxygen species production through the inhibition of PKC protein expression and enzymatic activity, also with inhibition of p47 phox phosphorylation. Taken together, these results suggest that B. trimera has a potential mechanism for inhibiting reactive oxygen species production through the PKC signaling pathway and inhibition subunit p47 phox phosphorylation of nicotinamide adenine dinucleotide phosphate oxidase.

Impact of LbSapSal Vaccine in Canine Immunological and Parasitological Features before and after Leishmania chagasi-Challenge.

Dogs represent the most important domestic reservoir of L. chagasi (syn. L. infantum). A vaccine against canine visceral leishmaniasis (CVL) would be an important tool for decreasing the anxiety related to possible L. chagasi infection and for controlling human visceral leishmaniasis (VL). Because the sand fly salivary proteins are potent immunogens obligatorily co-deposited during transmission of Leishmania parasites, their inclusion in an anti-Leishmania vaccine has been investigated in past decades. We investigated the immunogenicity of the "LbSapSal" vaccine (L. braziliensis antigens, saponin as adjuvant, and Lutzomyia longipalpis salivary gland extract) in dogs at baseline (T0), during the post-vaccination protocol (T3rd) and after early (T90) and late (T885) times following L. chagasi-challenge. Our major data indicated that immunization with "LbSapSal" is able to induce biomarkers characterized by enhanced amounts of type I (tumor necrosis factor [TNF]-α, interleukin [IL]-12, interferon [IFN]-γ) cytokines and reduction in type II cytokines (IL-4 and TGF-ß), even after experimental challenge. The establishment of a prominent pro-inflammatory immune response after "LbSapSal" immunization supported the increased levels of nitric oxide production, favoring a reduction in spleen parasitism (78.9%) and indicating long-lasting protection against L. chagasi infection. In conclusion, these results confirmed the hypothesis that the "LbSapSal" vaccination is a potential tool to control the Leishmania chagasi infection.