Tackling debt, biodiversity loss, and climate change.

Experience tells us how to maximize debt-for-nature effectiveness.

A diverse portfolio of marine protected areas can better advance global conservation and equity.

Marine protected areas (MPAs) are widely used for ocean conservation, yet the relative impacts of various types of MPAs are poorly understood. We estimated impacts on fish biomass from no-take and multiple-use (fished) MPAs, employing a rigorous matched counterfactual design with a global dataset of >14,000 surveys in and around 216 MPAs. Both no-take and multiple-use MPAs generated positive conservation outcomes relative to no protection (58.2% and 12.6% fish biomass increases, respectively), with smaller estimated differences between the two MPA types when controlling for additional confounding factors (8.3% increase). Relative performance depended on context and management: no-take MPAs performed better in areas of high human pressure but similar to multiple-use in remote locations. Multiple-use MPA performance was low in high-pressure areas but improved significantly with better management, producing similar outcomes to no-take MPAs when adequately staffed and appropriate use regulations were applied. For priority conservation areas where no-take restrictions are not possible or ethical, our findings show that a portfolio of well-designed and well-managed multiple-use MPAs represents a viable and potentially equitable pathway to advance local and global conservation.

Type I and III interferons shape the retinal cytokine network and barrier function in an in vitro model of ocular toxoplasmosis.

Introduction: The particularities of the ocular immune environment and its barrier protection in the context of infection are not well elucidated. The apicomplexan parasite Toxoplasma gondii is one of the pathogens successfully crossing this barrier and establishing chronic infection in retinal cells. Methods: As a first approach, we studied the initial cytokine network in vitro in four human cell lines: Retinal pigmented epithelial (RPE), microglial, astrocytic and Müller cells. Furthermore, we looked at the consequences of retinal infection on the integrity of the outer blood-retina barrier (oBRB). We particularly focused on the roles of type I and type III interferons, (IFN-ß and IFN-λ). Especially IFN-λ is known for its significant role in barrier defense. However, its effect on the retinal barrier or T. gondii infection remains unexplored, unlike IFN-γ, which has been extensively studied in this context. Results and Discussion: Here, we show that stimulation with type I and III interferons did not limit parasite proliferation in retinal cells we tested. However, IFN-ß and IFN-γ strongly induced inflammatory or cell-attracting cytokine production, whereas IFN-λ1 showed less inflammatory activity. Concomitant T. gondii infection influenced these cytokine patterns, distinctly depending on the parasite strain. Interestingly, all these cells could be stimulated to produce IFN-λ1. Using an in vitro oBRB model based on RPE cells, we observed that interferon stimulation strengthened membrane localization of the tight junction protein ZO-1 and enhanced their barrier function, in a STAT1-independent manner. Conclusion: Together, our model shows how T. gondii infection shapes the retinal cytokine network and barrier function, and demonstrates the role of type I and type III interferons in these processes.

Dynamic Immune Profile in French Toxoplasmosis Patients.

BACKGROUND: Toxoplasma gondii infection is usually benign in Europe due to the strong predominance of type II strains. Few studies have been conducted to examine the immunological course of infection in humans and have yielded conflicting results, maybe influenced by heterogeneous parasite strains. METHODS: We measured 23 immune mediators in 39, 40, and 29 sera of French noninfected, acutely infected, and chronically infected immunocompetent pregnant women, respectively. RESULTS: Four different cytokine patterns were identified regarding their dynamics through infection phases. For 11 of the cytokines (IFN-ß, IFN-γ, IL-4, IL5, IL-6, IL-10, IL-12, IL-15, CXCL9, CCL2, and CSF2) the serum levels were significantly elevated during acute infection. The inflammatory mediators IL-1ß, IL-17A, IL-18, TNF-α, and CSF3 remained unchanged during acute infection, while they were significantly lower in chronically infected compared to noninfected patients. As for the anti-inflammatory cytokines TGF-ß and CCL5, their levels remained significantly elevated during chronic infection. We also observed a significant negative correlation of several cytokine concentrations with IgG levels, indicating a rapid decline of serum concentrations during the acute phase. CONCLUSIONS: These results indicate an anti-inflammatory pattern in chronically infected patients in a type II dominated setting and demonstrate the highly dynamic immune situation during acute infection.

Protein undernutrition reduces the efficacy of praziquantel in a murine model of Schistosoma mansoni infection.

BACKGROUND: Undernutrition and schistosomiasis are public health problems and often occur in low and middle-income countries. Protein undernutrition can alter the host-parasite environment system and aggravate the course of schistosomiasis. This study aimed to assess the impact of a low-protein diet on the efficacy of praziquantel. METHODOLOGY/PRINCIPAL FINDINGS: Thirty-day-old mice were fed with a low-protein diet, and 40 days later, they were individually infected with fifty Schistosoma mansoni cercariae. A 28-day-treatment with praziquantel at 100 mg/kg for five consecutive days followed by distilled water begins on the 36th day post-infection. Mice were sacrificed on the 64th day post-infection. We determined the parasitological burden, liver and intestine histomorphometry, liver injury, and immunomodulation parameters. Praziquantel treatment of infected mice fed with a standard diet (IN-PZQ) resulted in a significant reduction of worm and egg burdens and a normalization of iron and calcium levels. The therapy also improved schistosomiasis-induced hepatopathy and oxidative stress. The anti-inflammatory and immunomodulatory activities of praziquantel were also significant in these mice. When infected mice receiving the low-protein diet were treated with praziquantel (ILP-PZQ), the body weight loss and hepatomegaly were not alleviated, and the worm and liver egg burdens were significantly higher than those of IN-PZQ mice (P < 0.001). The treatment did not reduce the increased activities of ALT and γ-GGT, the high malondialdehyde concentration, and the liver granuloma volume. The iron and calcium levels were not ameliorated and differed from those of IN-PZQ mice (P < 0.001 and P < 0.05). Moreover, in these mice, praziquantel treatment did not reverse the high level of IL-5 and the low mRNA expression of CCL3/MIP-1α and CXCL-10/IP-10 induced by S. mansoni infection. CONCLUSION/SIGNIFICANCE: These results demonstrated that a low-protein diet reduced the schistosomicidal, antioxidant, anti-inflammatory, and immunomodulatory activities of praziquantel.

Pathological and immunological evaluation of different regimens of praziquantel treatment in a mouse model of Schistosoma mansoni infection.

BACKGROUND: One of the considerable challenges of schistosomiasis chemotherapy is the inefficacy of praziquantel (PZQ) at the initial phase of the infection. Immature schistosomes are not susceptible to PZQ at the curative dose. Here, we investigated the efficacy of different PZQ regimens administered during the initial stage of Schistosoma mansoni infection in mice. METHODOLOGY/PRINCIPAL FINDINGS: Two months-old mice were individually infected with 80 S. mansoni cercariae and divided into one infected-untreated control group (IC) and four PZQ-treated groups: PZQ at 100 mg/kg/day for five consecutive days (group PZQ1), PZQ at 100 mg/kg/day for 28 days (group PZQ2), PZQ at 18 mg/kg/day for 28 days (group PZQ3) and a single dose of PZQ at 500 mg/kg (group PZQ4). The treatment started on day one post-infection (p.i), and each group of mice was divided into two subgroups euthanized on day 36 or 56 p.i, respectively. We determined the mortality rate, the parasitological burden, the hepatic and intestinal granulomas, the serum levels of Th-1, Th-2, and Th-17 cytokines, and gene expression. The treatment led to a significant (p < 0.001) reduction of worm burden and egg counts in the intestine and liver in groups PZQ2 and PZQ3. On 56th day p.i, there was a significant reduction (p < 0.001) of the number and volume of the hepatic granulomas in groups PZQ2 and PZQ3 compared to group PZQ1 or PZQ4. Moreover, in group PZQ3, the serum levels of IFN-γ, TNF-α, IL-13, and IL-17 and their liver mRNA expressions were significantly reduced while IL-10 and TGF-ß gene expression significantly increased. The highest mortality rate (81.25%) was recorded in group PZQ2. CONCLUSION/SIGNIFICANCE: This study revealed that the administration of PZQ at 18 mg/kg/day for 28 consecutive days was the optimal effective posology for treating S. mansoni infection at the initial stage in a murine model.

Babesia crassa-Like Human Infection Indicating Need for Adapted PCR Diagnosis of Babesiosis, France.

Human babesiosis in Europe is caused by multiple zoonotic species. We describe a case in a splenectomized patient, in which a routine Babesia divergens PCR result was negative. A universal Babesia spp. PCR yielded a positive result and enabled classification of the parasite into the less-described Babesia crassa-like complex.

Rapid and low-cost insect detection for analysing species trapped on yellow sticky traps.

While insect monitoring is a prerequisite for precise decision-making regarding integrated pest management (IPM), it is time- and cost-intensive. Low-cost, time-saving and easy-to-operate tools for automated monitoring will therefore play a key role in increased acceptance and application of IPM in practice. In this study, we tested the differentiation of two whitefly species and their natural enemies trapped on yellow sticky traps (YSTs) via image processing approaches under practical conditions. Using the bag of visual words (BoVW) algorithm, accurate differentiation between both natural enemies and the Trialeurodes vaporariorum and Bemisia tabaci species was possible, whereas the procedure for B. tabaci could not be used to differentiate this species from T. vaporariorum. The decay of species was considered using fresh and aged catches of all the species on the YSTs, and different pooling scenarios were applied to enhance model performance. The best performance was reached when fresh and aged individuals were used together and the whitefly species were pooled into one category for model training. With an independent dataset consisting of photos from the YSTs that were placed in greenhouses and consequently with a naturally occurring species mixture as the background, a differentiation rate of more than 85% was reached for natural enemies and whiteflies.

Pathophysiology of ocular toxoplasmosis: Facts and open questions.

Infections with the protozoan parasite Toxoplasma gondii are frequent, but one of its main consequences, ocular toxoplasmosis (OT), remains poorly understood. While its clinical description has recently attracted more attention and publications, the underlying pathophysiological mechanisms are only sparsely elucidated, which is partly due to the inherent difficulties to establish relevant animal models. Furthermore, the particularities of the ocular environment explain why the abundant knowledge on systemic toxoplasmosis cannot be just transferred to the ocular situation. However, studies undertaken in mouse models have revealed a central role of interferon gamma (IFNγ) and, more surprisingly, interleukin 17 (IL17), in ocular pathology and parasite control. These studies also show the importance of the genetic background of the infective Toxoplasma strain. Indeed, infections due to exotic strains show a completely different pathophysiology, which translates in a different clinical outcome. These elements should lead to more individualized therapy. Furthermore, the recent advance in understanding the immune response during OT paved the way to new research leads, involving immune pathways poorly studied in this particular setting, such as type I and type III interferons. In any case, deeper knowledge of the mechanisms of this pathology is needed to establish new, more targeted treatment schemes.

Toxoplasma gondii ROP16 kinase silences the cyclin B1 gene promoter by hijacking host cell UHRF1-dependent epigenetic pathways.

Toxoplasmosis, caused by the apicomplexan parasite Toxoplasma gondii, is one of the most common infections in the world due to the lifelong persistence of this parasite in a latent stage. This parasite hijacks host signaling pathways through epigenetic mechanisms which converge on key nuclear proteins. Here, we report a new parasite persistence strategy involving T. gondii rhoptry protein ROP16 secreted early during invasion, which targets the transcription factor UHRF1 (ubiquitin-like containing PHD and RING fingers domain 1), and leads to host cell cycle arrest. This is mediated by DNMT activity and chromatin remodeling at the cyclin B1 gene promoter through recruitment of phosphorylated UHRF1 associated with a repressive multienzymatic protein complex. This leads to deacetylation and methylation of histone H3 surrounding the cyclin B1 promoter to epigenetically silence its transcriptional activity. Moreover, T. gondii infection causes DNA hypermethylation in its host cell, by upregulation of DNMTs. ROP16 is already known to activate and phosphorylate protective immunity transcription factors such as STAT 3/6/5 and modulate host signaling pathways in a strain-dependent manner. Like in the case of STAT6, the strain-dependent effects of ROP16 on UHRF1 are dependent on a single amino-acid polymorphism in ROP16. This study demonstrates that Toxoplasma hijacks a new epigenetic initiator, UHRF1, through an early event initiated by the ROP16 parasite kinase.

The Trick of the Hedgehog: Case Report and Short Review About Archaeopsylla erinacei (Siphonaptera: Pulicidae) in Human Health.

Fleas are ectoparasites of various animals, including Homo sapiens Linnaeus, 1758 (Primates: Hominidae). Among the species relevant to the human health field, either due to their dermatopathological potential or because of their role as vectors of microorganisms responsible for infectious diseases, such as plague or murine typhus, are the human flea, oriental rat flea, closely related cat and dog fleas, and chigoe flea. However, other species can accidentally infest humans. We have herein reported two unusual cases of humans infested and bitten by Archaeopsylla erinacei, the hedgehog flea. This species has been identified using stereomicroscopy, on the base of key characteristics. Furthermore, a brief literature review has revealed that hedgehog fleas could carry human-infectious agents, such as Rickettsia felis Bouyer et al. 2001 (Rickettsiales: Rickettsiaceae) or Bartonella henselae Regnery et al.1992 (Rhizobiales: Bartonellaceae). Using molecular biology, we thus tested nine A. erinacei specimens taken from these patients, for several bacteria species commonly associated with hematophagous arthropods, implicated in human pathology. However, all our samples were proven negative. The role of A. erinacei in human epidemiology has never been evaluated to date. This report sought to remind us that these fleas can be accidental parasites in humans. In addition, recent findings pertaining to bacteria of medical interest that are present in these insects should be brought to the fore, given that the question of their role as vectors in human infections remains unanswered and deserves further investigation.

Locally acquired infection with Dibothriocephalus nihonkaiense (=Diphyllobothrium nihonkaiense) in France: the importance of molecular diagnosis.

Diphyllobothriasis is a parasitic fish-borne disease caused by tapeworms of the genus Dibothriocephalus (=Diphyllobothrium). The majority of reported cases are attributed to D. latum, based on morphological identification of eggs or proglottids. However, numerous reports in recent years suggested that other Dibothriocephalus species could be involved in human infections, mainly after consumption of salmonid fish. Among these, D. nihonkaiense has been predominantly reported from Eastern Asia and probably underestimated in the rest of the world. We report here a clinical case of D. nihonkaiense in a French patient (without history of travel abroad) after consumption of salmon. Suspected on morphological characteristics, the final identification of D. nihonkaiense was performed using molecular methods by sequencing nad1, cox1, and 5.8S rRNA (containing ITS1 and 2) genes sequences. The patient was successfully treated by a single dose of praziquantel. Reports of diphyllobothriasis due to D. nihonkaiense are rare outside Asia, but worldwide demand of seafood could lead to the globalization of cases and reflect the need to monitor the distribution of Dibothriocephalus species. Thus, clinical parasitologists should be aware of this risk and able to raise the possibility of infections by non-endemic Dibothriocephalus species in order to use the proper molecular tools.

Mitespotting: approaches for Aculops lycopersici monitoring in tomato cultivation.

Aculops lycopersici is a major pest in tomato cultivation worldwide, and lately its relevance in German tomato cultivation has increased markedly. Aculops lycopersici causes damage to tomato plants by feeding on the surface of leaves, stem and fruits and can lead to the loss of whole plants. Given the small size of the pest, A. lycopersici infestation may go unnoticed for quite a length of time. When discovered symptoms can be easily confused with those of diseases. In addition to these issues A. lycopersici has a very high reproduction rate. In this study, fluorescence measurements were performed on the stem of A. lycopersici-inoculated potted tomato plants and these were compared with a visual bare eye assessment and a sticky tape imprint method for classification of these plants as either infested or healthy. The best correct classification rate was achieved with sticky tape, but this method is time intensive, which makes it unsuitable for large-scale monitoring in practice. Classification based on a ridge regression performed on stem fluorescence measurements was at least as good as the classification based on the visual assessment, and detection was robust against symptoms of drought stress. In a second trial the specificity of stem fluorescence measurements for A. lycopersici against Trialeurodes vaporariorum was tested successfully. The fluorescence method is promising as this method allows for high automation and thereby has the potential to increase monitoring efficacy in practice considerably. The relevance of the tested monitoring methods for practical tomato cultivation and the next steps to be taken are discussed.

Pervasive human-driven decline of life on Earth points to the need for transformative change.

The human impact on life on Earth has increased sharply since the 1970s, driven by the demands of a growing population with rising average per capita income. Nature is currently supplying more materials than ever before, but this has come at the high cost of unprecedented global declines in the extent and integrity of ecosystems, distinctness of local ecological communities, abundance and number of wild species, and the number of local domesticated varieties. Such changes reduce vital benefits that people receive from nature and threaten the quality of life of future generations. Both the benefits of an expanding economy and the costs of reducing nature's benefits are unequally distributed. The fabric of life on which we all depend-nature and its contributions to people-is unravelling rapidly. Despite the severity of the threats and lack of enough progress in tackling them to date, opportunities exist to change future trajectories through transformative action. Such action must begin immediately, however, and address the root economic, social, and technological causes of nature's deterioration.

Biological Diagnosis of Ocular Toxoplasmosis: a Nine-Year Retrospective Observational Study.

Ocular toxoplasmosis (OT), i.e., the ocular manifestation of Toxoplasma gondii infection, is one of the leading causes of posterior uveitis. While ocular lesions are often typical, atypical forms often require biological confirmation of the diagnosis. Our study sought to review the biological OT diagnoses made in our laboratory to further assess the role of each test in the diagnostic procedure. All ocular samples sent to our laboratory over the last 9 years for OT diagnosis were included. These samples were analyzed using T. gondii PCR and antibody detection by means of immunoblotting and Candolfi coefficient (CC) determinations, either alone or in combination. Since serum analysis is required to interpret both the CC and immunoblotting, blood serology for T. gondii was also performed in most cases. Of the 249 samples analyzed, 80 (32.1%; 95% confidence interval [95%CI], 26.3 to 37.9) were positive for OT. Of these 80 cases, 52/80 (65.0%; 54.6 to 74.5) displayed a positive PCR, 15/80 (18.8%; 10.2 to 27.3) a positive CC, and 33/80 (41.3%; 95%CI, 30.5 to 52.0) a positive immunoblot result. Overall, 63 of the 80 OT diagnoses (78.8%; 95%CI, 69.8 to 87.7) were made on the basis of a single positive test result. Our study results remind us that current biological diagnostic tools for OT must be employed in combination to obtain an optimal diagnosis based on the precious ocular fluids sampled by ophthalmologists. Clinicobiological studies that are focused on correlating the performances of the different tests with clinical features are critically needed to improve our understanding of the pathophysiology and diagnosis of OT.IMPORTANCE Ocular toxoplasmosis (OT), a parasitic infection of the eye, is considered to be the most important infectious cause of posterior uveitis worldwide. Its prevalence is particularly high in South America, where aggressive Toxoplasma gondii strains are responsible for more-severe presentations. The particular pathophysiology of this infection leads, from recurrence to recurrence, to potentially severe vision impairment. The diagnosis of this infection is usually exclusively based on the clinical examination. However, the symptoms may be misleading and are not always sufficient to confirm a diagnosis of OT. In such cases, biological tests performed by means of several techniques on blood and ocular samples may facilitate the diagnosis. In this study, we analyzed the tests that were performed in our laboratory over a 9-year period every time OT was suspected. Our report highlights that the quality of ocular sampling by ophthalmologists and combinations of several techniques are critical for a reliable biological OT diagnosis.

Impacts of protected areas vary with the level of government: Comparing avoided deforestation across agencies in the Brazilian Amazon.

Protected areas (PAs) are the leading tools to conserve forests. However, given their mixed effectiveness, we want to know when they have impacts internally and, if they do, when they have spillovers. Political economy posits roles for the level of government. One hypothesis is that federal PAs avoid more internal deforestation than state PAs since federal agencies consider gains for other jurisdictions. Such political differences as well as economic mechanisms can cause PA spillovers to vary greatly, even from "leakage," more deforestation elsewhere, to "blockage," less deforestation elsewhere. We examine internal impacts and local spillovers for Brazilian Amazon federal and state agencies. Outside the region's "arc of deforestation," we confirm little internal impact and show no spillovers. In the "arc," we test impacts by state, as states are large and feature considerably different dynamics. For internal impacts, estimates for federal PAs and indigenous lands are higher than for state PAs. For local spillover impacts, estimates for most arc states either are not significant or are not robust; however, for Pará, federal PAs and indigenous lands feature both internal impacts and local spillovers. Yet, the spillovers in Pará go in opposite directions across agencies, leakage for indigenous lands but blockage for federal PAs, suggesting a stronger external signal from the environmental agency. Across all these tools, only federal PAs lower deforestation internally and nearby. Results suggest that agencies' objectives and capacities are critical parts of the contexts for conservation strategies.