A research agenda for helminth diseases of humans: diagnostics for control and elimination programmes

Diagnostic tools appropriate for undertaking interventions to control helminth infections are key to their success. Many diagnostic tests for helminth infection have unsatisfactory performance characteristics and are not well suited for use in the parasite control programmes that are being increasingly implemented. Although the application of modern laboratory research techniques to improve diagnostics for helminth infection has resulted in some technical advances, uptake has not been uniform. Frequently, pilot or proof of concept studies of promising diagnostic technologies have not been followed by much needed product development, and in many settings diagnosis continues to rely on insensitive and unsatisfactory parasitological or serodiagnostic techniques. In contrast, PCR-based xenomonitoring of arthropod vectors, and use of parasite recombinant proteins as reagents for serodiagnostic tests, have resulted in critical advances in the control of specific helminth parasites. The Disease Reference Group on Helminths Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR) was given the mandate to review helminthiases research and identify research priorities and gaps. In this review, the diagnostic technologies relevant to control of helminth infections, either available or in development, are reviewed. Critical gaps are identified and opportunities to improve needed technologies are discussed.     

Cocoa Consumption Alters the Global DNA Methylation of Peripheral Leukocytes in Humans with Cardiovascular Disease Risk Factors: A Randomized Controlled Trial

DNA methylation regulates gene expression and can be modified by different bioactive compounds in foods, such as polyphenols. Cocoa is a rich source of polyphenols, but its role in DNA methylation is still unknown. The objective was to assess the effect of cocoa consumption on DNA methylation and to determine whether the enzymes involved in the DNA methylation process participate in the mechanisms by which cocoa exerts these effects in humans. The global DNA methylation levels in the peripheral blood were evaluated in 214 volunteers who were pre-hypertensive, stage-1 hypertensive or hypercholesterolemic. The volunteers were divided into two groups: 110 subjects who consumed cocoa (6 g/d) for two weeks and 104 control subjects. In addition, the peripheral blood mononuclear cells (PBMCs) from six subjects were treated with a cocoa extract to analyze the mRNA levels of the DNA methyltransferases (DNMTs), methylenetetrahydrofolate reductase (MTHFR), and methionine synthase reductase (MTRR) genes. Cocoa consumption significantly reduced the DNA methylation levels (2.991±0.366 vs. 3.909±0.380, p<0.001). Additionally, we found an association between the cocoa effects on DNA methylation and three polymorphisms located in the MTHFR, MTRR, and DNMT3B genes. Furthermore, in PBMCs, the cocoa extract significantly lowered the mRNA levels of the DNMTs, MTHFR, and MTRR. Our study demonstrates for the first time that the consumption of cocoa decreases the global DNA methylation of peripheral leukocytes in humans with cardiovascular risk factors. In vitro experiments with PBMCs suggest that cocoa may exert this effect partially via the down-regulation of DNMTs, MTHFR and MTRR, which are key genes involved in this epigenetic process.

Trial Registration

Clinicaltrials.gov {"type":"clinical-trial","attrs":{"text":"NCT00511420","term_id":"NCT00511420"}}NCT00511420 and {"type":"clinical-trial","attrs":{"text":"NCT00502047","term_id":"NCT00502047"}}NCT00502047     

Psychological Distress, Depression, Anxiety, and Burnout among International Humanitarian Aid Workers: A Longitudinal Study

Background

International humanitarian aid workers providing care in emergencies are subjected to numerous chronic and traumatic stressors.

Objectives

To examine consequences of such experiences on aid workers'' mental health and how the impact is influenced by moderating variables.

Methodology

We conducted a longitudinal study in a sample of international non-governmental organizations. Study outcomes included anxiety, depression, burnout, and life and job satisfaction. We performed bivariate regression analyses at three time points. We fitted generalized estimating equation multivariable regression models for the longitudinal analyses.

Results

Study participants from 19 NGOs were assessed at three time points: 212 participated at pre-deployment; 169 (80%) post-deployment; and 154 (73%) within 3–6 months after deployment. Prior to deployment, 12 (3.8%) participants reported anxiety symptoms, compared to 20 (11.8%) at post-deployment (p = 0·0027); 22 (10.4%) reported depression symptoms, compared to 33 (19.5%) at post-deployment (p = 0·0117) and 31 (20.1%) at follow-up (p = .00083). History of mental illness (adjusted odds ratio [AOR] 4.2; 95% confidence interval [CI] 1·45–12·50) contributed to an increased risk for anxiety. The experience of extraordinary stress was a contributor to increased risk for burnout depersonalization (AOR 1.5; 95% CI 1.17–1.83). Higher levels of chronic stress exposure during deployment were contributors to an increased risk for depression (AOR 1·1; 95% CI 1·02–1.20) comparing post- versus pre-deployment, and increased risk for burnout emotional exhaustion (AOR 1.1; 95% CI 1.04–1.19). Social support was associated with lower levels of depression (AOR 0·9; 95% CI 0·84–0·95), psychological distress (AOR = 0.9; [CI] 0.85–0.97), burnout lack of personal accomplishment (AOR 0·95; 95% CI 0·91–0·98), and greater life satisfaction (p = 0.0213).

Conclusions

When recruiting and preparing aid workers for deployment, organizations should consider history of mental illness and take steps to decrease chronic stressors, and strengthen social support networks.     

Exclusive frugivory and seed dispersal of Rhamnus alaternus in the bird breeding season

We studied avian frugivory and seed dispersal in a dioecious shrub, Rhamnus alaternus, focusing on the quantitative and qualitative components of effectiveness. The study took place at three locations in the northeast of the Iberian Peninsula, and examined bird behaviour, intensity of feeding, and the consequences for seedling emergence. The coincidence between the bird breeding season and fruit ripening of R. alaternus in the absence of other ripe fruit, generates a monospecific interaction. The extant frugivorous species were mainly legitimate seed dispersers and their abundance was low. Sylvia melanocephala and S. undata were the most important at one site whereas S. atricapilla, Erithacus rubecula and Turdus merula predominated at the other two sites. Fruit handling took place directly on the branches. Bird species used microhabitats differently as first post-feeding perch, which usually was a short distance away. The low density of frugivorous birds in all localities, among others factors, resulted in satiation of the disperser community and many mature fruits unconsumed. Both adults and juveniles feed upon the plants and their foraging patterns are similar. Adults of S. melanocephala were observed to feed fruit to nestlings and consequently a second phase of dispersal potentially arises from the transport of fecal sacs. Pulp removal and passage through the digestive tract increased the probability of seedling emergence. This plant-dispersal interaction has important consequences, both positive and negative for the plant. Positively, the fruiting of R. alaternus at a time when other ripe fruits are not available avoids interspecific competition for seed dispersers. In addition, a low density of seed rain may reduce intraspecific competition. Negatively, the low density and small size of the breeding frugivorous bird community limit fruit handling and removal away from the parent plants, while the territorial behaviour of birds at that time of the year reduces the potential distances of seed dispersal.     

Tick survey and detection of Crimean-Congo hemorrhagic fever virus in tick species from a non-endemic area, South Marmara region, Turkey

Crimean-Congo hemorrhagic fever (CCHF) is an increasing health concern in Turkey since 2002. There were also some recent human cases from the South Marmara region of Turkey; thus, a tick survey was performed, and possible vector tick species for the CCHF virus were determined in the region. A total of 740 adult ticks were collected from infested livestock from five locations: Çanakkale-Biga, Bursa-Orhaneli, Bursa-Keles, Bal?kesir and Bilecik. Total of 11 tick species from the genera Hyalomma, Rhipicephalus, Dermacentor, Ixodes and Haemaphysalis were identified. Rhipicephalus ticks were dominant in the region; the most frequently observed tick species was R. turanicus, (53.1 %), and only 15.4 % of the identified ticks were H. marginatum. The occurrence of H. rufipes infestation in the region fort he first time. A total of 73 pools of adult ticks were tested with both an antigen-detecting ELISA and RT real-time PCR (RT rt PCR). The presence of the CCHF virus was demonstrated in 9 (12.3 %) of the tested tick pools. Although seven of the tick pools were positive for the CCHF virus with both of the methods, one pool was positive only with RT rt PCR and the other pool was only positive with the ELISA. Positive results were obtained from ticks collected from cattle, sheep and goats from two locations, Bursa-Orhaneli and Bilecik. The CCHF virus was detected in R. turanicus (n = 3), R. bursa (n = 2), H. marginatum (n = 2) and D. marginatus (n = 2) ticks. The results of this study confirm the presence of the CCHF virus and present preliminary data on the vector tick species in the southern Marmara region of Turkey.     

Using a Genome-Scale Metabolic Model of Enterococcus faecalis V583 To Assess Amino Acid Uptake and Its Impact on Central Metabolism

Increasing antibiotic resistance in pathogenic bacteria necessitates the development of new medication strategies. Interfering with the metabolic network of the pathogen can provide novel drug targets but simultaneously requires a deeper and more detailed organism-specific understanding of the metabolism, which is often surprisingly sparse. In light of this, we reconstructed a genome-scale metabolic model of the pathogen Enterococcus faecalis V583. The manually curated metabolic network comprises 642 metabolites and 706 reactions. We experimentally determined metabolic profiles of E. faecalis grown in chemically defined medium in an anaerobic chemostat setup at different dilution rates and calculated the net uptake and product fluxes to constrain the model. We computed growth-associated energy and maintenance parameters and studied flux distributions through the metabolic network. Amino acid auxotrophies were identified experimentally for model validation and revealed seven essential amino acids. In addition, the important metabolic hub of glutamine/glutamate was altered by constructing a glutamine synthetase knockout mutant. The metabolic profile showed a slight shift in the fermentation pattern toward ethanol production and increased uptake rates of multiple amino acids, especially l-glutamine and l-glutamate. The model was used to understand the altered flux distributions in the mutant and provided an explanation for the experimentally observed redirection of the metabolic flux. We further highlighted the importance of gene-regulatory effects on the redirection of the metabolic fluxes upon perturbation. The genome-scale metabolic model presented here includes gene-protein-reaction associations, allowing a further use for biotechnological applications, for studying essential genes, proteins, or reactions, and the search for novel drug targets.     

Matrix Metalloprotease 9 Mediates Neutrophil Migration into the Airways in Response to Influenza Virus-Induced Toll-Like Receptor Signaling

The early inflammatory response to influenza virus infection contributes to severe lung disease and continues to pose a serious threat to human health. The mechanisms by which neutrophils gain entry to the respiratory tract and their role during pathogenesis remain unclear. Here, we report that neutrophils significantly contributed to morbidity in a pathological mouse model of influenza virus infection. Using extensive immunohistochemistry, bone marrow transfers, and depletion studies, we identified neutrophils as the predominant pulmonary cellular source of the gelatinase matrix metalloprotease (MMP) 9, which is capable of digesting the extracellular matrix. Furthermore, infection of MMP9-deficient mice showed that MMP9 was functionally required for neutrophil migration and control of viral replication in the respiratory tract. Although MMP9 release was toll-like receptor (TLR) signaling-dependent, MyD88-mediated signals in non-hematopoietic cells, rather than neutrophil TLRs themselves, were important for neutrophil migration. These results were extended using multiplex analyses of inflammatory mediators to show that neutrophil chemotactic factor, CCL3, and TNFα were reduced in the Myd88 ^−/− airways. Furthermore, TNFα induced MMP9 secretion by neutrophils and blocking TNFα in vivo reduced neutrophil recruitment after infection. Innate recognition of influenza virus therefore provides the mechanisms to induce recruitment of neutrophils through chemokines and to enable their motility within the tissue via MMP9-mediated cleavage of the basement membrane. Our results demonstrate a previously unknown contribution of MMP9 to influenza virus pathogenesis by mediating excessive neutrophil migration into the respiratory tract in response to viral replication that could be exploited for therapeutic purposes.     

4α‐Acetoxyamijidictyol – A New Antifeeding Dolastane Diterpene from the Brazilian Brown Alga Canistrocarpus cervicornis

Chemical investigation of the CH₂Cl₂ crude extract from the brown alga Canistrocarpus cervicornis (Dictyotaceae) led to isolation of one new ( 1 ) and four previously reported dolastane diterpenes ( 2 – 5 ). Their structures were characterized by 1D‐ and 2D‐NMR spectroscopic techniques, including a full single crystal X‐ray diffraction analysis for 1, 2 , and 4 . In addition, the new structure 1 was assayed as chemical defense inhibiting the feeding by the sea urchin Lytechinus variegatus. This study constitutes an additional report broadening the known spectrum of action and defensive roles of secondary metabolites of the C. cervicornis and Dictyotales species.     

Conflict in Protected Areas: Who Says Co-Management Does Not Work?

Natural resource-related conflicts can be extremely destructive and undermine environmental protection. Since the 1990s co-management schemes, whereby the management of resources is shared by public and/or private sector stakeholders, have been a main strategy for reducing these conflicts worldwide. Despite initial high hopes, in recent years co-management has been perceived as falling short of expectations. However, systematic assessments of its role in conflict prevention or mitigation are non-existent. Interviews with 584 residents from ten protected areas in Colombia revealed that co-management can be successful in reducing conflict at grassroots level, as long as some critical enabling conditions, such as effective participation in the co-management process, are fulfilled not only on paper but also by praxis. We hope these findings will re-incentivize global efforts to make co-management work in protected areas and other common pool resource contexts, such as fisheries, agriculture, forestry and water management.