Genetic Selection of Low Fertile Onchocerca volvulus by Ivermectin Treatment

Onchocerca volvulus is the causative agent of onchocerciasis, or “river blindness”. Ivermectin has been used for mass treatment of onchocerciasis for up to 18 years, and recently there have been reports of poor parasitological responses to the drug and evidence of drug resistance. Drug resistance has a genetic basis. In this study, genetic changes in β-tubulin, a gene associated with ivermectin resistance in nematodes, were seen in parasites obtained from the patients exposed to repeated ivermectin treatment compared with parasites obtained from the same patients before any exposure to ivermectin. Furthermore, the extent of the genetic changes was dependent on the level of ivermectin treatment exposure. This genetic selection was associated with a lower reproductive rate in the female parasites. The data indicates that this genetic selection is for a population of O. volvulus that is more tolerant to ivermectin. This selection could have implications for the development of ivermectin resistance in O. volvulus and for the ongoing onchocerciasis control programmes. Monitoring for the possible development and spread of ivermectin resistance, as part of the control programmes, should be implemented so that any foci of resistant parasites can be treated by alternative control measures

Phenotypic Evidence of Emerging Ivermectin Resistance in Onchocerca volvulus

Onchocerciasis, commonly known as river blindness, is caused by the filarial nematode Onchocerca volvulus and is transmitted by a blackfly vector. Over 37 million people are thought to be infected, with over 90 million at risk. Infection predominantly occurs in sub-Saharan Africa. Foci also exist in the Arabian Peninsula and Central and South America. Ivermectin, the sole pharmaceutical available for mass chemotherapy, has been used on a community basis for annual or semi-annual treatment since 1987. Multiple treatments with ivermectin kill the microfilariae that are responsible for the pathology of onchocerciasis. More importantly, ivermectin suppresses the reproductive activity of the adult female worms, thus delaying or preventing the repopulation of the skin with new microfilariae and thereby reducing transmission. This study extends earlier reports of sub-optimal responses to ivermectin by examining repopulation levels of microfilaria one year after treatment, worm burdens per nodule, the age structure of adult female worms recovered from nodules, and the reproductive status of adult female worms 90 days after ivermectin treatment. In some communities which have shown a pattern of sub-optimal response to treatment, the data is consistent with an emergence of ivermectin non response or resistance manifested by a loss of the effect of ivermectin on the suppression of parasite reproduction

Human Tears Reveal Insights into Corneal Neovascularization

Corneal neovascularization results from the encroachment of blood vessels from the surrounding conjunctiva onto the normally avascular cornea. The aim of this study is to identify factors in human tears that are involved in development and/or maintenance of corneal neovascularization in humans. This could allow development of diagnostic tools for monitoring corneal neovascularization and combination monoclonal antibody therapies for its treatment. In an observational case-control study we enrolled a total of 12 patients with corneal neovascularization and 10 healthy volunteers. Basal tears along with reflex tears from the inferior fornix, superior fornix and using a corneal bath were collected along with blood serum samples. From all patients, ocular surface photographs were taken. Concentrations of the pro-angiogenic cytokines interleukin (IL)-6, IL-8, Vascular Endothelial Growth Factor (VEGF), Monocyte Chemoattractant Protein 1 (MCP-1) and Fas Ligand (FasL) were determined in blood and tear samples using a flow cytometric multiplex assay. Our results show that the concentration of pro-angiogenic cytokines in human tears are significantly higher compared to their concentrations in serum, with highest levels found in basal tears. Interestingly, we could detect a significantly higher concentration of IL- 6, IL-8 and VEGF in localized corneal tears of patients with neovascularized corneas when compared to the control group. This is the first study of its kind demonstrating a significant difference of defined factors in tears from patients with neovascularized corneas as compared to healthy controls. These results provide the basis for future research using animal models to further substantiate the role of these cytokines in the establishment and maintenance of corneal neovascularization

A one-year exercise intervention program in pre-pubertal girls does not influence hip structure

<p>Abstract</p> <p>Background</p> <p>We have previously reported that a one-year school-based exercise intervention program influences the accrual of bone mineral in pre-pubertal girls. This report aims to evaluate if also hip structure is affected, as geometry independent of bone mineral influences fracture risk.</p> <p>Methods</p> <p>Fifty-three girls aged 7 – 9 years were included in a curriculum-based exercise intervention program comprising 40 minutes of general physical activity per school day (200 minutes/week). Fifty healthy age-matched girls who participated in the general Swedish physical education curriculum (60 minutes/week) served as controls. The hip was scanned by dual X-ray absorptiometry (DXA) and the hip structural analysis (HSA) software was applied to evaluate bone mineral content (BMC), areal bone mineral density (aBMD), periosteal and endosteal diameter, cortical thickness, cross-sectional moment of inertia (CSMI), section modulus (Z) and cross-sectional area (CSA) of the femoral neck (FN). Annual changes were compared. Group comparisons were done by independent student's <it>t</it>-test between means and analyses of covariance (ANCOVA). Pearson's correlation test was used to evaluate associations between activity level and annual changes in FN. All children remained at Tanner stage 1 throughout the study.</p> <p>Results</p> <p>No between-group differences were found during the 12 months study period for changes in the FN variables. The total duration of exercise during the year was not correlated with the changes in the FN traits.</p> <p>Conclusion</p> <p>Evaluated by the DXA technique and the HSA software, a general one-year school-based exercise program for 7–9-year-old pre-pubertal girls seems not to influence the structure of the hip.</p

A randomised controlled trial of a community-based healthy lifestyle program for overweight and obese adolescents: the Loozit® study protocol

<p>Abstract</p> <p>Background</p> <p>There is a need to develop sustainable and clinically effective weight management interventions that are suitable for delivery in community settings where the vast majority of overweight and obese adolescents should be treated. This study aims to evaluate the effect of additional therapeutic contact as an adjunct to the Loozit^®group program – a community-based, lifestyle intervention for overweight and lower grade obesity in adolescents. The additional therapeutic contact is provided via telephone coaching and either mobile phone Short Message Service or electronic mail, or both.</p> <p>Methods and design</p> <p>The study design is a two-arm randomised controlled trial that aims to recruit 168 overweight and obese 13–16 year olds (Body Mass Index z-score 1.0 to 2.5) in Sydney, Australia. Adolescents with secondary causes of obesity or significant medical illness are excluded. Participants are recruited via schools, media coverage, health professionals and several community organisations. Study arm one receives the Loozit^®group weight management program (G). Study arm two receives the same Loozit^®group weight management program plus additional therapeutic contact (G+ATC). The 'G' intervention consists of two phases. Phase 1 involves seven weekly group sessions held separately for adolescents and their parents. This is followed by phase 2 that involves a further seven group sessions held regularly, for adolescents only, until two years follow-up. Additional therapeutic contact is provided to adolescents in the 'G+ATC' study arm approximately once per fortnight during phase 2 only. Outcome measurements are assessed at 2, 12 and 24 months post-baseline and include: BMI z-score, waist z-score, metabolic profile indicators, physical activity, sedentary behaviour, eating patterns, and psychosocial well-being.</p> <p>Discussion</p> <p>The Loozit^®study is the first randomised controlled trial of a community-based adolescent weight management intervention to incorporate additional therapeutic contact via a combination of telephone coaching, mobile phone Short Message Service, and electronic mail. If shown to be successful, the Loozit^®group weight management program with additional therapeutic contact has the potential to be readily translatable to a range of health care settings.</p> <p>Trial registration</p> <p>The protocol for this study is registered with the Australian Clinical Trials Registry (ACTRNO12606000175572).</p

Short-term outcomes of community-based adolescent weight management: The Loozit® Study

<p>Abstract</p> <p>Background</p> <p>The Loozit^®Study is a randomised controlled trial investigating extended support in a 24 month community-based weight management program for overweight to moderately obese, but otherwise healthy, 13 to 16 year olds.</p> <p>Methods</p> <p>This pre-post study examines the two month outcomes of the initial Loozit^®group intervention received by both study arms. Adolescents (n = 151; 48% male) and their parents separately attended seven weekly group sessions focused on lifestyle modification. At baseline and two months, adolescents' anthropometry, blood pressure, and fasted blood sample were assessed. Primary outcomes were two month changes in body mass index (BMI) z-score and waist-to-height-ratio (WHtR). Secondary outcomes included changes in metabolic profile, self-reported dietary intake/patterns, physical and sedentary activities, psychological characteristics and social status. Changes in outcome measures were assessed using paired samples t-tests for continuous variables or McNemar's test for dichotomous categorical variables.</p> <p>Results</p> <p>Of the 151 adolescents who enrolled, 130 (86%) completed the two month program. Among these 130 adolescents (47% male), there was a statistically significant (P < 0.01) reduction in mean [95% CI] BMI (0.27 kg/m²[0.41, 0.13]), BMI z-score (0.05 [0.06, 0.03]), WHtR (0.02 [0.03, 0.01]), total cholesterol (0.14 mmol/L [0.24, 0.05]) and low-density lipoprotein cholesterol (0.12 mmol/L [0.21, 0.04]). There were improvements in all psychological measures, the majority of the dietary intake measures, and some physical activities (P < 0.05). Time spent watching TV and participating in non-screen sedentary activities decreased (P < 0.05).</p> <p>Conclusions</p> <p>The Loozit^®program may be a promising option for stabilizing overweight and improving various metabolic factors, psychological functioning and lifestyle behaviors in overweight adolescents in a community setting.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry</p> <p><a href="http://www.anzctr.org.au/trial_view.aspx?ID=1277">ACTRNO12606000175572</a></p

Dentifrices, mouthwashes, and remineralization/caries arrestment strategies

While our knowledge of the dental caries process and its prevention has greatly advanced over the past fifty years, it is fair to state that the management of this disease at the level of the individual patient remains largely empirical. Recommendations for fluoride use by patients at different levels of caries risk are mainly based on the adage that more is better. There is a general understanding that the fluoride compound, concentration, frequency of use, duration of exposure, and method of delivery can influence fluoride efficacy. Two important factors are (1) the initial interaction of relatively high concentrations of fluoride with the tooth surface and plaque during application and (2) the retention of fluoride in oral fluids after application

A Research Agenda for Helminth Diseases of Humans: Towards Control and Elimination

Human helminthiases are of considerable public health importance in sub-Saharan Africa, Asia, and Latin America. The acknowledgement of the disease burden due to helminth infections, the availability of donated or affordable drugs that are mostly safe and moderately efficacious, and the implementation of viable mass drug administration (MDA) interventions have prompted the establishment of various large-scale control and elimination programmes. These programmes have benefited from improved epidemiological mapping of the infections, better understanding of the scope and limitations of currently available diagnostics and of the relationship between infection and morbidity, feasibility of community-directed or school-based interventions, and advances in the design of monitoring and evaluation (M&E) protocols. Considerable success has been achieved in reducing morbidity or suppressing transmission in a number of settings, whilst challenges remain in many others. Some of the obstacles include the lack of diagnostic tools appropriate to the changing requirements of ongoing interventions and elimination settings; the reliance on a handful of drugs about which not enough is known regarding modes of action, modes of resistance, and optimal dosage singly or in combination; the difficulties in sustaining adequate coverage and compliance in prolonged and/or integrated programmes; an incomplete understanding of the social, behavioural, and environmental determinants of infection; and last, but not least, very little investment in research and development (R&D). The Disease Reference Group on Helminth Infections (DRG4), established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR), was given the mandate to undertake a comprehensive review of recent advances in helminthiases research, identify research gaps, and rank priorities for an R&D agenda for the control and elimination of these infections. This review presents the processes undertaken to identify and rank ten top research priorities; discusses the implications of realising these priorities in terms of their potential for improving global health and achieving the Millennium Development Goals (MDGs); outlines salient research funding needs; and introduces the series of reviews that follow in this PLoS Neglected Tropical Diseases collection, “A Research Agenda for Helminth Diseases of Humans.

Situation analysis of parasitological and entomological indices of onchocerciasis transmission in three drainage basins of the rain forest of South West Cameroon after a decade of ivermectin treatment

BACKGROUND: Community-Directed Treatment with Ivermectin (CDTI) is the main strategy adopted by the African Programme for Onchocerciasis control (APOC). Recent reports from onchocerciasis endemic areas of savannah zones have demonstrated the feasibility of disease elimination through CDTI. Such information is lacking in rain forest zones. In this study, we investigated the parasitological and entomological indices of onchocerciasis transmission in three drainage basins in the rain forest area of Cameroon [after over a decade of CDTI]. River basins differed in terms of river number and their flow rates; and were characterized by high pre-control prevalence rates (60-98%). METHODS: Nodule palpation and skin snipping were carried out in the study communities to determine the nodule rates, microfilarial prevalences and intensity. Simulium flies were caught at capture points and dissected to determine the biting, parous, infection and infective rates and the transmission potential. RESULTS: The highest mean microfilaria (mf) prevalence was recorded in the Meme (52.7%), followed by Mungo (41.0%) and Manyu drainage basin (33.0%). The same trend was seen with nodule prevalence between the drainage basins. Twenty-three (23/39) communities (among which 13 in the Meme) still had mf prevalence above 40%. All the communities surveyed had community microfilarial loads (CMFL) below 10 mf/skin snip (ss). The infection was more intense in the Mungo and Meme. The intensity of infection was still high in younger individuals and children less than 10 years of age. Transmission potentials as high as 1211.7 infective larvae/person/month were found in some of the study communities. Entomological indices followed the same trend as the parasitological indices in the three river basins with the Meme having the highest values. CONCLUSION: When compared with pre-control data, results of the present study show that after over a decade of CDTI, the burden of onchocerciasis has reduced. However, transmission is still going on in this study site where loiasis and onchocerciasis are co-endemic and where ecological factors strongly favour the onchocerciasis transmission. The possible reasons for this persistent and differential transmission despite over a decade of control efforts using ivermectin are discussed. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13071-015-0817-2) contains supplementary material, which is available to authorized users

A Research Agenda for Helminth Diseases of Humans: Basic Research and Enabling Technologies to Support Control and Elimination of Helminthiases

Successful and sustainable intervention against human helminthiases depends on optimal utilisation of available control measures and development of new tools and strategies, as well as an understanding of the evolutionary implications of prolonged intervention on parasite populations and those of their hosts and vectors. This will depend largely on updated knowledge of relevant and fundamental parasite biology. There is a need, therefore, to exploit and apply new knowledge and techniques in order to make significant and novel gains in combating helminthiases and supporting the sustainability of current and successful mass drug administration (MDA) programmes. Among the fields of basic research that are likely to yield improved control tools, the Disease Reference Group on Helminth Infections (DRG4) has identified four broad areas that stand out as central to the development of the next generation of helminth control measures: 1) parasite genetics, genomics, and functional genomics; 2) parasite immunology; 3) (vertebrate) host–parasite interactions and immunopathology; and 4) (invertebrate) host–parasite interactions and transmission biology. The DRG4 was established in 2009 by the Special Programme for Research and Training in Tropical Diseases (TDR). The Group was given the mandate to undertake a comprehensive review of recent advances in helminthiases research in order to identify notable gaps and highlight priority areas. This paper summarises recent advances and discusses challenges in the investigation of the fundamental biology of those helminth parasites under the DRG4 Group's remit according to the identified priorities, and presents a research and development agenda for basic parasite research and enabling technologies that will help support control and elimination efforts against human helminthiases