Density dependence and the control of helminth parasites.

1. The transient dynamics and stability of a population are determined by the interplay between species density, its spatial distribution and the positive and negative density-dependent processes regulating population growth. 2. Using the human-helminth parasite system as an example, we propose that the life-stage upon which negative density dependence operates will influence the rate of host reinfection following anthelmintic chemotherapy, and the likely success of control programmes. 3. Simple deterministic models are developed which highlight how a parasite species whose population size is down-regulated by density-dependent establishment will reinfect a host population at a faster rate than a species with density-dependent parasite fecundity. 4. Different forms of density dependence can produce the same equilibrium behaviour but different transient dynamics. Under-representing the nature and magnitude of density-dependent mechanisms, and in particular those operating upon establishing life-stages, may cause the resilience of the parasite population to a control perturbation to be underestimated

Can field-based mosquito feeding assays be used for evaluating transmission-blocking interventions?

A recent meta-analysis of mosquito feeding assays to determine the Plasmodium falciparum transmission potential of naturally infected gametocyte carriers highlighted considerable variation in transmission efficiency between assay methodologies and between laboratories. This begs the question as to whether mosquito feeding assays should be used for the evaluation of transmission-reducing interventions in the field and whether these field-based mosquito assays are currently standardized sufficiently to enable accurate evaluations. Here, we address biological and methodological reasons for the observed variations, discuss whether these preclude the use of field-based mosquito feeding assays in field evaluations of transmission-blocking interventions, and propose how we can maximize the precision of estimates. Altogether, we underscore the significant advantages of field-based mosquito feeding assays in basic malaria research and field trials

Extinct equids from Limeworks Cave and Cave of Hearths, Makapansgat, Northern Province, and a consideration of variation in the cheek teeth of Equus capensis Broom

Dental specimens of Hipparion libycum from Limeworks Cave, and Equus capensis from Cave of the Horse’s Mandible in the Limeworks Cave entrance and from Cave of Hearths on the farm Makapansgat in the Makapansgat Valley are described. The concept of restricted local formations within each cave is discussed. Qualitative variation in the cheek teeth of E. capensis, based on a sample of 40 upper and 60 lower permanent premolars and molars from Cave of Hearths, demonstrates that there appears to be no correlation in the occurrence of one enamel feature with another between teeth of presumed different individuals. Teeth within a molar row show similar development of features between teeth, whether premolar or molar, as shown by plis, progressive migration of the protocone isthmus along the row, and penetration of the buccal valley to between the enamel loops of the metaconid and metastylid. Consequently, earlier descriptions of species of large Pleistocene Equus in Southern Africa founded on isolated teeth and, using such qualitative variation, are inept, unsuitable and inappropriate, and modem taxonomies synonymising them under E. capensis are supported. The Cave of Hearths ‘loose breccia’ (Beds 1-3 of Mason, 1988) containing earlier Stone Age/Later Acheulean artifacts, is circumstantially dated between 300 000 and 200 000 years BP.THE COUNCIL’S RESEARCH COMMITTEE, UNIVERSITY OF THE WITWATERSRAND; NATIONAL RESEARCH FOUNDATION (NRF

Amphioxus (Branchiostoma floridae) has orthologs of vertebrate odorant receptors

<p>Abstract</p> <p>Background</p> <p>A common feature of chemosensory systems is the involvement of G protein-coupled receptors (GPCRs) in the detection of environmental stimuli. Several lineages of GPCRs are involved in vertebrate olfaction, including trace amine-associated receptors, type 1 and 2 vomeronasal receptors and odorant receptors (ORs). Gene duplication and gene loss in different vertebrate lineages have lead to an enormous amount of variation in OR gene repertoire among species; some fish have fewer than 100 OR genes, while some mammals possess more than 1000. Fascinating features of the vertebrate olfactory system include allelic exclusion, where each olfactory neuron expresses only a single OR gene, and axonal guidance where neurons expressing the same receptor project axons to common glomerulae. By identifying homologous ORs in vertebrate and in non-vertebrate chordates, we hope to expose ancestral features of the chordate olfactory system that will help us to better understand the evolution of the receptors themselves and of the cellular components of the olfactory system.</p> <p>Results</p> <p>We have identified 50 full-length and 11 partial ORs in <it>Branchiostoma floridae</it>. No ORs were identified in <it>Ciona intestinalis</it>. Phylogenetic analysis places the <it>B. floridae </it>OR genes in a monophyletic clade with the vertebrate ORs. The majority of OR genes in amphioxus are intronless and many are also tandemly arrayed in the genome. By exposing conserved amino acid motifs and testing the ability of those motifs to discriminate between ORs and non-OR GPCRs, we identified three OR-specific amino acid motifs common in cephalochordate, fish and mammalian and ORs.</p> <p>Conclusion</p> <p>Here, we show that amphioxus has orthologs of vertebrate ORs. This conclusion demonstrates that the receptors, and perhaps other components of vertebrate olfaction, evolved at least 550 million years ago. We have also identified highly conserved amino acid motifs that may be important for maintaining receptor conformation or regulating receptor activity. We anticipate that the identification of vertebrate OR orthologs in amphioxus will lead to an improved understanding of OR gene family evolution, OR gene function, and the mechanisms that control cell-specific expression, axonal guidance, signal transduction and signal integration.</p

Late Pleistocene Vertebrate, Plant and Insect Remains from the lnnerkip Site, Southwestern Ontario

Remains of white-tailed deer (Odocoileus virginianus), meadow voles (Microtus pennsylvanicus), muskrat (Ondatra zibethicus) and Blanding's turtle (Emydoidea blandingi) have been recovered from a peat deposit exposed on a tributary of the Thames River in southwestern Ontario. Numerous insect fossils, principally Coleoptera, and a variety of plants recovered from the same stratigraphie horizon have permitted a partial reconstruction of a larger community at the site of peat deposition. The plant, vertebrate and invertebrate fossils represent part of an assemblage which existed in. or beside, a small pond. Deposition probably occurred at the end of the Sangamon Interglaciation (Isotope Stage 5e) or during warm Early Wisconsinan interstadial (Isotope Stage 5c or 5a).Les restes de cerf de Virginie (Odocoileus virginianus), de campagnols des champs (Microtus pennsylvanicus), de rat musqué (Ondatra zibethicus) et de tortue mouchetée (Emydoidea blandingi) ont été recueillis dans un dépôt de tourbe à découvert d'un tributaire de la rivière Thames. De nombreux fossiles d'insectes, surtout de coléoptères, et une certaine variété de végétaux faisant partie du même horizon stratigraphique ont permis de faire la reconstitution, du moins partielle, d'une communauté plus importante au site de la mise en place de la tourbe. Les fossiles de végétaux, de vertébrés et d'invertébrés représentent une partie d'un regroupement qui a vécu dans un petit étang ou à proximité. La mise en place a probablement eu lieu à la fin de l'Interglaciaire du Sangamonien (stade isotopique 5e) ou au cours d'un interstade chaud du Wisconsinien inférieur (stade isotopique 5c ou 5a).Reste von Virginia-Hirsch (Odocoileus virginianus), Wiesenmâusen (Microtus pennsylvanicus), Bisamratte (Ondatra zibethicus) und Blading's Schildkrôte (Emydoidea blandingi) wurden aus einer Torfablagerung wiedergewonnen, die an einem Nebenfluss des Thames River offengelegt war. Zahlreiche Insekten-fossile, hauptsàchlich Coleoptera, und eine Vielfalt von Pflanzen von demselben stratigraphischen Horizont erlaubten eine teilweise Rekonstruktion einer grôsseren Lebensgemeinschaft am Ort der Torfablagerung. Die Fossile von Pflanzen, Wirbeltieren und Wirbellosen sind Teil einer Einheit, die in oder neben einem kleinen Teich existierte. Die Ablagerung fand wahrscheinlich am Ende des sangamonischen Interglazial (lsotop Stadium 5e) oder wàhrend des fruhen Wisconsinischen Interstadial (lsotop Stadium 5c oder 5a) statt

The therapeutic efficacy and macrofilaricidal activity of doxycycline for the treatment of river blindness

Background. Onchocerca volvulus and lymphatic filariae, causing river blindness and elephantiasis, depend on endosymbiotic Wolbachia bacteria for growth, development, fertility, and survival. Clinical trials have shown that doxycycline treatment eliminates Wolbachia, causing long-term sterilization of adult female filariae and effecting potent macrofilaricidal activity. The continual reinfection by drug-naive worms that occurs in these trial settings dilutes observable anti-Wolbachia and antifilarial effects, making it difficult to estimate therapeutic efficacy and compare different doxycycline regimens, evaluated at different times after treatment. Methods. A meta-analytical modeling framework is developed to link all usable data collected from clinical trials measuring the Wolbachia status and viability of individual female adult worms collected at various times after treatment with 4, 5, or 6 weeks of daily 100 or 200 mg oral doxycycline. The framework is used to estimate efficacy parameters that are not directly measurable as trial outcomes. Results. The estimated efficacy of doxycycline (the maximum proportional reduction in the percentage of adult female O. volvulus positive for Wolbachia) is 91%–94% on average, irrespective of the treatment regimen. Efficacy is >95% in the majority of trial participants. The life span of Wolbachia-depleted worms is reduced by 70%–80%, from approximately 10 years to 2–3 years. Conclusions. The efficacy parameters are pertinent to the prospects of using doxycycline on a “test and treat” basis for onchocerciasis control and confirm doxycycline as a potent macrofilaricidal therapy. The modeling approach is more generally relevant to the design and evaluation of clinical trials for antifilarial drugs conducted in endemic settings

An Analysis of Genetic Diversity and Inbreeding in Wuchereria bancrofti: Implications for the Spread and Detection of Drug Resistance

Estimates of genetic diversity in helminth infections of humans often have to rely on genotyping (immature) parasite transmission stages instead of adult worms. Here we analyse the results of one such study investigating a single polymorphic locus (a change at position 200 of the β-tubulin gene) in microfilariae of the lymphatic filarial parasite Wuchereria bancrofti. The presence of this genetic change has been implicated in benzimidazole resistance in parasitic nematodes of farmed ruminants. Microfilariae were obtained from patients of three West African villages, two of which were sampled prior to the introduction of mass drug administration. An individual-based stochastic model was developed showing that a wide range of allele frequencies in the adult worm populations could have generated the observed microfilarial genetic diversity. This suggests that appropriate theoretical null models are required in order to interpret studies that genotype transmission stages. Wright's hierarchical F-statistic was used to investigate the population structure in W. bancrofti microfilariae and showed significant deficiency of heterozygotes compared to the Hardy-Weinberg equilibrium; this may be partially caused by a high degree of parasite genetic differentiation between hosts. Studies seeking to quantify accurately the genetic diversity of helminth populations by analysing transmission stages should increase their sample size to account for the variability in allele frequency between different parasite life-stages. Helminth genetic differentiation between hosts and non-random mating will also increase the number of hosts (and the number of samples per host) that need to be genotyped, and could enhance the rate of spread of anthelmintic resistance

Reducing Plasmodium falciparum malaria transmission in Africa: a model-based evaluation of intervention strategies.

BACKGROUND: Over the past decade malaria intervention coverage has been scaled up across Africa. However, it remains unclear what overall reduction in transmission is achievable using currently available tools. METHODS AND FINDINGS: We developed an individual-based simulation model for Plasmodium falciparum transmission in an African context incorporating the three major vector species (Anopheles gambiae s.s., An. arabiensis, and An. funestus) with parameters obtained by fitting to parasite prevalence data from 34 transmission settings across Africa. We incorporated the effect of the switch to artemisinin-combination therapy (ACT) and increasing coverage of long-lasting insecticide treated nets (LLINs) from the year 2000 onwards. We then explored the impact on transmission of continued roll-out of LLINs, additional rounds of indoor residual spraying (IRS), mass screening and treatment (MSAT), and a future RTS,S/AS01 vaccine in six representative settings with varying transmission intensity (as summarized by the annual entomological inoculation rate, EIR: 1 setting with low, 3 with moderate, and 2 with high EIRs), vector-species combinations, and patterns of seasonality. In all settings we considered a realistic target of 80% coverage of interventions. In the low-transmission setting (EIR approximately 3 ibppy [infectious bites per person per year]), LLINs have the potential to reduce malaria transmission to low levels (90%) or novel tools and/or substantial social improvements will be required, although considerable reductions in prevalence can be achieved with existing tools and realistic coverage levels. CONCLUSIONS: Interventions using current tools can result in major reductions in P. falciparum malaria transmission and the associated disease burden in Africa. Reduction to the 1% parasite prevalence threshold is possible in low- to moderate-transmission settings when vectors are primarily endophilic (indoor-resting), provided a comprehensive and sustained intervention program is achieved through roll-out of interventions. In high-transmission settings and those in which vectors are mainly exophilic (outdoor-resting), additional new tools that target exophagic (outdoor-biting), exophilic, and partly zoophagic mosquitoes will be required

Meningococcal genetic variation mechanisms viewed through comparative analysis of Serogroup C strain FAM18

Copyright @ 2007 Public Library of ScienceThe bacterium Neisseria meningitidis is commonly found harmlessly colonising the mucosal surfaces of the human nasopharynx. Occasionally strains can invade host tissues causing septicaemia and meningitis, making the bacterium a major cause of morbidity and mortality in both the developed and developing world. The species is known to be diverse in many ways, as a product of its natural transformability and of a range of recombination and mutation-based systems. Previous work on pathogenic Neisseria has identified several mechanisms for the generation of diversity of surface structures, including phase variation based on slippage-like mechanisms and sequence conversion of expressed genes using information from silent loci. Comparison of the genome sequences of two N. meningitidis strains, serogroup B MC58 and serogroup A Z2491, suggested further mechanisms of variation, including C-terminal exchange in specific genes and enhanced localised recombination and variation related to repeat arrays. We have sequenced the genome of N. meningitidis strain FAM18, a representative of the ST-11/ET-37 complex, providing the first genome sequence for the disease-causing serogroup C meningococci; it has 1,976 predicted genes, of which 60 do not have orthologues in the previously sequenced serogroup A or B strains. Through genome comparison with Z2491 and MC58 we have further characterised specific mechanisms of genetic variation in N. meningitidis, describing specialised loci for generation of cell surface protein variants and measuring the association between noncoding repeat arrays and sequence variation in flanking genes. Here we provide a detailed view of novel genetic diversification mechanisms in N. meningitidis. Our analysis provides evidence for the hypothesis that the noncoding repeat arrays in neisserial genomes (neisserial intergenic mosaic elements) provide a crucial mechanism for the generation of surface antigen variants. Such variation will have an impact on the interaction with the host tissues, and understanding these mechanisms is important to aid our understanding of the intimate and complex relationship between the human nasopharynx and the meningococcus.This work was supported by the Wellcome Trust through the Beowulf Genomics Initiative