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Alternative insecticides: an urgent need.

Most insecticides used against pests and vectors of human disease (e.g. fleas, flies and mosquitoes) are spin-offs from agrochemical research and development. The arsenal of safe and cost-effective public health insecticides is being depleted by restrictions for various reasons (e.g. insecticide resistance, unacceptable side effects and non re-registration) and the number of new products launched is dwindling. Mobilizing public resources and establishment of partnerships to support research and development of public health insecticides is crucial in the post-DDT and post-pyrethroid era.

Animals↗

[The plague].

The plague has been one of the most devastating diseases of human history. Despite major advances in diagnosis, prevention, and treatment, it has not been possible to eradicate this infection. Plague is still active in Africa, in Asia and in the Americas, and is classified as a currently re-emerging disease. The plague is mainly a disease of rodents, which is transmitted by fleabites. Humans develop two main clinical forms: bubonic plague (following bites of infected fleas, lethal in 50-70% of the cases in less than a week if an appropriate treatment is not started rapidly), and pneumonic plague (after inhalation of infected droplets, lethal in less than three days in 100% of cases without immediate treatment). Y. pestis, the causative agent of plague, is usually sensitive to most antibiotics, but the first multi-resistant strain was recently described. No efficient and safe vaccines are currently available. The plague bacillus is one of the few organisms that could be used for biological warfare.

Bioterrorism↗

Parental investment and child health in a Yanomamö village suffering short-term food stress.

The 1998 El Niño significantly reduced garden productivity in the Upper Orinoco region in Venezuela. Consequently, parents were forced to allocate food carefully to their children. Nutrition data collected from village children combined with genealogical data allowed the determination of which children suffered most, and whether the patterns of food distribution accorded with predictions from parental investment theory. For boys, three social variables accounted for over 70% of the variance in subcutaneous fat after controlling for age: number of siblings, age of the mother's youngest child, and whether the mother was the senior or junior co-wife, or was married monogamously. These results accord well with parental investment theory. Parents experiencing food stress faced a trade-off between quantity and quality, and between investing in younger versus older offspring. In addition, boys with access to more paternal investment (i.e. no stepmother) were better nourished. These variables did not account for any of the variance in female nutrition. Girls' nutrition was associated with the size of their patrilineage and the number of non-relatives in the village, suggesting that lineage politics may have played a role. An apparent lack of relationship between orphan status and nutrition is also interesting, given that orphans suffered high rates of skin flea infections. The large number of orphans being cared for by only two grandparents suggests that grooming time may have been the resource in short supply.

Adolescent↗

A reappraisal of the role of mosquitoes in the transmission of myxomatosis in Britain.

Field experiments were made in southern England to re-examine the possibility that mosquitoes in Britain might feed on wild rabbits and hence be vectors of myxomatosis. Mosquitoes of several species were attracted to rabbits enclosed in cylindrical traps and in a trap in which the animal was placed in a wire mesh cage. Substantial numbers of mosquitoes were also caught biting, or attempting to bite, tethered rabbits which were not in cages or traps. Evidence that mosquitoes fed on wild rabbits under natural conditions was obtained from results of precipitin tests made on blood-smears collected from mosquitoes caught resting amongst vegetation. On a few evenings mosquitoes were seen to be attracted to healthy wild rabbits and apparently attempting to feed on them. Batches of two mosquito species collected from the field were infected with myxoma virus.It was concluded that contrary to previous beliefs mosquitoes in Britain feed to a certain extent on wild rabbits, and therefore are potential vectors of myxomatosis. No attempts were made to assess their relative importance in the transmission of the disease, which in Britain is transmitted mainly by the rabbit flea.

Animals↗

Myxomatosis: the occurrence of antibody to a soluble antigen of myxoma virus in wild rabbits, Oryctolagus cuniculus (L.), in Victoria, Australia.

The occurrence of antibody of myxoma virus in wild rabbits following epizootics is highest in the semi-arid north-west of Victoria and lowest in temperate southern Victoria. Occurrence ranges up to about 90% in the north-west and to about 70% in the south except on the Western Plains where epizootics are rare and antibody occurrence seldom exceeds 30%. The establishment of the European rabbit flea may be changing the pattern of occurrence of antibody in the north-west by causing spring outbreaks of myxomatosis. It is suggested that the effects of the replacement of a simple recurring system of epizootic and breeding season several months apart by the occurrence of myxomatosis twice in the same year, once coincident with the breeding season, will be complex. The occurrence of detectable antibody may be less dependent on the infection rate and may be dependent to some extent on the relative timing of spring myxomatosis and the breeding season.

Animals↗

Isoenzyme characterization of trypanosomes of the subgenus Herpetosoma.

Isoenzyme analysis was used to characterize 6 species of trypanosomes of the subgenus Herpetosoma using 13 different enzyme systems. The species studied were Trypanosoma lewisi, T. musculi, T. grosi, T. microti, T. evotomys and T. nabiasi which cannot be distinguished on morphological grounds. Extracts for thin-layer starch-gel electrophoresis were prepared from cultures of insect forms in either Schneider's Drosophila or Grace's insect tissue culture media with foetal calf serum or a nutrient agar medium. Extracts of T. lewisi and T. musculi bloodstream forms were also run for comparison. All parasites gave distinct patterns which enabled them to be differentiated on one or more enzyme systems. Two types of computer analysis were used to group the parasites; using these techniques the murine parasites T. lewisi, T. musculi and T. grosi fell into one broad group, and T. microti and T. evotomys of microtine rodents formed another. These findings are in accord with earlier observations on the behavioural characteristics of these parasites in their mammalian host and their vector (fleas). The clear differences observed provide the basis for the application of other biochemical and immunological techniques for differentiation within this subgenus of trypanosomes.

Animals↗

Ectoparasite impacts on Gerbillus andersoni allenbyi under natural conditions.

To assess ectoparasite impact on individuals and populations of Gerbillus andersoni allenbyi under natural conditions, I addressed the following questions. Do ectoparasites affect their host fitness and, if so, how? Do ectoparasites affect host population level? Does this parasite-host interaction support the traditional concept of parasite evolution towards avirulence? For this purpose, host infestation, infection, survival, haematological indices, and physical condition were recorded. A field experiment which included manipulating host infestation while recording host survival was conducted to determine the causal relations between these variables. G. a. allenbyi was infested by 2 fleas (Synosternus cleopatrae and Stenoponia tripectinata), 5 mesostigmatid mites (Androlaelaps centrocarpus, A. hirsti, A. insculptus, A. marshalli and Hirstionyssus carticulatus), 1 tick (Rhipicephalus sanguineus), and 1 louse (polyplax gerbilli). Ectoparasite burden significantly reduced host survival and red blood cell indices (red cell concentration, haemoglobin concentration and haematocrit). Ectoparasite burden did not significantly affect white blood cell concentration. Gerbils were not infected by haemoparasites or gut helminths which potentially could cause anaemia. The causal relationship between S. cleopatrae burden and host survival was established by manipulation of host infestation. Both ectoparasite removal and initial level of infestation significantly affected host survival. Ectoparasites that caused anaemia were not associated with host physical condition (PC), measured as weight/length3. None of the red blood cell indices was correlated with host PC. These results suggest both that host PC was not affected by ectoparasite burden and that exsanguination leading to anaemia was the main effect of the ectoparasites. Ectoparasite pressure on the host population (based on the ectoparasite effects as estimated by statistical models, combined with dispersion of the infestation within the host population) changed seasonally and was greatest when host density was the highest. A large segment of the gerbil population was affected by ectoparasites during the entire year. An explanation for the evolution of parasite virulence, contrasting parasites that evolve towards increased virulence with parasites that evolve towards avirulence is presented. This classification is primarily based on whether parasite impact is equated with a higher efficiency of host exploitation, or whether it is a 'side effect' of parasite biology.

Animals↗

The neglected saliva: medically important toxins in the saliva of human lice.

Although there has been a great deal of research effort within the last two decades on identifying the active components of the saliva of blood-sucking ticks, mosquitoes, biting flies, fleas and bugs, essentially neglected have been the human lice. Despite initial reports in the early part of this century suggestive of vasodilatory, anticoagulant and immunosuppressive properties of the saliva, for the next 50 years there were no biochemical studies on the active principles. Very recently, anatomical and biochemical studies have begun to characterize the bioactive molecules in lice saliva. The louse stocks a salivary vasodilator in excess over what is needed for a single bite, and injects similar amounts at each successive bite. The vasodilator in lice saliva appears to have different pharmacological properties than peroxidative, oxidative and maxidilan types of vasodilators reported from other blood-sucking insects. Possible anticoagulant activities have also been characterized. This belated, but welcome, interest comes at a time of resurgence of lice-born disease in certain parts of Africa, and of resistance to chemical control in Europe and North America.

Animals↗

Anti-complement activity in the saliva of phlebotomine sand flies and other haematophagous insects.

The saliva of haematophagous insects has a series of pharmacological activities which may favour blood feeding. In the present study, an inhibitory effect on the complement system was observed in salivary extracts obtained from the phlebotomine sand flies Lutzomyia longipalpis and Lu. migonei. Saliva from Lu. longipalpis was capable of inhibiting both the classical and alternative pathways, while that from Lu. migonei acted only on the former. Other haematophagous insect species were screened for inhibition of the classical pathway. The triatomine bugs Panstrongylus megistus, Triatoma brasiliensis and Rhodnius prolixus were also able to inhibit the classical pathway whereas the mosquito Aedes aegyti and flea Ctenocephalides felis were not. The activity of Lu. longipalpis saliva on the classical pathway was partially characterized. The inhibitor is a protein of Mr 10000-30000 Da, which is very resistant to denaturation by heat. The inhibition of the complement system by phlebotomine sand flies may have a role in the transmission of Leishmania to the vertebrate hosts. The inhibitor molecule is thus a promising component of a vaccine to target salivary immunomodulators.

Animals↗

Emerging tick-borne infections: rediscovered and better characterized, or truly 'new' ?

The emergence of Lyme borreliosis as a public health burden within the last two decades has stimulated renewed interest in tick-borne infections. This attention towards ticks, coupled with advances in detection technologies, has promoted the recognition of diverse emergent or potentially emerging infections, such as monocytic and granulocytic ehrlichiosis, local variants of spotted fever group rickettsioses, WA-1 babesiosis, or a Lyme disease mimic (Masters' Disease). The distribution of pathogens associated with well-described tick-borne zoonoses such as human babesiosis due to Babesia microti or B. divergens seems wider than previously thought. Bartonellae, previously known to be maintained by fleas, lice or sandflies, have been detected within ticks. Purported 'new' agents, mainly identified by sequencing of PCR products and comparison with those sequences present in GenBank, are being increasingly reported from ticks. We briefly review the diversity of these infectious agents, identify aetiological enigmas that remain to be solved, and provide a reminder about 'old friends' that should not be forgotten in our pursuit of novelty. We suggest that newly recognised agents or tick/pathogen associations receive careful scrutiny before being declared as potential public health burdens.

Animals↗

Monitoring the spread of myxoma virus in rabbit Oryctolagus cuniculus populations on the southern tablelands of New South Wales, Australia. III. Release, persistence and rate of spread of an identifiable strain of myxoma virus.

An identifiable strain of myxoma virus was introduced into four local populations of wild rabbits Oryctolagus cuniculus on the southern tablelands of New South Wales (NSW) and its spread in the presence of other field strains was monitored for 6 months. The main vector in this region was considered to be the European rabbit flea Spilopsyllis cuniculi. Each population of rabbits was of a high density and living in groups of warrens covering areas from 59 to 87 hectares. Rabbits occupying centrally located warrens were inoculated with the virus in late September or early October (spring) and the subsequent appearance of myxomatosis across the sites monitored by trapping, shooting and visual observations. Samples, taken from rabbits with myxomatosis, were examined by polymerase chain reaction (PCR) that allowed identification of the introduced strain. On all four sites the introduced virus spread from the inoculated rabbits in the centrally located warrens to rabbits in surrounding warrens. On Sites 1 and 3, this spread continued across the entire site persisting for at least 118 and 174 days respectively. On Sites 2 and 4, the virus was detected for 78 and 62 days respectively and the subsequent inability to detect the introduced virus correlated with the appearance of an unrelated field strain. Using three different methods of calculation, rates of spread ranged from 3.7 to 17.8 m d(-1).

Animals↗

Monitoring the spread of myxoma virus in rabbit Oryctolagus cuniculus populations on the southern tablelands of New South Wales, Australia. I. Natural occurrence of myxomatosis.

A survey of rabbit populations in the southern tablelands of New South Wales, Australia, was carried out to establish the pattern of occurrence of myxomatosis in preparation for a deliberate release of myxoma virus. Myxomatosis was first detected in December and cases were found on most sites through to May. The serological profiles of rabbit populations suggested that their susceptibility to myxoma virus was generally low in winter and highest in spring and summer reflecting the presence of increasing numbers of susceptible young rabbits. This was consistent with the pattern of rabbit breeding, as determined from the distribution of births and reproductive activity in females and males, which occurred maximally in spring and early summer. The serology and age structure of rabbit populations on sites suggested that some rabbit populations can escape an annual myxomatosis epizootic. Although fleas were present on rabbits throughout the year and therefore not considered to be a limiting factor in the spread of myxomatosis, their numbers peaked at times coincident with peak rabbit breeding. It was concluded that mid to late spring was an optimal time for a deliberate release.

Animals↗

Temperature-dependent variations and intraspecies diversity of the structure of the lipopolysaccharide of Yersinia pestis.

Yersinia pestis spread throughout the Americas in the early 20th century, and it occurs predominantly as a single clone within this part of the world. However, within Eurasia and parts of Africa there is significant diversity among Y. pestis strains, which can be classified into different biovars (bv.) and/or subspecies (ssp.), with bv. orientalis/ssp. pestis most closely related to the American clone. To determine one aspect of the relatedness of these different Y. pestis isolates, the structure of the lipopolysaccharide (LPS) of four wild-type and one LPS-mutant Eurasian/African strains of Y. pestis was determined, evaluating effects of growth at mammalian (37 degrees C) or flea (25 degrees C) temperatures on the structure and composition of the core oligosaccharide and lipid A. In the wild-type clones of ssp. pestis, a single major core glycoform was synthesized at 37 degrees C whereas multiple core oligosaccharide glycoforms were produced at 25 degrees C. Structural differences occurred primarily in the terminal monosaccharides. Only tetraacyl lipid A was made at 37 degrees C, whereas at 25 degrees C additional pentaacyl and hexaacyl lipid A structures were produced. 4-Amino-4-deoxyarabinose levels in lipid A increased with lower growth temperatures or when bacteria were cultured in the presence of polymyxin B. In Y. pestis ssp. caucasica, the LPS core lacked D-glycero-D-manno-heptose and the content of 4-amino-4-deoxyarabinose showed no dependence on growth temperature, whereas the degree of acylation of the lipid A and the structure of the oligosaccharide core were temperature dependent. A spontaneous deep-rough LPS mutant strain possessed only a disaccharide core and a slightly variant lipid A. The diversity and differences in the structure of the Y. pestis LPS suggest important contributions of these variations to the pathogenesis of this organism, potentially related to innate and acquired immune recognition of Y. pestis and epidemiologic means to detect, classify, control and respond to Y. pestis infections.

Carbohydrate Conformation↗

Interspecies correlation estimates predict protective environmental concentrations.

Environmental risk assessments often use multiple single species toxicity test results and species sensitivity distributions (SSDs) to derive a predicted no-effect concentration in the environment, typically the 5th percentile of the SSD, termed the HC5. The shape and location of the distribution are best known when populated with numerous toxicity values. To help overcome the cost of multiple toxicity tests, we explored the potential of the U.S. EPA's Interspecies Correlation Estimation (ICE) program to predict single species toxicity values from a single known toxicity value. ICE uses the initial toxicity estimate for one species to produce correlation toxicity values for multiple species, which can be used to develop SSD and HC5. To test this approach to deriving HC5, we generated toxicity values based on measured toxicity values for three surrogate species Pimephales promelas (Fathead minnow), Onchorynchus mykiss (Rainbow trout), and Daphnia magna (water flea). Algal taxa were not used due to the paucity of high quality algal-aquatic invertebrate and algal-fish correlations. The compounds used (dodecyl linear alkylbenzenesulfonate (LAS), nonylphenol, fenvalerate, atrazine, and copper) have multiple measured toxicity values and diverse modes of action and toxicities. Distribution parameters and HC5 values from the measured toxicity values were compared with ICE predicted distributions and HC5 values. While distributional parameters (scale and intercept) differed between measured and predicted distributions, in general, the ICE-based SSDs had HC5 values that were within an order of magnitude of the measured HC5 values. Examination of species placements within the SSDs indicated that the most sensitive species were coldwater species (e.g., salmonids and Gammarus pseudolimnaeus). These results raise the potential of using quantitative structure activity models to estimate HC5s.

Animals↗

Ecotoxicological effects of benzoxazinone allelochemicals and their metabolites on aquatic nontarget organisms.

Before natural plant allelochemicals can be exploited as biological pesticides against weeds and for disease control, more than the effect on target organisms needs to be known. This study presents results of aquatic biotests using four organisms, namely, a water flea, a freshwater alga, a soil alga, and a luminescent bacterium. The tested substances were 10 benzoxazinone derivatives, 3 of them known to be wheat allelochemicals, benzoxazolin-2(3H)-one (BOA), 6-methoxybenzoxazolin-2(3H)-one (MBOA), and 2,4-dihydroxy-7-methoxy-2H-1,4-benzoxazin-3-one (DIMBOA), and 7 identified degradation intermediates and metabolites. For comparison, two commercial pesticide formulations (BAS, Betanal) were tested by applying the same set of biotests. The data set produced could be seen as an ecotoxicological evaluation for effects of allelochemicals against nontarget organisms and as a base for further risk assessment.

Aliivibrio fischeri↗

Nodulisporic acids C, C1, and C2: a series of D-ring-opened nodulisporic acids from the fungus Nodulisporium sp.

Nodulisporic acids C (4a), C1 (5a), and C2 (6a), a series of D-ring-opened nodulisporic acids, were isolated from fermentations of a mutant culture of Nodulisporium sp. MF5954. Nodulisporic acid C, the most potent of the three, showed good activity against fleas with an LD90 of 10 micro g/mL. These compounds tend to be unstable in the free acid form and were isolated as stable sodium salts.

Animals↗

Rediocides B-E, potent insecticides from Trigonostemon reidioides.

Four new congeners, rediocides B-E (2-5), of the previously reported rediocide A (1) were isolated from a methanol extract of the roots of the plant Trigonostemon reidioides. The structures of these minor analogues were elucidated by comparison of their NMR and mass spectral data with those of rediocide A and confirmed by extensive 2D NMR spectral analysis. They all possess potent activity against fleas (Ctenocephalides felis) in an artificial membrane feeding system and exhibited LD(90) values ranging from 0.25 to 0.5 ppm.

Animals↗

Biomarker candidate identification in Yersinia pestis using organism-wide semiquantitative proteomics.

The accurate mass and time tag mass spectrometry method and clustering analysis were used to compare the abundance change of 992 Yersinia pestis proteins under four contrasting growth conditions (26 and 37 degrees C, with or without Ca2+) that mimicked growth states in either a flea vector or mammalian host. Eighty-nine proteins were observed to have similar abundance change profiles to 29 known virulence associated proteins, providing identification of additional biomarker candidates. Eighty-seven hypothetical proteins, which clustered into 5 distinct clusters of like-protein abundance change, were identified as unique biomarkers related specifically to growth condition.

Bacterial Proteins↗

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