Inhalation anthrax: dose response and risk analysis

The notion that inhalation of a single Bacillus anthracis spore is fatal has become entrenched nearly to the point of urban legend, in part because of incomplete articulation of the scientific basis for microbial risk assessment, particularly dose-response assessment. Risk analysis (ie, risk assessment, risk communication, risk management) necessitates transparency: distinguishing scientific facts, hypotheses, judgments, biases in interpretations, and potential misinformation. The difficulty in achieving transparency for biothreat risk is magnified by misinformation and poor characterization of both dose-response relationships and the driving mechanisms that cause susceptibility or resistance to disease progression. Regrettably, this entrenchment unnecessarily restricts preparedness planning to a single response scenario: decontaminate until no spores are detectable in air, water, or on surfaces-essentially forcing a zero-tolerance policy inconsistent with the biology of anthrax. We present evidence about inhalation anthrax dose-response relationships, including reports from multiple studies documenting exposures insufficient to cause inhalation anthrax in laboratory animals and humans. The emphasis of the article is clarification about what is known from objective scientific evidence for doses of anthrax spores associated with survival and mortality. From this knowledge base, we discuss the need for future applications of more formal risk analysis processes to guide development of alternative non-zero criteria or standards based on science to inform preparedness planning and other risk management activities.     

Axon growth and guidance genes identify T-dependent germinal centre B cells

Selection of B cells subjected to hypermutation in germinal centres (GC) during T cell-dependent (TD) antibody responses yields memory cells and long-lived plasma cells that produce high affinity antibodies biased to foreign antigens rather than self-antigens. GC also form in T-independent (TI) responses to polysaccharide antigens but failed selection results in GC involution and memory cells are not generated. To date there are no markers that allow phenotypic distinction of T-dependent and TI germinal centre B cells. We compared the global gene expression of GC B cells purified from mice immunized with either TD or TI antigens and identified eighty genes that are differentially expressed in TD GC. Significantly, the largest cluster comprises genes involved in growth and guidance of neuron axons such as Plexin B2, Basp1, Nelf, Shh, Sc4mol and Sult4alpha. This is consistent with formation of long neurite (axon and dendrite)-like structures by mouse and human GC B cells, which may facilitate T:B cell interactions within GC, affinity maturation and B cell memory formation. Expression of BASP1 and PLEXIN B2 protein is very low or undetectable in resting and TI GC B cells, but markedly upregulated in GC B cells induced in the presence of T cell help. Finally we show some of the axon growth genes upregulated in TD-GC B cells including Basp1, Shh, Sult4alpha, Sc4mol are also preferentially expressed in post-GC B cell neoplasms.     

Compatibility of two systemic neonicotinoids, imidacloprid and thiamethoxam, with various natural enemies of agricultural pests

Two systemic neonicotinoids, imidacloprid and thiamethoxam, are widely used for residual control of several insect pests in cotton (Gossypium spp.), vegetables, and citrus (Citrus spp.). We evaluated their impact on six species of beneficial arthropods, including four parasitoid species--Aphytis melinus Debach, Gonatocerus ashmeadi Girault, Eretmocerus eremicus Rose & Zolnerowich, and Encarsia formosa Gahan--and two generalist predators--Geocoris punctipes (Say) and Orius insidiosus (Say)--in the laboratory by using a systemic uptake bioassay. Exposure to systemically treated leaves of both neonicotinoids had negative effects on adult survival in all four parasitoids, with higher potency against A. melinus as indicated by a low LC50. Mortality was also high for G. ashmeadi, E. eremicus, and E. formosa after exposure to both compounds but only after 48 h posttreatment. The two predators G. punctipes and O. insidiosus were variably susceptible to imidacloprid and thiamethoxam after 96-h exposure. However, toxicity to these predators may be related to their feeding on foliage and not just contact with surface residues. Our laboratory results contradict suggestions of little impact of these systemic neonicotinoids on parasitoids or predators but field studies will be needed to better quantify the levels of such impacts under natural conditions.     

Host‐Plant Choice Behavior at Multiple Life‐Cycle Stages: The Roles of Mobility and Early Growth in Decision‐Making

The choice of food plants often assumes critical importance for a herbivore. Although many studies have investigated host‐plant choice behavior, few have examined preferences (vs. growth and survival) at multiple stages of the life cycle, notwithstanding the importance of identifying the critical stage(s) in an animal’s life history. Fern moths Herpetogramma theseusalis (Lepidoptera: Crambidae) provide an excellent opportunity to test host‐plant choice at several stages. Fern moth larvae feed on distantly related ferns, sensitive Onoclea sensibilis and marsh fern Thelypteris palustris, and adults oviposit on both species. We examined newly hatched larvae, overwintered larvae and ovipositing females to test hypotheses predicting when host‐plant choice takes place (overwintering and mobility hypotheses: overwintering stage determines choice of substrate vs. most mobile stage chooses) and the basis for choice (optimal oviposition and enemy‐free space hypotheses: resource producing highest fecundity vs. lowest losses to enemies). We also evaluated the hypothesis that host‐associated fitness trade‐offs explain host specialization. Only ovipositing females, the most mobile stage, exhibited a clear preference (for marsh fern), consistent with the mobility hypothesis. However, their preference for marsh fern fits neither the optimal oviposition hypothesis nor the enemy‐free space hypothesis; although some larvae initially grew faster on marsh fern, adults reared from the two ferns did not differ significantly in mass and experienced marginally lower parasitism on sensitive fern. Thus, we found no host‐associated fitness trade‐offs. Overwintering losses in marsh fern plots exceeded those in sensitive fern, and mixed plots supported the most overwintered larvae. Preference for marsh fern suggests that early success drives host‐plant choice, an advantage that later disappears. Temporal variability may prevent closer fits to the hypotheses, because both ferns provide the moths with acceptable resources throughout their life cycles.