Developmental toxicity studies of lumefantrine and artemether in rats and rabbits

The combination of artemether plus lumefantrine is a type of artemisinin‐based combination therapy (ACT) recommended by the World Health Organization for uncomplicated falciparum malaria except in the first trimester of pregnancy. The first trimester restriction was based on the marked embryotoxicity in animals (including embryo death and cardiac and skeletal malformations) of artemisinins such as artesunate, dihydroartemisinin, and artemether. Before recommending ACTs for use in the first trimester, the World Health Organization has requested that all information relevant to the assessment of risk of ACTs to the embryo be made available to the public. This report describes the results of embryo‐fetal development studies of artemether alone, lumefantrine alone, and the combination in rats and rabbits as well as toxicokinetic studies of lumefantrine in pregnant rabbits. The developmental no‐effect levels for lumefantrine were 300 mg/kg/day in rats (based on a 25% decrease in litter size at 1000 mg/kg/day) and 1000 mg/kg/day in rabbits. The calculated safety margins based on human equivalent dose and plasma C_max and AUC values were in the range of 2.5‐ to 17‐fold. The developmental no‐effect levels for artemether were 3 mg/kg/day in rats and 25 mg/kg/day in rabbits. Lumefantrine caused no teratogenicity and was not a potent embryotoxin in rats and rabbits. Expected artemisinin‐like findings were seen with artemether alone and with artemether/lumefantrine combined except that no malformations were observed. There were no findings in pregnant rats and rabbits that would cause increased concern for the use of artemether–lumefantrine in the first trimester compared to other ACTs.     

Avian species diversity in different habitat types in and around North Nandi Forest,Kenya

Forest fragmentation and degradation leads to formation of modified habitats whose ability to support existing avifaunal diversity is still largely unknown. Bird diversity in indigenous forest, disturbed forest, plantation forest and farmlands adjacent to North Nandi Forest reserve was studied between January 2015 and June 2015. The distribution of bird feeding guilds in these habitat patches was also evaluated. Birds were surveyed using point counts, timed species counts and line transects and classified into six feeding guilds. A total of 3,232 individual birds of 151 species were recorded in the four habitats. Significant difference on bird abundance across the four habitats (F = 15.141, P ≤ 0.05, df = 3, 1121) was noted. Shannon–Weiner diversity index H′ for bird community ranged from 3.06 for plantation forest to 4.05 for disturbed forest showing a relatively diverse bird community. Insectivores (F = 3.090, P ≤ 0.05, df = 3, 297) dominated the foraging species assemblage in all the habitats significantly. Linear regression analysis revealed a strong linear relationship on bird species richness and abundance with vegetation variables (P < 0.01 in all cases). The results indicate that disturbed forest and indigenous forest support high bird species richness than plantation forest and farmlands. However, high bird abundance was observed in farmlands and plantation forest as opposed to indigenous forest and disturbed forest as they provide dispersal routes over a short distance and are important for creating corridors between primary forests.     

Do individual Activity Patterns of Brown Trout (Salmo trutta) alter the Exposure to Parasitic Freshwater Pearl Mussel (Margaritifera margaritifera) Larvae?

The hypothesis that interindividual differences in the activity of brown trout alter the exposure to parasitic freshwater pearl mussel glochidia was tested in a Swedish stream. Wild yearling brown trout (N = 103) were caught, individually tagged for identification and scored for open‐field activity during standardized laboratory tests in June. Fifty gravid freshwater pearl mussels were relocated to the stream, where after the trout were released back into the stream. The fish were recaptured in October (N = 35), checked for glochidia encystment (infested individuals: n = 6) and re‐scored for open‐field activity traits. Swimming velocity during the test was higher in fish infected with glochidia, suggesting that high activity could increase their exposure to glochidia. Potentially, as metabolism rate and ventilation rate typically increase with activity, elevated activity may lead to an increased likelihood of glochidia passing over the gills. This novel finding suggests that glochidia infestation is non‐random and that the behaviour of the host fish can influence the likelihood of glochidia infestation.     

Highly pathogenic avian influenza H5N1 Clade 2.3.2.1c virus in migratory birds, 2014–2015

A novel Clade 2.3.2.1c H5N1 reassortant virus caused several outbreaks in wild birds in some regions of China from late 2014 to 2015. Based on the genetic and phylogenetic analyses, the viruses possess a stable gene constellation with a Clade 2.3.2.1c HA, a H9N2-derived PB2 gene and the other six genes of Asian H5N1-origin. The Clade 2.3.2.1c H5N1 reassortants displayed a high genetic relationship to a human H5N1 strain (A/Alberta/01/2014). Further analysis showed that similar viruses have been circulating in wild birds in China, Russia, Dubai (Western Asia), Bulgaria and Romania (Europe), as well as domestic poultry in some regions of Africa. The affected areas include the Central Asian, East Asian-Australasian, West Asian-East African, and Black Sea/Mediterranean flyways. These results show that the novel Clade 2.3.2.1c reassortant viruses are circulating worldwide and may have gained a selective advantage in migratory birds, thus posing a serious threat to wild birds and potentially humans.

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The association of feeding behaviour with the resistance and tolerance to parasites in recently diverged sticklebacks

Divergent natural selection regimes can contribute to adaptive population divergence, but can be sensitive to human‐mediated environmental change. Nutrient loading of aquatic ecosystems, for example, might modify selection pressures by altering the abundance and distribution of resources and the prevalence and infectivity of parasites. Here, we used a mesocosm experiment to test for interactive effects of nutrient loading and parasitism on host condition and feeding ecology. Specifically, we investigated whether the common fish parasite Gyrodactylus sp. differentially affected recently diverged lake and stream ecotypes of three‐spined stickleback (Gasterosteus aculeatus). We found that the stream ecotype had a higher resistance to Gyrodactylus sp. infections than the lake ecotype, and that both ecotypes experienced a cost of parasitism, indicated by negative relationships between parasite load and both stomach fullness and body condition. Overall, our results suggest that in the early stages of adaptive population divergence of hosts, parasites can affect host resistance, body condition and diet.     

Histamine releasing factor and elongation factor 1 alpha secreted via malaria parasites extracellular vesicles promote immune evasion by inhibiting specific T cell responses

Protozoan pathogens secrete nanosized particles called extracellular vesicles (EVs) to facilitate their survival and chronic infection. Here, we show the inhibition by Plasmodium berghei NK65 blood stage‐derived EVs of the proliferative response of CD4⁺ T cells in response to antigen presentation. Importantly, these results were confirmed in vivo by the capacity of EVs to diminish the ovalbumin‐specific delayed type hypersensitivity response. We identified two proteins associated with EVs, the histamine releasing factor (HRF) and the elongation factor 1α (EF‐1α) that were found to have immunosuppressive activities. Interestingly, in contrast to WT parasites, EVs from genetically HRF‐ and EF‐1α‐deficient parasites failed to inhibit T cell responses in vitro and in vivo. At the level of T cells, we demonstrated that EVs from WT parasites dephosphorylate key molecules (PLCγ1, Akt, and ERK) of the T cell receptor signalling cascade. Remarkably, immunisation with EF‐1α alone or in combination with HRF conferred a long‐lasting antiparasite protection and immune memory. In conclusion, we identified a new mechanism by which P. berghei‐derived EVs exert their immunosuppressive functions by altering T cell responses. The identification of two highly conserved immune suppressive factors offers new conceptual strategies to overcome EV‐mediated immune suppression in malaria‐infected individuals.     

Length polymorphisms at two candidate genes explain variation of migratory behaviors in blackpoll warblers (Setophaga striata)

Migratory behaviors such as the timing and duration of migration are genetically inherited and can be under strong natural selection, yet we still know very little about the specific genes or molecular pathways that control these behaviors. Studies in candidate genes Clock and Adcyap1 have revealed that both of these loci can be significantly correlated with migratory behaviors in birds, though observed relationships appear to vary across species. We investigated geographic genetic structure of Clock and Adcyap1 in four populations of blackpoll warblers (Setophaga striata), a Neotropical–Nearctic migrant that exhibits geographic variation in migratory timing and duration across its boreal breeding distribution. Further, we used data on migratory timing and duration, obtained from light‐level geolocator trackers to investigate candidate genotype–phenotype relationships at the individual level. While we found no geographic structure in either candidate gene, we did find evidence that candidate gene lengths are correlated with five of the six migratory traits. Maximum Clock allele length was significantly and negatively associated with spring arrival date. Minimum Adcyap1 allele length was significantly and negatively associated with spring departure date and positively associated with fall arrival date at the wintering grounds. Additionally, we found a significant interaction between Clock and Adcyap1 allele lengths on both spring and fall migratory duration. Adcyap1 heterozygotes also had significantly shorter migration duration in both spring and fall compared to homozygotes. Our results support the growing body of evidence that Clock and Adcyap1 allele lengths are correlated with migratory behaviors in birds.