Repellent and acaricidal properties of Ocimum suave against Rhipicephalus appendiculatus ticks

An oil extracted from the leaves of a tropical shrub Ocimum suave was found to repel as well as kill all stages of the tick Rhipicephalus appendiculatus. In an in vitro bioassay for the larvae, the LC₅₀ of the oil in liquid paraffin was 0.024%. A 10% solution was found to kill all immatures and more than 70% of adults feeding on rabbits. Rabbits were protected for 5 days against attaching larvae using a 10% solution. Preliminary experiments undertaken with cattle kept in the field suggest that the oil may have potential in tick control, and a role in integrated tick management.     

Prospects for biological control of the western flower thrips,Frankliniella occidentalis,with the entomopathogenic fungus,Metarhizium anisopliae,on chrysanthemum

The potential of Metarhizium anisopliae (Metsch.) Sorok. for the control of Frankliniella occidentalis (Pergande) on chrysanthemum cuttings was evaluated in greenhouse experiments. The fungus significantly reduced both the adult and larval populations of F. occidentalis, although the level of control of larval populations was much lower than for adults. Combined application of M. anisopliae and Methomyl (Lannate), however, resulted in a significant reduction of both the larval and adult stages. The use of both control agents might be helpful in reducing the selection pressure for resistance to chemical insecticides, thereby delaying or preventing the build-up of resistant populations in greenhouses.     

Structure-activity relationships of oxime neurokinin antagonists: oxime modifications

A thorough SAR study of the oxime region of the dual NK(1)/NK(2) antagonist 1 revealed several modifications that result in potent dual antagonists. Follow up SAR studies on a second-generation scaffold demonstrate that certain polar groups on the oxime can improve the dual binding affinity to the subnanomolar range.     

DNA-encoded fetal liver tyrosine kinase 3 ligand and granulocyte macrophage-colony-stimulating factor increase dendritic cell recruitment to the inoculation site and enhance antigen-specific CD4+ T cell responses induced by DNA vaccination of outbred animals

DNA-based immunization is a contemporary strategy for developing vaccines to prevent infectious diseases in animals and humans. Translating the efficacy of DNA immunization demonstrated in murine models to the animal species that represent the actual populations to be protected remains a significant challenge. We tested two hypotheses directed at enhancing DNA vaccine efficacy in outbred animals. The first hypothesis, that DNA-encoding fetal liver tyrosine kinase 3 ligand (Flt3L) and GM-CSF increases dendritic cell (DC) recruitment to the immunization site, was tested by intradermal inoculation of calves with plasmid DNA encoding Flt3L and GM-CSF followed by quantitation of CD1(+) DC. Peak DC recruitment was detected at 10-15 days postinoculation and was significantly greater (p < 0.05) in calves in the treatment group as compared with control calves inoculated identically, but without Flt3L and GM-CSF. The second hypothesis, that DNA encoding Flt3L and GM-CSF enhances immunity to a DNA vector-expressed Ag, was tested by analyzing the CD4(+) T lymphocyte response to Anaplasma marginale major surface protein 1a (MSP1a). Calves immunized with DNA-expressing MSP1a developed strong CD4(+) T cell responses against A. marginale, MSP1a, and specific MHC class II DR-restricted MSP1a epitopes. Administration of DNA-encoding Flt3L and GM-CSF before MSP1a DNA vaccination significantly increased the population of Ag-specific effector/memory cells in PBMC and significantly enhanced MSP1a-specific CD4(+) T cell proliferation and IFN-gamma secretion as compared with MHC class II DR-matched calves vaccinated identically but without Flt3L and GM-CSF. These results support use of these growth factors in DNA vaccination and specifically indicate their applicability for vaccine testing in outbred animals.     

Impact of land use and tenure changes on the Kitenden wildlife corridor,Amboseli Ecosystem,Kenya

This study assesses the ecological pressure exerted by changing land use and tenure on the Kitenden wildlife corridor, a critical cross‐border link between the Amboseli and Kilimanjaro national parks. The implications on viability of the two high‐value protected areas and their respective dispersal areas are both negative and serious. The extent of land use change and its impacts were assessed through household and vegetation surveys, while wildlife abundance was measured using transect walks. Approximately 30% of the study area has shifted from community to private land ownership over the last two decades. Except for baboon and vervet monkey, most wildlife avoided the cultivated area. Vegetation composition on the noncultivated area has been greatly altered by intense wildlife and livestock use, where mean herbaceous vegetation cover differed significantly among range‐plant categories (F_{3, 524} = 29.015, p < 0.05). The frequency of increaser I (21.4%) differs greatly from that of decreaser and forbs, at 8.3% and 7.4%, respectively Tree recruitment was low, with a significant difference in mean density among age classes (F_{2, 110} = 3.663, p < 0.05). Only through land leasing agreements between landowners and conservation organisations, and a widely supported land use plan, can the spread of cultivation be controlled and complete cessation of wildlife movement be prevented.     

Identification of a novel, orally bioavailable histamine H(3) receptor antagonist based on the 4-benzyl-(1H-imidazol-4-yl) template

A novel series of histamine H(3) receptor antagonists, based on the 4-benzyl-(1H-imidazole-4-yl) template, incorporating urea and carbamate linkers has been prepared. Compound 3j is a selective H(3) antagonist and demonstrates excellent oral plasma levels in the rat and monkey.     

Performance of health workers in the management of seriously sick children at a kenyan tertiary hospital: before and after a training intervention

Background

Implementation of WHO case management guidelines for serious common childhood illnesses remains a challenge in hospitals in low-income countries. The impact of locally adapted clinical practice guidelines (CPGs) on the quality-of-care of patients in tertiary hospitals has rarely been evaluated.

Methods and Findings

We conducted, in Kenyatta National Hospital, an uncontrolled before and after study with an attempt to explore intervention dose-effect relationships, as CPGs were disseminated and training was progressively implemented. The emergency triage, assessment and treatment plus admission care (ETAT+) training and locally adapted CPGs targeted common, serious childhood illnesses. We compared performance in the pre-intervention (2005) and post-intervention periods (2009) using quality indicators for three diseases: pneumonia, dehydration and severe malnutrition. The indicators spanned four domains in the continuum of care namely assessment, classification, treatment, and follow-up care in the initial 48 hours of admission. In the pre-intervention period patients'' care was largely inconsistent with the guidelines, with nine of the 15 key indicators having performance of below 10%. The intervention produced a marked improvement in guideline adherence with an absolute effect size of over 20% observed in seven of the 15 key indicators; three of which had an effect size of over 50%. However, for all the five indicators that required sustained team effort performance continued to be poor, at less than 10%, in the post-intervention period. Data from the five-year period (2005–09) suggest some dose dependency though the adoption rate of the best-practices varied across diseases and over time.

Conclusion

Active dissemination of locally adapted clinical guidelines for common serious childhood illnesses can achieve a significant impact on documented clinical practices, particularly for tasks that rely on competence of individual clinicians. However, more attention must be given to broader implementation strategies that also target institutional and organisational aspects of service delivery to further enhance quality-of-care.     

Correlation of memory T cell responses against TRAP with protection from clinical malaria, and CD4 CD25 high T cells with susceptibility in Kenyans

Background

Immunity to malaria develops naturally in endemic regions, but the protective immune mechanisms are poorly understood. Many vaccination strategies aim to induce T cells against diverse pre-erythrocytic antigens, but correlates of protection in the field have been limited. The objective of this study was to investigate cell-mediated immune correlates of protection in natural malaria. Memory T cells reactive against thrombospondin-related adhesive protein (TRAP) and circumsporozoite (CS) protein, major vaccine candidate antigens, were measured, as were frequencies of CD4⁺ CD25^high T cells, which may suppress immunity, and CD56⁺ NK cells and γδ T cells, which may be effectors or may modulate immunity.

Methodology and Principal Findings

112 healthy volunteers living in rural Kenya were entered in the study. Memory T cells reactive against TRAP and CS were measured using a cultured IFNγ ELISPOT approach, whilst CD4⁺ CD25^high T cells, CD56⁺ NK cells, and γδ T cells were measured by flow cytometry. We found that T cell responses against TRAP were established early in life (<5 years) in contrast to CS, and cultured ELISPOT memory T cell responses did not correlate with ex-vivo IFNγ ELISPOT effector responses. Data was examined for associations with risk of clinical malaria for a period of 300 days. Multivariate logistic analysis incorporating age and CS response showed that cultured memory T cell responses against TRAP were associated with a significantly reduced incidence of malaria (p = 0.028). This was not seen for CS responses. Higher numbers of CD4⁺ CD25^high T cells, potentially regulatory T cells, were associated with a significantly increased risk of clinical malaria (p = 0.039).

Conclusions

These data demonstrate a role for central memory T cells in natural malarial immunity and support current vaccination strategies aimed at inducing durable protective T cell responses against the TRAP antigen. They also suggest that CD4⁺ CD25^high T cells may negatively affect naturally acquired malarial immunity.