Protective Efficacy of Menthol Propylene Glycol Carbonate Compared to N, N-diethyl-Methylbenzamide Against Mosquito Bites in Northern Tanzania.

The reduction of malaria parasite transmission by preventing human-vector contact is critical in lowering disease transmission and its outcomes. This underscores the need for effective and long lasting arthropod/insect repellents. Despite the reduction in malaria transmission and outcomes in Tanzania, personal protection against mosquito bites is still not well investigated. This study sought to determine the efficacy of menthol propylene glycol carbonate (MR08), Ocimum suave as compared to the gold standard repellent N, N-diethyl-methylbenzamide (DEET), either as a single dose or in combination (blend), both in the laboratory and in the field against Anopheles gambiae s.l and Culex quinquefasciatus. In the laboratory evaluations, repellents were applied on one arm while the other arm of the same individual was treated with a base cream. Each arm was separately exposed in cages with unfed female mosquitoes. Repellents were evaluated either as a single dose or as a blend. Efficacy of each repellent was determined by the number of mosquitoes that landed and fed on treated arms as compared to the control or among them. In the field, evaluations were performed by human landing catches at hourly intervals from 18:00  hr to 01:00  hr. A total of 2,442 mosquitoes were collected during field evaluations, of which 2,376 (97.30%) were An. gambiae s.l while 66 (2.70%) were Cx. quinquefaciatus. MR08 and DEET had comparatively similar protective efficacy ranging from 92% to 100 for both single compound and blends. These findings indicate that MR08 has a similar protective efficacy as DEET for personal protection outside bed nets when used singly and in blends. Because of the personal protection provided by MR08, DEET and blends as topical applicants in laboratory and field situations, these findings suggest that, these repellents could be used efficiently in the community to complement existing tools. Overall, Cx. quinquefasciatus were significantly prevented from blood feeding compared to An. gambiae s.l. The incorporation of these topical repellents for protection against insect bites can be of additional value in the absence or presence of IRS and ITNs coverage. However, a combination of both the physical (bed nets) and the repellent should be used in an integrated manner for maximum protection, especially before going to bed. Additional research is needed to develop repellents with longer duration of protection

Antibody response to sand fly saliva is a marker of transmission intensity but not disease progression in dogs naturally infected with Leishmania infantum

BACKGROUND: Antibody responses to sand fly saliva have been suggested to be a useful marker of exposure to sand fly bites and Leishmania infection and a potential tool to monitor the effectiveness of entomological interventions. Exposure to sand fly bites before infection has also been suggested to modulate the severity of the infection. Here, we test these hypotheses by quantifying the anti-saliva IgG response in a cohort study of dogs exposed to natural infection with Leishmania infantum in Brazil. METHODS: IgG responses to crude salivary antigens of the sand fly Lutzomyia longipalpis were measured by ELISA in longitudinal serum samples from 47 previously unexposed sentinel dogs and 11 initially uninfected resident dogs for up to 2 years. Antibody responses were compared to the intensity of transmission, assessed by variation in the incidence of infection between seasons and between dogs. Antibody responses before patent infection were then compared with the severity of infection, assessed using tissue parasite loads and clinical symptoms. RESULTS: Previously unexposed dogs acquired anti-saliva antibody responses within 2 months, and the rate of acquisition increased with the intensity of seasonal transmission. Over the following 2 years, antibody responses varied with seasonal transmission and sand fly numbers, declining rapidly in periods of low transmission. Antibody responses varied greatly between dogs and correlated with the intensity of transmission experienced by individual dogs, measured by the number of days in the field before patent infection. After infection, anti-saliva antibody responses were positively correlated with anti-parasite antibody responses. However, there was no evidence that the degree of exposure to sand fly bites before infection affected the severity of the infection. CONCLUSIONS: Anti-saliva antibody responses are a marker of current transmission intensity in dogs exposed to natural infection with Leishmania infantum, but are not associated with the outcome of infection

Leveraging information between multiple population groups and traits improves fine-mapping resolution

Statistical fine-mapping helps to pinpoint likely causal variants underlying genetic association signals. Its resolution can be improved by (i) leveraging information between traits; and (ii) exploiting differences in linkage disequilibrium structure between diverse population groups. Using association summary statistics, MGflashfm jointly fine-maps signals from multiple traits and population groups; MGfm uses an analogous framework to analyse each trait separately. We also provide a practical approach to fine-mapping with out-of-sample reference panels. In simulation studies we show that MGflashfm and MGfm are well-calibrated and that the mean proportion of causal variants with PP > 0.80 is above 0.75 (MGflashfm) and 0.70 (MGfm). In our analysis of four lipids traits across five population groups, MGflashfm gives a median 99% credible set reduction of 10.5% over MGfm. MGflashfm and MGfm only require summary level data, making them very useful fine-mapping tools in consortia efforts where individual-level data cannot be shared

The South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLAM BRC) case register: development and descriptive data

Background: Case registers have been used extensively in mental health research. Recent developments in electronic medical records, and in computer software to search and analyse these in anonymised format, have the potential to revolutionise this research tool. Methods: We describe the development of the South London and Maudsley NHS Foundation Trust (SLAM) Biomedical Research Centre (BRC) Case Register Interactive Search tool (CRIS) which allows research-accessible datasets to be derived from SLAM, the largest provider of secondary mental healthcare in Europe. All clinical data, including free text, are available for analysis in the form of anonymised datasets. Development involved both the building of the system and setting in place the necessary security (with both functional and procedural elements). Results: Descriptive data are presented for the Register database as of October 2008. The database at that point included 122,440 cases, 35,396 of whom were receiving active case management under the Care Programme Approach. In terms of gender and ethnicity, the database was reasonably representative of the source population. The most common assigned primary diagnoses were within the ICD mood disorders (n = 12,756) category followed by schizophrenia and related disorders (8158), substance misuse (7749), neuroses (7105) and organic disorders (6414). Conclusion: The SLAM BRC Case Register represents a 'new generation' of this research design, built on a long-running system of fully electronic clinical records and allowing in-depth secondary analysis of both numerical, string and free text data, whilst preserving anonymity through technical and procedural safeguards