Genomic analysis of two phlebotomine sand fly vectors of Leishmania from the New and Old World.

Phlebotomine sand flies are of global significance as important vectors of human disease, transmitting bacterial, viral, and protozoan pathogens, including the kinetoplastid parasites of the genus Leishmania, the causative agents of devastating diseases collectively termed leishmaniasis. More than 40 pathogenic Leishmania species are transmitted to humans by approximately 35 sand fly species in 98 countries with hundreds of millions of people at risk around the world. No approved efficacious vaccine exists for leishmaniasis and available therapeutic drugs are either toxic and/or expensive, or the parasites are becoming resistant to the more recently developed drugs. Therefore, sand fly and/or reservoir control are currently the most effective strategies to break transmission. To better understand the biology of sand flies, including the mechanisms involved in their vectorial capacity, insecticide resistance, and population structures we sequenced the genomes of two geographically widespread and important sand fly vector species: Phlebotomus papatasi, a vector of Leishmania parasites that cause cutaneous leishmaniasis, (distributed in Europe, the Middle East and North Africa) and Lutzomyia longipalpis, a vector of Leishmania parasites that cause visceral leishmaniasis (distributed across Central and South America). We categorized and curated genes involved in processes important to their roles as disease vectors, including chemosensation, blood feeding, circadian rhythm, immunity, and detoxification, as well as mobile genetic elements. We also defined gene orthology and observed micro-synteny among the genomes. Finally, we present the genetic diversity and population structure of these species in their respective geographical areas. These genomes will be a foundation on which to base future efforts to prevent vector-borne transmission of Leishmania parasites

Investigating risk factors associated with hyponatremia in hospitalised patients using an electronic prescribing system with health records

Hyponatraemia, defined as a serum sodium concentration of <135mmol/l, is the most commonly encountered electrolyte disturbance in hospital patients. Various studies have shown that hyponatraemia occurs in up to 30% of hospitalised patients. Hyponatraemia has been associated with older age, low body weight, chronic diseases and diuretic therapy to name but a few. This study set out to identify risk factors for hyponatraemia in a large dataset of patients in a UK teaching hospital and to ascertain patient outcomes. Methodology A retrospective case-control study design was used to explore risk factors associated with hyponatraemia. Hospital episode data were extracted from an electronic prescribing system with health records used in an English teaching hospital. We used serum sodium levels measured in adult patients admitted over a one year period (2010-2011) to group patients. A patient was classed as hyponatraemic if their lowest serum sodium result during their in-patient spell was <135mmol/l and classed as non- hyponatraemic if serum sodium was ?135mmol/l (controls). Statistical tests for categorical and non-parametric data were used to examine the null hypothesis that there was no difference in risk factors and outcomes between hyponatraemic and non-hyponatraemic patients. A multivariate logistic regression model of risk factors associated with hyponatraemia was fitted. Results Data from 22,306 patients were analysed and 19% were classified as hyponatraemic during their in-patient spell. The risk of hyponatraemia was greater with increasing age - especially in those aged 60-69 (adjusted OR 2.2; 95% C.I. 1.6-2.9; p<0.001). The risk of hyponatraemia was also found to be greater for patients who were underweight (unadjusted OR 1.4; 1.1-1.7; p<0.001). Patients with Stage 5 renal failure were found to have a three-fold increased risk of hyponatraemia compared to those with less severe renal failure (adjusted OR 2.5; 1.9-3.2; p<0.001). Those patients with a higher Charlson Comorbidity Index (?13) were more likely to have hyponatraemia (adjusted OR 1.3; 1.1-1.6; p<0.05). More hyponatraemic patients were prescribed diuretics compared to non-hyponatraemic patients (thiazides 10.4% vs. 5.1%, loop 6.9% vs. 4.9% and potassium sparing 1.9% vs. 1%, all p<0.001), when entered into the multivariate logistic regression model, thiazide diuretic administration was associated with an increased risk of developing hyponatraemia (adjusted OR 1.7; 95% C.I. 1.3-2.1; p<0.001). Patients who were on NSAIDs and SSRIs were less likely to have hyponatraemia (adjusted OR 0.5; 95% 0.3-0.6 and adjusted OR 0.2; 0.1-0.8; p<0.05 respectively). Increasing severity of hyponatraemia was found to have a higher incidence of all-cause mortality (20% vs. 3%, p<0.001). Conclusions This study demonstrated that approximately 1 in 5 patients experienced hyponatraemia during their admission in this hospital and were more likely to have poorer outcomes than non-hyponatraemics. We concluded that this is a relatively convenient form of data extraction and the results can be used to better understand the risk factors associated with hyponatraemia. Some associations, such as diuretics, have a direct causal relationship and in some cases hyponatraemia may be a marker of increasing comorbidity. The next steps would be to use these results (incorporating them into algorithms) to alert health care professionals and guide them whilst they use electronic prescribing systems, thereby ensuring that patients receive the most appropriate care and management whilst in hospital