Advances and challenges in barcoding pathogenic and environmental Leptospira

Leptospirosis is a zoonotic bacterial disease of global importance. A large spectrum of asymptomatic animal hosts can carry the infection and contribute to the burden of human disease. Environmental sources of human contamination also point to the importance of a hydrotelluric reservoir. Leptospirosis can be caused by as many as 15 different pathogenic or intermediate Leptospira species. However, classification of these bacteria remains complicated through the use of both serological and genetic classification systems that show poor correlation. With the advent of molecular techniques, DNA-based barcoding offers a conceptual framework that can be used for leptospirosis surveillance as well as source tracking. In this review, we summarize some of the current techniques, highlight significant successes and weaknesses and point to the future opportunities and challenges to successfully establish a widely applicable barcoding scheme for Leptospira

Leptospirosis in northern Tanzania: exploring the role of rodents and ruminant livestock in a neglected public health problem

Leptospirosis is an important but neglected zoonotic disease that is often overlooked in Africa. Although comprehensive data on the incidence of human disease are lacking, robust evidence of infection has been demonstrated in people and animals from all regions of the continent. However, to date, there are few examples of direct epidemiological linkages between human disease and animal infection. In East Africa, awareness of the importance of human leptospirosis as a cause of non-malarial febrile illness is growing. In northern Tanzania, acute leptospirosis has been diagnosed in 9% of patients with severe febrile illness compared to only 2% with malaria. However, little is known about the relative importance of different potential animal hosts as sources of human infection in this area. This project was established to investigate the roles of rodents and ruminant livestock, important hosts of Leptospira in other settings, in the epidemiology of leptospirosis in northern Tanzania. A cross-sectional survey of rodents living in and around human settlements was performed alongside an abattoir survey of ruminant livestock. Unusual patterns of animal infection were detected by real-time PCR detection. Renal Leptospira infection was absent from rodents but was detected in cattle from several geographic areas. Infection was demonstrated for the first time in small ruminants sub-Saharan Africa. Two major Leptospira species and a novel Leptospira genotype were detected in livestock. L. borgpetersenii was seen only in cattle but L. kirschneri infection was detected in multiple livestock species (cattle, sheep and goats), suggesting that at least two distinct patterns of Leptospira infection occur in livestock in northern Tanzania. Analysis of samples from acute leptospirosis in febrile human patients could not detect Leptospira DNA by real-time PCR but identified social and behavioural factors that may limit the utility of acute-phase diagnostic tests in this community. Analysis of serological data revealed considerable overlap between serogroups detected in cattle and human leptospirosis cases. Human disease was most commonly attributed to the serogroups Mini and Australis, which were also predominant reactive serogroups in cattle. Collectively, the results of this study led to the hypothesis that livestock are an important reservoir of Leptospira infection for people in northern Tanzania. These results also challenge our understanding of the relationship between Leptospira and common invasive rodent species, which do not appear to maintain infection in this setting. Livestock Leptospira infection has substantial potential to affect the well-being of people in East Africa, through direct transmission of infection or through indirect effects on food production and economic security. Further research is needed to quantify the impact of livestock leptospirosis in Africa and to develop effective interventions for the control of human and animal disease

Renewing the momentum for leptospirosis research in Africa

No abstract available

Evaluation of polycaprolactone matrices for sustained intravaginal delivery of a natural macromolecular microbicide, lactoferrin

Polycaprolactone (PCL) matrices incorporating lactoferrin as a natural macromolecular microbicide, were prepared by rapidly cooling a suspension of lactoferrin particulates in PCL solution to induce crystallisation and hardening of the polymer. Thermal analysis revealed a 7% decrease in crystallinity of the PCL phase for 10% lactoferrin-loaded matrices compared with lactoferrin-free matrices and a 41% decrease in hardness of lactoferrin -loaded matrices, indicating a major influence of lactoferrin through inhibition of PCL crystal nucleation and growth. Exposure of the matrices to simulated vaginal fluid (SVF) at 37 °C resulted in rapid release of 13–14% of the lactoferrin content on day 1 and sustained delivery of the glycoprotein with high efficiency (90–95% of the content) over 14 days. SDS-PAGE analysis confirmed molecular weight preservation of the lactoferrin released from PCL matrices into SVF, indicating that it was not degraded during formulation and release. These findings recommend further investigations of PCL matrices as vaginal delivery systems for controlled release of macromolecular microbicides in the treatment and prevention of sexually transmitted infections

Incidence and clinical characteristics of group A rotavirus infections among children admitted to hospital in Kilifi, Kenya

Background Rotavirus, predominantly of group A, is a major cause of severe diarrhoea worldwide, with the greatest burden falling on young children living in less-developed countries. Vaccines directed against this virus have shown promise in recent trials, and are undergoing effectiveness evaluation in sub-Saharan Africa. In this region limited childhood data are available on the incidence and clinical characteristics of severe group A rotavirus disease. Advocacy for vaccine intervention and interpretation of effectiveness following implementation will benefit from accurate base-line estimates of the incidence and severity of rotavirus paediatric admissions in relevant populations. The study objective was to accurately define the incidence and severity of group A rotavirus disease in a resource-poor setting necessary to make informed decisions on the need for vaccine prevention. Methods and Findings Between 2002 and 2004 we conducted prospective surveillance for group A rotavirus infection at Kilifi District Hospital in coastal Kenya. Children < 13 y of age were eligible as "cases" if admitted with diarrhoea, and "controls" if admitted without diarrhoea. We calculated the incidence of hospital admission with group A rotavirus using data from a demographic surveillance study of 220,000 people in Kilifi District. Of 15,347 childhood admissions 3,296 (22%) had diarrhoea, 2,039 were tested for group A rotavirus antigen and, of these, 588 (29%) were positive. 372 (63%) rotavirus-positive cases were infants. Of 620 controls 19 (3.1%, 95% confidence interval [CI] 1.9–4.7) were rotavirus positive. The annual incidence (per 100,000 children) of rotavirus-positive admissions was 1,431 (95% CI 1,275–1,600) in infants and 478 (437–521) in under-5-y-olds, and highest proximal to the hospital. Compared to children with rotavirus-negative diarrhoea, rotavirus-positive cases were less likely to have coexisting illnesses and more likely to have acidosis (46% versus 17%) and severe electrolyte imbalance except hyponatraemia. In-hospital case fatality was 2% among rotavirus-positive and 9% among rotavirus-negative children. Conclusions In Kilifi > 2% of children are admitted to hospital with group A rotavirus diarrhoea in the first 5 y of life. This translates into over 28,000 vaccine-preventable hospitalisations per year across Kenya, and is likely to be a considerable underestimate. Group A rotavirus diarrhoea is associated with acute life-threatening metabolic derangement in otherwise healthy children. Although mortality is low in this clinical research setting this may not be generally true in African hospitals lacking rapid and appropriate management

Providing Feedback Following Leadership Walkrounds is Associated with Better Patient Safety Culture, Higher Employee Engagement and Lower Burnout

Background There is a poorly understood relationship between Leadership WalkRounds (WR) and domains such as safety culture, employee engagement, burnout and work-life balance. Methods This cross-sectional survey study evaluated associations between receiving feedback about actions taken as a result of WR and healthcare worker assessments of patient safety culture, employee engagement, burnout and work-life balance, across 829 work settings. Results 16 797 of 23 853 administered surveys were returned (70.4%). 5497 (32.7% of total) reported that they had participated in WR, and 4074 (24.3%) reported that they participated in WR with feedback. Work settings reporting more WR with feedback had substantially higher safety culture domain scores (first vs fourth quartile Cohen’s d range: 0.34–0.84; % increase range: 15–27) and significantly higher engagement scores for four of its six domains (first vs fourth quartile Cohen’s d range: 0.02–0.76; % increase range: 0.48–0.70). Conclusion This WR study of patient safety and organisational outcomes tested relationships with a comprehensive set of safety culture and engagement metrics in the largest sample of hospitals and respondents to date. Beyond measuring simply whether WRs occur, we examine WR with feedback, as WR being done well. We suggest that when WRs are conducted, acted on, and the results are fed back to those involved, the work setting is a better place to deliver and receive care as assessed across a broad range of metrics, including teamwork, safety, leadership, growth opportunities, participation in decision-making and the emotional exhaustion component of burnout. Whether WR with feedback is a manifestation of better norms, or a cause of these norms, is unknown, but the link is demonstrably potent

Spatial epidemiological approaches to inform leptospirosis surveillance and control: a systematic review and critical appraisal of methods

Leptospirosis is a global zoonotic disease that the transmission is driven by complex geographical and temporal variation in demographics, animal hosts and socioecological factors. This results in complex challenges for the identification of high‐risk areas. Spatial and temporal epidemiological tools could be used to support leptospirosis control programs, but the adequacy of its application has not been evaluated. We searched literature in six databases including PubMed, Web of Science, EMBASE, Scopus, SciELO and Zoological Record to systematically review and critically assess the use of spatial and temporal analytical tools for leptospirosis and to provide general framework for its application in future studies. We reviewed 115 articles published between 1930 and October 2018 from 41 different countries. Of these, 65 (56.52%) articles were on human leptospirosis, 39 (33.91%) on animal leptospirosis and 11 (9.5%) used data from both human and animal leptospirosis. Spatial analytical (n = 106) tools were used to describe the distribution of incidence/prevalence at various geographical scales (96.5%) and to explored spatial patterns to detect clustering and hot spots (33%). A total of 51 studies modelled the relationships of various variables on the risk of human (n = 31), animal (n = 17) and both human and animal infection (n = 3). Among those modelling studies, few studies had generated spatially structured models and predictive maps of human (n = 2/31) and animal leptospirosis (n = 1/17). In addition, nine studies applied time‐series analytical tools to predict leptospirosis incidence. Spatial and temporal analytical tools have been greatly utilized to improve our understanding on leptospirosis epidemiology. Yet the quality of the epidemiological data, the selection of covariates and spatial analytical techniques should be carefully considered in future studies to improve usefulness of evidence as tools to support leptospirosis control. A general framework for the application of spatial analytical tools for leptospirosis was proposed

Exploring secondary bonding in p-block chemistry – an experimental study of [GeX 2 {o-C 6 H 4 (PMe 2 ) 2 }] using variable pressure single crystal X-ray diffraction

Secondary bonding interactions play a major role in governing the overall structures adopted. The low energy contributions from these weak interactions make structure prediction very difficult, hence there is a need for experimental techniques that contribute to understanding the interplay between different types of secondary bonding. Variable pressure single crystal X-ray diffraction studies on the homologous series, [GeX2{o-C6H4(PMe2)2}], X = Cl 1, Br 2, I 3, show that probing the different interfaces between layers of structural building blocks, rather than conventional molecular units, provides very valuable insights. 1 and 3 undergo a smooth compression as the pressure is increased, whereas a phase transition occurs for 2 at a pressure between 29 and 41 kbar. This is associated with an abrupt change in the β angle (from 111.33(2)° to 92.24(8)°). The structural consequences are most evident in the aromatic⋯aromatic layer interface. Below the phase transition there is an edge-to-face C–H⋯π arrangement (like 1), with the angle between the planes of adjacent rings of ~75°, whereas above the transition this interface has transformed to an offset-parallel face-to-face π–π stacking interaction (like 3). The GeX2⋯X2Ge interface undergoes a concomitant, but smoother compression with increasing pressure. 2 also has the highest void volume at ambient pressure (11.9%), and as expected the phase transition results in a structure with much more efficient packing. This, the first such study involving p-block coordination complexes, reveals the subtlety and complexity of the interplay between the different forms of weak, secondary (supramolecular) interactions present. The results indicate that this type of experimental study can provide valuable additional information to help guide crystal structure prediction by computational methods, an important and very challenging target

Comparison of the estimated incidence of acute leptospirosis in the Kilimanjaro Region of Tanzania between 2007-08 and 2012-14

Background: The sole report of annual leptospirosis incidence in continental Africa of 75–102 cases per 100,000 population is from a study performed in August 2007 through September 2008 in the Kilimanjaro Region of Tanzania. To evaluate the stability of this estimate over time, we estimated the incidence of acute leptospirosis in Kilimanjaro Region, northern Tanzania for the time period 2012–2014. Methodology and Principal Findings: Leptospirosis cases were identified among febrile patients at two sentinel hospitals in the Kilimanjaro Region. Leptospirosis was diagnosed by serum microscopic agglutination testing using a panel of 20 Leptospira serovars belonging to 17 separate serogroups. Serum was taken at enrolment and patients were asked to return 4–6 weeks later to provide convalescent serum. Confirmed cases required a 4-fold rise in titre and probable cases required a single titre of ≥800. Findings from a healthcare utilisation survey were used to estimate multipliers to adjust for cases not seen at sentinel hospitals. We identified 19 (1.7%) confirmed or probable cases among 1,115 patients who presented with a febrile illness. Of cases, the predominant reactive serogroups were Australis 8 (42.1%), Sejroe 3 (15.8%), Grippotyphosa 2 (10.5%), Icterohaemorrhagiae 2 (10.5%), Pyrogenes 2 (10.5%), Djasiman 1 (5.3%), Tarassovi 1 (5.3%). We estimated that the annual incidence of leptospirosis was 11–18 cases per 100,000 population. This was a significantly lower incidence than 2007–08 (p&lt;0.001). Conclusions: We estimated a much lower incidence of acute leptospirosis than previously, with a notable absence of cases due to the previously predominant serogroup Mini. Our findings indicate a dynamic epidemiology of leptospirosis in this area and highlight the value of multi-year surveillance to understand leptospirosis epidemiology