Multiple human herpesvirus-8 infection

In Malawian patients with Kaposi sarcoma (KS) and their relatives, we investigated nucleotide-sequence variation in human herpesvirus-8 (HHV-8) subgenomic DNA, amplified from oral and blood samples by use of polymerase chain reaction. Twenty-four people had amplifiable HHV-8 DNA in >1 sample; 9 (38%) were seropositive for human immunodeficiency virus type 1, 21 (88%) were anti-HHV-8-seropositive, and 7 (29%) had KS. Sequence variation was sought in 3 loci of the HHV-8 genome: the internal repeat domain of open-reading frame (ORF) 73, the KS330 segment of ORF 26, and variable region 1 of ORF K1. Significant intraperson/intersample and intrasample sequence polymorphisms were observed in 14 people (60%). For 3 patients with KS, intraperson genotypic differences, arising from nucleotide sequence variations in ORFs 26 and K1, were found in blood and oral samples. For 2 other patients with KS and for 9 people without KS, intraperson genotypic and subgenotypic differences, originating predominantly from ORF K1, were found in oral samples; for the 2 patients with KS and for 4 individuals without KS, intrasample carriage of distinct ORF K1 sequences also were discernible. Our findings imply HHV-8 superinfection

The influence of power and actor relations on priority setting and resource allocation practices at the hospital level in Kenya: a case study

Abstract Background Priority setting and resource allocation in healthcare organizations often involves the balancing of competing interests and values in the context of hierarchical and politically complex settings with multiple interacting actor relationships. Despite this, few studies have examined the influence of actor and power dynamics on priority setting practices in healthcare organizations. This paper examines the influence of power relations among different actors on the implementation of priority setting and resource allocation processes in public hospitals in Kenya. Methods We used a qualitative case study approach to examine priority setting and resource allocation practices in two public hospitals in coastal Kenya. We collected data by a combination of in-depth interviews of national level policy makers, hospital managers, and frontline practitioners in the case study hospitals (n = 72), review of documents such as hospital plans and budgets, minutes of meetings and accounting records, and non-participant observations in case study hospitals over a period of 7 months. We applied a combination of two frameworks, Norman Long’s actor interface analysis and VeneKlasen and Miller’s expressions of power framework to examine and interpret our findings Results The interactions of actors in the case study hospitals resulted in socially constructed interfaces between: 1) senior managers and middle level managers 2) non-clinical managers and clinicians, and 3) hospital managers and the community. Power imbalances resulted in the exclusion of middle level managers (in one of the hospitals) and clinicians and the community (in both hospitals) from decision making processes. This resulted in, amongst others, perceptions of unfairness, and reduced motivation in hospital staff. It also puts to question the legitimacy of priority setting processes in these hospitals. Conclusions Designing hospital decision making structures to strengthen participation and inclusion of relevant stakeholders could improve priority setting practices. This should however, be accompanied by measures to empower stakeholders to contribute to decision making. Strengthening soft leadership skills of hospital managers could also contribute to managing the power dynamics among actors in hospital priority setting processes

Two stories

The purpose of this thesis is, quite simply, to tell two stories. They are stories I thought worth telling, and they are told as I believe they should be told. Each centers about a single character because I believe that people are the essence of fiction. It will perhaps be most effective to write about the stories Individually, Inasmuch as talking generally about fiction—its goals and methods--seems a sure and ready way to make oneself foolish. Indeed, talking too much about even the individual ones of one's stories is a way to seem foolish. If what one feels about the story could be summed up in a quick sentence or two, then there would have been no point ever in writing the story

Performance Characteristics of Combinations of Host Biomarkers to Identify Women with Occult Placental Malaria: A Case-Control Study from Malawi

Because of its propensity to sequester in the placental intervillous space, Plasmodium falciparum can evade detection by peripheral smear in women with placental malaria (PM). We evaluated host biomarkers as potential indicators of occult PM infections.Using a case-control design, we evaluated the ability of biomarkers to identify PM in the absence of circulating peripheral parasites (n = 24) compared to placental smear-negative controls (n = 326). We measured levels of biomarkers (C3a, C5a, CRP, angiopoietin-1, angiopoietin-2, sTie-2, sEndoglin, VEGF, sFlt-1, tissue factor, and leptin) in maternal peripheral plasma at delivery. Using ROC curve analysis, we assessed the ability of clinical parameters and biomarkers to accurately detect PM infections identified by placental smear. We show that decreases in sFlt-1 and leptin and increases in CRP were associated with occult PM infections (p<0.01) and correlated with placental parasitaemia (p<0.01). Individually, all markers had moderate ability to diagnose occult PM infections with areas under the ROC between 0.62 and 0.72. In order to improve diagnostic performance, we generated simple scoring systems to identify PM infections using either a clinical score (0-2), a biomarker score (0-3) or a clinical plus biomarker score (0-5). The combinatorial model that incorporated both clinical parameters and biomarkers had an area under curve (AUC) of 0.85 (95% CI, 0.81-0.89), which was significantly better at identifying occult PM infections than the clinical score alone (p = 0.001).These data suggest that host biomarkers in the maternal peripheral blood may improve the detection of PM in the absence of peripheral parasitaemia

Using an Improved Phagocytosis Assay to Evaluate the Effect of HIV on Specific Antibodies to Pregnancy-Associated Malaria

Background: Pregnant women residing in malaria endemic areas are highly susceptible to Plasmodium falciparum malaria, particularly during their first pregnancy, resulting in low birth weight babies and maternal anaemia. This susceptibility is associated with placental sequestration of parasitised red blood cells expressing pregnancy-specific variant surface antigens. Acquisition of antibodies against these variant surface antigens may protect women and their offspring. Functions of such antibodies may include prevention of placental sequestration or opsonisation of parasitised cells for phagocytic clearance. Methodology/Findings: Here we report the development and optimisation of a new high-throughput flow cytometry-based phagocytosis assay using undifferentiated Thp-1 cells to quantitate the amount of opsonizing antibody in patient sera, and apply this assay to measure the impact of HIV on the levels of antibodies to a pregnancy malaria-associated parasite line in a cohort of Malawian primigravid women. The assay showed high reproducibility, with inter-experimental correlation of r2 = 0.99. In primigravid women, concurrent malaria infection was associated with significantly increased antibodies, whereas HIV decreased the ability to acquire opsonising antibodies (Mann-Whitney ranksum: p = 0.013). This decrease was correlated with HIV-induced immunosuppression, with women with less than 350×106 CD4+ T- cells/L having less opsonising antibodies (coef: −11.95,P = 0.002). Levels of antibodies were not associated with protection from low birth weight or anaemia. Conclusions/Significance: This flow cytometry-based phagocytosis assay proved to be efficient and accurate for the measurement of Fc-receptor mediated phagocytosis-inducing antibodies in large cohorts. HIV was found to affect mainly the acquisition of antibodies to pregnancy-specific malaria in primigravidae. Further studies of the relationship between opsonising antibodies to malaria in pregnancy and HIV are indicated.Ricardo Ataíde, Wina Hasang, Danny W. Wilson, James G. Beeson, Victor Mwapasa, Malcolm E. Molyneux, Steven R. Meshnick, Stephen J. Rogerso

Electron-electron scattering in linear transport in two-dimensional systems

We describe a method for numerically incorporating electron--electron scattering in quantum wells for small deviations of the distribution function from equilibrium, within the framework of the Boltzmann equation. For a given temperature $T$ and density $n$, a symmetric matrix needs to be evaluated only once, and henceforth it can be used to describe electron--electron scattering in any Boltzmann equation linear-response calculation for that particular $T$ and $n$. Using this method, we calculate the distribution function and mobility for electrons in a quantum-well, including full finite-temperature dynamic screening effects. We find that at some parameters which we investigated, electron--electron scattering reduces mobility by approximately 40\%.Comment: 12 pages, 2 figures (uuencoded

Spatial distribution of podoconiosis in relation to environmental factors in Ethiopia: a historical review

BACKGROUND An up-to-date and reliable map of podoconiosis is needed to design geographically targeted and cost-effective intervention in Ethiopia. Identifying the ecological correlates of the distribution of podoconiosis is the first step for distribution and risk maps. The objective of this study was to investigate the spatial distribution and ecological correlates of podoconiosis using historical and contemporary survey data. METHODS Data on the observed prevalence of podoconiosis were abstracted from published and unpublished literature into a standardized database, according to strict inclusion and exclusion criteria. In total, 10 studies conducted between 1969 and 2012 were included, and data were available for 401,674 individuals older than 15 years of age from 229 locations. A range of high resolution environmental factors were investigated to determine their association with podoconiosis prevalence, using logistic regression. RESULTS The prevalence of podoconiosis in Ethiopia was estimated at 3.4% (95% CI 3.3%-3.4%) with marked regional variation. We identified significant associations between mean annual Land Surface Temperature (LST), mean annual precipitation, topography of the land and fine soil texture and high prevalence of podoconiosis. The derived maps indicate both widespread occurrence of podoconiosis and a marked variability in prevalence of podoconiosis, with prevalence typically highest at altitudes >1500 m above sea level (masl), with >1500 mm annual rainfall and mean annual LST of 19-21°C. No (or very little) podoconiosis occurred at altitudes 24°C. CONCLUSION Podoconiosis remains a public health problem in Ethiopia over considerable areas of the country, but exhibits marked geographical variation associated in part with key environmental factors. This is work in progress and the results presented here will be refined in future work