Effect of transmission setting and mixed species infections on clinical measures of malaria in Malawi

<p>Background: In malaria endemic regions people are commonly infected with multiple species of malaria parasites but the clinical impact of these Plasmodium co-infections is unclear. Differences in transmission seasonality and transmission intensity between endemic regions have been suggested as important factors in determining the effect of multiple species co-infections.</p> <p>Principal Findings: In order to investigate the impact of multiple-species infections on clinical measures of malaria we carried out a cross-sectional community survey in Malawi, in 2002. We collected clinical and parasitological data from 2918 participants aged >6 months, and applied a questionnaire to measure malaria morbidity. We examined the effect of transmission seasonality and intensity on fever, history of fever, haemoglobin concentration ([Hb]) and parasite density, by comparing three regions: perennial transmission (PT), high intensity seasonal transmission (HIST) and low intensity seasonal transmission (LIST). These regions were defined using multi-level modelling of PCR prevalence data and spatial and geo-climatic measures. The three Plasmodium species (P. falciparum, P. malariae and P. ovale) were randomly distributed amongst all children but not adults in the LIST and PT regions. Mean parasite density in children was lower in the HIST compared with the other two regions. Mixed species infections had lower mean parasite density compared with single species infections in the PT region. Fever rates were similar between transmission regions and were unaffected by mixed species infections. A history of fever was associated with single species infections but only in the HIST region. Reduced mean [Hb] and increased anaemia was associated with perennial transmission compared to seasonal transmission. Children with mixed species infections had higher [Hb] in the HIST region.</p> <p>Conclusions: Our study suggests that the interaction of Plasmodium co-infecting species can have protective effects against some clinical outcomes of malaria but that this is dependent on the seasonality and intensity of malaria transmission.</p&gt

Findings of the International Subarachnoid Aneurysm Trial and the National Study of Subarachnoid Haemorrhage in context.

Concern has been expressed about the applicability of the findings of the International Subarachnoid Aneurysm Trial (ISAT) with respect to the relative effects on outcome of coiling and clipping. It has been suggested that the findings of the National Study of Subarachnoid Haemorrhage may have greater relevance for neurosurgical practice. The objective of this paper was to interpret the findings of these two studies in the context of differences in their study populations, design, execution and analysis. Because of differences in design and analysis, the findings of the two studies are not directly comparable. The ISAT analysed all randomized patients by intention-to-treat, including some who did not undergo a repair, and obtained the primary outcome for 99% of participants. The National Study only analysed participants who underwent clipping or coiling, according to the method of repair, and obtained the primary outcome for 91% of participants. Time to repair was also considered differently in the two studies. The comparison between coiling and clipping was susceptible to confounding in the National Study, but not in the ISAT. The two study populations differed to some extent, but inspection of these differences does not support the view that coiling was applied inappropriately in the National Study. Therefore, there are many reasons why the two studies estimated different sizes of effect. The possibility that there were real, systematic differences in practice between the ISAT and the National Study cannot be ruled out, but such explanations must be seen in the context of other explanations relating to chance, differences in design or analysis, or confounding

The Implementation and Effects of Direct Facility Funding in Kenya’s Health Centres and Dispensaries

Direct facility funding (DFF) is an initiative that was developed in response to concern that Ministry of Health funds allocated to districts rarely filter down to the health centres and dispensaries, and that these facilities have also lost revenue due to the reduction in official user fees in 2004. Piloted in Coast Province from late 2005, DFF involved facilities receiving funds for recurrent expenditure directly into their bank accounts. This report presents an evaluation of the implementation and effects of DFF in health centres and dispensaries. The findings in this report are based on data collected between October 2007 and March 2008, about 2 to 3 years after DFF implementation. A structured survey that included an interview with facility in-charges, records review, and outpatient exit interviews was conducted at a random sample of 15 facilities in each of the two purposively selected districts (Kwale and Tana River). In addition, focus group discussions with health facility committee (HFC) members and key informant interviews with in-charges and DHMTs were conducted in a subset of 6 facilities in each district

Pharmacokinetics of Antituberculosis Drugs in HIV-Positive and HIV-Negative Adults in Malawi

Limited data address the impact of HIV co-infection on the pharmacokinetics of anti-tuberculosis drugs in Sub-Saharan Africa. 47 Malawian adults underwent rich pharmacokinetic sampling at 0-0.5-1-2-3-4-6-8 and 24 hours post-dose. 51% were male; mean age was 34 years. 65% were HIV-positive with a mean CD4 count of 268 cells/μL. Anti-tuberculosis drugs were administered as fixed-dose combinations (rifampicin150mg/isoniazid75mg/pyrazinamide400mg/ethambutol275mg) according to recommended weight bands. Plasma drug concentrations were determined by high-performance liquid chromatography (rifampicin and pyrazinamide) or liquid chromatography-mass spectrometry (isoniazid and ethambutol). Data were analysed by non-compartmental methods and analysis of variance of log-transformed summary parameters. Pharmacokinetic parameters were: rifampicin Cmax 4.129 (2.474-5.596)μg/mL, AUC0-24 21.32 (13.57-28.60)μg/mL*h, half-life 2.45 (1.86-3.08)h; isoniazid Cmax 3.97 (2.979-4.544)μg/mL, AUC0-24 22.5 (14.75-34.59)μg/mL*h, half-life 3.93 (3.18-4.73)h.; pyrazinamide Cmax 34.21 (30.00-41.60)μg/mL, AUC0-24 386.6 (320.0-463.7)μg/mL*h, half-life 6.821 (5.71-8.042)h; ethambutol Cmax 2.278 (1.694-3.098)μg/mL, AUC0-24 20.41 (16.18-26.27)μg/mL*h, half-life 7.507 (6.517-8.696)h. Isoniazid PK data analysis suggested that around two-thirds were slow acetylators. Dose, weight and weight-adjusted dose were not significant predictors of PK exposure probably due to weight-banded dosing. In this first pharmacokinetic study of tuberculosis drugs in Malawian adults, measures of pharmacokinetic exposure were comparable with other studies for all first line drugs except for rifampicin, for which Cmax and AUC0-24 were notably lower. Contrary to some earlier observations, HIV status did not significantly affect AUC of any of the drugs. Increasing the dose of rifampicin could be beneficial in African adults, irrespective of HIV status. Current co-trimoxazole prophylaxis was associated with an increase in half-life of isoniazid of 41% (p=0.022). Possible competitive interactions between isoniazid and sulphamethoxazole mediated by the N-acetyltransferase pathway should therefore be explored further

The Changing Epidemiology of Malaria in Ifakara Town, Southern Tanzania.

Between 1995 and 2000 there were marked changes in the epidemiology of malaria in Ifakara, southern Tanzania. We documented these changes using parasitological and clinical data from a series of community- and hospital-based studies involving children up to the age of 5 years. There was a right shift and lowering in the age-specific parasite prevalence in the community-based cohort studies. The incidence of clinical malaria in placebo-receiving infants in additional study cohorts dropped from 0.8 in 1995 to 0.43 episodes per infant per year in 2000, an incidence rate ratio of 0.53 (95% confidence interval: 0.404, 0.70, P<0.0001). At the same time, there was an increase in the total number of malaria admissions and a marked right shift in the age pattern of these admissions (median age in 1995 1.55 years vs. 2.33 in 2000, P<0.0001). However, the burden of malaria deaths remained in infants. We discuss how these dramatic changes in the epidemiology of malaria may have arisen from the use of currently available malaria control tools. Caution is required in the interpretation of hospital-based data as it is likely to underestimate the impact of anaemia on mortality in the community, where most paediatric deaths occur. Even in low/moderate malaria transmission settings, where older children suffer most malaria episodes, targeting effective malaria control at infants may produce important reductions in infant mortality caused by malaria

Coulomb scattering lifetime of a two-dimensional electron gas

Motivated by a recent tunneling experiment in a double quantum-well system, which reports an anomalously enhanced electronic scattering rate in a clean two-dimensional electron gas, we calculate the inelastic quasiparticle lifetime due to electron-electron interaction in a single loop dynamically screened Coulomb interaction within the random-phase-approximation. We obtain excellent quantitative agreement with the inelastic scattering rates in the tunneling experiment without any adjustable parameter, finding that the reported large ($\geq$ a factor of six) disagreement between theory and experiment arises from quantitative errors in the existing theoretical work and from the off-shell energy dependence of the electron self-energy.Comment: 11 pages, RevTex, figures included. Also available at http://www-cmg.physics.umd.edu/~lzheng

Vascular endothelial cells cultured from patients with cerebral or uncomplicated malaria exhibit differential reactivity to TNF.

Plasmodium falciparum malaria is a major cause of morbidity and mortality in African children, and factors that determine the development of uncomplicated (UM) versus cerebral malaria (CM) are not fully understood. We studied the ex vivo responsiveness of microvascular endothelial cells to pro-inflammatory stimulation and compared the findings between CM and UM patients. In patients with fatal disease we compared the properties of vascular endothelial cells cultured from brain tissue to those cultured from subcutaneous tissue, and found them to be very similar. We then isolated, purified and cultured primary endothelial cells from aspirated subcutaneous tissue of patients with CM (EC(CM) ) or UM (EC(UM) ) and confirmed the identity of the cells before analysis. Upon TNF stimulation in vitro, EC(CM) displayed a significantly higher capacity to upregulate ICAM-1, VCAM-1 and CD61 and to produce IL-6 and MCP-1 but not RANTES compared with EC(UM) . The shedding of endothelial microparticles, a recently described parameter of severity in CM, and the cellular level of activated caspase-3 were both significantly greater in EC(CM) than in EC(UM) . These data suggest that inter-individual differences in the endothelial inflammatory response to TNF may be an additional factor influencing the clinical course of malaria

Patterns of epidemiology and control of onchocerciasis in West Africa

This paper summarizes the work of the Onchocerciasis Control Programme (OCP) in West Africa, a programme which over a 22 year history has reduced the public health problems of blinding onchocerciasis in eleven countries of West Africa through vector control and, more recently, ivermectin distribution. The paper emphasizes the different approaches to control the programme has developed in the different parts of the programme area which have been determined by the epidemiology of the disease (savanna/forest form), the migratory characteristics of the vectors, intensity of the disease before commencement of treatment, the combined impact of vector control and ivermectin and the likelihood of infiltration of infective blackflies from outside the programme area. The programme has constantly monitored the impact of operations on the trends in prevalence, incidence, annual transmission potential, ocular morbidity and species of fly populations, and as a result, has identified areas where special interventions are required until the programme comes to an end in 2002. The paper illustrates the changes in intensity of infection as measured by community microfilarial load and annual transmission potential over the duration of the programme control activities. The paper also defines and justifies the control strategies in different areas and identifies areas for special intervention

Five rules of thumb for post-ELSI interdisciplinary collaborations

In this paper we identify five rules of thumb for interdisciplinary collaboration across the natural and social sciences. We link these to efforts to move away from the ‘ethical, legal and social issues’ framework of interdisciplinarity and towards a post-ELSI collaborative space. It is in trying to open up such a space that we identify the need for: collaborative experimentation, taking risks, collaborative reflexivity, opening-up discussions of unshared goals and neighbourliness

The first GCT camera for the Cherenkov Telescope Array

The Gamma Cherenkov Telescope (GCT) is proposed to be part of the Small Size Telescope (SST) array of the Cherenkov Telescope Array (CTA). The GCT dual-mirror optical design allows the use of a compact camera of diameter roughly 0.4 m. The curved focal plane is equipped with 2048 pixels of ~0.2{\deg} angular size, resulting in a field of view of ~9{\deg}. The GCT camera is designed to record the flashes of Cherenkov light from electromagnetic cascades, which last only a few tens of nanoseconds. Modules based on custom ASICs provide the required fast electronics, facilitating sampling and digitisation as well as first level of triggering. The first GCT camera prototype is currently being commissioned in the UK. On-telescope tests are planned later this year. Here we give a detailed description of the camera prototype and present recent progress with testing and commissioning.Comment: In Proceedings of the 34th International Cosmic Ray Conference (ICRC2015), The Hague, The Netherlands. All CTA contributions at arXiv:1508.0589