Early detection of malaria foci for targeted interventions in endemic southern Zambia

<p>Abstract</p> <p>Background</p> <p>Zambia has achieved significant reductions in the burden of malaria through a strategy of "scaling-up" effective interventions. Progress toward ultimate malaria elimination will require sustained prevention coverage and further interruption of transmission through active strategies to identify and treat asymptomatic malaria reservoirs. A surveillance system in Zambia's Southern Province has begun to implement such an approach. An early detection system could be an additional tool to identify foci of elevated incidence for targeted intervention.</p> <p>Methods</p> <p>Based on surveillance data collected weekly from 13 rural health centres (RHCs) divided into three transmission zones, early warning thresholds were created following a technique successfully implemented in Thailand. Alert levels were graphed for all 52 weeks of a year using the mean and 95% confidence interval upper limit of a Poisson distribution of the weekly diagnosed malaria cases for every available week of historic data (beginning in Aug, 2008) at each of the sites within a zone. Annually adjusted population estimates for the RHC catchment areas served as person-time of weekly exposure. The zonal threshold levels were validated against the incidence data from each of the 13 respective RHCs.</p> <p>Results</p> <p>Graphed threshold levels for the three zones generally conformed to observed seasonal incidence patterns. Comparing thresholds with historic weekly incidence values, the overall percentage of aberrant weeks ranged from 1.7% in Mbabala to 36.1% in Kamwanu. For most RHCs, the percentage of weeks above threshold was greater during the high transmission season and during the 2009 year compared to 2010. 39% of weeks breaching alert levels were part of a series of three or more consecutive aberrant weeks.</p> <p>Conclusions</p> <p>The inconsistent sensitivity of the zonal threshold levels impugns the reliability of the alert system. With more years of surveillance data available, individual thresholds for each RHC could be calculated and compared to the technique outlined here. Until then, "aberrant" weeks during low transmission seasons, and during high transmission seasons at sites where the threshold level is less sensitive, could feasibly be followed up for household screening. Communities with disproportionate numbers of aberrant weeks could be reviewed for defaults in the scaling-up intervention coverage.</p

Malaria Research Challenges in Low Prevalence Settings

The prevalence of malaria has reduced significantly in some areas over the past decade. These reductions have made local elimination possible and the research agenda has shifted to this new priority. However, there are critical issues that arise when studying malaria in low transmission settings, particularly identifying asymptomatic infections, accurate detection of individuals with microparasitaemic infections, and achieving a sufficient sample size to have an adequately powered study. These challenges could adversely impact the study of malaria elimination if they remain unanswered

Malaria Research Challenges in Low Prevalence Settings

The prevalence of malaria has reduced significantly in some areas over the past decade. These reductions have made local elimination possible and the research agenda has shifted to this new priority. However, there are critical issues that arise when studying malaria in low transmission settings, particularly identifying asymptomatic infections, accurate detection of individuals with microparasitaemic infections, and achieving a sufficient sample size to have an adequately powered study. These challenges could adversely impact the study of malaria elimination if they remain unanswered

Designing a sustainable strategy for malaria control?

Malaria in the 21st century is showing signs of declining over much of its distribution, including several countries in Africa where previously this was not thought to be feasible. Yet for the most part the strategies to attack the infection are similar to those of the 1950s. Three major Journals have recently drawn attention to the situation, stressing the importance of research, describing the successes and defining semantics related to control. But there is a need to stress the importance of local sustainability, and consider somewhat urgently how individual endemic countries can plan and implement the programmes that are currently financed, for the most part, by donor institutions. On an immediate basis research should be more focused on a data driven approach to control. This will entail new thinking on the role of local infrastructure and in training of local scientists in local universities in epidemiology and field malariology so that expanded control programmes can become operational. Donor agencies should encourage and facilitate development of career opportunities for such personnel so that local expertise is available to contribute appropriately

Nuclear magnetic resonance spectrum of 31P donors in silicon quantum computer

The influence of the electric field created by a gate potential of the silicon quantum computer on the hyperfine interaction constant (HIC) is obtained. The errors due to technological inaccuracy of location of donor atoms under a gate are evaluated. The energy spectra of electron-nuclear spin system of two interacting donor atoms with various values of HIC are calculated. The presence of two pairs of anticrossing levels in the ground electronic state is shown. Parameters of the structure at which errors rate can be greatly minimized are found.Comment: 12 pages,, 3 figure

Gravitational Collapse of a Shell of Quantized Matter

The semi-classical collapse, including lowest order back-reaction, of a thin shell of self-gravitating quantized matter is illustrated. The conditions for which self-gravitating matter forms a thin shell are first discussed and an effective Lagrangian for such matter is obtained. The matter-gravity system is then quantized, the semi-classical limit for gravitation is taken and the method of adiabatic invariants is applied to the resulting time dependent matter Hamiltonian. The governing equations are integrated numerically, for suitable initial conditions, in order to illustrate the effect of back-reaction, due to the creation of matter, in slowing down the collapse near the horizon.Comment: 20 pages, 1 eps figure. Problem with figure fixe

Responders vs clinical response: a critical analysis of data from linaclotide phase 3 clinical trials in IBS-C

Background: US Food and Drug Administration (FDA) set a rigorous standard for defining patient responders in irritable bowel syndrome-C (IBS-C; i.e., FDA's Responder Endpoint) for regulatory approval. However, this endpoint's utility for health-care practitioners to assess clinical response has not been determined. We analyzed pooled IBS-C linaclotide trial data to evaluate clinically significant responses in linaclotide-treated patients who did not meet the FDA responder definition. Methods: Percentages of FDA non-responders reporting improvement in abdominal pain, bowel function and/or global relief measures were determined using pooled data from two linaclotide Phase 3 IBS-C trials. Key Results 1602 IBS-C patients enrolled; 34% of linaclotide-treated and 17% of placebo-treated patients met the FDA Responder Endpoint (p < 0.0001). Among FDA non-responders at week 12, 63% of linaclotide-treated patients reported their abdominal pain was at least somewhat relieved, compared with 48% of placebo-treated patients. For stool frequency, 62% of linaclotide-treated patients reported that they were at least somewhat improved at week 12, compared with 46% of placebo-treated patients. For global IBS symptoms, 65% of linaclotide-treated patients reported at least some IBS-symptom relief, 43% reported adequate relief of IBS symptoms, and 57% reported being satisfied with linaclotide treatment, vs placebo rates of 48%, 34%, and 41% respectively. Conclusions & Inferences Most linaclotide-treated IBS-C patients who were FDA non-responders reported some improvement in abdominal pain and stool frequency, and global relief/satisfaction. In addition to the FDA Responder Endpoint, differing response thresholds and symptom-specific change from baseline should be considered by clinicians for a complete understanding of clinical response to linaclotide and other IBS-C therapies

Group Approach to the Quantization of the P\"oschl-Teller dynamics

The quantum dynamics of a particle in the Modified P\"oschl-Teller potential is derived from the group $SL(2,R)$ by applying a Group Approach to Quantization (GAQ). The explicit form of the Hamiltonian as well as the ladder operators is found in the enveloping algebra of this basic symmetry group. The present algorithm provides a physical realization of the non-unitary, finite-dimensional, irreducible representations of the $SL(2,R)$ group. The non-unitarity manifests itself in that only half of the states are normalizable, in contrast with the representations of SU(2) where all the states are physical.Comment: 17 pages, LaTe

Change in Composition of the Anopheles Gambiae Complex and its Possible Implications for the Transmission of Malaria and Lymphatic Filariasis in North-Eastern Tanzania.

A dramatic decline in the incidence of malaria due to Plasmodium falciparum infection in coastal East Africa has recently been reported to be paralleled (or even preceded) by an equally dramatic decline in malaria vector density, despite absence of organized vector control. As part of investigations into possible causes for the change in vector population density, the present study analysed the Anopheles gambiae s.l. sibling species composition in north-eastern Tanzania. The study was in two parts. The first compared current species complex composition in freshly caught An. gambiae s.l. complex from three villages to the composition reported from previous studies carried out 2-4 decades ago in the same villages. The second took advantage of a sample of archived dried An. gambiae s.l. complex specimens collected regularly from a fourth study village since 2005. Both fresh and archived dried specimens were identified to sibling species of the An. gambiae s.l. complex by PCR. The same specimens were moreover examined for Plasmodium falciparum and Wuchereria bancrofti infection by PCR. As in earlier studies, An. gambiae s.s., Anopheles merus and Anopheles arabiensis were identified as sibling species found in the area. However, both study parts indicated a marked change in sibling species composition over time. From being by far the most abundant in the past An. gambiae s.s. was now the most rare, whereas An. arabiensis had changed from being the most rare to the most common. P. falciparum infection was rarely detected in the examined specimens (and only in An. arabiensis) whereas W. bancrofti infection was prevalent and detected in all three sibling species. The study indicates that a major shift in An. gambiae s.l. sibling species composition has taken place in the study area in recent years. Combined with the earlier reported decline in overall malaria vector density, the study suggests that this decline has been most marked for An. gambiae s.s., and least for An. arabiensis, leading to current predominance of the latter. Due to differences in biology and vectorial capacity of the An. gambiae s.l. complex the change in sibling species composition will have important implications for the epidemiology and control of malaria and lymphatic filariasis in the study area

A 12-Week, Randomized, Controlled Trial with a 4-Week Randomized Withdrawal Period to Evaluate the Efficacy and Safety of Linaclotide in Irritable Bowel Syndrome with Constipation

Objectives: Linaclotide is a minimally absorbed guanylate cyclase-C agonist. The objective of this trial was to determine the efficacy and safety of linaclotide in patients with irritable bowel syndrome with constipation (IBS-C). Methods: This phase 3, double-blind, parallel-group, placebo-controlled trial randomized IBS-C patients to placebo or 290 μg oral linaclotide once daily in a 12-week treatment period, followed by a 4-week randomized withdrawal (RW) period. There were four primary end points, the Food and Drug Administration's (FDA's) primary end point for IBS-C (responder: improvement of ≥30% in average daily worst abdominal pain score and increase by ≥1 complete spontaneous bowel movement (CSBM) from baseline (same week) for at least 50% of weeks assessed) and three other primary end points, based on improvements in abdominal pain and CSBMs for 9/12 weeks. Adverse events (AEs) were monitored. Results: The trial evaluated 800 patients (mean age=43.5 years, female=90.5%, white=76.9%). The FDA end point was met by 136/405 linaclotide-treated patients (33.6%), compared with 83/395 placebo-treated patients (21.0%) (P<0.0001) (number needed to treat: 8.0, 95% confidence interval: 5.4, 15.5). A greater percentage of linaclotide patients, compared with placebo patients, reported for at least 6/12 treatment period weeks, a reduction of ≥30% in abdominal pain (50.1 vs. 37.5%, P=0.0003) and an increase of ≥1 CSBM from baseline (48.6 vs. 29.6%, P<0.0001). A greater percentage of linaclotide patients vs. placebo patients were also responders for the other three primary end points (P<0.05). Significantly greater improvements were seen in linaclotide vs. placebo patients for all secondary end points (P<0.001). During the RW period, patients remaining on linaclotide showed sustained improvement; patients re-randomized from linaclotide to placebo showed return of symptoms, but without worsening of symptoms relative to baseline. Diarrhea, the most common AE, resulted in discontinuation of 5.7% of linaclotide and 0.3% of placebo patients. Conclusions: Linaclotide significantly improved abdominal pain and bowel symptoms associated with IBS-C for at least 12 weeks; there was no worsening of symptoms compared with baseline following cessation of linaclotide during the RW period