Enhancement of mobilities in a pinned multidomain crystal

Mobility properties inside and around degenerate domains of an elastic lattice partially pinned on a square array of traps are explored by means of a fully controllable model system of macroscopic particles. We focus on the different configurations obtained for filling ratios equal to 1 or 2 when the pinning strength is lowered. These theoretically expected but never observed configurations are degenerated, which implies the existence of a multidomain crystal. We show that the distinction between trapped and untrapped particles that is made in the case of strong pinning is not relevant for such a weaker pinning. Indeed, one ought to distinguish between particles inside or around the domains associated to positional degeneracies. The possible consequences on the depinning dynamics of the lattice are discussed.Comment: 7 pages, 10 figures Version 2 : longer versio

Different methodological approaches to the assessment of in vivo efficacy of three artemisinin-based combination antimalarial treatments for the treatment of uncomplicated falciparum malaria in African children.

BACKGROUND: Use of different methods for assessing the efficacy of artemisinin-based combination antimalarial treatments (ACTs) will result in different estimates being reported, with implications for changes in treatment policy. METHODS: Data from different in vivo studies of ACT treatment of uncomplicated falciparum malaria were combined in a single database. Efficacy at day 28 corrected by PCR genotyping was estimated using four methods. In the first two methods, failure rates were calculated as proportions with either (1a) reinfections excluded from the analysis (standard WHO per-protocol analysis) or (1b) reinfections considered as treatment successes. In the second two methods, failure rates were estimated using the Kaplan-Meier product limit formula using either (2a) WHO (2001) definitions of failure, or (2b) failure defined using parasitological criteria only. RESULTS: Data analysed represented 2926 patients from 17 studies in nine African countries. Three ACTs were studied: artesunate-amodiaquine (AS+AQ, N = 1702), artesunate-sulphadoxine-pyrimethamine (AS+SP, N = 706) and artemether-lumefantrine (AL, N = 518).Using method (1a), the day 28 failure rates ranged from 0% to 39.3% for AS+AQ treatment, from 1.0% to 33.3% for AS+SP treatment and from 0% to 3.3% for AL treatment. The median [range] difference in point estimates between method 1a (reference) and the others were: (i) method 1b = 1.3% [0 to 24.8], (ii) method 2a = 1.1% [0 to 21.5], and (iii) method 2b = 0% [-38 to 19.3].The standard per-protocol method (1a) tended to overestimate the risk of failure when compared to alternative methods using the same endpoint definitions (methods 1b and 2a). It either overestimated or underestimated the risk when endpoints based on parasitological rather than clinical criteria were applied. The standard method was also associated with a 34% reduction in the number of patients evaluated compared to the number of patients enrolled. Only 2% of the sample size was lost when failures were classified on the first day of parasite recurrence and survival analytical methods were used. CONCLUSION: The primary purpose of an in vivo study should be to provide a precise estimate of the risk of antimalarial treatment failure due to drug resistance. Use of survival analysis is the most appropriate way to estimate failure rates with parasitological recurrence classified as treatment failure on the day it occurs

Particle acceleration at ultrarelativistic shocks: an eigenfunction method

We extend the eigenfunction method of computing the power-law spectrum of particles accelerated at a relativistic shock fronts to apply to shocks of arbitrarily high Lorentz factor. In agreement with the findings of Monte-Carlo simulations, we find the index of the power-law distribution of accelerated particles which undergo isotropic diffusion in angle at an ultrarelativistic, unmagnetized shock is s=4.23 (where s=-d(ln f)/dp with f the Lorentz invariant phase-space density and p the momentum). This corresponds to a synchrotron index for uncooled electrons of a=0.62 (taking cooling into account a=1.12), where a=-d(ln F)/dn, F is the radiation flux and n the frequency. We also present an approximate analytic expression for the angular distribution of accelerated particles, which displays the effect of particle trapping by the shock: compared with the non-relativistic case the angular distribution is weighted more towards the plane of the shock and away from its normal. We investigate the sensitivity of our results to the transport properties of the particles and the presence of a magnetic field. Shocks in which the ratio of Poynting to kinetic energy flux upstream is not small are less compressive and lead to larger values of $s$.Comment: Minor additions on publicatio

Unacceptably High Mortality Related to Measles Epidemics in Niger, Nigeria, and Chad

BACKGROUND: Despite the comprehensive World Health Organization (WHO)/United Nations Children's Fund (UNICEF) measles mortality–reduction strategy and the Measles Initiative, a partnership of international organizations supporting measles mortality reduction in Africa, certain high-burden countries continue to face recurrent epidemics. To our knowledge, few recent studies have documented measles mortality in sub-Saharan Africa. The objective of our study was to investigate measles mortality in three recent epidemics in Niamey (Niger), N'Djamena (Chad), and Adamawa State (Nigeria). METHODS AND FINDINGS: We conducted three exhaustive household retrospective mortality surveys in one neighbourhood of each of the three affected areas: Boukoki, Niamey, Niger (April 2004, n = 26,795); Moursal, N'Djamena, Chad (June 2005, n = 21,812); and Dong District, Adamawa State, Nigeria (April 2005, n = 16,249), where n is the total surveyed population in each of the respective areas. Study populations included all persons resident for at least 2 wk prior to the study, a duration encompassing the measles incubation period. Heads of households provided information on measles cases, clinical outcomes up to 30 d after rash onset, and health-seeking behaviour during the epidemic. Measles cases and deaths were ascertained using standard WHO surveillance-case definitions. Our main outcome measures were measles attack rates (ARs) and case fatality ratios (CFRs) by age group, and descriptions of measles complications and health-seeking behaviour. Measles ARs were the highest in children under 5 y old (under 5 y): 17.1% in Boukoki, 17.2% in Moursal, and 24.3% in Dong District. CFRs in under 5-y-olds were 4.6%, 4.0%, and 10.8% in Boukoki, Moursal, and Dong District, respectively. In all sites, more than half of measles cases in children aged under 5 y experienced acute respiratory infection and/or diarrhoea in the 30 d following rash onset. Of measles cases, it was reported that 85.7% (979/1,142) of patients visited a health-care facility within 30 d after rash onset in Boukoki, 73.5% (519/706) in Moursal, and 52.8% (603/1,142) in Dong District. CONCLUSIONS: Children in these countries still face unacceptably high mortality from a completely preventable disease. While the successes of measles mortality–reduction strategies and progress observed in measles control in other countries of the region are laudable and evident, they should not overshadow the need for intensive efforts in countries that have just begun implementation of the WHO/UNICEF comprehensive strategy

Diagnostic and prognostic utility of an inexpensive rapid on site malaria diagnostic test (ParaHIT f) among ethnic tribal population in areas of high, low and no transmission in central India

BACKGROUND: Malaria presents a diagnostic challenge in most tropical countries. Rapid detection of the malaria parasite and early treatment of infection still remain the most important goals of disease management. Therefore, performance characteristics of the new indigenous ParaHIT f test (Span diagnostic Ltd, Surat, India) was determined among ethnic tribal population in four districts of different transmission potential in central India to assess whether this rapid diagnostic test (RDT) could be widely applied as a diagnostic tool to control malaria. Beyond diagnosis, the logical utilization of RDTs is to monitor treatment outcome. METHODS: A finger prick blood sample was collected from each clinically suspected case of malaria to prepare blood smear and for testing with the RDT after taking informed consent. The blood smears were read by an experienced technician blinded to the RDT results and clinical status of the subjects. The figures for specificity, sensitivity, accuracy and predictive values were calculated using microscopy as gold standard. RESULTS: The prevalence of malaria infection estimated by RDT in parallel with microscopy provide evidence of the type of high, low or no transmission in the study area. Analysis revealed (pooled data of all four epidemiological settings) that overall sensitivity, specificity and accuracy of the RDT were >90% in areas of different endemicity. While, RDT is useful to confirm the diagnosis of new symptomatic cases of suspected P. falciparum infection, the persistence of parasite antigen leading to false positives even after clearance of asexual parasitaemia has limited its utility as a prognostic tool. CONCLUSION: The study showed that the ParaHIT f test was easy to use, reliable and cheap. Thus this RDT is an appropriate test for the use in the field by paramedical staff when laboratory facilities are not available and thus likely to contribute greatly to an effective control of malaria in resource poor countries

An Open Label, Randomised Trial of Artesunate+Amodiaquine, Artesunate+Chlorproguanil-Dapsone and Artemether-Lumefantrine for the Treatment of Uncomplicated Malaria

BACKGROUND: Artesunate+amodiaquine (AS+AQ) and artemether-lumefantrine (AL) are now the most frequently recommended first line treatments for uncomplicated malaria in Africa. Artesunate+chlorproguanil-dapsone (AS+CD) was a potential alternative for treatment of uncomplicated malaria. A comparison of the efficacy and safety of these three drug combinations was necessary to make evidence based drug treatment policies. METHODS: Five hundred and thirty-four, glucose-6-phosphate dehydrogenase (G6PD) normal children were randomised in blocks of 15 to the AS+AQ, AL or AS+CD groups. Administration of study drugs was supervised by project staff and the children were followed up at r home on days 1,2,3,7,14 and 28 post treatment. Parasitological and clinical failures and adverse events were compared between the study groups. MAIN FINDINGS: In a per-protocol analysis, the parasitological and clinical failure rate at day 28 post treatment (PCF28) was lower in the AS+AQ group compared to the AL or AS+CD groups (corrected for re-infections: 6.6% vs 13.8% and 13.8% respectively, p = 0.08; uncorrected: 14.6% vs 27.6% and 28.1% respectively, p = 0.005). In the intention to treat analysis, the rate of early treatment failure was high in all three groups (AS+AQ 13.3%; AL 15.2%; and AS+CD 9.3%, p = 0.2) primarily due to vomiting. However, the PCF28 corrected for re-infection was lower, though not significantly, in the AS+AQ group compared to the AL or the AS+CD groups (AS+AQ 18.3%; AL 24.2%; AS+CD 20.8%, p = 0.4) The incidence of adverse events was comparable between the groups. CONCLUSIONS: AS+AQ is an appropriate first line treatment for uncomplicated malaria in Ghana and possibly in the neighbouring countries in West Africa. The effectiveness of AL in routine programme conditions needs to be studied further in West Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT00119145

Don't spin the pen: two alternative methods for second-stage sampling in urban cluster surveys

In two-stage cluster surveys, the traditional method used in second-stage sampling (in which the first household in a cluster is selected) is time-consuming and may result in biased estimates of the indicator of interest. Firstly, a random direction from the center of the cluster is selected, usually by spinning a pen. The houses along that direction are then counted out to the boundary of the cluster, and one is then selected at random to be the first household surveyed. This process favors households towards the center of the cluster, but it could easily be improved. During a recent meningitis vaccination coverage survey in Maradi, Niger, we compared this method of first household selection to two alternatives in urban zones: 1) using a superimposed grid on the map of the cluster area and randomly selecting an intersection; and 2) drawing the perimeter of the cluster area using a Global Positioning System (GPS) and randomly selecting one point within the perimeter. Although we only compared a limited number of clusters using each method, we found the sampling grid method to be the fastest and easiest for field survey teams, although it does require a map of the area. Selecting a random GPS point was also found to be a good method, once adequate training can be provided. Spinning the pen and counting households to the boundary was the most complicated and time-consuming. The two methods tested here represent simpler, quicker and potentially more robust alternatives to spinning the pen for cluster surveys in urban areas. However, in rural areas, these alternatives would favor initial household selection from lower density (or even potentially empty) areas. Bearing in mind these limitations, as well as available resources and feasibility, investigators should choose the most appropriate method for their particular survey context

The rationale and plan for creating a World Antimalarial Resistance Network (WARN)

Drug resistant malaria was a major factor contributing to the failure of a worldwide campaign to eradicate malaria in the last century, and now threatens the large investment being made by the global community in the rollout of effective new drug combinations to replace failed drugs. Four related papers in this issue of Malaria Journal make the case for creating the World Antimalarial Resistance Network (WARN), which will consist of four linked open-access global databases containing clinical, in vitro, molecular and pharmacological data, and networks of reference laboratories that will support these databases and related surveillance activities. WARN will serve as a public resource to guide antimalarial drug treatment and prevention policies and to help confirm and characterize the new emergence of new resistance to antimalarial drugs and to contain its spread

Dihydroartemisinin-Piperaquine Versus Chloroquine in the Treatment of Plasmodium vivax Malaria in Thailand: A Randomized Controlled Trial

The efficacy of chloroquine in the treatment of Plasmodium vivax malaria is declining on the Northwestern border of Thailand. This randomized controlled trial in 500 adults and children shows that dihydroartemisinin-piperaquine is a safe and effective alternative treatment

Detection of infectious disease outbreaks in twenty-two fragile states, 2000-2010: a systematic review.

Fragile states are home to a sixth of the world's population, and their populations are particularly vulnerable to infectious disease outbreaks. Timely surveillance and control are essential to minimise the impact of these outbreaks, but little evidence is published about the effectiveness of existing surveillance systems. We did a systematic review of the circumstances (mode) of detection of outbreaks occurring in 22 fragile states in the decade 2000-2010 (i.e. all states consistently meeting fragility criteria during the timeframe of the review), as well as time lags from onset to detection of these outbreaks, and from detection to further events in their timeline. The aim of this review was to enhance the evidence base for implementing infectious disease surveillance in these complex, resource-constrained settings, and to assess the relative importance of different routes whereby outbreak detection occurs.We identified 61 reports concerning 38 outbreaks. Twenty of these were detected by existing surveillance systems, but 10 detections occurred following formal notifications by participating health facilities rather than data analysis. A further 15 outbreaks were detected by informal notifications, including rumours.There were long delays from onset to detection (median 29 days) and from detection to further events (investigation, confirmation, declaration, control). Existing surveillance systems yielded the shortest detection delays when linked to reduced barriers to health care and frequent analysis and reporting of incidence data.Epidemic surveillance and control appear to be insufficiently timely in fragile states, and need to be strengthened. Greater reliance on formal and informal notifications is warranted. Outbreak reports should be more standardised and enable monitoring of surveillance systems' effectiveness