Intra- and interspecific polymorphisms ofLeishmania donovani andL. tropica minicircle DNA

A pair of degenerate polymerase chain reaction (PCR) primers (LEI-1, TCG GAT CC[C,T] [G,C]TG GGT AGG GGC GT; LEI-2, ACG GAT CC[G,C] [G,C][A,C]C TAT [A,T]TT ACA CC) defining a 0.15-kb segment ofLeishmania minicircle DNA was constructed. These primers amplified not only inter- but also intraspecifically polymorphic sequences. Individual sequences revealed a higher intraspecific than interspecific divergence. It is concluded that individual sequences are of limited relevance for species determination. In contrast, when a data base of 19 different sequences was analyzed in a dendrographic plot, an accurate species differentiation was feasible

Narrow-band imaging versus white light for the detection of proximal colon serrated lesions: a randomized, controlled trial

Background The value of narrow-band imaging (NBI) for detecting serrated lesions is unknown. Objective To assess NBI for the detection of proximal colon serrated lesions. Design Randomized, controlled trial. Setting Two academic hospital outpatient units. Patients Eight hundred outpatients 50 years of age and older with intact colons undergoing routine screening, surveillance, or diagnostic examinations. Interventions Randomization to colon inspection in NBI versus white-light colonoscopy. Main Outcome Measurements The number of serrated lesions (sessile serrated polyps plus hyperplastic polyps) proximal to the sigmoid colon. Results The mean inspection times for the whole colon and proximal colon were the same for the NBI and white-light groups. There were 204 proximal colon lesions in the NBI group and 158 in the white light group (P = .085). Detection of conventional adenomas was comparable in the 2 groups. Limitations Lack of blinding, endoscopic estimation of polyp location. Conclusion NBI may increase the detection of proximal colon serrated lesions, but the result in this trial did not reach significance. Additional study of this issue is warranted. (Clinical trial registration number: NCT01572428.

Impact of a ring fitted cap on insertion time and adenoma detection: a randomized controlled trial

Background and Aims: Devices for flattening colon folds can improve polyp detection at colonoscopy. However, there are few data on the endoscopic ring fitted cap (EndoRings, EndoAid, Caesarea, Israel). We sought to compare adenoma detection with EndoRings with that of standard high-definition colonoscopy. Methods: A single-center randomized controlled trial of 562 patients (284 randomized to EndoRings and 278 to standard colonoscopy) at 2 outpatient endoscopy units in the Indiana University Hospital system. Adenoma detection was the primary outcome measured as adenoma detection rate (ADR) and adenomas per colonoscopy (APC). We also compared sessile serrated polyp detection rate (SSPDR), insertion times, withdrawal times, and ease of passage through the sigmoid colon. Results: EndoRings was superior to standard colonoscopy in terms of APC (1.46 vs 1.06, p=0.025) but there were no statistically significant differences in ADR or SSPDR. Mean withdrawal time (in patients with no polyps) was shorter and insertion time (all patients) was longer in the EndoRings arm by 1.8 minutes and 0.75 minutes, respectively. One provider had significantly higher detection with EndoRings and contributed substantially to the overall results. Conclusions: EndoRings can increase adenoma detection without significant increase in procedure time, but the effect varies between operators. EndoRings slows colonoscope insertion

Economic impact of infections and antibiotics

In this chapter, we review several aspects with respect to the burden of infectious diseases, its impact in morbidity and mortality, and its economic burden. Furthermore, we referenced the actual situation with relation to the use of antimicrobial, the resistance problem and misuse of antibiotic, and the economic impact in the health systems

Health Centre Surveys as a Potential Tool for Monitoring Malaria Epidemiology by Area and over Time

BACKGROUND: Presently, many malaria control programmes use health facility data to evaluate the impact of their interventions. Facility-based malaria data, although useful, have problems with completeness, validity and representativeness and reliance on routinely collected health facility data might undermine demonstration of the magnitude of the impact of the recent scaleups of malaria interventions. To determine whether carefully conducted health centre surveys can be reliable means of monitoring area specific malaria epidemiology, we have compared malaria specific indices obtained from surveys in health centres with indices obtained from cross-sectional surveys conducted in their catchment communities. METHODS: A series of age stratified, seasonal, cross-sectional surveys were conducted during the peak malaria transmission season in 2008 and during the following dry season in 2009 in six ecologically diverse areas in The Gambia. Participants were patients who attended the health centres plus a representative sample from the catchment villages of these health facilities. Parasitaemia, anaemia, attributable proportion of fever and anti-MSP1-(19) antibody seroprevalence were compared in the health facility attendees and community participants. RESULTS: A total of 16,230 subjects completed the study; approximately half participated in the health centre surveys and half in the wet season surveys. Data from both the health centre and community surveys showed that malaria endemicity in The Gambia is now low, heterogeneous and seasonal. In the wet season, parasitaemia, seroprevalence and fever prevalence were higher in subjects seen in the health centres than in the community surveys. Age patterns of parasitaemia, attributable proportions of fever and seroprevalence rates were similar in subjects who participated in the community and health centre surveys. CONCLUSION: Health centre surveys have potential as a surveillance tool for evaluating area specific malaria control activities and for monitoring changes in local malaria epidemiology over time

Sterile Protection against Plasmodium knowlesi in Rhesus Monkeys from a Malaria Vaccine: Comparison of Heterologous Prime Boost Strategies

Using newer vaccine platforms which have been effective against malaria in rodent models, we tested five immunization regimens against Plasmodium knowlesi in rhesus monkeys. All vaccines included the same four P. knowlesi antigens: the pre-erythrocytic antigens CSP, SSP2, and erythrocytic antigens AMA1, MSP1. We used four vaccine platforms for prime or boost vaccinations: plasmids (DNA), alphavirus replicons (VRP), attenuated adenovirus serotype 5 (Ad), or attenuated poxvirus (Pox). These four platforms combined to produce five different prime/boost vaccine regimens: Pox alone, VRP/Pox, VRP/Ad, Ad/Pox, and DNA/Pox. Five rhesus monkeys were immunized with each regimen, and five Control monkeys received a mock vaccination. The time to complete vaccinations was 420 days. All monkeys were challenged twice with 100 P. knowlesi sporozoites given IV. The first challenge was given 12 days after the last vaccination, and the monkeys receiving the DNA/Pox vaccine were the best protected, with 3/5 monkeys sterilely protected and 1/5 monkeys that self-cured its parasitemia. There was no protection in monkeys that received Pox malaria vaccine alone without previous priming. The second sporozoite challenge was given 4 months after the first. All 4 monkeys that were protected in the first challenge developed malaria in the second challenge. DNA, VRP and Ad5 vaccines all primed monkeys for strong immune responses after the Pox boost. We discuss the high level but short duration of protection in this experiment and the possible benefits of the long interval between prime and boost

Chronic non-specific low back pain - sub-groups or a single mechanism?

Copyright 2008 Wand and O'Connell; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Background: Low back pain is a substantial health problem and has subsequently attracted a considerable amount of research. Clinical trials evaluating the efficacy of a variety of interventions for chronic non-specific low back pain indicate limited effectiveness for most commonly applied interventions and approaches. Discussion: Many clinicians challenge the results of clinical trials as they feel that this lack of effectiveness is at odds with their clinical experience of managing patients with back pain. A common explanation for this discrepancy is the perceived heterogeneity of patients with chronic non-specific low back pain. It is felt that the effects of treatment may be diluted by the application of a single intervention to a complex, heterogeneous group with diverse treatment needs. This argument presupposes that current treatment is effective when applied to the correct patient. An alternative perspective is that the clinical trials are correct and current treatments have limited efficacy. Preoccupation with sub-grouping may stifle engagement with this view and it is important that the sub-grouping paradigm is closely examined. This paper argues that there are numerous problems with the sub-grouping approach and that it may not be an important reason for the disappointing results of clinical trials. We propose instead that current treatment may be ineffective because it has been misdirected. Recent evidence that demonstrates changes within the brain in chronic low back pain sufferers raises the possibility that persistent back pain may be a problem of cortical reorganisation and degeneration. This perspective offers interesting insights into the chronic low back pain experience and suggests alternative models of intervention. Summary: The disappointing results of clinical research are commonly explained by the failure of researchers to adequately attend to sub-grouping of the chronic non-specific low back pain population. Alternatively, current approaches may be ineffective and clinicians and researchers may need to radically rethink the nature of the problem and how it should best be managed

Active case detection, treatment of falciparum malaria with combined chloroquine and sulphadoxine/pyrimethamine and vivax malaria with chloroquine and molecular markers of anti-malarial resistance in the Republic of Vanuatu

<p>Abstract</p> <p>Background</p> <p>Chloroquine-resistant <it>Plasmodium falciparum </it>was first described in the Republic of Vanuatu in the early 1980s. In 1991, the Vanuatu Ministry of Health instituted new treatment guidelines for uncomplicated <it>P. falciparum </it>infection consisting of chloroquine/sulphadoxine-pyrimethamine combination therapy. Chloroquine remains the recommended treatment for <it>Plasmodium vivax</it>.</p> <p>Methods</p> <p>In 2005, cross-sectional blood surveys at 45 sites on Malo Island were conducted and 4,060 adults and children screened for malaria. Of those screened, 203 volunteer study subjects without malaria at the time of screening were followed for 13 weeks to observe peak seasonal incidence of infection. Another 54 subjects with malaria were followed over a 28-day period to determine efficacy of anti-malarial therapy; chloroquine alone for <it>P. vivax </it>and chloroquine/sulphadoxine-pyrimethamine for <it>P. falciparum </it>infections.</p> <p>Results</p> <p>The overall prevalence of parasitaemia by mass blood screening was 6%, equally divided between <it>P. falciparum </it>and <it>P. vivax</it>. Twenty percent and 23% of participants with patent <it>P. vivax </it>and <it>P. falciparum </it>parasitaemia, respectively, were febrile at the time of screening. In the incidence study cohort, after 2,303 person-weeks of follow-up, the incidence density of malaria was 1.3 cases per person-year with <it>P. vivax </it>predominating. Among individuals participating in the clinical trial, the 28-day chloroquine <it>P. vivax </it>cure rate was 100%. The 28-day chloroquine/sulphadoxine-pyrimethamine <it>P. falciparum </it>cure rate was 97%. The single treatment failure, confirmed by <it>merozoite surface protein-2 </it>genotyping, was classified as a day 28 late parasitological treatment failure. All <it>P. falciparum </it>isolates carried the Thr-76 <it>pfcrt </it>mutant allele and the double Asn-108 + Arg-59 <it>dhfr </it>mutant alleles. <it>Dhps </it>mutant alleles were not detected in the study sample.</p> <p>Conclusion</p> <p>Peak seasonal malaria prevalence on Malo Island reached hypoendemic levels during the study observation period. The only <it>in vivo </it>malaria drug efficacy trial thus far published from the Republic of Vanuatu showed chloroquine/sulphadoxine-pyrimethamine combination therapy for <it>P. falciparum </it>and chloroquine alone for <it>P. vivax </it>to be highly efficacious. Although the chloroquine-resistant <it>pfcrt </it>allele was present in all <it>P. falciparum </it>isolates, mutant alleles in the <it>dhfr </it>and <it>dhps </it>genes do not yet occur to the extent required to confer sulphadoxine-pyrimethamine resistance in this population.</p