Bacillus Thuringiensis-Derived Cry5B Has Potent Anthelmintic Activity Against Ascaris Suum.

Bacillus thuringiensis-derived Cry5B Has Potent Anthelmintic Activity against Ascaris suum.

PLoS Negl Trop Dis. 2013 Jun; 7(6): e2263
Urban JF, Hu Y, Miller MM, Scheib U, Yiu YY, Aroian RV

Ascaris suum and Ascaris lumbricoides are two closely related geo-helminth parasites that ubiquitously infect pigs and humans, respectively. Ascaris suum infection in pigs is considered a good model for A. lumbricoides infection in humans because of a similar biology and tissue migration to the intestines. Ascaris lumbricoides infections in children are associated with malnutrition, growth and cognitive stunting, immune defects, and, in extreme cases, life-threatening blockage of the digestive tract and aberrant migration into the bile duct and peritoneum. Similar effects can be seen with A. suum infections in pigs related to poor feed efficiency and performance. New strategies to control Ascaris infections are needed largely due to reduced treatment efficacies of current anthelmintics in the field, the threat of resistance development, and the general lack of new drug development for intestinal soil-transmitted helminths for humans and animals. Here we demonstrate for the first time that A. suum expresses the receptors for Bacillus thuringiensis crystal protein and novel anthelmintic Cry5B, which has been previously shown to intoxicate hookworms and which belongs to a class of proteins considered non-toxic to vertebrates. Cry5B is able to intoxicate A. suum larvae and adults and triggers the activation of the p38 mitogen-activated protein kinase pathway similar to that observed with other nematodes. Most importantly, two moderate doses of 20 mg/kg body weight (143 nM/kg) of Cry5B resulted in a near complete cure of intestinal A. suum infections in pigs. Taken together, these results demonstrate the excellent potential of Cry5B to treat Ascaris infections in pigs and in humans and for Cry5B to work effectively in the human gastrointestinal tract. HubMed – drug


Immunoprotection of Mice against Schistosomiasis Mansoni Using Solubilized Membrane Antigens.

PLoS Negl Trop Dis. 2013 Jun; 7(6): e2254
Sulbarán G, Noya O, Brito B, Ballén DE, Cesari IM

Schistosomiasis continues to be one of the most prevalent parasitic diseases in the world. Despite the existence of a highly effective antischistosome drug, the disease is spreading into new areas, and national control programs do not arrive to complete their tasks particularly in low endemic areas. The availability of a vaccine could represent an additional component to chemotherapy. Experimental vaccination studies are however necessary to identify parasite molecules that would serve as vaccine candidates. In the present work, C57BL/6 female mice were subcutaneously immunized with an n-butanol extract of the adult worm particulate membranous fraction (AWBE) and its protective effect against a S. mansoni challenge infection was evaluated.Water-saturated n-butanol release into the aqueous phase a set of membrane-associated (glyco)proteins that are variably recognized by antibodies in schistosome-infected patients; among the previously identified AWBE antigens there is Alkaline Phosphatase (SmAP) which has been associated with resistance to the infection in mice. As compared to control, a significantly lower number of perfuse parasites was obtained in the immunized/challenged mouse group (P<0.05, t test); and consequently, a lower number of eggs and granulomas (with reduced sizes), overall decreasing pathology. Immunized mice produced high levels of sera anti-AWBE IgG recognizing antigens of ?190-, 130-, 98-, 47-, 28-23, 14-, and 9-kDa. The ?130-kDa band (the AP dimer) exhibited in situ SmAP activity after addition of AP substrate and the activity was not apparently inhibited by host antibodies. A preliminary proteomic analysis of the 25-, 27-, and 28-kDa bands in the immunodominant 28-23 kDa region suggested that they are composed of actin.Immunization with AWBE induced the production of specific antibodies to various adult worm membrane molecules (including AP) and a partial (43%) protection against a challenging S. mansoni infection by mechanism(s) that still has to be elucidated. HubMed – drug


Drug Administration Errors in Hospital Inpatients: A Systematic Review.

PLoS One. 2013; 8(6): e68856
Berdot S, Gillaizeau F, Caruba T, Prognon P, Durieux P, Sabatier B

Drug administration in the hospital setting is the last barrier before a possible error reaches the patient.We aimed to analyze the prevalence and nature of administration error rate detected by the observation method.Embase, MEDLINE, Cochrane Library from 1966 to December 2011 and reference lists of included studies.Observational studies, cross-sectional studies, before-and-after studies, and randomized controlled trials that measured the rate of administration errors in inpatients were included.Two reviewers (senior pharmacists) independently identified studies for inclusion. One reviewer extracted the data; the second reviewer checked the data. The main outcome was the error rate calculated as being the number of errors without wrong time errors divided by the Total Opportunity for Errors (TOE, sum of the total number of doses ordered plus the unordered doses given), and multiplied by 100. For studies that reported it, clinical impact was reclassified into four categories from fatal to minor or no impact. Due to a large heterogeneity, results were expressed as median values (interquartile range, IQR), according to their study design.Among 2088 studies, a total of 52 reported TOE. Most of the studies were cross-sectional studies (N=46). The median error rate without wrong time errors for the cross-sectional studies using TOE was 10.5% [IQR: 7.3%-21.7%]. No fatal error was observed and most errors were classified as minor in the 18 studies in which clinical impact was analyzed. We did not find any evidence of publication bias.Administration errors are frequent among inpatients. The median error rate without wrong time errors for the cross-sectional studies using TOE was about 10%. A standardization of administration error rate using the same denominator (TOE), numerator and types of errors is essential for further publications. HubMed – drug


HIV and Hepatitis C Virus Testing Delays at Methadone Clinics in Guangdong Province, China.

PLoS One. 2013; 8(6): e66787
Xia YH, McLaughlin MM, Chen W, Ling L, Tucker JD

In China, injection drug use is a major transmission route for HIV and hepatitis C virus (HCV) infection. Timely HIV and HCV testing among drug users is vital to earlier diagnosis, linkage to care, and retention. This study aimed to examine HIV and hepatitis C virus (HCV) testing delays at methadone clinics in Guangdong Province, China, and identify individual-level and clinic-level factors associated with delayed testing. Data from 13,270 individuals at 45 methadone clinics in Guangdong were abstracted from a national web-based surveillance database. A two-level binomial logit model was used to examine the association between individual- and clinic-level factors and delayed HIV and HCV testing, defined as receiving a test seven or more days after initial entry into the methadone system. Among 10,046 patients tested for HIV, 1882 (18.7%) had delayed testing; among 10,404 patients tested for HCV, 1542 (14.8%) had delayed testing. Among delayed testers, the median time to HCV testing was significantly longer than the median time to HIV testing (73 vs. 54 days, p<0.05). In the multivariate analysis, the likelihood of delayed HIV testing was higher among individuals with high school or greater education (adjusted odds ratio [aOR] 1.32, 95% confidence interval [CI] 1.02-1.72) and individuals enrolled at clinics with more patients (aOR 1.41, 95% CI 1.05-1.91, for each increase in 100). The likelihood of delayed HCV testing was higher among women (aOR 1.51, 95% CI 1.11-2.06) and employed individuals (aOR 1.21, 95% CI 1.02-1.43). Delayed testing for HIV and HCV is common among patients at methadone clinics in Guangdong, with many patients experiencing delays of two or more months. Structural interventions are needed to expedite testing once individuals enter the methadone maintenance program. HubMed – drug