Randomized Controlled Trial of RTS,S/AS02D and RTS,S/AS01E Malaria Candidate Vaccines Given According to Different Schedules in Ghanaian Children

Background:The target delivery channel of RTS,S candidate malaria vaccines in malaria-endemic countries in Africa is the World Health Organisation Expanded Program on Immunization. As an Adjuvant System, age de-escalation and schedule selection step, this study assessed 3 schedules of RTS,S/AS01E and RTS,S/AS02D in infants and young children 5–17 months of age in Ghana.Methodology:A Phase II, partially-blind randomized controlled study (blind to vaccine, not to schedule), of 19 months duration was conducted in two (2) centres in Ghana between August 2006 and May 2008. Subjects were allocated randomly (1:1:1:1:1:1) to one of six study groups at each study site, each defining which vaccine should be given and by which schedule (0,1-, 0,1,2- or 0,1,7-months). For the 0,1,2-month schedule participants received RTS,S/AS01E or rabies vaccine at one center and RTS,S/AS01E or RTS,S/AS02D at the other. For the other schedules at both study sites, they received RTS,S/AS01E or RTS,S/AS02D. The primary outcome measure was the occurrence of serious adverse events until 10 months post dose 1.Results:The number of serious adverse events reported across groups was balanced. One child had a simple febrile convulsion, which evolved favourably without sequelae, considered to be related to RTS,S/AS01E vaccination. Low grade reactions occurred slightly more frequently in recipients of RTS,S/AS than rabies vaccines; grade 3 reactions were infrequent. Less local reactogenicity occurred with RTS,S/AS01E than RTS,S/AS02D. Both candidate vaccines were highly immunogenic for anti-circumsporozoite and anti-Hepatitis B Virus surface antigen antibodies. Recipients of RTS,S/AS01E compared to RTS,S/AS02D had higher peak anti-circumsporozoite antibody responses for all 3 schedules. Three dose schedules were more immunogenic than 2 dose schedules. Area under the curve analyses for anti-circumsporozoite antibodies were comparable between the 0,1,2- and 0,1,7-month RTS,S/AS01E schedules.Conclusions:Both candidate malaria vaccines were well tolerated. Anti-circumsporozoite responses were greater with RTS,S/AS01E than RTS,S/AS02D and when 3 rather than 2 doses were given. This study supports the selection of RTS,S/AS01E and a 3 dose schedule for further development in children and infants

Repellent and larvicidal properties of selected indigenous plants in the control of Anopheles mosquitoes

Background & objectives: Widespread pyrethroid resistance and plastic-feeding behaviour of most malaria vectors across Africa threaten the efficacy of current insecticide-based vector control interventions like Insecticide-Treated Nets (ITNs) and Indoor Residual Spraying (IRS). This study examined the larvicidal activity ofMorinda citrifolia against Anopheles gambiae larvae and the repellent properties of Morinda citrifolia (Noni), Moringa oleifera (Moringa), and Ocimum basilicum (Basil) as complementary vector control tools against Anopheles gambiae sensu lato (s.l.). Methods: Noni, Basil, and Moringa oil extracts were obtained with the extraction techniques; Soxhlet, steam distillation and maceration respectively, using hexane and ethanol. The effectiveness of the extracts was assessed using the WHO standard larval susceptibility bioassay and guidelines for repellent efficacy. Following bioassays, effective doses (ED) and lethal concentrations (LC) were determined. Gas Chromatography-Mass Spectroscopy analysis was performed to identify the bioactive chemical components of the extracts of Moringa oleifera and Ocimum basilicum. Results: Emulsified Morinda citrifolia seed oil had LC50=68.3, LC90=130.9 and LC99.9=222.5, and ED99. 9=308.3%v/v, the ethanolic extract of Moringa oleifera leaves had ED99.9= 1.25g/ml, and essential oil of Ocimum basilicum leaves had ED99.9=0.28g/ml against Anopheles gambiae. Interpretation & conclusion: The results obtained indicated that seed oil of Morinda citrifolia, essential oil of Ocimum basilicum, and crude extract of Moringa oleifera have repellent activity against An. gambiae s.l. The complete protection time (CPT) of Morinda citrifolia, Moringa oleifera, and Ocimum basilicum was 120 min, 72 min and 84 min at ED99.9 respectively. Morinda citrifolia oil exhibited larvicidal effects against the larvae of An. gambiae s.l. The results provide valuable information for the use of the plants as biocides

Development and Validation of an RP-HPLC Method for the Quantitative Analysis of Triclosan in Human Urine

Funder: National Institute for Health Research; doi: http://dx.doi.org/10.13039/501100000272Triclosan (TCS), a synthesized chlorinated phenolic compound, is commonly utilized in consumable products as an antimicrobial agent. TCS has sparked widespread awareness because of its toxicity and possible negative effect on public health in recent years. In this study, a highly sensitive, fast, and cost-effective isocratic reversed-phase high-performance liquid chromatography (RP-HPLC) method coupled with solid-phase extraction for analysis of triclosan in human urine samples was developed. The method utilized methanol and water in a ratio of 90 : 10 as the mobile phase on a Phenomenex Luna 3 µm C18(2) 100 Å, 150 × 4.60 mm stationary phase, with a runtime of 5 minutes. The method showed good resolution of triclosan in the presence of the sample matrix. Validation of the method was performed according to the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). Linearity was tested over a range of 0.00625 µg/mL to 6.4 µg/mL, as accuracy recorded a recovery of 89.25%, 91.0%, and 92.75%. Limits of detection (LOD) and quantification (LOQ) were obtained to be 0.0173 µg/mL and 0.0525 µg/mL, respectively. The method proved to be robust over a temperature range of 26°C, 30°C, and 35°C and a flow rate of 0.5 ml, 1.0 ml, and 1.5 ml. The developed method was employed to detect and quantify triclosan in 153 urine samples, comprising 60 samples from Ibadan, Nigeria, and 93 samples from Kumasi, Ghana. Triclosan was detected in a total of 52 samples with an average content of 0.054588 µg/ml. This method can therefore be used for the routine analysis of triclosan in urine samples