Pneumococcal conjugate vaccination schedules in infants—acquisition, immunogenicity, and pneumococcal conjugate and yellow fever vaccine co-administration study

Background Pneumococcal conjugate vaccines (PCVs) effectively prevent pneumococcal disease, but the global impact of pneumococcal vaccination is hampered by its cost. The evaluation of reduced dose schedules of PCV includes measurement of effects on immunogenicity and carriage acquisition compared to standard schedules. The relevance and feasibility of trials of reduced dose schedules is greatest in middle- and low-income countries, such as The Gambia, where the introduction of PCV resulted in good disease control but where transmission of vaccine-type pneumococci persists. We designed a large cluster-randomised field trial of an alternative reduced dose schedule of PCV compared to the standard schedule, the PVS trial. We will also conduct a sub-study to evaluate the individual-level effect of the two schedules on carriage acquisition, immunogenicity, and co-administration of PCV with yellow fever vaccine, the PVS-AcqImm trial. Methods PVS-AcqImm is a prospective, cluster-randomised trial of one dose of PCV scheduled at age 6 weeks with a booster dose at age 9 months (i.e. alternative ‘1+1’ schedule) compared to three primary doses scheduled at 6, 10, and 14 weeks of age (i.e. standard ‘3+0’ schedule). Sub-groups within the alternative schedule group will receive yellow fever vaccine separately or co-administered with PCV at 9 months of age. The primary endpoints are (a) rate of nasopharyngeal vaccine-type pneumococcal acquisition from 9 to 14 months of age, (b) geometric mean concentration of vaccine-type pneumococcal IgG at 18 months of age, and (c) proportions with yellow fever neutralising antibody titre ≥8 four weeks after administration of yellow fever vaccine. Participants and field staff will not be masked to group allocation while the measurement of laboratory endpoints will be masked. Approximately equal numbers of participants will be resident in each of 28 geographic clusters (14 clusters in alternative and standard schedule groups); 784 enrolled for acquisition measurements and 336 for immunogenicity measurements. Discussion Analysis will account for potential non-independence of measurements by cluster and so interpretation of effects will be at the individual level (i.e. a population of individuals). PVS-AcqImm will evaluate whether acquisition of vaccine-type pneumococci is reduced by the alternative compared to the standard schedule, which is required if the alternative schedule is to be effective. Likewise, evidence of superior immune response at 18 months of age and safety of PCV co-administration with yellow fever vaccine will support decision-making regarding the use of the alternative 1+1 schedule. Acquisition and immunogenicity outcomes will be essential for the interpretation of the results of the large field trial comparing the two schedules. Trial registration International Standard Randomised Controlled Trial Number 72821613.

Semi-field evaluations of three botanically derived repellents against the blacklegged tick, Ixodes scapularis (Acari: Ixodidae)

Three compounds derived from botanicals sources, ethyl perillyl carbonate, geranyl isovalerate, and citronellyl cyclobutane carboxylate, were tested for repellent activity against Ixodes scapularis Say in a semi-field trial. Tick drags were treated with the compounds or with N, N-diethyl-m-toluamide (DEET) at high (0.25mg/cm2) or low (0.15mg/cm2) concentrations. Negative controls included untreated drags and drags treated with acetone, the carrier for all repellents. Freshly treated drags (within 20 minutes) were used to collect I. scapularis ticks at a county park in Wisconsin. To assess effectiveness, we measured tick encounter rates, detachment rate, and time to detachment. None of the repellent treatments resulted in significantly fewer encounters compared to both control treatments. However, the percentage of ticks that detached within 3 min was significantly higher on drags treated with repellents compared to controls. DEET was the most effective, repelling 69.7 - 87% of ticks by 3 min, but the effectiveness of the three test compounds was still high, ranging from 42% to 87% of ticks detaching by 3 min. For time to detachment, there were no significant differences between DEET and the three test compounds. We conclude that these botanically-derived repellents were effective against I. scapularis in a semi-field trial and could be viable alternatives to DEET.

Assessing the growth response of Vitis vinifera L. cv. Xynisteri, Maratheftiko, Shiraz and Sauvignon Blanc to different irrigation regimes.

The world’s changing climate is placing great pressure on the resources for sustainable viticulture. With this, it has become necessary to investigate grape varieties that are well adapted to hot climates. The aims of this study were to (1) assess the response of Xynisteri to different irrigation regimes, and (2) compare the performance of Xynisteri, Maratheftiko, Shiraz and Sauvignon Blanc grown in pots with different irrigation regimes. Trial one was established in a commercial Xynisteri vineyard in Cyprus under three different irrigation regimes - full, 50% and no irrigation in 2019. Trial two compared three irrigation regimes - full, 50% and 25% in a potted trial of Xynisteri and Sauvignon Blanc conducted in Cyprus in 2019. Trial three was a potted trial of Xynisteri, Sauvignon Blanc, Maratheftiko and Shiraz with the same three irrigation regimes conducted in Australia in 2020/21. Vine performance and physiology measurements were taken in both trials. Fruit composition analysis, yield (field trial only), shoot, trunk and root mass measurements were performed at the end of the season. Few differences between measures were found between irrigation regimes in the field trial. Fruit composition analysis revealed fructose to be lowest in the full irrigation group compared to deficit and no irrigation treatments. The potted trial in 2019 demonstrated that for all three irrigation regimes, Xynisteri had higher stem water potential, stomatal conductance and chlorophyll content than Sauvignon Blanc. Xynisteri produced greater end of season root, shoot and leaf mass than Sauvignon Blanc under all irrigation regimes. In 2020/21, Xynisteri had greater end of season root, shoot and leaf mass than Maratheftiko and Sauvignon Blanc with Shiraz the lowest. Few significant differences in stem water potential were observed in the early stages of the trial. However, toward the end of the trial and with reduced irrigation, Xynisteri and Maratheftiko had higher stem water potential than Shiraz and Sauvignon Blanc. Xynisteri had higher stomatal conductance and chlorophyll content than Maratheftiko and both were higher than Sauvignon Blanc and Shiraz. These results indicate that Xynisteri in particular may possess better cultivar specific growth traits than Shiraz and Sauvignon Blanc when grown under the same environmental conditions and in turn may be a more appropriate choice in areas where water is limited.