Effect of 13-valent pneumococcal conjugate vaccine on experimental carriage of Streptococcus pneumoniae serotype 6B in Blantyre, Malawi: a randomised controlled trial and controlled human infection study

Background The effect of childhood pneumococcal conjugate vaccine implementation in Malawi is threatened by absence of herd effect. There is persistent vaccine-type pneumococcal carriage in both vaccinated children and the wider community. We aimed to use a human infection study to measure 13-valent pneumococcal conjugate vaccine (PCV13) efficacy against pneumococcal carriage. Methods We did a double-blind, parallel-arm, randomised controlled trial investigating the efficacy of PCV13 or placebo against experimental pneumococcal carriage of Streptococcus pneumoniae serotype 6B (strain BHN418) among healthy adults (aged 18–40 years) from Blantyre, Malawi. We randomly assigned participants (1:1) to receive PCV13 or placebo. PCV13 and placebo doses were prepared by an unmasked pharmacist to maintain research team and participant masking with identification only by a randomisation identification number and barcode. 4 weeks after receiving either PCV13 or placebo, participants were challenged with 20 000 colony forming units (CFUs) per naris, 80 000 CFUs per naris, or 160 000 CFUs per naris by intranasal inoculation. The primary endpoint was experimental pneumococcal carriage, established by culture of nasal wash at 2, 7, and 14 days. Vaccine efficacy was estimated per protocol by means of a log-binomial model adjusting for inoculation dose. The trial is registered with the Pan African Clinical Trials Registry, PACTR202008503507113, and is now closed. Findings Recruitment commenced on April 27, 2021 and the final visit was completed on Sept 12, 2022. 204 participants completed the study protocol (98 PCV13, 106 placebo). There were lower carriage rates in the vaccine group at all three inoculation doses (0 of 21 vs two [11%] of 19 at 20 000 CFUs per naris; six [18%] of 33 vs 12 [29%] of 41 at 80 000 CFUs per naris, and four [9%] of 44 vs 16 [35%] of 46 at 160 000 CFUs per naris). The overall carriage rate was lower in the vaccine group compared with the placebo group (ten [10%] of 98 vs 30 [28%] of 106; Fisher's p value=0·0013) and the vaccine efficacy against carriage was estimated at 62·4% (95% CI 27·7–80·4). There were no severe adverse events related to vaccination or inoculation of pneumococci. Interpretation This is, to our knowledge, the first human challenge study to test the efficacy of a pneumococcal vaccine against pneumococcal carriage in Africa, which can now be used to establish vaccine-induced correlates of protection and compare alternative strategies to prevent pneumococcal carriage. This powerful tool could lead to new means to enhance reduction in pneumococcal carriage after vaccination

Natural carriage of Streptococcus pneumoniae is associated with increased experimental pneumococcal carriage but reduced conjugate vaccine efficacy in a human challenge model

Background In Malawi, the national pneumococcal conjugate vaccine (PCV13) demonstrated less herd immunity than the USA, likely due to higher natural pneumococcal carriage rates. We assessed PCV13 efficacy against experimental pneumococcal carriage in healthy Malawian adults. We explored how natural carriage (pneumococcal carriage of any other serotype apart from 6B) influenced experimental carriage rates and vaccine efficacy. Methods Healthy adults aged 18-40 were randomly assigned PCV13 (n=98) or saline (n=106), followed by intranasal SPN 6B inoculation at 20,000 (n=40), 80,000 (n=74), or 160,000 (n=90) CFU/100µl, 28 days post-vaccination. We evaluated natural and experimental pneumococcal carriage before and after vaccination on days 2, 7, and 14 post-inoculation using culture and multiplex qPCR targeting lytA/cpsA genes and compared carriage rates by vaccination status. Results Of 204 participants, 19.6% (40) exhibited experimental carriage, detected by culture and 25.5% (52) by qPCR. Vaccinated individuals had lower experimental carriage rates (10.2%, n=10/98) compared to the placebo group (28.3%, n=30/106). This difference in vaccine efficacy was more pronounced in participants without natural carriage (PCV13=8% n=6/75 vs. placebo=25.9%, n=21/81) compared to those with natural carriage (PCV13=14.8%, n=4/27 vs. placebo=26.5%, n=9/34). Using a log-binomial model, vaccine effectiveness (VE) was 62%, whether assessed by culture or qPCR. Natural carriers had a lower VE of 52% compared to participants with no natural carriage (VE=69%). Conclusion We have shown that PCV13 VE estimate (62%) is robust whether carriage is assessed by culture or qPCR. PCV13 had lower VE in natural carriers compared to those without natural carriage at the inoculation visit

Dynamic Adsorption Properties of Insoluble Humic Acid/Tourmaline Composite Particles for Iron and Manganese in Mine Wastewater

Iron- and manganese-contaminated mine water is widespread around the world, and economical and efficient remediation has become a priority. Insoluble humic acid/tourmaline composite particles (IHA/TM) were prepared by combining inorganic tourmaline (TM) with the natural organic polymer humic acid (HA), and the effects of different calcination temperatures and calcination times of TM and IHA on the adsorption of Fe2+ and Mn2+ were analyzed. Based on the microscopic characterization of Scanning electron microscopy (SEM), Energy Dispersive Spectroscopy (EDS), Brunnauer–Emmet–Teller (BET), X-ray diffractometer (XRD) and Fourier transform infrared (FTIR), the simultaneous adsorption performance of IHA/TM on Fe2+ and Mn2+ was studied through dynamic adsorption tests, and a dynamic adsorption model was established. Adsorption regeneration experiments were carried out to further investigate the effectiveness of the composite particles in practical applications. The results show that, when the calcination temperature was 330 °C and the calcination time was 90 min, the removal rates of iron and manganese by the IHA/TM composite particles reached 99.85% and 99.51%, respectively. The curves for penetration of Fe2+ and Mn2+ ions into the IHA/TM composite particles were affected by the bed height, flow rate and influent concentration. Decreasing the flow rate, decreasing the influent concentration, or increasing the bed height prolonged the operation time of the dynamic column. If the bed height was too low, the penetration point was reached before the expected treatment was achieved, and when the bed height was too high, the removal of Fe2+ and Mn2+ was slow, and the utilization rate of the adsorbent was also reduced. If the flow rate was too low, longitudinal remixing easily occurred in the column. However, when the flow rate was too high, the speed of Fe2+ and Mn2+ ions passing through the adsorption layer increased, which reduced the total amount of adsorption. The increase in influent concentration not only reduces the removal rate, but also greatly shortens the total operation time of the dynamic column and reduces the treatment water. The dynamic process for the adsorption of Fe2+ and Mn2+ by IHA/TM was fitted best by the Thomas model. The adsorption column was continuously regenerated five times, and the results show that the IHA/TM composite particles were suitable for iron and manganese removal from mine wastewater. The research results will provide a reference for the effectiveness of the IHA/TM composite particles in practical applications

Removal of Fe2+ and Mn2+ from Polluted Groundwater by Insoluble Humic Acid/Tourmaline Composite Particles

Insoluble humic acid/tourmaline composite particles (IHA/TM) were prepared by combining inorganic tourmaline (TM) with the natural organic polymer humic acid (HA) and carbonizing them at 330 °C to study the removal characteristics and mechanism of Fe2+ and Mn2+. The results showed that the optimal ratio of TM to IHA is 2:3. When the temperature of the IHA/TM composite particles was 35 °C and the pH was 6, the adsorption of Fe2+ and Mn2+ by IHA/TM reached equilibrium at 240 min. The optimum dose of the adsorbent was 10 g/L, and the equilibrium adsorption capacities of Fe2+ and Mn2+ were 5.645 mg/g and 3.574 mg/g, respectively. The process of IHA/TM adsorption of Fe2+ and Mn2+ in water was spontaneous, endothermic and sustainable, and cooling was not conducive to adsorption. The pseudo-second order kinetic equation can well reflect the adsorption mechanism of IHA/TM on Fe2+ and Mn2+, and the Langmuir adsorption model better describes the isothermal adsorption behaviour. The material characterisation and adsorption experiments indicate that surface coordination and chemical precipitation are the main mechanisms of Fe2+ and Mn2+ removal by IHA/TM