Recruitment strategies used to enrol healthy volunteers in the first pneumococcal human infection study in Africa: Lessons from Blantyre, Malawi

Background Human infection studies (HIS) also known as Controlled Human Infection Models (CHIM) are a relatively new concept in African countries to clinicians, scientists, and communities alike. We have introduced HIS/CHIM studies to Malawi during the last four years by developing an experimental human pneumococcal carriage model. This CHIM was used to test the efficacy of a licensed 13-valent Pneumococcal Conjugate Vaccine (PCV13) against experimental nasal pneumococcal carriage. Traditional and digital recruitment strategies into this novel trial were explored. Objectives To describe various methods of recruitment in this first CHIM study in Malawi. Methods The clinical trial within the context of which these data were recorded was registered with the Pan African Clinical Trials Registry (REF: PACTR202008503507113) on 03 August 2020. The project was conducted at the Malawi Liverpool Wellcome Programme (MLW) in Blantyre, Malawi between April 2021, and September 2022. Source populations were college students and community members within Blantyre. Recruitment strategies included sharing study information in written or visual form, community sensitization meetings, snowball contacts (word of mouth from previous volunteers), branded clothing and participating in radio and television programs. Results 299 volunteers attended screening clinic, of whom 278 were recruited. Sixty-six recruited volunteers (23.7%) were college students and 212 (76.3%) were from the community. Snowball word-of-mouth contacting was the most successful recruitment strategy, with 201 (72.3%) participants recruited using this method. 195 (70.1%) were men of whom 149 (76.4%) joined the study through snowballing. Conclusion or recommendation Using a variety of recruitment strategies led to successful recruitment in this novel controlled human infection study. Most participants were recruited through snowballing

Piloting electronic informed consenting in a pneumococcal human infection study in Blantyre, Malawi

Background Electronic consent can potentially improve accuracy, workflow, and overall patient experience in clinical research but has not been used in Malawi, owing to uncertainty about data security and technical support. Objectives We explored the feasibility of using electronic consent (e-consent) in an ongoing human infection study in Blantyre Malawi. We dual-consented participants by both electronic and paper methods to assess the feasibility of electronic consent, and then compared benefits and challenges of the two methods. Methods The approved paper consent forms were digitized using Open Data Kit (ODK). Following participant information giving by the research staff, healthy literate adult participants with no audio-visual impairments completed a self-administered e-consent and provided an electronic signature. Signed e-consent forms were uploaded to a secure study server. While the participants were in clinic, the signed electronic consent form was printed as a copy for the participant. The feasibility, advantages and disadvantages including data safety consideration for e-consenting were evaluated by exploring issues surrounding use of e-consenting versus paper-based consenting. Consent forms were analysed by research staff for errors such as overwriting and legibility. Results We piloted 109 participants to e-consenting. It was found to be user friendly, had 0% (n 0/109) errors compared to 43.1% (n 47/109) in paper based methods along with enhanced data safety. The challenges included difficult digitization of ethics stamped documents, volunteer unfamiliarity with tablet user interface and its requirement for a working internet and printer. Conclusion E-consenting was feasible but required additional resource investment. Benefits included error minimization and data security

Poor association between 13-valent pneumococcal conjugate vaccine-induced serum and mucosal antibody responses with experimental Streptococcus pneumoniae serotype 6B colonisation

Background Pneumococcal carriage is the primary reservoir for transmission and a prerequisite for invasive pneumococcal disease. Pneumococcal Conjugate Vaccine 13 (PCV13) showed a 62% efficacy in protection against experimental Streptococcus pneumoniae serotype 6B (Spn6B) carriage in a controlled human infection model (CHIM) of healthy Malawian adults. We, therefore, measured humoral responses to experimental challenge and PCV-13 vaccination and determined the association with protection against pneumococcal carriage. Methods We vaccinated 204 young, healthy Malawian adults with PCV13 or placebo and nasally inoculated them with Spn6B at least four weeks post-vaccination to establish carriage. We collected peripheral blood and nasal lining fluid at baseline, 4 weeks post-vaccination (7 days pre-inoculation), 2, 7, 14 and > 1 year post-inoculation. We measured the concentration of anti-serotype 6B Capsular Polysaccharide (CPS) Immunoglobulin G (IgG) and IgA antibodies in serum and nasal lining fluid using the World Health Organization (WHO) standardised enzyme-linked immunosorbent assay (ELISA). Results PCV13-vaccinated adults had higher serum IgG and nasal IgG/IgA anti-Spn6B CPS-specific binding antibodies than placebo recipients 4 to 6 weeks post-vaccination, which persisted for at least a year after vaccination. Nasal challenge with Spn6B did not significantly alter serum or nasal anti-CPS IgG binding antibody titers with or without experimental pneumococcal carriage. Pre-challenge titers of PCV13-induced serum IgG and nasal IgG/IgA anti-Spn6B CPS binding antibodies did not significantly differ between those that got experimentally colonised by Spn6B compared to those that did not. Conclusion This study demonstrates that despite high PCV13 efficacy against experimental Spn6B carriage in young, healthy Malawian adults, robust vaccine-induced systemic and mucosal anti-Spn6B CPS binding antibodies did not directly relate to protection