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 transmissionand 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.

Simple measures are as effective as invasive techniques in the diagnosis of pulmonary tuberculosis in Malawi.

SETTING: Detection of smear-positive pulmonary tuberculosis (PTB) cases is vital for tuberculosis (TB) control. Methods to augment sputum collection are available, but their additional benefit is uncertain in resource-limited settings. OBJECTIVE: To compare the diagnostic yields using five methods to obtain sputum from adults diagnosed with smear-negative PTB in Malawi. DESIGN: Self-expectorated sputum was collected under supervision for microscopy and mycobacterial culture in the study laboratory. Confirmed smear-negative patients provided physiotherapy-assisted sputum and induced sputum, followed the next morning by gastric washing and bronchoalveolar lavage (BAL) samples. RESULTS: A total of 150 patients diagnosed with smear-negative PTB by the hospital service were screened; 39 (26%) were smear-positive from supervised self-expectorated sputum examined in the study laboratory. The remaining 111 confirmed smear-negative patients were enrolled in the study; 89% were human immunodeficiency virus positive. Seven additional smear-positive cases were diagnosed using the augmented sputum collection techniques. No differences were observed in the numbers of cases detected using the different methods. Of the 46 smear-positive cases, 44 (95.6%) could be detected from self-expectorated and physiotherapy-assisted samples. CONCLUSIONS: For countries such as Malawi, the best use of limited resources to detect smear-positive PTB cases would be to improve the quality of self-expectorated sputum collection and microscopy. The additional diagnostic yield using BAL after induced sputum is limited.