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Chikaonda, Tarsizio, Chirwa, Anthony Emeritus, Lipunga, Gareth, Thole, Faith, Galafa, Bridgette, Kamanga, Morrison Peace, Nsomba, Edna, Nkhoma, Vitumbiko S., Toto, Neema, Kudowa, Evarista, Chiwala, Gift, Dula, Dingase, Tembo, Godwin, Chimgoneko, Lorensio, Ndaferankhande, John, Makhaza, Lumbani, Ngoliwa, Clara, Banda, Ndaziona Peter Kwanjo, Henrion, Marc, Ferreira, Daniela M., Jambo, Kondwani 
ORCID: https://orcid.org/0000-0002-3195-2210 and Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116
(2024)
'Experimental Human Pneumococcal Carriage using Streptococcus pneumoniae serotype 3 in Malawi: a dose ranging and reproducibility human infection study'. Wellcome Open Research, Vol 9, e467.
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Abstract
Background
Streptococcus pneumoniae is a major cause of morbidity and mortality from respiratory tract infections, pneumonia, meningitis, and sepsis. Nasopharyngeal carriage of pneumococcus is a prerequisite for pneumococcal disease and transmission. Since the global introduction of pneumococcal conjugated vaccines, rates of pneumococcal disease have declined for many vaccine type serotypes but serotype 3 (SPN3) continues to cause significant disease. The Experimental Human Pneumococcal Challenge (EHPC) model is a unique method of determining pneumococcal colonisation, understanding the impact of colonisation on acquired immunity and for testing pneumococcal vaccines. This study will develop a serotype 3 EHPC model to address some pertinent questions on the burden of pneumococcal disease in Malawi.
Methods
Healthy adults aged 18-50 years will be recruited, with a maximum target of 83 participants to complete all study visits. The study will consist of a dose ranging and safety study, followed by a reproducibility study. Sequential cohorts of 10 healthy participants will be challenged with escalating doses of SPN3 in the dose ranging study. Samples will be collected before inoculation and on days 2, 7, 13, 16, 21 and 28 following inoculations, for determination of carriage. A total of 33 participants will be enrolled in the reproducibility part and will use a dose that established ≥60% of carriage, and with a high safety profile. Samples will be collected for determination of both local and systemic immunological responses to pneumococcal challenge. Upon completion of study visits, participants will complete a questionnaire establish acceptability.
Interpretations
We expect to establish an optimal SPN3 dose required to establish nasopharyngeal colonisation in healthy adults in an EHPC model. The model can then be used to evaluate pneumococcal vaccines in both healthy and at-risk populations.
| Item Type: | Article |
|---|---|
| Subjects: | WC Communicable Diseases > Virus Diseases > Viral Respiratory Tract Infections. Respirovirus Infections > WC 505 Viral respiratory tract infections WF Respiratory System > WF 140 Diseases of the respiratory system (General) |
| Faculty: Department: | Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > Malawi-Liverpool-Wellcome Programme (MLW) |
| Digital Object Identifer (DOI): | https://doi.org/10.12688/wellcomeopenres.20987.1 |
| SWORD Depositor: | JISC Pubrouter |
| Depositing User: | JISC Pubrouter |
| Date Deposited: | 11 Sep 2024 13:11 |
| Last Modified: | 11 Sep 2024 13:11 |
| URI: | https://archive.lstmed.ac.uk/id/eprint/25198 |
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