A pneumococcal controlled human infection model in Malawi: Transfer of an established pneumococcal carriage model from Liverpool, UK to Blantyre, Malawi – A feasibility study

Morton, Ben, Burr, Sarah, Jambo, Kondwani ORCID: https://orcid.org/0000-0002-3195-2210, Rylance, Jamie ORCID: https://orcid.org/0000-0002-2323-3611, Henrion, Marc, Ndaziona, Banda, Nsomba, Edna, Kaumpa, Blessings, Manda Taylor, Lucinda, Masesa, Clemens, Ferreira, Daniela ORCID: https://orcid.org/0000-0002-0594-0902 and Gordon, Stephen ORCID: https://orcid.org/0000-0001-6576-1116 (2020) 'A pneumococcal controlled human infection model in Malawi: Transfer of an established pneumococcal carriage model from Liverpool, UK to Blantyre, Malawi – A feasibility study'. Wellcome Open Research, Vol 5, e25.

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Abstract

Streptococcus pneumoniae is the leading cause of morbidity and mortality due to community acquired pneumonia, bacterial meningitis and bacteraemia worldwide. Pneumococcal conjugate vaccines protect against invasive disease, but are expensive to manufacture, limited in serotype coverage, associated with serotype replacement and demonstrate reduced effectiveness against mucosal colonisation. As asymptomatic colonisation of the human nasopharynx is a prerequisite for pneumococcal disease, this is proposed as a marker for novel vaccine efficacy. Our team established a safe and reproducible pneumococcal controlled human infection model at Liverpool School of Tropical Medicine (LSTM). This has been used to test vaccine induced protection against nasopharyngeal carriage for ten years in over 1000 participants.

We will transfer established standardised operating procedures from LSTM to Malawi and test in up to 36 healthy participants. Primary endpoint: detection of the inoculated pneumococci by classical culture from nasal wash recovered from the participants after pneumococcal challenge. Secondary endpoints: confirmation of robust clinical and laboratory methods for sample capture and processing. Tertiary endpoints: participant acceptability of study and methods. We will test three doses of pneumococcal inoculation (20,000, 80,000 and 160,000 colony forming units [CFUs] per naris) using a parsimonious study design intended to reduce unnecessary exposure to participants. We hypothesise that 80,000 CFUs will induce nasal colonisation in approximately half of participants per established LSTM practice.

The aims of the feasibility study are: 1) Establish Streptococcus pneumoniae experimental human pneumococcal carriage in Malawi; 2) Confirm optimal nasopharyngeal pneumococcal challenge dose; 3) Confirm safety and measure potential symptoms; 4) Confirm sampling protocols and laboratory assays; 5) Assess feasibility and acceptability of consent and study procedures. Confirmation of pneumococcal controlled human infection model feasibility in Malawi will enable us to target pneumococcal vaccine candidates for an at-risk population who stand the most to gain from new and improved vaccine strategies.

Item Type:	Article
Subjects:	QV Pharmacology > Drug Standardization. Pharmacognosy. Medicinal Plants > QV 771 Standardization and evaluation of drugs QW Microbiology and Immunology > Bacteria > QW 142 Gram-positive bacteria (General) WC Communicable Diseases > Infection. Bacterial Infections > Bacterial Infections > WC 217 Pneumococcal infections WF Respiratory System > WF 140 Diseases of the respiratory system (General) WF Respiratory System > WF 20 Research (General)
Faculty: Department:	Clinical Sciences & International Health > Clinical Sciences Department Clinical Sciences & International Health > International Public Health Department
Digital Object Identifer (DOI):	https://doi.org/10.12688/wellcomeopenres.15689.2
Depositing User:	Catherine Molloy
Date Deposited:	16 Apr 2020 11:52
Last Modified:	17 Apr 2020 16:23
URI:	https://archive.lstmed.ac.uk/id/eprint/14161

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