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The goal of this experimental pneumococcal carriage study is to to characterise rates and determinants of experimental pneumococcal carriage in PLHIV.
The main questions it aims to answer are:
Participants will be inoculated intranasally with a controlled concentration of pneumococcus after which they will be monitored for 21 days during which nasal and systemic immune dynamics and pneumococcal carriage dynamics will be evaluated. At the end of the study any participants exhibiting carriage will have the pneumococcus cleared with antibiotics.
The EHPC has been established at the Malawi-Liverpool Wellcome centre (MLW) and demonstrated acceptability and feasibility in this setting. To date, over 250 participants have been enrolled on the EHPC at MLW without any study complications. Participants will be inoculated in both nostrils with a controlled concentration of penicillin-sensitive Streptococcus pneumoniae. Participants will be followed up for 25 days following inoculation during which sampling will occur at established time-points to establish pneumococcal carriage and immune cell/immunoglobulin dynamics. After 21 days, participants who demonstrate pneumococcal carriage will commence an antibiotic course to clear the bacteria (participants may be advised by the clinical study team to commence antibiotics earlier if they develop any symptoms of pneumococcal disease). Participants will remain under close observation in study accommodation for the first 3 days following inoculation, and will then be monitored daily at home via text message and telephone calls. A final health-check and exit interview will be conducted on day 25 to evaluate participant satisfaction with study participation. The overall objective is to characterise rates and determinants of experimental pneumococcal carriage in PLHIV in Blantyre, Malawi in order to inform vaccine evaluations and vaccine policy.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Inoculation with Streptococcus pneumoniae serotype 6B | Experimental | Participants will be inoculation with a controlled concentration of full sequenced, fully antibiotic sensitive Streptococcus pneumonia serotype 6B |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Streptococcus pneumoniae serotype 6B | Other | A controlled concentration of streptococcus pneumoniae serotype 6B is placed in both nares of participants |
|
| Measure | Description | Time Frame |
|---|---|---|
| Proportion of participants with pneumococcal carriage in the nasopharynx post-inoculation | Measured by classic culture and PCR-based methods | From inoculation up to 21 days post-inoculation |
| Measure | Description | Time Frame |
|---|---|---|
| Average pneumococcal carriage density in the nasopharynx post-inoculation | Measured by classic culture and PCR-based methods | From inoculation up to 21 days post-inoculation |
| Nasal immunoglobulin concentration at baseline |
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Inclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Klara Doherty, MBChB | Contact | +265885908115 | klara.doherty@lstmed.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| Stephen Gordon, MA MD | Malawi-Liverpool Wellcome Centre | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Malawi-Liverpool Wellcome City | Blantyre | Malawi |
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| ID | Term |
|---|---|
| D011014 | Pneumonia |
| D000163 | Acquired Immunodeficiency Syndrome |
| ID | Term |
|---|---|
| D012141 | Respiratory Tract Infections |
| D007239 | Infections |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
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Measured in nasal fluid
| Baseline |
| Change in nasal immunoglobulin concentration following inoculation | Measured in nasal fluid | Baseline to 21 days post-inoculation |
| Density of immune cells in the nasal mucosa at baseline | Immune cell to epithelial cell ratio measured in nasal mucosal cell samples | Baseline |
| Change in density of immune cells in the nasal mucosa following inoculation | Immune cell to epithelial cell ratio measured in nasal mucosal cell samples | Baseline up to 21 days post-inoculation |
| Immune cell activation activation in the nasal mucosa at baseline | Concentration of markers of immune cell activation measured in nasal fluid and cell samples | Baseline |
| Change in immune cell activation in the nasal mucosa following inoculation | Concentration of markers of immune cell activation measured in nasal fluid and cell samples | Baseline up to 21 days post-inoculation |
| D015658 |
| HIV Infections |
| D000086982 | Blood-Borne Infections |
| D003141 | Communicable Diseases |
| D015229 | Sexually Transmitted Diseases, Viral |
| D012749 | Sexually Transmitted Diseases |
| D016180 | Lentivirus Infections |
| D012192 | Retroviridae Infections |
| D012327 | RNA Virus Infections |
| D014777 | Virus Diseases |
| D012897 | Slow Virus Diseases |
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
| D007153 | Immunologic Deficiency Syndromes |
| D007154 | Immune System Diseases |