Measuring the change in genetic markers of antibiotic resistance carried in the nasopharynx of children with pneumonia in Blantyre, Malawi, and assessing whether this is associated with poor health outcomes
| ISRCTN | ISRCTN64027792 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN64027792 |
| Secondary identifying numbers | 24-076 |
- Submission date
- 12/08/2025
- Registration date
- 13/08/2025
- Last edited
- 13/08/2025
- Recruitment status
- Recruiting
- Overall study status
- Ongoing
- Condition category
- Respiratory
Prospectively registered
Protocol
Statistical analysis plan
Results
Individual participant data
Record updated in last year
Plain English summary of protocol
Background and study aims
Antimicrobial resistance (AMR) happens when bacteria become resistant to antibiotics, making infections harder to treat. This is a big problem worldwide, especially in Sub-Saharan Africa, where many children die from infections like pneumonia. However, there’s not much data from this region to help us understand the issue.
This study is looking at how hospital stays and antibiotic treatment affect the bacteria and antibiotic resistance found in the nose and throat of young children in Malawi. Researchers want to find out if these changes in bacteria are linked to worse health outcomes, like needing to go back to hospital.
Who can participate?
The study will include 350 children aged 12 to 24 months from Blantyre, Malawi. Children will be grouped as follows:
-Healthy children from the community
-Children with pneumonia treated with antibiotics at home
-Children hospitalised with pneumonia
-Children who are re-hospitalised with pneumonia within 3 months of a previous hospital stay
What does the study involve?
Children will have a swab taken from their nose and throat, and a urine sample collected. These samples will help researchers study the bacteria and antibiotic resistance present. Some children will be followed up after hospital discharge or after 3 months, depending on their group.
The swabs will be tested using advanced lab techniques to identify bacteria and resistance genes. Researchers will also test for viruses like RSV and flu in children with pneumonia. Information about the child’s health, any other illnesses, and antibiotic use will be recorded.
What are the possible benefits and risks of participating?
There are no direct benefits for children taking part, and they will receive the same medical care as other patients. However, the study may help improve how pneumonia is treated in the future.
Risks are minimal. In rare cases, a child might have a small nosebleed after the swab is taken, especially if they have a condition that makes them prone to bleeding.
Where is the study run from?
The study is being carried out by the Malawi Liverpool Wellcome Research Programme, in partnership with the Kamuzu University of Health Sciences in Malawi and the Liverpool School of Tropical Medicine in the UK.
When is the study starting and how long is it expected to run for?
April 2025 to February 2027
Who is funding the study?
Wellcome Trust (UK)
Who is the main contact?
Dr Lucy O’Connor, lucy.oconnor@lstmed.ac.uk
Contact information
Dr Lucy O'Connor
Public, Scientific, Principal Investigator
Public, Scientific, Principal Investigator
Pembroke Place
Liverpool
L3 5QA
United Kingdom
 ORCID ID |
0009-0002-6592-6106 |
|---|---|
| Phone | +44(0)151 705 3100 |
| lucy.oconnor@lstmed.ac.uk |
Study information
| Study design | Multi-site extended observational case-control study with a preliminary cohort component |
|---|---|
| Primary study design | Observational |
| Secondary study design | Case-control study |
| Study setting(s) | Community, Hospital |
| Study type | Other |
| Participant information sheet | 47835 Community_Pneumonia_Participant_Information_Sheet_and_Consent_Form_Chichewa_V5.0_21May2025.pdf |
| Scientific title | Nasopharyngeal resistome evolution under selective pressure and association with adverse health outcomes in a paediatric population in Blantyre, Malawi |
| Study acronym | NP Resistome |
| Study objectives | Our study aims to answer the following research question; does hospital admission and antibiotic treatment for pneumonia generate a persistent hospital-acquired nasopharyngeal resistome in Malawian children, and is this associated with adverse health outcomes in a resource limited setting? The primary objectives of this study are: 1. To measure how the diversity and relative abundance of the nasopharyngeal resistome of children hospitalised with pneumonia differs from the nasopharyngeal resistome of healthy children in the community. 2. To measure how the diversity and relative abundance of the nasopharyngeal resistome of children hospitalised with pneumonia differs from the nasopharyngeal resistome of children with pneumonia treated with antibiotics in the community. 3. To investigate whether there is measurable persistence of a hospital-acquired nasopharyngeal resistome post-discharge, and whether this is associated with adverse health outcomes, including recurrent hospitalisation. |
| Ethics approval(s) |
1. Approved 01/07/2025, Liverpool School of Tropical Medicine Research Ethics Committee (Liverpool School of Tropical Medicine, Pembroke Place, Liverpool, L3 5QA, United Kingdom; +44(0)1517053100; lstmrec@lstmed.ac.uk), ref: Research Protocol (24-076) 2. Approved 01/04/2025, Malawi College of Medicine Research & Ethics Committee (Room #822, Chimutu Building, Mahatma Gandhi Road, P/Bag 360 Chichiri, Blantyre, -, Malawi; (+265) 01 871 911/01 874 377; comrec@medcol.mw), ref: P.10/24-1200 |
| Health condition(s) or problem(s) studied | Pneumonia |
| Intervention | This observational study will recruit 350 children aged 12-24 months in four groups: healthy children in the community, children with pneumonia being treated with oral antibiotics in the community, children hospitalised with pneumonia and children re-hospitalised with pneumonia within 3-months of their previous admission. The study will be conducted at Ndirande community healthcare centre and Queen Elizabeth Central Hospital. Nasopharyngeal swabs (NPS) and urine samples will be taken at recruitment. NPS will also be taken at hospital discharge for children hospitalised with pneumonia, and at 3-month follow up study visits for children with pneumonia in the community and children hospitalised with pneumonia. NPS will undergo metagenomic sequencing to identify the nasopharyngeal microbiome (NPM) and nasopharyngeal resistome (NPR). NPS from participants with pneumonia will also be tested using a viral PCR for Respiratory Syncytial Virus (RSV), Influenza A and B. Urine samples will be used for an antibiotic bio-assay. Demographics, co-morbidities, health outcomes and antibiotic exposure will be recorded at recruitment for all participants, and subsequent study visits where applicable. |
| Intervention type | Other |
| Primary outcome measure | 1. Diversity of antibiotic resistance genes (ARGs) in the nasopharyngeal resistome (NPR) of healthy children in Blantyre, children with pneumonia in the community and children hospitalised with pneumonia when measured using metagenomic sequencing of nasopharyngeal swabs (NPS), to assess whether there is a significant difference. The NPS will be taken at recruitment for healthy community participants, and 3-month follow up for participants with pneumonia. 2. Relative abundance of ARGs in the NPR of healthy children in Blantyre, children with pneumonia in the community and children hospitalised with pneumonia, as above. 3. Diversity of ARGs in the NPR of children hospitalised with pneumonia and children re-hospitalised with pneumonia at the point of hospitalisation. 4. Diversity of ARGs in the NPR of children hospitalised with pneumonia and children re-hospitalised with pneumonia at the point of hospitalisation. |
| Secondary outcome measures | 1. Diversity of antibiotic resistance genes (ARGs) in the nasopharyngeal resistome (NPR) of children hospitalised with pneumonia when measured at admission, discharge and 3-month follow up using metagenomic sequencing of nasopharyngeal swabs (NPS), to assess whether there is a significant difference between these time-points. 2. Relative abundance of ARGs in the NPR of children hospitalised with pneumonia when measured at admission, discharge and 3-month follow (as above). 3. Diversity of ARGs in the NPR of children with pneumonia in the community at presentation to a healthcare centre and 3-month follow up. 4. Relative abundance of ARGs in the NPR of children with pneumonia in the community at presentation to a healthcare centre and 3-month follow up. 5. Diversity of ARGs in the NPR of healthy children in Blantyre and children with pneumonia in the community at presentation to a healthcare centre. 6. Relative abundance of ARGs in the NPR of healthy children in Blantyre and children with pneumonia in the community at presentation to a healthcare centre. 7. Repeat antibiotic exposure is measured using caregiver report and health passport records at 3-month follow-up in children discharged from hospital 8. Re-hospitalisation for pneumonia is measured using caregiver report and health passport records at 3-month follow-up in children discharged from hospital |
| Overall study start date | 01/04/2025 |
| Completion date | 12/02/2027 |
Eligibility
| Participant type(s) | Healthy volunteer, Patient |
|---|---|
| Age group | Child |
| Lower age limit | 12 Months |
| Upper age limit | 24 Months |
| Sex | Both |
| Target number of participants | 350 |
| Key inclusion criteria | Inclusion criteria for healthy children in the community: 1. Child aged between 12-24 months living in Ndirande community, in Blantyre, Malawi. Inclusion criteria for children with pneumonia in the community: 1. Child aged between 12-24 months presenting to Ndirande community healthcare centre, Blantyre, Malawi. 2. Presence of ALL of the following symptoms: fever, cough, difficulty in breathing and fast breathing. 3. Participant has been prescribed antibiotics for treatment of a lower respiratory tract infection on this presentation. Inclusion criteria for children hospitalised with pneumonia: 1. Child aged between 12-24 months admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi. 2. Presence of ALL of the following symptoms: fever, cough, difficulty in breathing and fast breathing. 3. Participant has been prescribed antibiotics for treatment of a lower respiratory tract infection on this presentation. Inclusion criteria for children re-hospitalised with pneumonia: 1. Child aged between 12-24 months admitted to Queen Elizabeth Central Hospital, Blantyre, Malawi. 2. Presence of all of the following symptoms: fever, cough, difficulty in breathing and fast breathing. 3. Participant has been prescribed antibiotics for treatment of a lower respiratory tract infection on this admission. 4. Hospital admission to ANY hospital with a lower respiratory tract infection within the past 3 months. |
| Key exclusion criteria | Exclusion criteria for healthy children in the community: 1. Presence of any of the following symptoms: fever, cough, difficulty in breathing or fast breathing. 2. Currently taking long-term antibiotic prophylaxis, TB treatment or immunosuppressive medications. 3. Diagnosis of an immunosuppressive illness, including HIV infection. 4. Hospital admission within the past six months. Exclusion criteria for children with pneumonia in the community and children hospitalised with pneumonia: 1. Severe anaemia, with a recorded haemoglobin level < 70 grams per Litre. 2. Currently taking long-term antibiotic prophylaxis, TB treatment or immunosuppressive medications. 3. Diagnosis of an immunosuppressive illness, including HIV infection. 4. Hospital admission within the past six months. Exclusion criteria for children re-hospitalised with pneumonia: 1. Severe anaemia, with a recorded haemoglobin level < 70 grams per Litre. 2. Currently taking long-term antibiotic prophylaxis, TB treatment or immunosuppressive medications. 3. Diagnosis of an immunosuppressive illness, including HIV infection. |
| Date of first enrolment | 13/08/2025 |
| Date of final enrolment | 13/02/2027 |
Locations
Countries of recruitment
- Malawi
Study participating centres
Ndirande Health Centre
Ndirande Ring Road
Blantyre
-
Malawi
Blantyre
-
Malawi
Queen Elizabeth Central Hospital
Chipatala Avenue
Blantyre
-
Malawi
Blantyre
-
Malawi
Sponsor information
Liverpool School of Tropical Medicine
University/education
University/education
Pembroke Place
Liverpool
L3 5QA
England
United Kingdom
| Phone | +44(0)151 705 3100 |
|---|---|
| lstmgov@lstmed.ac.uk | |
| Website | https://www.lstmed.ac.uk |
"ROR" |
https://ror.org/03svjbs84 |
Funders
Funder type
Charity
Wellcome
Private sector organisation / International organizations
Private sector organisation / International organizations
- Location
- United Kingdom
Results and Publications
| Intention to publish date | 01/11/2027 |
|---|---|
| Individual participant data (IPD) Intention to share | Yes |
| IPD sharing plan summary | Stored in publicly available repository |
| Publication and dissemination plan | The study is expected to describe nasopharyngeal resistome evolution following antibiotic selective pressure and healthcare exposure for pneumonia in children in Blantyre, Malawi. It will provide contemporary data on antibiotic resistance carriage in the community, hospital admission and re-admission rates with pneumonia, and antibiotic use patterns. A report of the study will be submitted to the College of Medicine Research Ethics Committee (COMREC), Blantyre district health office and Liverpool School of Tropical Medicine (LSTM). The findings will be presented at an international scientific conference and published in a peer-reviewed medical journal. |
| IPD sharing plan | The datasets generated during and/or analysed during the current study will be stored in a publicly available repository on GitHub: https://github.com/locucl/NP_Resistome_Study After completion of the study, the following types of data will be shared: • Anonymised, curated microbiome and resistome data will be shared with researchers on the GitHub repository. • R code for statistical analysis of the metagenomic sequence data and clinical metadata will be shared with researchers on the GitHub repository. • Anonymised clinical metadata will only be shared with scientific collaborators. All human genome sequence data will be removed in the bioinformatic pipeline; no human genome sequence data will be shared with researchers. The following types of anonymised metadata will be stored, but not shared publicly: • Human subject demographic data, including age in months and gender. • Clinical metadata, including mid-upper arm circumference in centimetres, co-morbidities, HIV status, haemoglobin level, malaria test result, antibiotic use (type and number of days). Non-collaborating scientific researchers must submit a formal project proposal for review by investigators to access the metadata, which if approved, will be released following receipt of a signed data user’s agreement setting out roles and responsibilities of data originators and recipients. Consent has been obtained from participants for sharing of anonymised data. |
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Participant information sheet | Community_Pneumonia_Participant_Information_Sheet_and_Consent_Form_Chichewa version 5.0 |
21/05/2025 | 13/08/2025 | No | Yes |
| Participant information sheet | Community_Pneumonia_Participant_Information_Sheet_and_Consent_Form_English version 5.0 |
21/05/2025 | 13/08/2025 | No | Yes |
| Participant information sheet | Healthy_Community_Participant_Information_Sheet_and_Consent_Form_Chichewa version 5.0 |
21/05/2025 | 13/08/2025 | No | Yes |
| Participant information sheet | Healthy_Community_Participant_Information_Sheet_and_Consent_Form_English version 5.0 |
21/05/2025 | 13/08/2025 | No | Yes |
| Participant information sheet | Hospital_Pneumonia_First_Admission_Participant_Information_Sheet_and_Consent_Form_Chichewa version 5.0 |
21/05/2025 | 13/08/2025 | No | Yes |
| Participant information sheet | Hospital_Pneumonia_First_Admission_Participant_Information_Sheet_and_Consent_Form_English version 5.0 |
21/05/2025 | 13/08/2025 | No | Yes |
| Participant information sheet | Hospital_Pneumonia_Readmission_Participant_Information_Sheet_and_Consent_Form_Chichewa version 5.0 |
21/05/2025 | 13/08/2025 | No | Yes |
| Participant information sheet | Hospital_Pneumonia_Readmission_Participant_Information_Sheet_and_Consent_Form_English version 5.0 |
21/05/2025 | 13/08/2025 | No | Yes |
| Protocol file | version 5.0 | 21/05/2025 | 13/08/2025 | No | No |
Additional files
- 47835 NP_Resistome_Study_Protocol_V5.0_21May2025.pdf
- 47835 Healthy_Community_Participant_Information_Sheet_and_Consent_Form_English_V5.0_21May2025.pdf
- Healthy_Community_Participant_Information_Sheet_and_Consent_Form_English
- 47835 Healthy_Community_Participant_Information_Sheet_and_Consent_Form_Chichewa_V5.0_21May2025.pdf
- Healthy_Community_Participant_Information_Sheet_and_Consent_Form_Chichewa
- 47835 Community_Pneumonia_Participant_Information_Sheet_and_Consent_Form_English_V5.0_21May2025.pdf
- Community_Pneumonia_Participant_Information_Sheet_and_Consent_Form_English
- 47835 Community_Pneumonia_Participant_Information_Sheet_and_Consent_Form_Chichewa_V5.0_21May2025.pdf
- Community_Pneumonia_Participant_Information_Sheet_and_Consent_Form_Chichewa
- 47835 Hospital_Pneumonia_First_Admission_Participant_Information_Sheet_and_Consent_Form_English_V5.0_21May2025.pdf
- Hospital_Pneumonia_First_Admission_Participant_Information_Sheet_and_Consent_Form_English
- 47835 Hospital_Pneumonia_First_Admission_Participant_Information_Sheet_and_Consent_Form_Chichewa_V5.0_21May2025.pdf
- Hospital_Pneumonia_First_Admission_Participant_Information_Sheet_and_Consent_Form_Chichewa
- 47835 Hospital_Pneumonia_Readmission_Participant_Information_Sheet_and_Consent_Form_English_V5.0_21May2025.pdf
- Hospital_Pneumonia_Readmission_Participant_Information_Sheet_and_Consent_Form_English
- 47835 Hospital_Pneumonia_Readmission_Participant_Information_Sheet_and_Consent_Form_Chichewa_V5.0_21May2025.pdf
- Hospital_Pneumonia_Readmission_Participant_Information_Sheet_and_Consent_Form_Chichewa
Editorial Notes
13/08/2025: Trial's existence confirmed by Liverpool School of Tropical Medicine.
